In order to enhance cell mediated cytotoxicity, bispecific antibodies (BsAbs), molecules combining two or more antibodies with different antigenic specificities, have been developed as new agents for immunotherapy. Our recent studies revealed that simultaneous administration of two kinds of BsAbs (anti-tumor×anti-CD3 plus anti-tumor×anti-CD28) together with lymphokine activated killer cells with a T cell phenotype (T-LAK cells) inhibited growth of human xenotransplanted tumors in severe combined immunodeficient (SCID) mice, while single BsAb was without effect. Three kinds of BsAbs (anti-tumor×anti-CD3, anti-tumor×anti-CD28, anti-tumor×anti-CD2) showed the highest cytotoxicity against tumor cells when given simultaneously with T-LAK cells or peripheral blood mononuclear cells in vitro and in vivo. BsAbs can be preserved for immediate application, while cytotoxic T lymphocytes (CTLs) must be made-to-order, and are time-consuming to prepare. Tumor associated antigens, such as MAGE antigens, SART antigens, MUC1 antigen, c-erbB 2 antigen or cancer/testis antigens can be served to target antigens for BsAb production. By conjugation with antibodies to effector cells (anti-CD3, anti-CD28, anti-CD16, anti-CD64, anti-CD89 or anti-CD2), many kinds of BsAbs can be produced to cover most types of cancers from different organs. Therefore this strategy might be ubiquitously applicable to most malignancies.
Sixty of 128 (46.9%) residents of a nursing home were immunized with two doses of the trivalent split influenza vaccine. They developed 7.4-11.5-fold antibody increases, with a 69-82% protection rate, presenting good immune response rates to the influenza vaccine. Two outbreaks of influenza A (H3N2) occurred. There were no significant antigenic differences among the vaccine strain and the strains isolated from both outbreaks in haemagglutination-inhibition tests, suggesting that the second might have been a reoccurrence. There were no residents who were infected in both outbreaks. The vaccine efficacy against clinical illness in the first outbreak of typical influenza-like-illness (ILI) was 51% (relative risk: 0.49), and the febrile period was reduced significantly by vaccination. In the second outbreak, however, in which all patients had atypical ILI with a high fever but not respiratory symptoms, vaccine efficacy was not apparent for unknown reason.
The aim of this study was to evaluate morphological changes of the cardiovascular system in fetal rats during late gestation. We used the rapid whole-body freezing technique for rats of day 17 through 21 of gestation. The right and left ventricular volumes increased markedly and significantly during this period by about 11- and 24-fold, respectively. Although the right ventricular volume was 108% larger with statistical significance than the left ventricular volume on day 17, they were almost equal after day 19. The length of the primum septum of the atrium significantly increased by 92% within 4 days, but the opening distance of foramen ovale significantly decreased by 14%. The ratio of the inner diameter (the sum of right and left pulmonary arteries to ductus arteriosus) significantly increased from 0.72±0.03 on day 17 to 1.17±0.07 on day 21. There was also a significant increase in the ratio of the inner diameters of the ascending to descending aorta. These observations suggest that the reduction of the opening distance of foramen ovale reflect the growth of pulmonary arteries.
The southern district of N city (U area), Yamagata Prefecture, is highly endemic for hepatitic C virus (HCV) infection. Around 20% of the general population are positive for antibodies to HCV (anti-HCV). Community-acquired, acute non-A, non-B hepatitis was epidemic from 1967 to 1972 in this area. Our previous study revealed that these people are actually infected with HCV, but a relationship between this outbreak and the high positivity rate of anti-HCV in the U area has not been shown. We followed up 15 anti-HCV-positive individuals who developed hepatitis during the epidemic and used the serum collected to conduct molecular evolutional analysis to reveal the characteristics of the HCV epidemic in the U area. HCV genotypes in the U area were also analyzed. Phylogenetic analysis of the HCV core gene sequences showed that the subjects' HCV sequences were closely related and derived from the same cluster. All subjects were infected with HCV genotype 1b, which was frequently detected with a high positivity of over 80% of HCV-infected individuals in the U area. These results confirm that the community-acquired hepatitis C epidemic occurred around three decades ago through an unidentified route, and suggest that this episode may result in a continuing increase in the number of HCV-1b positive patients in this small area.
We have developed a personal computer-based system designed for automated metabolic profiling of urinary organic acids by gas chromatography-mass spectrometry (GC/MS) and data interpretation for organic acidemia screening. For the automated profiling, we compiled retention indices, two target ions and their intensity ratio for 126 urinary metabolites. Metabolites above the cut-off values were flagged as abnormal compounds. The data interpretation was based on combination of the flagged metabolites. Diagnostic or index metabolites were categorized into three groups, “AND,” “OR” and “NO,” and compiled for each disorder to improve the specificity of the diagnosis. Groups “AND” and “OR” comprised essential and optional compounds, respectively, which and both to reach a specific diagnosis. Group “NO” comprised metabolites that must be absent to make a definite diagnosis. We tested this system by analyzing urine specimens from 48 patients previously diagnosed as having organic acidemias. In all cases, the diagnostic metabolites were identified and each correct diagnosis could be found among the possible diseases suggested by the system. Hence, with this simplified automated system, more people will be able to participate extensively in any screening programs using GC/MS.
The interaction between prostaglandins and α-adrenoceptors in neural control of tubular sodium reabsorption was examined in anesthetized dogs. Renal nerve stimulation (RNS; 0.5-1.0 Hz, 10 V, 1.0-milliseconds duration) reduced fractional excretion of Na+ (FENa) with minimal changes in hemodynamics and glomerular filtration. Intrarenal arterial infusion of prazosin (0.7 μg·kg−1·min−1), an α1-adrenoceptor antagonist, inhibited the RNS-induced reduction in FENa. However, the RNS-induced reduction in FENa was resistant to prazosin under pretreatment with indomethacin (5 mg/kg, i.v.), a cyclooxygenase inhibitor. Intrarenal arterial infusion of yohimbine (1 μg·kg−1·min−1), an α2-adrenoceptor antagonist, failed to inhibit the RNS-induced reduction in FENa in the absence or presence of indomethacin, but combined infusion of prazosin and yohimbine abolished the RNS-induced reduction in FENa in the presence of indomethacin. These results suggest that both α1- and α2-adrenoceptors mediate the RNS-induced antinatriuresis, but the α2-adrenoceptor-mediated portion is impaired by prostaglandins.