Human monoclonal antibodies (mAbs) are very useful for treatment of cancer, but they are difficult to obtain since immunization of humans is not a practical proposition at present. As an approach to circumvent this problem, we have simultaneously inoculated cancer tissues and regional lymph node cells obtained from lung cancer patients into SCID mice to allow in vivo stimulation of human lymphocytes against autologous cancer tissues. Human immunoglobulins, especially IgG, were observed in the SCID-hu sera, and some showed high reactivity to lung cancer cell lines. Testing of human B-lymphoblastoid cell lines obtained from SCID-hu spleen and thymus for antibody activity revealed 16-45% of them to be reactive to lung cancer cells. These percentages are high as compared with previous reports. Furthermore, we could establish 4 human IgG mAbs reactive to lung cancer cell lines. These results indicate successful stimulation of specific human lymphocytes in vivo, which thereby enables efficient generation of human monoclonal antibodies using SCID-hu mice.

Adenocarcinoma↗

PubMedDate not supplied

Effects of flushing temperature and preservation solution on alveolar fluid clearance in the preserved rat lungs.

Explore the source record for details and available documents.

Adenosine↗

PubMedDate not supplied

Na+/K(+)-ATPase activity in rat lungs preserved with EP4 solution.

Explore the source record for details and available documents.

Animals↗

PubMedDate not supplied

Difference in the effect of phloridzin on alveolar fluid absorption in anesthetized rats and in ex vivo rat lungs.

We reexamined the effect of phloridizin on alveolar fluid absorption by utilizing ex vivo rat lungs, which are considered to be a useful tool to investigate electrolyte and fluid transport across alveolar epithelium. Alveolar fluid absorption was almost completely reduced by 10(-3) M phloridzin with 10(-4) M amiloride as reported previously. However, we found that phloridzin alone was also able to significantly reduce alveolar fluid absorption. We then examined the effect of phloridzin on lung metabolism and compared the data with those determined in the presence of iodoacetic acid (IAA) and NaCN. Phloridzin reduced alveolar glucose uptake with no decrease in lung ATP content. Both IAA and NaCN decreased lung ATP content significantly. Our data indicate that the effect of phloridzin on alveolar fluid absorption in ex vivo rat lungs is not the secondary effect to the alteration of lung energy metabolism. Therefore our data support the current concept that Na(+)-glucose cotransport is involved with transalveolar active Na+ transport, which is a separated pathway from amiloride-sensitive Na+ channels.

Adenosine Triphosphate↗

PubMedDate not supplied

Ribose-transfer activity from uridine to 5-fluorouracil in Ehrlich ascites tumor cells.

Anabolism of 5-fluorouracil (5-FU) in the presence of uracil was examined using the cell-free extract of Ehrlich ascites tumor cells. FU-nucleoside formation from 5-FU with ribose 1-phosphate (R-1-P) or 2'-deoxyribose 1-phosphate was not readily inhibited even by the addition of uracil at 100 times higher concentration than 5-FU. FU-nucleotide formation from 5-FU with R-1-P and adenosine 5'-triphosphate or with 5-phosphoribosyl 1-pyrophosphate was slightly reduced as the concentration of uracil was increased. It was also found that 5-fluorouridine (5-FUR) was produced by "nucleoside N-ribosyltransferase," transferring a ribose moiety from uridine (UR) to 5-FU directly. This activity might play a role in the preferential formation of 5-FUR. However, 5-fluoro-2'-deoxyuridine was not produced by directly transferring a deoxyribose moiety. On the basis of several column chromatographies and characterization of kinetics, pH dependency, and response to inhibitors, the enzyme protein of the ribosyltransferase could not be distinguished from that of the phosphorylase.

Animals↗

PubMedDate not supplied

Comparative in vitro activity of vancomycin and other antimicrobial agents against methicillin-resistant staphylococcus aureus and enterococcus faecium in the Tohoku district of Japan.

Susceptibility patterns of methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecium obtained from various hospitals of the Tohoku district were documented. MICs of 6 antimicrobial agents against a total of 480 strains (380 strains were MRSA and 100 were E. faecium) were estimated. All MRSAs were susceptible to vancomycin, teicoplanin and quinupristin/dalfopristin, but all of them were resistant to ampicillin and benzylpenicillin. None of the E. faecium strains were found to be resistant to vancomycin, teicoplanin and quinupristin/dalfopristin. Excluding these, almost all strains of E. faecium were resistant to the remaining drugs. These data suggest that despite the emergence of vancomycin resistance to E. faecium in Europe and in the United States, vancomycin, teicoplanin and quinupristin/dalfopristin will nevertheless provide effective bactericidal activity in the Tohoku area of Japan.

Ampicillin↗

PubMedDate not supplied

Comparative in vitro activity of S-4661, a new parenteral carbapenem, and other antimicrobial agents against respiratory pathogens.

The activity of S-4661, a new parenteral carbapenem antibiotic, was evaluated against 202 recent clinical isolates of respiratory pathogens. S-4661 was similar to or 2 times more active than imipenem, meropenem, and biapenem, and 8-128 times more active than ceftazidime against gram-positive bacteria. Against gram-negative bacteria, S-4661 was slightly less active than meropenem, but 2-8 times more active than the other agents. In particular, against Pseudomonas aeruginosa S-4661 showed the most potent activity. Thus it was found that S-4661 possesses a potent and well-balanced activity against respiratory pathogens.

Anti-Bacterial Agents↗