Minoru Ishizawa

A Distinct mRNA Encoding a Soluble Form of ICAM-1 Molecule Expressed in Human Tissues

A soluble form of ICAM-1 (sICAM-1) have been observed in normal human serum (Rothlein et al., J. Immunol. 147, 3788-3793) and at elevated levels in inflammatory and tumor bearing status (Seth et al., Lancet, 338, 83-84; Giavazzi et al., Canc. Res. 52, 2628-2630; Harning et al., Canc. Res., 51, 5003-5005). However, the mechanism to produce the sICAM-1 has been still unknown. In this report we presented evidence for the presence of the mRNA specifically encoding sICAM-1, which is probably generated by alternative splice donor site selection. A 19-base deletion occurred right upstream of the transmembrane region gave rise to reading frameshift and eliminate the entire transmembrane and cytoplasmic domains, resulting in incapability of ICAM-1 molecules to reside in the membrane. A reverse transcription-polymerase chain reaction (RT-PCR) using a primer pair specific to sICAM-1 revealed a positive expression in all tissues analyzed, though the amount and the ratio to the conventional species varied slightly from tissue to tissue. Inflammatory cytokines displayed a complex pattern in the ICAM-1 mRNA expression depending on the combination of cytokines and the cultured cell lines used.

Inactivation of cis-diamminedichloroplatinum (II) in blood and protection of its toxicity by sodium thiosulfate in rabbits.

SummaryThe mode of inactivation of cis-diamminedichloroplatinum(II) (DDP) in the bloodstream and protection from its toxicity by sodium thiosulfate (STS) were investigated in rabbits.Plasma ultrafiltrate in rabbits given 5 mg/kg DDP IV and various excess molar ratios of STS IV were assayed for the active platinum levels with a new microbiological assay system using an E. coli strain. The active platinum species in the plasma were inactivated completely by coadministration of a 400-fold excess of STS IV. The rabbits were almost completely protected against both BUN increase and body weight loss normally caused by DDP when 400-fold doses of STS were given. Diuretic effects were also observed.Our data provide evidence for the basis of optimum use of STS to protect against DDP toxicity. [6, 9]. This TRC with DDP and STS is now in clinical trial [7, 8], but the precise mode of protective action of STS against DDP toxicity has not been determined.We now present evidence that this protective effect is due to inactivation of biologically active DDP in the bloodstream.

Mutagenesis of bacteriophage T4 by a carcinogen, 4-nitroquinoline 1-oxide

Abstract The mutagenic behaviour of a carcinogen, 4-nitroquinoline 1-oxide (4NQO), was investigated in bacteriophage T4. 4NQO was mutagenic for intracellular but not for extracellular phages. Mutations induced in the r II region of T4 by treatment of intracellular phages with 4NQO were classified according to their susceptibilities to induced reversion by 2-aminopurine, 5-bromodeoxyuridine, hydroxylamine, proflavine, and 4NQO. More than half the mutants were of the transition type revertible with the base analogues, but nearly all of these failed to respond to hydroxylamine mutagenesis. These were therefore classified as mutants of a transition class presumably carrying an AT base pair at the mutant site. None of the induced mutants was capable of reverting with 4NQO or proflavine. These results suggest that the guanine-hydroxymethylcytosine base pair of phage T4DNA is the major mutagenic target in the induction of transition mutations by 4NQO.

Ingestion of parsley inhibits the mutagenicity of male human urine following consumption of fried salmon

The urinary mutagenicity of 3 nonsmoking, healthy men was investigated after strictly defined meals by means of the Ames Salmonella/microsome test. When the subjects ate 150 g of fried salmon at one meal, a potent mutagenicity of almost 5000 revertants of TA98 strain was present in all 6-h urine samples. On the other hand, less than 2500 revertants was present in the urine when the subjects simultaneously consumed 70 g of parsley and 150 g of fried salmon. Thus, the protection against mutagenicity affected by parsley warrants further attention.

Mutagenicity of human urine after the consumption of fried salted salmon

Mutagenicity in the urine of four non-smoking individuals who had eaten salted salmon cooked at home for both lunch and supper was monitored by means of Salmonella/microsome mutagenicity tests. Extracts from fresh and salted salmon had the same level of mutagenicity after being cooked for 10 min at 200 degrees C, but no activity was detected before cooking. Salmonella strains TA98 and TA1538 were equally sensitive to the mutagens and required metabolic activation. No mutagenicity was shown with TA100 and TA1535. Urine samples were tested using a concentrate prepared by means of an XAD-2 resin column. Mutagenicity was detected mainly in urine excreted during 4-5 hr after the ingestion of cooked salmon, but only weak mutagenicity, or none at all, was detected in the urine after the ingestion of vegetables. The levels of urinary mutagenicity due to salmon consumption were not affected when cabbage was eaten simultaneously. The excretion of mutagenic substances was completed within about 20 hr, and there were almost no mutagens in the urine 24 hr after the ingestion of cooked salmon.

Novel Inducers and Inhibitors of Differentiation of Friend Erythroleukemia Cells: Application of an Opal Glass Transmission Method to Study of Erythroid Differentiation

The potencies of poly(ADP‐ribosylation)‐inhibitors in inducing erythroid differentiation of Friend erythroleukemia cells were surveyed. Picolinamide and m‐aminobenzamide were newly found to be inducers, whereas compounds related caffeine did not induce differentiation. In other series of experiments some bile acids suspected of being tumor promoters were found to inhibit the differentiation like typical tumor promoters such as phorbol esters. These modifications of erythroid differentiation were detected by an opal glass transmission method. This method is simpler than any previously reported methods, and is sufficiently reliable to use in determining hemoglobin in living cells as a quantitative marker of erythroid differentiation.