The alpha-form of S-adenosylmethionine synthetase isozymes from liver is principally functional

Treatment of rats with an ethionine plus adenine or a methionine diet leads not only to a marked increase of the alpha-form isozyme of S-adenosylmethionine synthetase in liver, but also to the accumulation of comparable amounts of S-adenosylethionine and S-adenosylmethionine in liver. Transplantation of ascites tumor cells into mice leads to a marked increase only of the beta-form isozyme in the host liver, but the levels of S-adenosylmethionine do not significantly change in liver.     

Determination of fragment D-dimer derivatives in serum reactive with antiserum against human fragment D-dimer

A previous study demonstrated the preparation of an antiserum having enough specificity and sensitivity for a radioimmunoassay to determine fragment D-dimer derivatives. Using the antiserum the contents of fragment D-dimer derivatives in the sera of normal subjects and patients were determined. The content in normal subjects was 0.260 +/- 0.07 micrograms/ml (mean +/- SD) an that in patients with elevated levels of FDP ranged from 0.30 to 28 micrograms/ml. The values of fragment D-dimer derivatives and FDP in sera of some patients did not necessarily change in parallel, although there seems to be generally a positive correlation between them.     

Behavior of Japanese monkey (Macaca fuscata) mothers and neonates at parturition

Parturitional behavior in 12 caged Macaca fuscatawas analyzed. Wild-caught mothers showed adequate maternal behaviors immediately following the neonate’s expulsion. Parity differences existed in the behaviors; primiparae were more idiosyncratic than were multiparae. Among multiparae, those with two or more offspring were uniformly adequate, but those with a single birth experience varied in the adequacy of the maternal care they provided at parturition. Mothers embraced and licked their neonates and had ventroventral contact with them frequently immediately after parturition but decreased these behaviors after expulsion of the placenta. In contrast, mothers showed allogrooming after consuming the placenta. Placentophagy was correlated with the level of orality represented by maternal licking behaviors. An isolation-reared primipara reacted to her newborn in a basically negative manner, although she showed little actual aggression. She showed a rapid shift in her negative behavior during the immediate postpartum period. This mother’s newborn sought contact with her, indicating the neonate’s active role in establishing a stable mother-neonate bond.     

Effect of absolute and relative changes of hematocrit on erythropoiesis in mice

The serial changes of peripheral reticulocytes and marrow erythroid progenitor cells (CFU-e) in mice were monitored under the conditions of absolute or relative changes in red cell mass to study the regulatory mechanism of erythropoiesis. A decreased number of marrow CFU-e and peripheral reticulocytes was observed in the mice with relative polycythemia induced by dehydration as well as in the mice with absolute polycythemia induced by hypertransfusion. On the other hand, a transient increase in the number of marrow CFU-e followed by a gradual increase in the number of peripheral reticulocytes was seen after a considerable amount of exsanguination. Similar stimulatory effects on marrow CFU-e were also observed either by rehydrating the dehydrated mice or by overhydrating the untreated mice to relatively decrease the level of hematocrit. The results suggested that in addition to factors relating to the balance between oxygen supply and requirement, which has been well known, erythropoiesis is greatly affected by hematocrit.     

Effect of ethionine on synthesis and methylation of ribosomal ribonucleic acid in regenerating rat liver

Ethionine, a hepatocarcinogen, was administered into rats 24 h before partial hepatectomy and immediately thereafter. Hepatic precursor ribosomal RNA (pre-rRNA) obtained 20 h after the operation of rats injected with ethionine and adenine resulted in methyl deficiency as judged by the incorporation of [3H]methyl group of S-adenosylmethionine into nuclear rRNA by partially purified rRNA methylase. The ethionine and adenine treatment causes methyl deficiency of nuclear rRNA at 2'-hydroxyribose sites of cytidine and uridine, but not at base sites. Although the ethionine and adenine treatment produced no significant change in total hepatic RNA synthesis in vivo assayed by the incorporation of labeled orotate, a one-third increase in nuclear rRNA synthesis as well as a one-third decrease in microsomal rRNA synthesis was found under the treatment. These results suggest that the undermethylation at 2'-hydroxyribose of pre-rRNA in liver nucleus, which is caused by ethionine and adenine administration into rats, causes an inhibition of the processing of nuclear pre-rRNA to cytoplasmic rRNA.     

The effect of bispecific monoclonal antibody recognizing both hepatoma-specific membrane glycoprotein and anthracycline drugs on the metastatic growth of hepatoma AH66

A monoclonal mouse antibody (MoHG) was produced using in vitro cultured AH66R tumor cells treated with cholesteryl hemisuccinate as an immunogen. The antibody identified a 90 kd membrane glycoprotein (HG-90) which is expressed on in vitro cultured hepatoma cell lines AH66 and AH66R. A monoclonal antibody was prepared to the anthracycline drug daunomycin, and it also reacted with adriamycin. A fusion was made of the hybridoma HG-90 with the hybridoma which recognized daunomycin/adriamycin. This bispecific hybridoma A8C recognized both determinants. We studied the therapeutic effect of the A8C bispecific antibody with adriamycin treatment and compared it to the effect of the bispecific antibody to which adriamycin had been conjugated via an albumin (Alb) bridge. The therapy model used was the tumor AH66R in Donryu rats. Tumor bearing rats had their subcutaneous tumors resected on day 10, a time when distant metastases were present. After the surgical resection of the tumor the rats were injected intravenously for two cycles with the bispecific antibodies, followed by the administration of adriamycin (ADR) or MoHG.Alb.ADR conjugates. A slight therapeutic effect occurred with either MoHG or ADR alone but treatment with the bispecific antibody followed by the administration of ADR or with the MoHG.Alb.ADR conjugates significantly prolonged survival, with 60% of the treated animals being "tumor free" when sacrificed on day 80. Lower serum concentrations of alphafetoprotein were observed with the bispecific antibody and drug treatment. This suggests that the bispecific antibody/drug treatment is potentially more beneficial in the suppression of distant metastases than the MoHG.Alb.ADR conjugate. This may be due to an increase in the local drug concentration of unmodified adriamycin.