Masahiro Fujii

12-O-tetradecanoylphorbol-13-acetate induces the enhancer function of human T-cell leukemia virus type I

Phorbol esters were employed in studies on the molecular mechanism of the induction of expression of human T‐cell leukemia virus type I (HTLV‐I) by a tumor promoter, 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). Experiments using the chloramphenicol acetyltransferase (CAT) system showed that CAT expression directed by the long terminal repeat (LTR) of HTLV‐I was induced by TPA, but not by 4α‐phorbol‐12,13‐didecanoate, which is not an activator of protein kinase C, and that like other known enhancers, irrespective of its position and orientation, a 230‐bp fragment in the U3 region of the HTLV‐I LTR confers susceptibility to induction by TPA.

Determination of hepatic fractional clearance of radioactive gold colloids for a measure of effective hepatic blood flow

Abstract As a measure of effective hepatic blood flow, hepatic fractional clearance of 198 Ar colloids was determined from the disappearance rate multiplied by the fraction of injected dose taken up by the liver. The hepatic uptake was determined with a gamma camera, the count over the liver being corrected for body weight and height. The method was considered sufficiently simple for routine use. Quality control tests were performed over a six-year period on colloids from Dainabot Lab., Japan, and CIS. Results indicated that 31.0% higher values are given by the former than the latter, without any change in the organ distribution. Reproducibility within 95% confidence limits was found for both groups. In 28 normal subjects, hepatic fractional clearance of the colloids from Dainabot Lab. was 18.5 ± 3.4%/min. In patients with advanced hepatic disease, both hepatic fractional clearance and final hepatic uptake was decreased, showing that the determination of hepatic uptake is necessary in measuring effective hepatic blood flow by the colloidal clearance method. The influence of splenic uptake is discussed in relation to hepatic blood flow measurement.

The Incorporation of Delta Aminolaevulinic Acid and Glycine into Faecal Stercobilin and Coproporphyrin in Man

The incorporation of [4‐14C]ALA and [2‐14C]glycine into haem, faecal coproporphyrin and stercobilin was studied in patients with various disorders. After the administration of [4‐14C]ALA, the specific activities of isolated faecal copropor‐phyrin and stercobilin increased and declined quickly within 3–4 days. These changes were associated with each other, and this relationship suggests that they arise from a common source. Incorporation of the labelled precursor into haem was minimal. When [2‐14C]glycine was the precursor, the rise and fall of faecal Coproporphyrin activity was independent of that of stercobilin and the stercobilin activity maintained a plateau for several days after the fall of faecal Coproporphyrin activity. This was associated with incorporation of the precursor into red cell haem. The activity peak in stercobilin which appeared at the end of red cell life span was not associated with faecal Coproporphyrin activity. These findings are consistent with the presence of two components of early‐labelled bilirubin. The first of these is associated with faecal Coproporphyrin activity and independent of erythropoiesis and the second is unassociated with faecal Coproporphyrin and closely related to erythropoiesis.

Drug-related hepatitis.

Excerpt To the editor: We have read with interest the paper by Miller and associates on halothane hepatitis in the August 1978 issue. During the last 6 years, we have seen 35 patients with a drug-i...

Selective Inhibition of High- but Not Low-Affinity Interleukin 2 Binding by Lectins and Anti-Interleukin 2 Receptor α Antibody

The present study demonstrated that various reagents can specifically reduce the affinity of high‐affinity interleukin 2 receptor (IL‐2R) but not that of low‐affinity IL‐2R. They included lectins such as wheat germ agglutinin (WGA), concanavalin A and phytohemagglutinin, and a chemical cross‐linker, glutaraldehyde, in addition to anti‐IL‐2R monoclonal antibodies, HIEI and H‐47. The affinity of the high‐affinity IL‐2R was reduced when the cells were treated with WGA or H‐47 before, but not after, addition of 125I‐labeled interleukin 2 (IL‐2). Their inhibitory effects were also demonstrated by the chemical cross‐linking method. On treatment with the reagents, the IL‐2 binding to both IL‐2Rα and β chains was inhibited and these inhibitory effects were seen only when the reagents were added before IL‐2 addition, like their high‐affinity reducing effects. These results support a supposition that the high affinity IL‐2R is generated by assembly of the α and β chains, and suggest that the IL‐2 binding to IL‐2Rα and β chains could induce stable constitution of the high‐affinity state of IL‐2R, but these affinity modulating reagents could perturb the optimum association between α and β chains to generate the high‐affinity IL‐2R.

High affinity interleukin 2 receptors in HTLV-1-Infected T cells can mediate signals for gene expression

The expression of transcripts of the c-myb and c-myc protooncogenes and the interleukin 2 receptor (IL-2R) gene in human T cells infected with human T-cell leukemia virus type 1 (HTLV-1) after exposure to interleukin 2 (IL-2) were examined. Infection with HTLV-1 is known to be associated with constitutive expression of IL-2R, although infected cells do not require IL-2 for growth. Northern blot analysis showed that expression of the mRNAs of the c-myb, c-myc, and IL-2R genes were markedly increased by addition of IL-2 into the cultures, indicating that IL-2R transduced signals for gene expression in these cells as in normal T cells. Studies on distinct HTLV-1-infected T cell clones that differed in numbers of high-affinity IL-2R, showed that the extents of increase in mRNA expression by IL-2 were correlated with the number of high-affinity IL-2R. This correlation was confirmed by demonstration that the levels of mRNA expression were proportional to the numbers of IL-2-bound high-affinity but not low-affinity receptors. Thus, the signals induced by IL-2 for gene expression may be through high-affinity IL-2R.

Throughput Evaluation of CSMA Assuming Carrier Detection Probability in Wireless Ad Hoc Networks

In performance evaluations of wireless ad hoc networks, both successful data reception and carrier detection probabilities are assumed to be 1 within a circle with certain radius and 0 outside the circle. In real systems, however, those probabilities are gradually changes from 1 to 0 as the distance between a terminal and access point increases. In this paper, we evaluate the throughput of wireless ad hoc networks assuming successful data reception and carrier detection probabilities to be continuous functions of the distance between a terminal and access point. We also show that new additional factors which decrease the throughput will appear under these assumptions, compared to the case where only probabilities 1 and 0 are assumed

Abnormality of serum immunoglobulins in chronic liver disease-immune complex like substances, abnormaly basic γ-globulin, secretory IgA and anti-DNA antibody

1) Serum secretory IgA was reduced in chronic liver disease while it was increased in obstructive jaundice. 2) Serum anti-dsDNA antibody was slightly increased in chronic liver disease, especially it was significantly increased in lupoid hepatitis in which its titer paralelled with the course of disease activity. 3) Serum Clq binding activity, Clq binding inhibition activity and polyclonal rheumatoid factor binding inhibition activity were increased in chronic liver disease and their disease activity was correlated with concentration of macromolecular immune complexes which were fractionated with sucrose density gradient ultracentrifugation. 4) Abnormally basic y-globulin which was dominantly found in chronic hepatitis B sera was determined to be monomeric IgG. I t was increased in aggravation of the disease but has no correlation with Clq binding monomeric IgG. 5) Liver membrane specific lipoprotein (LP-1), Espinosas liver specific antigen (LSA), Nerenbergs hepatorenal antigen (HRA) and Tamm-Horsfall glycoprotein (THGP) had positive charge, and LP-2 and F-antigen did negative charge. 6) Human liver cell membrane fraction could not be obtained by the method of Ray or aqueous two phase polymer system which have been used for rat liver.

Studies on the synthesis of bilirubin

The incorporat ion of 4 14C delta aminolebulinic acid (ALA)and 2 14C glycine into heme, fecal coproporphyrin (FCP) and stercobil in (STB) were studied in cases with various disorders. Following the adminis t ra t ion of 4 14C ALA, activi t ies of FCP and STB appeared and declined within 4 or 5 days and the changes of two kinds of activity were associated with each other. This relat ionship suggested tha t they were produced from the common source. When 2 14C glycine was given, the r ise and the fall of FCP activity was independent of those of STB act ivi ty and FCP showed activi ty only on earl iest few days and no activity at the t ime of the end of red cell life span. STB activi ty kept a plateau for several days after the disappearance of FCP activity and then declined to lower level. The incorporat ion of 2 14C glycine into heme was active whereas tha t of 4 14C ALA was minimal. These re la t ions suggested the exis tence of two components of early appearing stercobilin. The first component associated with FCP activity and was independent of erythropoiesis and the second component was free f rom FCP product ion and dependent on erythropoiesis. In two cases of normal red cell life span who received 2 14C glycine the first component of STB was much less than the second component in each case (1 : 3.7, 1 : ]0.4). FCP activit ies showed no relat ion to the red cell destruct ion but associated with hepatic production of b i l i rubin tha t was observed in 4 14C ALA exper iments . It seems likely from these relat ions tha t FCP is of hepatic in origin.

The studies on shunt bilirubin (III)

We have already reported the exsistence of b i l i rubin phosphate in serum and urine paperchromatographical ly using molibdic-acid color reaction. In this report we confirmed the exsistence of bi l i rubin phosphate us ing p32 as a tracer. We made the fistula on bile ducts of normal rats, injected 0.5 ml of Na2P320~ into the duodenum, gathered bile for 24 hours and est imated radioactivi ty wi th G.M. counter. At first, b i l i rubin extracted from this bile was f ract ionated by paperchromatography, then radioautography or radiochromatography was carr ied out. The 3rd spot of b i l i rubin on paperchromatogram was agreed with the radioact ive spot on radioautogram or radiochromatogram. On the o ther hand, we separated the bile b i l i rubin ex t rac t into indirect, saIt-form and esterform bi l i rubin using Kosaka-Hara s method and es t imated bi l i rubin concentra t ion and radioact ivi ty of each fract ion Ester-form bi l i rubin exhibited 98.9% radioactivity.