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Biomedical subjects

H Esumi

Publications and source records attributed to H Esumi.

At least 145 records · Page 8Linked to original sources
PubMed1990

Heterocyclic amines produced in cooked food: unavoidable xenobiotics.

Humans are continuously exposed to naturally occurring and industrial xenobiotics in their daily lives. Heterocyclic amines, which are formed during the cooking of proteinaceous foods, have been categorized as a new class of naturally occurring xenobiotics. They are divided into 2-amino-3-methylimidazo[4,5-f] quinoline (IQ)- and non-IQ-types. The amounts and proportion of total mutagenicity contributed by the IQ-type heterocyclic amines in cooked food are greater than those of the non-IQ-types. Precursors of the IQ-type heterocyclic amines including IQ, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are creatinine, amino acids and sugars in meat and fish. Both types of heterocyclic amines are carcinogenic in mice and rats. All heterocyclic amines except PhIP frequently induce cancers in the liver, while PhIP induces lymphomas in mice and carcinomas of the colon and mammary gland in rats. Based on quantitative analysis of heterocyclic amines in cooked food and levels of excretion of unchanged heterocyclic amines in human urine, total heterocyclic amine intake was calculated to be around 0.4-16 micrograms/person per day. As in the case of other naturally occurring xenobiotics, and degree of exposure is small and is presumably insufficient alone to account for the development of human cancer. Nevertheless, a linear relationship has been demonstrated between DNA adduct levels and a wide range of doses of MeIQx in animals. In addition, combined treatment with five heterocyclic amines yielded additive or synergistic effects in the development of glutathione S-transferase placental form (GST-P) positive foci. Taking these results and current observations of multiple genetic alterations in human cancers into consideration together, heterocyclic amines are probably involved in the development of human cancer in the presence of other carcinogens, tumor promoters and factors stimulating cancer progression.

Amines↗
PubMed1990

Demonstration by in situ hybridization of ret proto-oncogene mRNA in developing placenta during mid-term of rat gestation.

Expression of the ret proto-oncogene (proto-ret) in rat conceptus tissues during development was examined by in situ hybridization using photobiotin-labeled oligodeoxyribonucleic acid probes corresponding to regions coding for the kinase and transmembrane domains of proto-ret gene product. High levels of the proto-ret transcripts were detected in the cytotrophoblasts in the placenta in the mid-gestational period (days 10 and 11), but on day 14 of gestation, when the placenta was undergoing morphological changes, transcripts could no longer be detected in the trophoblasts. These results suggest that the increased expression of proto-ret may be associated with the proliferation and/or differentiation of trophoblast cells at a specific stage. Improvements in the in situ hybridization technique by introduction of an ultrafast microwave energy fixation method, and repeated-reaction cycling of avidin-alkaline phosphatase and a biotinylated anti-avidin antibody for signal amplification, are also briefly discussed.

Animals↗
PubMed1989

Cisplatin combination chemotherapy in squamous cell carcinoma and adenoid cystic carcinoma of the skin.

Seven patients with skin cancers, six with squamous cell carcinoma (SCC) and one with adenoid cystic carcinoma, were treated with cisplatin in combination with vindesine or adriamycin. Partial response was observed in three patients with squamous cell carcinomas: two cases with metastatic lung lesions and one with a primary skin lesion and lymph node metastasis. Two of the responding SCC had been resistant to previous chemotherapy, including peplomycin and mitomycin C. Multiple metastatic lesions of adenoid cystic carcinoma of the skin completely regressed after two courses of the combination chemotherapy with cisplatin and adriamycin. This report showed that cisplatin combination chemotherapy may be useful for the treatment of cutaneous squamous cell carcinoma, which is resistant to peplomycin, and adenoid cystic carcinoma of the skin.

Adult↗
PubMed1986

Presence of albumin-positive cells in the liver of analbuminemic rats and their increase on treatment with hepatocarcinogens.

The analbuminemic rat is a mutant in which albumin mRNA processing is blocked owing to a seven-base-pair deletion in the 9th intron of the albumin gene. A small amount of albumin is detected in the serum of this rat. Production of serum albumin in the liver of this mutant rat was studied by an immunohistochemical method. The results showed that a few albumin-positive cells were present in the liver of the mutant rat, whereas all the hepatocytes in normal rat liver were albumin-positive. In the mutant the number of albumin-positive cells increased with age: their frequency was 10(-5) at birth and 6 X 10(-3) at 45 weeks of age. On administration of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) and 2-acetylaminofluorene, albumin-positive cells increased dramatically. Their numbers were 7 to 10 times those of untreated rats after 10 to 16 weeks of carcinogen treatment. The number of albumin-positive cells did not decrease after 3'-Me-DAB feeding was discontinued. In regenerating liver after partial hepatectomy, clusters of albumin-positive cells increased while the number of singlet albumin-positive cells decreased. These observations suggest that the appearance of albumin-positive cells in analbuminemic rat liver may be due to a somatic mutation of the hepatocytes.

2-Acetylaminofluorene↗
PubMed1985

Appearance of albumin-producing cells in the liver of analbuminemic rats on aging and administration of mutagens.

The lack in serum albumin in analbuminemic rats, a strain derived from Sprague-Dawley rats, was found to be due to deficient synthesis of albumin in the liver caused by a disturbance in the processing of albumin mRNA. The serum albumin gene was cloned from analbuminemic rats and from parental normal Sprague-Dawley rats. Analyses of the nucleotide sequences of these albumin genes revealed that there is a seven base pair deletion in the HI intron of the albumin gene of analbuminemic rats. This deletion extends from the 5th to the 11th base of the 5'-end of the intron causing change in the nucleotide sequence of the 5'-end of the HI intron from GTAGGTT to GTAGCGA. The HI intron sequence was found to be accumulated in the nuclear RNA of analbuminemic rat liver indicating blocking of mRNA splicing. Although analbuminemic rats are almost completely deficient in serum albumin, a small but appreciable amount of "albumin" was detected in their serum. This protein was purified by immunoprecipitation and SDS-gel electrophoresis and shown to have the same immunological crossreactivity and digestion patterns with V8 protease and papain as those of normal rat serum albumin. The concentration of "albumin" increased slightly upon aging of analbuminemic rats. The existence of serum albumin in hepatocytes of analbuminemic rats was studied immunohistochemically by the peroxidase anti-peroxidase method. There were about 1/10(5) albumin-positive cells, presumably albumin-producing hepatocytes at birth, and their number increased gradually to 100 approximately 200/10(4) about 24 months after birth. When the hepatocarcionogenic mutagen 3'-methyl-4-dimethylaminoazobenzene was administered to analbuminemic rats, the number of albumin-positive cells in the liver increased 8-fold in 5 weeks and 10-fold in 15 weeks. A similar increase was observed after administration of acetylaminofluorene, but not after partial hepatectomy or administration of diethylnitrosamine.

Aging↗
PubMed1985

[Multidisciplinary treatment of malignant melanoma].

Prognosis was obviously poor in PPSM-treated stage Ib cases, compared with extra PPSM-treated counterparts (P less than 0.01). Out of the PPSM-treated stage Ib cases, those where prophylactic lymph node dissection was performed ran a prognosis similar to the extra PPSM-treated stage Ib cases: it is advisable therefore to perform the prophylactic lymph node dissection actively in the PPSM-treated stage Ib cases. A response rate of 28.6% was achieved with PAV therapy in stage IV cases, with metastases to the skin, subcutaneous tissue, lymph nodes and bone responding to the therapy. PAV therapy, when applied in operable cases, brought about excellent 5-year survival rates as 100% high as in stage Ia, 92.9% in stage Ib, 53.1% in stage II, and 66.9% in stage Ib + II cases. In a randomized, controlled study of bestatin in stage Ib and II cases over about 4 years has revealed that both the disease-free rate and the survival rate were significantly high in the bestatin-treated group, compared with the control group.

Adult↗
PubMed1984

Integration of v-rasH does not necessarily transform an immortalized murine cell line.

Plasmids containing v-rasH and Ecogpt were constructed, and used to transfect two established cell lines of mouse origin, NIH3T3 cells and m5S cells. After transfection, most NIH3T3 cells, which are resistant to mycophenolic acid, showed phenotypes characteristic of neoplastic transformation, whereas no mycophenolic acid-resistant m5S cells showed these phenotypes; integration of functionally intact v-rasH in immortalized murine cells is not sufficient for neoplastic transformation in m5S cells. The resistance to the transformation was probably due to a lower level of the v-rasH gene transcripts in m5S cells.

Animals↗
PubMed1983

A seven-base-pair deletion in an intron of the albumin gene of analbuminemic rats.

Analbuminemic rats, which genetically lack serum albumin, have a mutation affecting albumin mRNA processing. Serum albumin genes were cloned from analbuminemic and normal parental Sprague-Dawley rats. Structural analyses of the two albumin genes showed that the gene from analbuminemic rats had a seven-base-pair deletion in an intron. The deletion extended from base 5 to base 11 from the 5' end of intron HI of the albumin gene. This deletion converted the sequence, G-T-A-G-G-T, which is normally located at the 5' end of intron HI, to G-T-A-G-C-G. RNA blot hybridization of analbuminemic and normal rat liver nuclear RNA using a DNA fragment containing the intron HI as a probe showed that this intron sequence persisted in albumin mRNA precursors of analbuminemic rats.

Animals↗
PubMed1983

Establishment and characterization of 10 cell lines derived from patients with adult T-cell leukemia.

By using human T-cell growth factor (TCGF), 10 cell lines were established from tissue samples of 10 patients with adult T-cell leukemia (ATL). Three cell lines were adapted to growth in medium lacking TCGF. The surface markers of all cell lines were characteristic of inducer/helper T cells, i.e., OKT3+, OKT4+, OKT6-, OKT8-, OKIa1+, and human Lyt2+ and Lyt3+, except that one cell line was OKT3-. The expression of the viral antigen was examined during establishment of 8 of the 10 cell lines. The viral antigen was not expressed in leukemic cells before cultivation. In 5 lines, the viral antigen was detected by immunofluorescent staining after a short period of cultivation. However, 3 cell lines, ATL-6A, ATL-9Y, and ATL-1K did not express the viral antigen during short-term culture: the ATL-6A and ATL-9Y cell lines became positive for the viral antigen after 5 and 2 months of cultivation, respectively; the ATL-1K cell line remained antigen-negative throughout a culture period of 13 months. Southern blot hybridization assay showed that all of the cell lines, including the viral antigen-negative ATL-1K cell line, contained the viral genome. Thus, the retrovirus was associated with all 10 cell lines established from ATL patients, but there was a heterogeneity in the expression time of the retroviral antigen in leukemic cells maintained in vitro. Our findings suggested that the expression of the viral antigen was not required for maintenance of the leukemic state in vivo and for growth of leukemic cells in vitro.

Antigens, Surface↗
PubMed1983

Molecular mechanism of change in serum alpha-fetoprotein concentration during neonatal development of analbuminemic rats.

Analbuminemic rats, which lack albumin synthesis in the liver, have been shown to have a defect in splicing of albumin mRNA precursors. Change in serum alpha-fetoprotein concentration during the neonatal period in these mutant rats was compared with change of their gene expression of albumin. In analbuminemic rats the serum alpha-fetoprotein concentration at birth was almost the same as that of normal rats, and its concentration gradually decreased to a nondetectable level within 3 to 4 weeks after birth, as in normal rats, without increase in serum albumin concentration. In spite of the absence of increase in serum albumin, increase in transcripts of the albumin gene was observed. The level of "albumin mRNA precursors" in nuclei of the liver was less than 0.05 ng/micrograms of nuclear RNA at birth, but increased to 1 ng/micrograms within 3 weeks after birth in normal rats. Although the extent of increase was less, a similar switch-on of the albumin gene was observed in analbuminemic rats in the developmental period. These data clearly indicated that even in analbuminemic rats, coordinated regulation of the alpha-fetoprotein and albumin genes took place at a transcriptional level during development.

Animals↗
PubMed1982

Restriction fragment length polymorphism of the rat albumin gene in Sprague-Dawley rats and its application in genetic study of analbuminemia.

Restriction fragment length polymorphism of the rat albumin gene was discovered in a stock of Sprague-Dawley rats by Southern blots of rat liver DNAs using cloned albumin cDNA, prAlb-1 (1), as a probe. The polymorphic DNA fragments were observed when rat DNAs were digested with either Hind III or Pst 1 and the difference in length of the DNA fragments in Hind III or Pst 1 digests was estimated as 1.4 kbp. When DNAs were digested with EcoR I, restriction fragment length polymorphism was not observed. Therefore, this polymorphic DNA was concluded to be located in the flanking sequence. Structural analysis of the cloned albumin gene showed that the polymorphism was located in the 3'-flanking sequence. With this polymorphism as a marker of the albumin structural gene, the phenotype of analbuminemia, which is an autosomally recessive trait, was found to be linked to the structural gene of albumin.

Animals↗
PubMed1982

Presence of albumin mRNA precursors in nuclei of analbuminemic rat liver lacking cytoplasmic albumin mRNA.

Analbuminemic rats, which lack serum albumin, were previously found to have no albumin mRNA in the cytoplasm of the liver. In the present study, the existence of nuclear albumin mRNA precursors in the liver of analbuminemic rats was examined by RNA X cDNA hybridization kinetics. Albumin mRNA precursors were present in the nuclei of analbuminemic rat liver at almost normal levels, despite the absence of albumin mRNA from the cytoplasm. Nuclear RNA of analbuminemic rat liver was subjected to electrophoresis on 1% agarose gel in parallel with nuclear RNA of normal rat liver. RNA was transferred from the gel to diazobenzyloxymethyl-paper and hybridized to cloned cDNA. Several bands of putative albumin mRNA precursors were obtained with nuclear RNA of analbuminemic rat liver and some of them were indistinguishable from those of normal rat liver. Nuclear RNA of analbuminemic rats was hybridized to 3'-end-labeled cloned cDNA under the conditions of RNA excess and then digested completely with S1 nuclease and subjected to electrophoresis on polyacrylamide gel. By this technique, nuclear RNA that could hybridized to cDNA was found to have the albumin mRNA sequence in at least the 3' half of the mRNa that was covered by cloned cDNA. For comparison of the structures of the albumin genes of analbuminemic and normal rats, DNAs from rat livers of both types were digested completely with EcoRI, HindIII, and Pst I; the fragments were separated by electrophoresis on 1% agarose gel, transferred to nitrocellulose paper, and hybridized to cloned cDNA. The intensities of the corresponding bands and the digestion patterns of the analbuminemic and normal rat genes were indistinguishable. From these data, it is concluded that analbuminemic rats have a unique type of mutation(s) affecting albumin mRNA maturation.

Animals↗
PubMed1982

Perinatal changes of alpha-fetoprotein concentration in the serum and its synthesis in the liver of analbuminemic rats.

The profile of appearance of disappearance of alpha-fetoprotein (AFP) in the serum of analbuminemic rats, which have a genetically controlled lack of serum albumin, was studied. During the perinatal stage, AFP was present in the serum of analbuminemic rats, its concentration at birth being 10 mg/ml as in normal rats. In analbuminemic rats, the concentration of serum AFP remained at about 10 mg/ml during the first week after birth and then decreased rapidly during the next 2 weeks, becoming undetectable about 4 weeks after birth. In normal rats, the serum AFP concentration reached a maximum of 11.5 mg/ml at birth and then decreased sharply to an undetectable level within 4 weeks after birth, although a small rebound of AFP concentration was observed about 1 week after birth. AFP synthesis in analbuminemic and normal rats was examined by injecting [3H]leucine i.p. and then measuring the radioactivity incorporated into the acid-insoluble fraction and immunoprecipitable fraction using anti-AFP antiserum. In analbuminemic rats, synthesis of AFP amounted to 7.5% of the total protein synthesis at birth and was maintained at about 7% of the total for the first week after birth and then decreased to 2% at 2 weeks after birth. In normal rats, AFP synthesis also amounted to 7.5% of the total protein synthesis at birth but decreased to about 2% at 2 days after birth and then remained at a low level for about 2 weeks. In both normal and analbuminemic rats, AFP synthesis was undetectable at 4 weeks after birth. These data show that AFP synthesis is shutoff after birth irrespective of the serum albumin concentration during neonatal development.

Animals↗
PubMed1980

Purificaton and characterization of a pepsinogen and its pepsin from proventriculus of the Japanese quail.

A crude extract of the proventriculus of the Japanese quail gave at least five bands of peptic activity at pH 2.2 on polyacrylamide gel electrophoresis. The main component, constituting about 40% of the total acid protease activity, was purified to homogeneity by hydroxyapatite and DEAE-Sepharose column chromatographies. At below pH 4.0, the pepsinogen was converted to a pepsin, which had the same electrophoretic mobility as one of the five bands of peptic activity present in the crude extract. The molecular weights of the pepsinogen and the pepsin were 40 000 and 36 000, respectively. Quail pepsin was stable in alkali up to pH 8.5. The optimal pH of the pepsin on hemoglobin was pH 3.0. The pepsin had about half the milk-clotting activity of purified porcine pepsin, but the pepsinogen itself had no activity. The hydrolytic activity of quail pepsin on N-acetyl-L-phenylalanyl-3,5-diiodo-L-tyrosine was about 1% of that of porcine pepsin. Among the various protease inhibitors tested, only pepstatin inhibited the proteolytic activity of the pepsin. The amino acid composition of quail pepsinogen was found to be rather similar to that of chick pepsinogen C, and these two pepsinogens possessed common antigenicity.

Animals↗