Res Commun Mol Pathol Pharmacol

Mutation in the exon 10 (R173W) of the hydroxymethylbilane synthase gene in two unrelated Japanese families with acute intermittent porphyria.

Year 1998
Tomie Y. Horie Y. Tajima F. Kitaoka S. Nanba E. Yuasa I. Kawasaki H.
Second Department of Internal Medicine, Faculty of Medicine Tottori University, Japan.
Acute intermittent porphyria (AIP) is an inherited disorder characterized by a deficiency of hydroxymethylbilane synthase (EC 4.3.1.8.; HMBS), the third enzyme in the heme biosynthetic pathway. To date, 113 different HMBS gene mutations have been reported in the world. However, there were a few reports of the gene mutations in the Japanese AIP patients. We studied the gene mutation in two unrelated AIP families in the San-in district, a local area of Western Japan. The overlapping 6 fragments of the HMBS gene, amplified by the reverse transcript-polymerase chain reaction, were analyzed by the single-strand conformation polymorphism with silver staining technique. The abnormal fragment from a member of one family was sequenced to detect the C to T substitution at 517 nucleic acid position of cDNA, which led to a missense mutation of arginine to tryptophan exchange at an amino acid level (R173W). This mutation located in exon 10 created a new site of the MSP 1 restriction endonuclease and was screened by the amplified fragment of exon 10 from genomic DNA with the MSP 1 digestion. The mutation was detected totally in three members of the family and interestingly also in two patients of an unrelated family. This mutation has been reported widely in the world independently, such as in a Swedish, a Canadian, a Finnish, and a French family, but is the first in Japanese patients. The screening method for this mutation is useful for diagnosis in Japanese AIP patients.

Clinical significance of serum P53 antibody in patients with gastric cancer.

Year 1998
Shiota G. Ishida M. Noguchi N. Takano Y. Oyama K. Okubo M. Katayama S. Harada K. Hori K. Ashida K. Kishimoto Y. Hosoda A. Suou T. Ito H. Kawasaki H.
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
The presence of serum p53 antibody has been reported to have prognostic significance in patients with breast and ovarian cancers. In order to clarify clinical and prognostic significance of p53 antibody in serum, we measured p53 antibody in patients with gastric cancer. Twenty-five patients with gastric cancer were examined as well as 9 patients with gastric polyp as controls. Eight of 25 patients (32%) with gastric cancer were positive for p53 antibody, while no patients with gastric polyp were positive in gastric polyp group (p < 0.05). The presence of p53 antibody was significantly associated with histology, liver metastasis and stage classification in gastric cancer (p < 0.05, respectively). Presence of liver metastasis, type of histology and presence of p53 antibody are independent prognostic factors (p < 0.05, respectively). The overall survival in patients with p53 antibody was significantly shorter survival than for those without antibody (p < 0.05%). These data suggest that p53 antibody serves as one of the prognostic factors in gastric cancer.

Antitumor-activities of coumarin, 7-hydroxy-coumarin and its glucuronide in several human tumor cell lines.

Year 1998
Weber US. Steffen B. Siegers CP.
Institute of Toxicology, Medical University of Lubeck, Germany.
Coumarin is found in many medicinal plants and therefore also used in phytomedicine for the treatment of venous diseases. The metabolic pathways of coumarin in the human body lead to the intermediate 7-hydroxy-coumarin and consequent glucuronidation in the intestine and liver. The antitumor activities of coumarin (C) and its known metabolite 7-hydroxy-coumarin (7-OH-C) were tested in several human tumor cell lines. C as well as 7-OH-C inhibited cell proliferation of a gastric carcinoma cell line, a colon-carcinoma cell line (Caco-2), a hepatoma-derived cell line (HepG2) and a lymphoblastic cell line (CCRF CEM) in a concentration-dependent way, the IC50-values were 1.59-3.57 mM for C and 0.68-2.69 mM for 7-OH-C. The glucuronide of 7-OH-C was ineffective in this respect.

Molecular weight of hyaluronate in the serum of patients with chronic liver disease.

Year 1998
Murawaki Y. Ikuta Y. Idobe Y. Koda M. Kawasaki H.
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Hyaluronate in tissue and lymph is known to be heterogenous and to show a wide range of molecular weights (10(4) to 10(7) Da). Serum hyaluronate concentrations are increased under various pathophysiological conditions such as liver disease, post-gastrectomy, and after the ingestion of food. To clarify whether the chromatographic patterns of hyaluronate in serum from patients with chronic liver disease are different under these conditions, we subjected sera to chromatography using a Sephacryl S 400 HR column. The chromatograms revealed that the hyaluronate in serum was eluted as a single peak at the position corresponding to the molecular weight of blue dextran, the molecular weight being more than 2 x 10(6) Da. The patterns of the chromatogram were similar among the patients with liver disease and the healthy subject although the heights of the peaks were different. Ingestion of food and a history of gastrectomy for gastric cancer did not influence the elution patterns of serum hyaluronate. These results indicate that hyaluronate in serum has molecular weight of more than 2 x 10(6) Da, and that its elution patterns are not influenced by pathophysiological factors, such as the severity of liver disease, or history of gastrectomy or by food intake in patients with chronic liver disease.