Biomedical subjects
Publications and source records attributed to K Imai.
Cadystins induced in a fission yeast treated with Cd2+ are the higher homologs of glutathione. In the present work, glutathione was incubated with Carboxypeptidase Y at a high substrate concentration. The reaction afforded not only the degraded product, but also cadystins and their analogs. A possible transformation pathway for glutathione by this enzyme is proposed.
A new lipophilic peptide was isolated from the MeOH-CH2Cl2 extract of adult heads of the male silkworm, Bombyx mori, by monitoring the diapause egg-inducing activity. Partial amino acid sequencing (1-55) revealed this peptide to be a unique type having a high content of lipophilic amino acids, Val, Ala, and Pro, and many repeating sequences. The compound was thus named VAP peptide.
We developed a sensitive and specific method, reverse transcriptase-polymerase chain reaction (RT-PCR) method, for detection of turkey rhinotracheitis virus (TRTV). Two sets of primers were designed from F protein gene sequence of TRTV 3B strain. Sensitivity of detection by nested PCR with the primers corresponded to 0.4 TCID50. Applying this method to a field case of swollen head syndrome (SHS), TRTV could be detected directly from chicken trachea and turbinates. It was identified that this method was very useful to examine the relation of TRTV and SHS.
Three patients with non-traumatic arteriovenous fistulas (AVFs) of the scalp were treated by embolization using acrylate glue through the transarterial route or by direct puncture of the lesions and then surgical resection. Complete cure was achieved in all three patients. Selective angiography is indispensable in the correct diagnosis of scalp AVFs. Embolization facilitates surgical removal when necessary, and this combination is the treatment of choice for scalp AVFs.
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A 27-year-old female was admitted to a hospital because of severe anemia (hemoglobin 4.9 g/dl) after taking PL (a drug for common cold consisted of Salicylamide, Acetaminophen, Caffeine and Promethazine methylene di-salicylate) and Cefadroxil (an oral antibiotic) for ten days. History and laboratory data leaded to a diagnosis of drug induced hemolytic anemia. 6 units of concentrated red blood cells were transfused and the suspected drugs were discontinued immediately. Though resolution of anemia and no further hemolysis were observed, progressive leukocytopenia developed since four days after the admission. Bone marrow aspiration revealed marked decrease of granulocytic series. The patient was transferred to our hospital and was isolated under laminar air-flow to prevent her from bacterial and fungal infections. She was treated with prednisolone and granulocyte-colony stimulating factor. She recovered from leukocytopenia in two weeks without suffering from any life-threatening infection. We extensively analyzed the suspected drugs and mechanism of hemolysis and granulocytopenia. Cefadroxil is turned out to be contributed to hemolysis by an immune complex mechanism. Cefadroxil and Salicylamide were suggested to be involved in granulocytopenia by the induction of antibodies against the leukocytes to which these drugs were bound. Thus Cefadroxil was regarded as a causative drug of both hemolysis and granulocytopenia. This case is of interest for analyzing drug-induced blood abnormality because it is very rare that two lineage of blood were injured by one drug at the same time as far as we know.
Molecular epidemiology of cancer has been developed along with rapid advances in molecular carcinogenesis, introducing new approaches to etiology and prevention of cancer. First, research activities in Japan are briefly reviewed in this issue focusing on studies of genetic susceptibility, DNA damages, and immunological defense. Then we make an estimation of age periods of initiation for several cancer on the basis of multistaged carcinogenesis. The results are discussed in relation to strategies of cancer prevention in molecular epidemiology, introducing our trials previous and on-going as examples.
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BACKGROUND: The age eligibility for the mass screening (MS) for prostate cancer was investigated. METHODS AND MATERIALS: This study was performed in subjects examined by MS from 1981 to 1994 in Gunma Prefecture, Japan. MS was performed by digital rectal examination (DRE) and prostatic acid phosphatase from 1981 to 1991, and by DRE, transrectal ultrasonography and prostate specific antigen from 1992 to 1994. RESULTS: It was demonstrated that the prostate cancer detection rate was affected by the ratio of subjects newly and previously examined, the age distribution in the group examined and the diagnostic modality. It was also demonstrated that the detection rate of early stage prostate cancer was also affected by the age distribution and the diagnostic modality. The effective detection rate was determined on the assumption that the purpose of MS is the detection of the subjects who have the indication for the radical prostatectomy, and the effective detection rate was calculated in the range from 50 to 69 years for age eligibility, and B and C for clinical stage. It was estimated that effective detection rate was 0.37 to 0.61%. They were higher than the detection rate of MS for other organ cancers. CONCLUSION: The eligibility is 50 to 69 years. If subjects in the range of 70 to 74 are included in this project, it is necessary to make an effort practice a subject-education about the prostate cancer natural history and the radical prostatectomy indication.
Human giant cell tumor (GCT) consists of multinucleated giant cells and mononuclear stromal cells, and is characterized by frequent vascular invasion without distant metastases. To study the role of matrix metalloproteinases (MMPs) in the vascular invasion, we examined production of MMP-1 (tissue collagenase), -2 (gelatinase A), -3 (stromelysin-1), -9 (gelatinase B), and tissue inhibitors of metalloproteinases (TIMP-1 and -2) in GCT. MMP-9 was highly and predominantly expressed in giant cells by both immunohistochemistry and in situ hybridization. Expression of other MMPs was also observed in some cases but was inconstant. Sandwich enzyme immunoassays demonstrated that MMP-9 is the predominant MMP secreted by GCT. There was a definite imbalance between the amounts of MMP-9 and those of TIMPs in the culture media of GCT, leading to detectable gelatinolytic activity in an assay using 14C-gelatin. Gelatin zymography demonstrated the main activity at about 90 kd, which was identified as the zymogen of MMP-9 by immunoblotting. Immunohistochemistry for type IV collagen and laminin, major basement membrane components, showed that disappearance of the proteins is closely associated with MMP-9-positive giant cells. These results indicate the production of MMP-9 by multinucleated giant cells and suggest that the metalloproteinase may contribute to proteolysis associated with vascular invasion and local bone resorption in human GCT.
Studies about the function of mucin molecules as surface molecule of adenocarcinoma of gastrointestinal tract had just started, and several important function of mucins had been revealed. In the process of the malignant transformation, class of the expressed mucin core protein and content of glycochain of mucin molecule was changed. Changes of glycoprotein of mucin molecule during transformation affect immunogenesity, tumorigenesity, metastatic ability and sensitivity for anti-cancer drugs. Glycosylated mucin acts important roles during metastatic sequence and prognosis of the gastrointestinal cancer was collerated with expression of immatured mucin of cancer cells. A type of mucin with immature type of glycochain, MUC1, had a protective function for cytotoxicity, e.g. natural killer cell and cytotoxic T-cell, and deglycosilation of MUC1 sensitize cancer cells for cytotoxicity. And MUC1 reduce sensitivity for anti-cancer drugs and MUC1 was glycosilated during process to get resistance for anti-cancer drug. The functions of mucin molecules is not fully revealed, but further studies will indicate importance of mucin molecules in tumor progression.
Recent molecular biological approach has revealed the primary structure of some mucin core proteins. Most prominent characteristic is tandemly repeated sequences. cDNA cloning of 8 kinds of mucin core proteins, MUC1-7, have thus been performed. Among them, the entire structure was revealed on MUC1,2 and 7. MUC1 is a type I transmembrane protein with a large number of tandem repeat consisting of 20 amino acids. We have found that mouse MoAb MUSE11 against adenocarcinoma, which detects circulating MUC1 in patients with gastrointestinal and pancreatic cancers, recognizes part of the tandem repeat of MUC1 using synthetic peptides. We have transfected MUC1 cDNA to some cell lines, and they indicated that cell-cell and cell-matrix adhesion, growth rate and reactivity with growth factor were suppressed. To date, some of the MoAbs to adenocarcinoma have been shown to react with PDTRP sequence in the tandem repeat of MUC1 (MUC1 epitope), suggesting that MUC1 epitope could be highly immunogenic in human. Recently, cytotoxic T-cells against MUC1 epitope were established from breast and pancreas cancer patients. We also induce those T-cells from the patient with multiple myeloma. Interestingly, CTL functions in an HLA-unrestricted manner, and may be of use an adoptive immunotherapy. MUC2, a large secretory type mucin, cysteine-rich subdomains located both upstream and downstream of its central repetitive region, and these subdomains have sequence similarity with von Willebrand factor. We have shown that anti MUC2 core-protein MoAb CCP58 reacts intestinal metaplasia and cancer in stomach, but not normal gastric mucous membrane. Recently we established a new monoclonal antibody against purified deglycosylated gastric mucin. This antigen was expressed in the deep portion of metaplastic glands and cancers in the stomach. Two cDNA clones coding for this antigenic molecule were obtained.
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The incidence and mortality rate of prostate cancer in Japan are lower than in Western countries. Though studies of migrating populations would suggest that dietary or environmental factors may influence the etiology of the disease. The Westernized lifestyle after the Second World War may have influenced the increasing incidence of this disease in Japan. The screening by prostate specific antigen (PSA) on an asymptomatic healthy population can detect early prostate cancer. It is expected that the mortality may be decreased through such a system. However, some scientists hesitate to perform an aggressive program of early detection because of the possibility of latent cancer detection, the difficulty of distinguishing between clinically important and unimportant cancer, a high false positive rate to detect early stage cancer, and the lack of well-executed randomized prospective studies. Current clinical studies of the prostate cancer have demonstrated that the unimportant cancer detection rate by PSA was less than 10%. When a 4.0 ng/ml PSA cut-off value is applied for early detection, the false positive rate is approximately 80%. It is important to make subjects examined by the screening program aware of its the meaning. However, there is not a complete and cost-effective diagnostic modality to detect early prostate cancer. Moreover, it is confirmed that radical prostatectomy improves survival, but it has not been confirmed to improve the mortality based on population. We propose that well-executed randomized studies by the end point of the survival, cancer death rate, cost effective, QOL and etc. are urgently needed.