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Biomedical subjects

M Ishiguro

Publications and source records attributed to M Ishiguro.

At least 163 records · Page 9Linked to original sources
PubMed1989

Levels of tissue polypeptide antigen in serum and the progression of gastric cancer.

Correlations between levels of tissue polypeptide antigen (TPA) in serum and histologic stage or progression of cancer were studied in 94 patients with gastric cancer. Levels of TPA in serum from patients with cancerous invasion into the vein of the stomach wall (v-invasion) were elevated in parallel to the progression of cancer by stage, and were significantly higher in each positive case than in each negative case of lymph node metastasis or of cancerous invasion into lymph vessels of the stomach wall (P less than 0.05 and P less than 0.01, respectively). There were no differences in levels of TPA in serum from patients without v-invasion when these cancers were classified by stage, progression, or histologic type. It appears that elevation of levels of TPA in serum is associated with v-invasion, and that a determination of the level of TPA in serum is useful for the prediction of hematogenic metastasis in cases of gastric cancer.

Antigens, Neoplasm↗
PubMed1989

Penetration of macrolides into human polymorphonuclear leucocytes.

Five 14C-labelled macrolide antibiotics (erythromycin, josamycin, clarithromycin (TE-031), rokitamycin and roxithromycin) were studied for their transport into human polymorphonuclear leucocytes. Intracellular/extracellular concentration ratios (transport ratios) of these macrolides were quite high: erythromycin, 6.6; josamycin, 15.5; clarithromycin, 16.4; rokitamycin, 30.5; and roxithromycin, 21.9. When polymorphonuclear leucocytes were pre-treated with formaldehyde or incubated at 4 degrees C, or at low pH, transport ratios were reduced. When extracellular macrolide was removed, intracellular macrolide concentrations became as low as 30% of the pre-wash concentrations in 5 min. KF lowered the transport ratios of josamycin and rokitamycin in particular and NaCN reduced the transport ratios of erythromycin and josamycin strikingly. Ouabain slightly lowered transport ratios of all the antibiotics tested except roxithromycin, and 2, 4-dinitrophenol decreased the transport ratio of clarithromycin markedly. The addition of various amino acids or hexose did not inhibit the transfer. Adenosine, however, inhibited the transfer of these antibiotics except erythromycin and lowered transport ratios by 83 to 92%. Puromycin reduced transport ratios of the same antibiotics by 59 to 95%. With polymorphonuclear leucocytes that had phagocytosed Legionella pneumophila serogroup 1, transport ratios of all five drugs tended to decrease. However, when Staphylococcus aureus ATCC 25923 or opsonized zymosan was phagocytosed, transport ratios for macrolides, except for roxithromycin, increased.

Adult↗
PubMed1989

Human chorionic gonadotropin-ricin A chain hybrid protein: a hormone analog for the study of signal transduction.

We have prepared a disulfide cross-linked hybrid consisting of human chorionic gonadotropin and the toxic ricin A chain, utilizing N-succinimidyl-3-(2-pyridyldithio)-propionate. The purified hybrid exhibited cytotoxicity toward rat testis Leydig cells due to inhibition of protein synthesis within the cells, although it inhibited protein synthesis in a cell-free system of a rabbit reticulocyte lysate only after treatment of the hCG-A hybrid with dithiothreitol. On the other hand, pretreatment of the hCG-A hybrid with dithiothreitol completely abolished its cytotoxicity. The hCG-A hybrid stimulated the testosterone production by rat testis Leydig cells to a similar degree to hCG. The hCG-A hybrid could elicit full testosterone production in the presence of about 1/3-1/2 less accumulated cAMP compared with in the case of hCG stimulation. The steroidogenetic effect of the hCG-A hybrid was largely inhibited by anti-hCG antibody but not by anti-ricin A chain antibody. These results suggest that the hCG-A hybrid first binds to Leydig cells via an hCG receptor and then is internalized into the cells, and finally the inhibition of cellular protein synthesis occurs on the release of the ricin A chain from the hybrid. Furthermore, it was suggested that hCG may stimulate testosterone production via another second messenger system as well as via the cAMP system, since the hCG-A hybrid stimulated full testosterone production without maximal cAMP accumulation.

Animals↗
PubMed1989

Existence of associated, non-associated, and oligomeric forms of human chorionic gonadotropin subunits in placental extracts.

The molecular sizes of human chorionic gonadotropin (hCG) subunits in the native state in normal first trimester placental extracts were determined by gel filtration on Sephacryl S-300, followed by SDS-polyacrylamide gel electrophoresis, protein blotting, and immunobinding analysis using anti-alpha and - beta antibodies. Mature forms of hCG subunits in the extracts were only found in the same fraction as that which contained standard urinary hCG, indicating an alpha beta dimer. On the other hand, immature forms were detected with a wide range of molecular weights, which were higher than that of standard hCG, suggesting oligomerization of associated or non-associated immature subunits. In order to determine the associated state of these subunits, various forms of associated subunits (hCG alpha beta) in placental extracts were immunoprecipitated with anti-hCG antiserum, which only recognized hCG alpha beta, and Protein A-Sepharose. They were then analyzed by SDS-polyacrylamide gel electrophoresis under reducing and non-reducing conditions, followed by immunobinding assaying. It has been suggested that there are three kinds of hCG alpha beta S (one mature and two immature). To confirm the above results and to clarify the existence of free subunits, placental extracts were subjected to two-dimensional SDS-polyacrylamide gel electrophoresis. With this technique, high molecular weight forms of immature hCG subunits were found to be present in placental cells as an oligomer of not only the alpha beta dimer but of each subunit as well.

Chorionic Gonadotropin↗
PubMed1989

[A case of infective endocarditis (IE) improving with orally administered amoxicillin (AMPC)].

Progress in chemotherapy and cardiosurgery has remarkably decreased the mortality due to infective endocarditis (IE) in recent years. In chemotherapy for IE, parental administration of antibiotics has been used routinely, the patients suffer from the psychological and physiological burden due to frequent injections and long period of therapy, even though the therapy for IE is successful. In this report, we present a case of IE caused by S. mitis, which was remarkably improved by oral administration of AMPC. A case, 69. y.o. female. She felt like a common cold and visited a G.P. Cardiomegaly was pointed out and positive inflammatory findings in serological examination were found. A low grade fever continued, and she was admitted to the hospital. Blood cultures were positive for S. mitis. For further examination, she was transferred to the university hospital. Based on the extensive blood cultures and cardioechogram, she was diagnosed IE caused by S. mitis. Because there were no symptoms of heart failure, we decided to try oral administration of AMPC, 4 g/day or 6 g/day at an interval of 6 hours. On the second day of therapy, the blood culture turned to be negative for pathogens, and on the fourth day body temperature became normal. On about the 60th day, the CRP finding became negative. Concentrations in the serum of AMPC were more than 10 folds of AMPC-MIC (0.5 microgram/ml) for S. mitis. The patient, however, suffer from complications of lung embolism and was operated for exchange of heart valves. After surgery, she has been well without any symptoms from IE.

Administration, Oral↗
PubMed1989

[Effects of prophylactic intraportal chemotherapy on liver function, blood profile and survival in patients with colo-rectal cancer].

Postoperative intraportal anti-cancer chemotherapy was used for 51 patients with curatively resected colorectal cancer who were selected in the randomized controlled study to evaluate its inhibitory effect on liver metastasis from colo-rectal cancer. In cases of intraportal chemotherapy, 30 mg of Mitomycin-C (in 3 doses) and 5 mg/kg (B.W.)/day (1985-1986) or 3 mg/kg/day (1987-1988) of 5-FU was injected through the catheter inserted into the portal vein during postoperative 14 days. In cases of the control group (58 patients), the same doses of the drugs were injected into the peripheral vein during the same term. Six patients with recurrences were observed in the intraportal chemotherapy group, and 3 of them had liver metastases. In the control group, more liver metastases were observed (5 of 7 recurrences were liver metastases). Intraportally injected 5 mg/kg/day of 5-FU slightly disturbed the liver function. The averages of the serum GOT, GPT and gamma-GTP level of these cases were higher than those of the control cases. Three mg/kg/day of intraportally injected 5-FU had no influence on the liver function. There were no differences in the incidence of leukocytopenia or thrombocytopenia between the two groups.

Aged↗
PubMed1989

[Enlarging of intracranial hemorrhagic lesions and coagulative-fibrinolytic abnormalities in multiple-injury patients].

The clinical course of ten cases of head injury complicated with multiple systemic injuries were studied by comparing two groups divided according to the presence or absence of associated coagulative-fibrinolytic abnormality. All these cases had intracranial hemorrhagic lesions proven by the high density area in the initial CT scan. Five cases showed signs of disseminated intravascular coagulation (DIC) as evidenced by decreased counts of platelet, and/or elevated value of FDP at the time of admission. Four cases out of these five were in a state of hemorrhagic shock. All these five cases showed a subsequent enlargement of intracranial hematoma. Four cases died. Two of them, who had low initial Glasgow Coma Scale (G.C.S) died of uncontrollable increase of intracranial pressure. The other two, who had high initial G.C.S., died of acute renal failure and multiple organ failure. In contrast with these cases, five cases without signs of DIC intracranial hematomas did not enlarge in spite of the similar neurological conditions to the former group. In head injured patients with systemic injury, DIC frequently causes secondary hemorrhage in the intracranial lesions of minor severity.

Adolescent↗
PubMed1989

[Clinical course of acute intracerebral hematoma which shows a fluid level presentation by X-ray CT].

Three cases of intracranial hematomas which showed a fluid level presentation and/or mixed density in the acute stage by X-ray CT were reported. Case 1 is a 7-year-old boy who had the epidural and intracerebral hematomas three hours after the traffic accident. During the course, intracerebral hematomas which showed a fluid-level presentation had grown both 6 and 17 hours after the episode. Case 2 is a 39-year-old female who had received an aortic valve replacement 20 years ago. She was diagnosed as cerebral infarction due to the occlusion of the right middle cerebral artery. Intracerebral hematomas with a fluid level presentation developed in the infarcted area 20 days after the embolectomy. Case 3 is a 67-year-old female who had a mild subarachnoid hemorrhage by the traffic accident. Intracerebral hematoma with mixed density developed 68 hours after the episode and it enlarged again 89 hours after the accident. All three cases showed the abnormalities in the coagulofibrinolytic activities during the hemorrhage and showed a growth of the hematomas. It should be noticed that the case which shows a mixed density and/or a fluid level presentation in the X-ray CT requires more intensive care in both neurosurgical and general management.

Acute Disease↗
PubMed1988

A single amino acid substitution converts cytochrome P450(14DM) to an inactive form, cytochrome P450SG1: complete primary structures deduced from cloned DNAS.

Genes for lanosterol 14-demethylase, cytochrome P450(14DM), and a mutated inactive cytochrome P450SG1 were cloned from S. cerevisiae strains D587 and SG1, respectively. A single nucleotide change resulting in substitution of Asp for Gly-310 of cytochrome P450(14DM) was found to have occurred in cytochrome P450SG1. In this protein the 6th ligand to heme iron is a histidine residue instead of a water molecule, which may be the ligand for the active cytochrome P450(14DM). Molecular models of the active sites of the cytochrome P450(14DM) and cytochrome P450SG1 were built by computer modeling on the basis of the known structure of that of cytochrome P450CAM whose crystallographic data are available. The mechanisms which may cause a histidine residue to gain access to the heme iron are discussed.

Amino Acid Sequence↗
PubMed1988

Carcinogenic potential of the noncancerous epithelium in patients with oesophageal cancer.

Detailed histopathological examination of serial blocks and subserial sections of the entire resected oesophagus in 63 patients operated upon for oesophageal cancer revealed 11 associated minute superficial cancers, independent and apart from the main tumours, in 10 patients (15.9 per cent). Only one of these eleven lesions was diagnosed preoperatively, and only three of the eleven lesions were detected macroscopically on the resected specimens. The high incidence of such coexisting independent lesions may indicate a possible increased multicentric carcinogenic potential in the non-cancerous epithelium of patients who have had an antecedent oesophageal cancer. These results emphasize the need for careful attention to the choice of margins during surgical resection of the oesophagus.

Aged↗
PubMed1988

Intra-hepato-arterial chemotherapy with CDDP and 5-FU for metastases to the liver from colorectal and gastric cancers.

Thirty-five patients with metastases to the liver from colorectal (26 patients) and gastric (nine patients) cancers were treated with intra-hepato-arterial (IHA) injections of cis-diamminedichloroplatinum (II) (CDDP) plus 5-fluorouracil (5-FU). Therapeutic schedules consisted of manual bolus injections of CDDP. (25-35 mg/m2/week) and 5-FU (150-180 mg/m2/day) Regimen I, and CDDP (25-35 mg/m2/10-14 days) and 5-FU (60-70 mg/m2/day Regimen II. In patients with colorectal cancer metastatic to the liver, partial response (PR) rates in Regimens I and II were 38% and 62%, respectively. By contrast, in patients with metastases to the liver from gastric cancer, a PR was obtained in only one of nine patients (11%). IHA chemotherapy CDDP plus 5-FU, especially following Regimen II, appears to be a strongly recommendable strategy for treatment of metastatic liver tumors derived from colorectal cancer.

Adult↗
PubMed1988

[Hepatic arterial chemotherapy combined with hyperthermia or arterial embolization in unresectable liver tumor].

Fifty-four patients with unresectable malignant liver tumors (14 of hepatocellular carcinoma, 40 of metastasis to the liver from gastric or colo-rectal cancer) were treated with intra-hepato-arterial (IHA) injections of cis-diamminedichloroplatinum (II) (CDDP) plus 5-fluorouracil (5-FU). In 32 of the patients, the liver tumors were detected synchronously with the diagnosis of the primary cancers, which were resected palliatively. Therapeutic schedules consisted of bolus injections of CDDP (50 mg/body/week) and 5-FU (250 mg/body/day) [Regimen I], and CDDP (50 mg/body/10-14 days) and 5-FU (100 mg/body/day) [Regimen II]. In 48 patients treated with IHA chemotherapy only, a partial response (PR) was obtained in 6 of 14 (43%) evaluable patients for Regimen I and in 11 of 30 (37%) patients for Regimen II. The dose-limiting factor for treatment with CDDP was bone marrow toxicity, but this toxicity was remarkably alleviated in Regimen II without any decrease in antitumor effectiveness. In 13 patients, other modalities, such as total-body hyperthermia (4 patients), radiofrequency capacitive local hyperthermia (5), and temporary arterial embolization (4), were combined with IHA chemotherapy. PR was obtained in 7 of 13 (54%) patients with the combined therapy. This combined therapy was efficacious in 7 patients in whom no desired results were obtained by IHA chemotherapy only. The survival rate was 50% at 12 months. IHA chemotherapy with CDDP plus 5-FU, especially when according to Regimen II, appears to be a strongly recommended strategy for treatment of unresected primary or metastatic liver tumor. Further, addition of the hyperthermia or the arterial embolization might enhance the antitumor effect of IHA chemotherapy.

Aged↗
PubMed1988

[Computer aided design of anticancer drugs].

The recent advances in computer science and technology enabled us to use computer for drug-design. Calculation of structural features of drugs and modeling of biomacromolecules by means of 3D-computer graphics afford a new approach to comprehend a molecular interaction which is important for drug action. As target molecules for anticancer drug, DNA structure can be elucidated and drug-DNA complex model can be constructed to give further insight for drug design. For example, complex of DNA double helix and bleomycin was built and by conjunction with other complex model such as mitomycin C, anthramycin, and netropsin it would be able to design a base sequence specific DNA-groove binding molecule. In addition, DNA is also a target molecule for antibiotics which intercalate between base pairs. Rational design of intercalator and groove binder thus would lead a novel anticancer drug. On the other hand, combination of the fruitful results of molecular biology and gene engineering with computer technology, will give a detail of protein structure which is one of most desired information for designing novel drugs.

Antineoplastic Agents↗