Medicinal chemical studies on antiplasmin drugs. II. Separation of stereoisomers of 4-aminomethylcyclohexanecarboxylic acid and assignment of their configuration.
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Biomedical subjects
Publications and source records attributed to A Okano.
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OBJECTIVE: A novel 2-amino acid insertion between codons 69 and 70 of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) which confers multiple drug resistance has recently been reported. Independently, we have identified similar insertion mutations in Japanese hemophiliacs and attempted to analyze their emergence in conjunction with therapy regimens and their contribution to drug resistance using recombinant technology. METHODS: The plasma and peripheral blood mononuclear cells (PBMCs) of 348 HIV-1-infected hemophiliacs were screened for HIV-1 RT mutations relevant to nucleoside analogue inhibitors and isolating viruses. Contribution of each insertion to drug resistance was studied by introducing the mutations into a T-cell line-tropic NL4-3 infectious clone and testing the drug susceptibilities of the recovered virus. RESULTS: Insertion of the 2-amino acid residue was found in 4 of the 348 cases and was strongly associated with prolonged chemotherapy with zidovudine (AZT) and didanosine (ddI). The virus isolated from 1 of the 4 cases possessed the same insertion. Characterization of these virus and the recombinant NL4-3 with the insertion strongly suggested that the insertion caused resistance not only to AZT and ddI but also to lamivudine (3TC) and zalcitabine (ddC). CONCLUSION: A 2-amino acid insertion between codons 69 and 70 of RT was detected in 4 of 348 (1.1%) Japanese hemophiliacs and was found to be associated with multiple drug resistance to nucleoside analogue RT inhibitors.
BACKGROUND/AIMS: An early diffuse type in the pattern of the postoperative intrahepatic recurrence of hepatocellular carcinoma has been recognized. The purpose of this study was to elucidate risk factors for diffuse recurrence of hepatocellular carcinoma. METHODOLOGY: The subjects involved in the present study were 114 patients with hepatocellular carcinomas resected in Tenri Hospital during the past 12 years. Univariate analysis was used for retrospective determination of the factors related to diffuse recurrences after surgery in 10 cases among 114 patients. RESULTS: The risk factors linked to diffuse recurrence were microscopical portal infiltration (P < 0.01), elevated alpha-fetoprotein (more than 1000 ng/mL) (P < 0.05), the absence of preoperative transcatheter arterial embolization (P < 0.01), and two or more segmentectomies of the liver (P < 0.01). Six of 10 patients with microscopical portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL) had diffuse recurrence (P < 0.01). Six of 8 patients with two or more segmentectomies without preoperative TAE had diffuse recurrence (P < 0.01). CONCLUSIONS: When patients with the diagnosis of operable hepatocellular carcinoma have portal infiltration and elevated alpha-fetoprotein (more than 1000 ng/mL), two or more segmentectomies of the liver without preoperative transcatheter arterial embolization should be avoided.
The peanut agglutinin (PNA) receptors isolated from a tumor cell line could elicit antitumor activity by an active immunization. We report here the results of active immunization with a human PNA receptor glycoprotein on the tumor progression of cancer patients. A remarkable regression of cancer and a prolonged life span in patients were obtained after active immunization with a tumor cell-associated carbohydrate antigen.
BACKGROUND/AIMS: Lymph node dissection has been carried out for two decades in Japan, resulting in improved survival of patients with gastric cancer. By analyzing dissected nodes of resected advanced gastric cancers, we intend to determine which parameter(s) are more concerned in node metastasis. PATIENTS AND METHODS: Curative gastrectomy with dissection of lymph nodes was performed for 78 of the 108 patients with advanced gastric cancer. Metastases were found in 171 of 1359 nodes (13%) dissected. In each node, the maximum and minimum diameters were measured, and the ratio of the former to the latter was calculated. RESULTS: The minimum diameter of node was closely related to node metastasis. When the minimum diameter in node metastatic criteria was "3 mm or more", a sensitivity of 81% and specificity of 54% were calculated. In false negative node, signet-ring cell carcinoma (SIG) (33%) and poorly differentiated adenocarcinoma (POR) (22%) were more frequently found as primary lesions. Half or more of these nodes were invaded by only a few carcinoma cells. When the primary lesion is histologically SIG or POR, endoscopic treatment is contraindicated for possible nodes metastasis. CONCLUSIONS: It is impossible to distinguish nodes with micrometastasis from nodes without metastasis. The minimum diameter of node is more important in node metastasis of gastric cancer than the maximum diameter of node or the ratio of both.