Studies of copolymers containing L-proline residue as a main constituent. 1. The synthesis of copolymers of L-proline with the gamma ester of L-glutamic acid.
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Chemistry, Organic↗
Biomedical subjects
R Sakai
Publications and source records attributed to R Sakai.
Didemnins and tunichlorin: novel natural products from the marine tunicate Trididemnum solidum.
Didemnins A, B, and C, cyclic depsipeptides previously reported by our laboratory from the Caribbean tunicate Trididemnum solidum, have now been synthesized and, in the process, their structures have been revised to include the new amino acid (3S,4R,5S)-isostatine,C2H5CH(CH3)CHNH2CHOHCH2COOH. All other isomers of isostatine have also been prepared. Didemnin B is currently in Phase II clinical trials as an anticancer agent, and the antineoplastic activity, as well as the antiviral and immunosuppressive activities, of the didemnins are reviewed. A highly unusual porphynoid has also been isolated from T. solidum. The compound has been named tunichlorin and is apparently the first nickel-containing chlorin (and only the second nickel-containing porphyrin-related compound) identified from a living organism.
Animals↗
Bioactive compounds from aquatic and terrestrial sources.
The world of nature provides a never-ending set of fascinating problems for the chemist. Many of the most intriguing problems, however, concern compounds available in only truly minute quantities. One solution is to focus on bioassay-guided separations. In so doing one can isolate compounds with novel structures or unsuspected activities from almost any phylum, including tunicates, sponges, insects, or even the much-studied terrestrial plants, as exemplified in several recent studies in our laboratory involving activities ranging from antiviral and antimicrobial activity to cytotoxicity and immunomodulation. Moreover, newer spectroscopic techniques, especially fast atom bombardment mass spectrometry and tandem mass spectrometry, enhance one's ability to study compounds present in minute quantities, including those of importance to the host organism, such as neuropeptides in insects or marine invertebrates.
Amino Acid Sequence↗
Dose-response relationship between tobacco consumption and melanin pigmentation in the attached gingiva.
The dose response relationship between tobacco consumption and melanin pigmentation in the attached gingiva was examined on two occasions 4 years apart in a group of Japanese lead workers with blood lead concentrations below 2.0 mu mol/kg (40 micrograms/100 g). In the two examinations, 12% and 18% of the total group of workers and 17% and 24% of the smokers had melanin pigmentation. The prevalence of pigmentation was significantly higher in smokers who inhaled more than 10 cigarettes per day (17% and 25%) than in nonsmokers (0% and 2%), and tended to increase significantly with tobacco consumption. Lead absorption was not associated with melanin pigmentation.
Adult↗
Circulating immune complexes in Kawasaki syndrome.
Sera of 42 patients with Kawasaki syndrome were evaluated for the presence of circulating immune complexes (CICs) by Raji cell radioimmune and C1q solid phase assays. Overall 69% of sera tested were positive by one or both assays, 52% by Raji cell radioimmune and 48% by C1q solid phase assay. CICs were detected most frequently 2 to 4 weeks after the onset of illness, but their presence did not correlate with the clinical severity of the illness or incidence of coronary artery aneurysms. Antibody to mite antigen was found in only 2 of 30 patients tested, and only one of these had CICs. CICs are frequently associated with Kawasaki syndrome, but their role in its pathogenesis remains to be determined.
Aneurysm↗
Apocrine carcinoma vs. apocrine metaplasia with atypia of the breast. Use of aspiration biopsy cytology.
OBJECTIVE: To solve the problem of diagnosing apocrine carcinoma (APCA) through distinguishing it from benign apocrine metaplasia with atypia (APMA). STUDY DESIGN: The study group consisted of five histologically confirmed cases of uncommon infiltrating apocrine carcinoma and a case of noninfiltrating apocrine carcinoma of the breast by aspiration biopsy cytology. The control group consisted of 103 cases of benign apocrine metaplasia with no atypia (APMN), 4 cases of APMA and 34 cases of common-type adenocarcinoma that were encountered in 662 breast aspirations from 1988 to 1992 at Hekinan Municipal Hospital. RESULTS: In APCA the average age of patients (65 +/- 17.7 SD)(mean +/- SD) was more than 20 years older than APMA, and APCA generally measured > or = 2 cm or more in diameter as compared to < or = 2 cm in APMA lesions. In APCA the apocrine cells had high cellularity, with the cells occur singly and with syncytia in the background. Numerous degenerated apocrine cells and characteristic cell detritus were found. APCA was also characterized by apocrine cells with more marked nuclear abnormalities, including hyperchromasia and irregular nuclear shape, frequently with irregular nucleoli; more nuclei measure > or = 12 micron in diameter than in APMA. These findings, however, were present only to a mild degree in APMA, if at all. APMA may coexist with APCA. CONCLUSION: If APMA is diagnosed, an open biopsy should be performed to distinguish it from APCA.
Adult↗
An effective salvage regimen with aclarubicin for daunorubicin-resistant acute non-lymphocytic leukemia in children.
We evaluated the efficacy and toxicity of aclarubicin for acute non-lymphocytic leukemia (ANLL) refractory to daunorubicin in childhood. Twenty-four patients were treated with aclarubicin and prednisolone with or without 6-mercaptopurine and behenoyl-cytosine arabinoside daily for 5 to 14 days. Of 21 evaluable patients, 14 (67%) responded: 12 obtained complete remission and 2 partial remission. The median time to reach complete remission was 37 days (range, 16 to 60 days), and the median duration of complete remission was 5.5 months (range, 2 to 41 months). The cumulative dose of anthracycline administered before the study was not considered significant for the response. The only major complication was severe bone marrow suppression; infectious episodes occurred in 14 patients (58%) and three died of sepsis and/or bleeding. The observed non-hematologic toxicities included hematuria, an elevation of serum amylase, nausea/vomiting, and angitis. In addition, one patient showed abnormal cardiac function. Aclarubicin is therefore considered a highly active drug for remission reinduction of previously treated children suffering from ANLL with an acceptable toxicity.
Aclarubicin↗
Mechanism of thrombocytosis in hepatoblastoma: a case report.
Although thrombocytosis has long been recognized as a common finding in children with hepatoblastoma, its mechanism is still unknown. In this study, to confirm the role of thrombopoietin (Tpo) in the thrombocytosis in hepatoblastoma, the expression of Tpo mRNA in tumor cells was examined and the serum Tpo level was analyzed during the course of the disease. A 1-year, 6-month-old girl was diagnosed as having advanced hepatoblastoma. At diagnosis, she had marked thrombocytosis with 1220 x 10(9)/microL. After resection of the tumor and after four courses of chemotherapy, the level of alpha-fetoprotein normalized but the platelet count remained high. However, after the fifth course of chemotherapy, the platelet count decreased and normalized within 3 months. By enzyme-linked immunosorbent assay, the serum Tpo level was not high at diagnosis, whereas high Tpo levels were observed after chemotherapy. By polymerase chain reaction, Tpo mRNA was detected in both normal liver and tumor tissues, but the level of expression was not different between them. Therefore, in hepatoblastoma the serum Tpo level is not correlated with a high platelet count, and there is no difference in Tpo expression between normal liver and tumor tissues. Other unknown factors and their production sites to induce thrombocytosis should be examined in further studies.
Female↗
Cutaneous infiltration by leukemic cells in acute promyelocytic leukemia of a child after treatment with all-trans retinoic acid.
We describe here the first case of childhood acute promyelocytic leukemia (APL) with cutaneous infiltration of leukemic cells following treatment with all-trans retinoic acid (ATRA) confirmed by immunostaining and polymerase chain reaction for PML/RAR alpha. An 11-year-old girl was diagnosed as having APL. Chromosomal analysis demonstrated the characteristic karyotype of t(15;17). ATRA therapy was begun at a dose of 45 mg/m2 daily. During ATRA therapy, leukocytosis and retinoic acid syndrome were observed but were resolved by dexamethasone. Two months after commencement of ATRA therapy, complete remission was achieved. During the course of consolidation chemotherapy, however, multiple cutaneous nodules developed in her trunk, the size and number of which increased despite intensive chemotherapy. Histological and immunological studies of the cutaneous nodules showed infiltration of leukemic cells. PML/RAR alpha mRNA was detected in both the cutaneous nodules and bone marrow by means of polymerase chain reaction. ATRA treatment for APL may be associated with an increased incidence of extramedullary disease such as cutaneous lesions. The best available therapy for APL may be a combination of ATRA and chemotherapy, especially when a marked leukocytosis occurs during ATRA therapy.
Antineoplastic Agents↗
An application of a microcomputer compiler program to multiple logistic regression analysis.
Microcomputer programs for multiple logistic regression analysis were written in BASIC language to determine the usefulness of microcomputers for multivariate analysis, which is an important method in epidemiological studies. The program, carried out by an interpreter system, required a comparatively long computing time for a small amount of data. For example, it took approximately thirty minutes to compute the data of 6 independent variables and 63 matched sets of case and controls (1:4). The majority of the calculation time was spent computing a matrix. The matrix computation time increased cumulatively in proportion to additions in the number of subjects, and increased exponentially with the number of variables. A BASIC compiler was utilized for the program of multiple logistic regression analysis. The compiled program carried out the same computations as above, but within 4 minutes. Therefore, it is evident that a compiler can be an extremely convenient tool for computing multivariate analysis. The two programs produced here were also easily linked with spreadsheet packages to enter data.
Computers↗