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1.
The purine path to chemotherapy 总被引:4,自引:0,他引:4
Gertrude B. Elion 《Bioscience reports》1989,9(5):509-529
Antimetabolites of purine metabolism have found a use as anti-leukaemic, antiprotozoal and antiviral drugs, in immunosuppression and transplantation, and in gout and hyperuricemia. Their mechanisms of action are reviewed.Nobel Lecture given on December 8, 1988; by Dr Gertrude B. Elion and published inLes Prix Nobel 1988, printed in Sweden by Norstedts Tryckeri, Stockholm, Sweden, 1989, republished here with the permission of the Nobel Foundation, the copyright holder. 相似文献
2.
Yaffa Mizrachi Peter I. Lelkes Richard L. Ornberg Gertrude Goping Harvey B. Pollard 《Cell and tissue research》1989,256(2):365-372
Summary Chromaffin cells in the adrenal medulla are found in close proximity to capillary endothelial cells, thereby forming the classical endocrine complex. To examine the possible chemical basis of their interaction in more detail, we have grown bovine adrenal medullary endothelial (BAME) cells in monolayer cultures and added to them pheochromocytoma (PC12) cells, a chromaffin tumor cell line of rats. The PC12 cells were chosen because of the similarities they share with adrenal medullary chromaffin cells. PC12 cells rapidly attached to BAME cells cultures, their rate of adhesion being significantly enhanced over binding of PC12 cells to either uncoated plates or to monolayers of unrelated cell cultures. Consistent with this observation, we noted that the extracellular matrix (ECM) derived from the BAME cells did not enhance PC12 cell adhesion and did not promote neurite sprouting as previously described for ECM derived from corneal endothelial cells. The specific adhesion between PC12 and BAME cells could be abolished by cell surface extracts derived from these two cells but not by extracts derived from unrelated cell types. This activity was heat-labile, sensitive to trypsin and, to a lesser extent, to neuraminidase. We therefore conclude that PC12 cells may interact with BAME cells by specific proteinaceous adhesive factors associated with their plasma membranes. These interactions might represent the formative role of cell-cell contacts in the organization of the developing adrenal gland.Abbreviations
BAME
bovine adrenal medullary endothelial cells
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DMEM
Dulbecco's modified essential medium
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ECM
extracellular matrix
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EMEM
Eagle's modified essential medium
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FCS
fetal calf serum
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PBS
phosphate-buffered saline
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PC12
rat pheochromocytoma cells 相似文献
3.
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5.
Comparative Study of Cultured Burkitt Tumor Cells by Immunofluorescence, Autoradiography, and Electron Microscopy 总被引:13,自引:6,他引:7 下载免费PDF全文
Harald Zur Hausen Werner Henle Klaus Hummeler Volker Diehl Gertrude Henle 《Journal of virology》1967,1(4):830-837
Cultured Burkitt cells were examined by immunofluorescence, autoradiography, and electron microscopy in an effort to identify the stainable cells with those harboring herpes-type virus particles. Immediately after a 2-hr pulse of (3)H-thymidine, from 30 to 60% of the cells revealed heavy nuclear labeling. In most cases the grains were evenly dispersed, but in about 3 to 5% the grains showed a focal distribution and occasionally they extended into the cytoplasm. Such nuclear foci were rarely seen at 8 hr after the pulse. When the analysis was restricted to preselected immunofluorescent cells, up to 80% showed label at 8 hr and cytoplasmic grains were prominent. To reduce cellular deoxyribonucleic acid (DNA) synthesis, cells were X-irradiated with 3,000 to 6,000 R, and the isotope pulse was applied 1, 4, or 7 days later. Whereas the total number of labeled cells decreased in roughly twofold steps at the respective intervals (from 40 to 10%), the incorporation of (3)H-thymidine into fluorescent cells was not affected by X irradiation. In each series, about 70% of the fluorescent cells contained label when they were examined at 24 and 48 hr after the pulse, whereas at 8 and 72 hr fewer were positive. At the earlier intervals, unlabeled fluorescent cells most likely represented cells which had completed viral DNA synthesis prior to the pulse; at the later intervals, unlabeled fluorescent cells were probably cells which commenced viral replication after the pulse. These data support the conclusion that the immunofluorescent cells are the ones which harbor virus, and also confirm the expectation that the virus is a DNA virus from a member of the herpes group. This conclusion was firmly established by sectioning and electron microscopic examination of individual fluorescent cells, all of which contained numerous virus particles, whereas the nonstained cells prepared in a similar manner were free of them. 相似文献
6.
The available amino acid sequences of the α-amylase family (glycosyl hydrolase family 13) were searched to identify their
domain B, a distinct domain that protrudes from the regular catalytic (β/α)8-barrel between the strand β3 and the helix α3. The isolated domain B sequences were inspected visually and also analyzed
by Hydrophobic Cluster Analysis (HCA) to find common features. Sequence analyses and inspection of the few available three-dimensional
structures suggest that the secondary structure of domain B varies with the enzyme specificity. Domain B in these different
forms, however, may still have evolved from a common ancestor. The largest number of different specificities was found in
the group with structural similarity to domain B from Bacillus cereus oligo-1,6-glucosidase that contains an α-helix succeeded by a three-stranded antiparallel β-sheet. These enzymes are α-glucosidase,
cyclomaltodextrinase, dextran glucosidase, trehalose-6-phosphate hydrolase, neopullulanase, and a few α-amylases. Domain B
of this type was observed also in some mammalian proteins involved in the transport of amino acids. These proteins show remarkable
similarity with (β/α)8-barrel elements throughout the entire sequence of enzymes from the oligo-1,6-glucosidase group. The transport proteins, in
turn, resemble the animal 4F2 heavy-chain cell surface antigens, for which the sequences either lack domain B or contain only
parts thereof. The similarities are compiled to indicate a possible route of domain evolution in the α-amylase family.
Received: 4 December 1996 / Accepted: 13 March 1997 相似文献
7.
Gertrude M. Pfaffenbach Roger W. Melvold Stanley G. Nathenson 《Biochemical genetics》1990,28(7-8):433-441
The “bg” series of MHC mutations is the most prevalent type of mutations of Kb in C57BL/6 mice screened by reciprocal tail skin grafting. The basis for identification of this series of mutations is the
incompatibility of grafts between the parental B6 and the mutant. This series takes the longest to reciprocally reject the
skin grafts. The series can be subdivided into “bg 1” and “bg 2” groups based on Kb-restricted recognition of virus-infected mutant target cells. The biochemical basis for these mutations are amino acid substitutions
at residues 116 and 121 of the Kb transplantation antigen. These substitutions do not alter monoclonal antibody binding sites. The structural basis of MAb
binding and the genetic basis of the mutation are discussed.
This study was supported in part by USPHS Grants AI-07289, AI-10702, NCI P30-CA-13330, American Cancer Society Grant IM-236,
and American Cancer Society Fellowship PF-2126. Stanley G. Nathenson is a member of the Irvington House Institute for Medical
Research. 相似文献
8.
Fluorimetric measurements and chromatin condensation patterns of nuclei from 3T3 cells throughout G1
Gertrude C. Moser Robert J. Fallon Harriet K. Meiss 《Journal of cellular physiology》1981,106(2):293-301
Using two cytological methods based on nuclear morphology, quinacrine dihydrochloride (QDH) staining and premature chromosome condensation (PCC), it has been possible to identify cell cyle positions within G1 of growing and arrested 3T3 cells. The fluorescent intensity of QDH-stained interphase cells appears to decrease as the cells pass from mitosis to S phase. Likewise, the length and thickness of prematurely condensed chromatids can be related to the cells' position within the G1 period. Data are presented that deal with three interrelated topics: (1) We determined by fluorometric measurements of nuclei from 3T3 cells that the visual observation of the decrease in QDH fluorescence during G1 reflects an actual decrease in total fluorescence and not a dispersion of the fluorescent chromatin in a larger nuclear area. (2) We correlated the results obtained by QDH staining with those of PCC on the same cell samples blocked in G1 by different conditions. Serum-starved and contact-inhibited cell nuclei had the highest intensity, hydroxyurea-treated ones had the lowest intensity, while that of isoleucine-deprived cells was in between. The same relative order of G1 positions was obtained based on PCC morphology. Thus, both methods monitor the state of chromatin condensation and can be used to identify cell cycle position within G1.(3) We showed with both methods that the states of chromatin resulting from the various G1 blocking conditions differ from each other. 相似文献
9.
Paula Klevjer-Anderson Gertrude Case Buehring 《In vitro cellular & developmental biology. Plant》1980,16(6):491-501
Summary The individual effects of seven hormones on the in vitro growth rate of different classifications of human mammary epithelium
were compared. Hormones used were: 17β-estradiol, estriol, progesterone, hydrocortisone, testosterone, prolactin, and growth
hormone. Cell cultures included three established breast cell lines and primary monolayer cultures established form breast
fluids and excised mammary tissue from 40 women and 4 men. Specimens comprised three classifications: normal, nonmalignant
atypical, and malignant. Growth was quantitated in situ and expressed as population doubling time. Principal findings were:
(a) estrogens, prolactin, and growth hormone stimulated growth of normal cells more frequently than growth of malignant cells,
whereas testosterone and hydrocortisone stimulated growth of malignant cells more frequently than growth of normal cells;
(b) cells cultured from nonmalignant atypias generally showed hormone response profiles intermediate between those of normal
and malignant cells; (c) progesterone stimulated the growth of cells from malignant specimens but not the growth of cells
from normal and nonmalignant atypical samples.
This research was supported by NIAID Research Training Grant 5-TO1-A1-00332-06. 相似文献
10.