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141.
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143.
Philip S. Rudland Christine M. Hughes Sharon A. Ferns Michael J. Warburton 《In vitro cellular & developmental biology. Plant》1989,25(1):23-36
Summary Parenchymal organoidal structures that were obtained from collagenase digestion of reduction mammoplasty specimens of apparently
normal human breasts have been grown in short-term primary cultures, either on plastic or on floating gels of polymerized
rat-tail collagen. Three morphologically distinct major cell types are readily observed in both systems: cuboidal cells, which
occupy apical positions on collagen gels; larger, epithelioid, or basal cells on gels; and elongated cells which penetrate
into the gel. In addition, a fourth cell type, that of a large, flat cell, is observed less readily by phase contrast microscopy
on the surface of cultures grown on plastic. Immunofluorescent and immunocytochemical staining of cultures on plastic or histologic
sections of cultures on gels have been undertaken with antisera and other histochemical reagents that stain the different
parenchymal cell types in vivo. Thus antisera to epithelial membrane antigen(s), monoclonal antibodies (MABs) to the defatted
mammary milk fat globule membrane, peanut lectin, and keratin MAB LE61, which preferentially stain the epithelial cells of
ducts in vivo, also stain the cuboidal/apical cells in vitro. The large, flat cells are stained intensely by the first three
reagents but not by the last one. Antisera to collagen IV, laminin, fibronectin, actin, keratin MAB LP34, MABs to the common
acute lymphoblastic leukemia antigen, and MAB LICR-LON-23.10, which showed enhanced staining for the ductal myoepithelial
cells in vivo, also stain the epithelioid/elongated cells in vitro. However, the effect of the last four reagents is reduced
considerably in most elongated cells, and MAB LP34 stains the large, flat cells intensely. Heterogeneous cells of intermediate
morphologies and staining patterns between the cuboidal/flat cells and large epithelioid cells have also been identified.
The results suggest that the cuboidal cells and large, flat cells are related to mammary epithelial cells, whereas the large
epithelioid/elongated cells have some characteristics of myoepithelial cells, and that intermediate forms may exist in culture
between the two parenchymal cell types.
This work was supported in part by the Ludwig Institute for Cancer Research and the Cancer and Polio Research Fund. Dr. M.
J. Warburton is supported by the Cancer Research Campaign. 相似文献
144.
Jonathan E. Schwartz Philip Scuderi Cyndy Wiggins Alfred Rudolph Evan M. Hersh 《Biotherapy》1989,1(3):207-214
rTNF was administered to 28 patients with advanced metastatic cancers by continuous intra venous infusion for 5 consecutive days every 2 weeks. The dose levels were 30, 40, 70, 110, 180 and 290 µg/M2/day. Groups of 3 patients were started at each successive dose level and then on subsequent courses treated with the next dose level through 4 escalations as tolerated. Tumor types were: colon cancer 14; adenocarcinoma of unknown primary, 2; renal cancer, 2; leiomyosarcoma, 2; lung cancer, 1; prostate cancer, 1; thymona, 1; bladder cancer; 1; parotid, 1; Kaposi's sarcoma 2; ovarian 1. Toxicities included fever and chills (usually within the first 8 hours of infusion), fatigue, headache, decreased performance status, hypotension and CNS. All patients experienced leukopenia and thrombocytopenia within 24 hours or less after start of infusion with return of baseline by 72 hours after rTNF was stopped. The fall in these counts averaged 50% and was not dose related. No major changes in liver or renal function, coagulation or blood lipids were seen. Major dose limiting toxicities were fatigue, confusion, thrombocytopenia, seizures, hypotension and decreased performance status. NK cell activity measured against K562 target cells was augmented from about 30% target cell lysis to about 70% target cell lysis over the first 7 days of treatment. Two patients, both with metastatic colon cancer showed transient, objective tumor regression which did not qualify as a partial response. One patient with ovarian cancer had a stable partial response but progressed after 13 courses of treatment. Continuous infusion of TNF can be safely administered to patients with a maximum tolerated dose of only between 30 and 40 µg/M2/day. In addition, the MTD with continuous infusion seems to be highly variable and unpredictable from patient to patient. These data suggest that continuous infusion will not be an optimal way to administer TNF. 相似文献
145.
Human natural killer cell adhesion molecules. Differential expression after activation and participation in cytolysis. 总被引:19,自引:0,他引:19
M J Robertson M A Caligiuri T J Manley H Levine J Ritz 《Journal of immunology (Baltimore, Md. : 1950)》1990,145(10):3194-3201
Cell adhesion molecules (CAM) participate in interactions between lymphocytes, accessory cells, and target cells that are critical in the generation of effective immune responses. To characterize the involvement of CAM in NK and lymphokine activated killer (LAK) activities, we examined the expression of several CAM by freshly isolated human NK cells and by NK cells activated in vitro with IL-2, and compared this to CAM expression by T lymphocytes under similar conditions. Freshly isolated human NK cells were uniformly LFA-3 (CD58)+ and expressed two to three-fold higher surface levels of LFA-1 (CD11a/CD18) than resting T lymphocytes. More NK cells than T cells also expressed phenotypically detectable levels of intercellular adhesion molecule-1 (CD54). After in vitro incubation with IL-2, human NK cells demonstrated four- to sixfold increases in surface levels of CD11a/CD18, CD2, CD54, CD58, and the NK cell-associated Ag NKH-1 (CD56). Furthermore, essentially all NK cells became CD54+ within 3 days of exposure to IL-2. T cells did not demonstrate comparable up-regulation of CAM after incubation with IL-2. Increases in NK cell CAM expression were associated with enhanced formation of E:T cell conjugates, enhanced killing of NK-sensitive targets, and the induction of cytotoxicity for previously NK-resistant targets (LAK activity). The LAK activity induced by exogenous IL-2 could be partially inhibited by anti-CD2, anti-CD11a, or anti-CD54 antibodies and almost completely abrogated by anti-CD2 and anti-CD11a in combination. These studies suggest that CAM play a central role in the regulation of NK cytolysis, and that changes in CAM expression may alter the target cell specificity of activated NK effectors. 相似文献
146.
Philip W. Beesley Toni Paladino Irene Hill Claude Gravel Richard B. Hawkes James W. Gurd 《Journal of neurochemistry》1990,54(2):505-512
Glycoprotein gp50 is a neurone-specific, granule cell-enriched glycoprotein that is also a major component of isolated synaptic membranes. Here, we describe the use of a monoclonal antibody, mab SM gp50, to study the postnatal development of gp50 in the brain of normal and thyroid-deficient rats. Radioimmunoassay, enzyme-linked immunosorbent assay, and Western blotting show that gp50 is not detectable in brain until postnatal day 4 (P4) in both forebrain and cerebellum. In forebrain, the rate of increase of gp50 levels is maximal between P12 and P20. It is somewhat later in cerebellum, where peak levels are attained between P30 and P35. Immunocytochemical studies show little detectable gp50-like immunoreactivity before P16, and the staining is still weak, relative to adult tissue, at P25. The intense staining of the granule cell layer characteristic of adult cerebellum predominantly appears after P25. Development of gp50 is severely retarded in the cerebellum of thyroid-deficient rats, particularly during the second and third postnatal weeks. However, by the fourth postnatal week, gp50 levels in normal and hypothyroid animals are comparable. The results indicate that significant alterations in the pattern of gp50 expression continue to occur at a late stage of cerebellar development. In particular, the increase in immunocytochemical staining of the granule cells after P25 is striking in that by this time most major events associated with cerebellar development are essentially complete. 相似文献
147.
Subacute and Chronic In Vivo Lithium Treatment Inhibits Agonist- and Sodium Fluoride-Stimulated Inositol Phosphate Production in Rat Cortex 总被引:11,自引:9,他引:2
Philip P. Godfrey Steven J. McClue Alison M. White rew J. Wood David G. Grahame-Smith 《Journal of neurochemistry》1989,52(2):498-506
We have investigated the effects of in vivo lithium treatment on cerebral inositol phospholipid metabolism. Twice-daily treatment of rats with LiCl (3 mEq/kg) for 3 or 16 days resulted in a 25-40% reduction in agonist-stimulated inositol phosphate production, compared with NaCl-treated controls, in cortical slices prelabelled with [3H]inositol. A small effect was also seen with 5-hydroxytryptamine (5-HT) 24 h after a single dose of LiCl (10 mEq/kg). Dose-response curves to carbachol and 5-HT showed that lithium treatment reduced the maximal agonist response without altering the EC50 value. This inhibition was not affected by the concentration of LiCl in the assay buffer. Stimulation of inositol phosphate formation by 10 mM NaF in membranes prepared from cortex of 3-day lithium-treated rats was also inhibited, by 35% compared with NaCl-treated controls. Lithium treatment did not alter the kinetic profile of inositol polyphosphate formation in cortical slices stimulated with carbachol. Muscarinic cholinergic and 5-HT2 bindings were unaltered by lithium, as was cortical phospholipase C activity and isoproterenol-stimulated cyclic AMP formation. [3H]Inositol labelling of phosphatidylinositol 4,5-bisphosphate was significantly enhanced by 3-day lithium treatment. The results, therefore, indicate that subacute or chronic in vivo lithium treatment reduces agonist-stimulated inositol phospholipid metabolism in cerebral cortex; this persistent inhibition appears to be at the level of G-protein-phospholipase C coupling. 相似文献
148.
Frequency and space representation in the primary auditory cortex of the frequency modulating batEptesicus fuscus 总被引:2,自引:0,他引:2
Philip H. -S. Jen Xinde Sun Paul J. J. Lin 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》1989,165(1):1-14
1. Frequency and space representation in the auditory cortex of the big brown bat, Eptesicus fuscus, were studied by recording responses of 223 neurons to acoustic stimuli presented in the bat's frontal auditory space. 2. The majority of the auditory cortical neurons were recorded at a depth of less than 500 microns with a response latency between 8 and 20 ms. They generally discharged phasically and had nonmonotonic intensity-rate functions. The minimum threshold, (MT) of these neurons was between 8 and 82 dB sound pressure level (SPL). Half of the cortical neurons showed spontaneous activity. All 55 threshold curves are V-shaped and can be described as broad, intermediate, or narrow. 3. Auditory cortical neurons are tonotopically organized along the anteroposterior axis of the auditory cortex. High-frequency-sensitive neurons are located anteriorly and low-frequency-sensitive neurons posteriorly. An overwhelming majority of neurons were sensitive to a frequency range between 30 and 75 kHz. 4. When a sound was delivered from the response center of a neuron on the bat's frontal auditory space, the neuron had its lowest MT. When the stimulus amplitude was increased above the MT, the neuron responded to sound delivered within a defined spatial area. The response center was not always at the geometric center of the spatial response area. The latter also expanded with stimulus amplitude. High-frequency-sensitive neurons tended to have smaller spatial response areas than low-frequency-sensitive neurons. 5. Response centers of all 223 neurons were located between 0 degrees and 50 degrees in azimuth, 2 degrees up and 25 degrees down in elevation of the contralateral frontal auditory space. Response centers of auditory cortical neurons tended to move toward the midline and slightly downward with increasing best frequency. 6. Auditory space representation appears to be systematically arranged according to the tonotopic axis of the auditory cortex. Thus, the lateral space is represented posteriorly and the middle space anteriorly. Space representation, however, is less systematic in the vertical direction. 7. Auditory cortical neurons are columnarly organized. Thus, the BFs, MTs, threshold curves, azimuthal location of response centers, and auditory spatial response areas of neurons sequentially isolated from an orthogonal electrode penetration are similar. 相似文献
149.
Thomas F. Hourigan Frank G. Stanton Philip J. Motta Christopher D. Kelley Bruce Carlson 《Environmental Biology of Fishes》1989,24(2):105-116
Synopsis The foraging behavior and associated morphology of the feeding apparatus of three sympatric species of angelfishes, Holacanthus tricolor, Pomacanthus arcuatus and Pomacanthus paru were studied at St. Croix, U.S. Virgin Islands. All three had overlapping diets, consisting of algae and numerous species of sponges. The two Pomacanthus species also fed on gorgonians. The morphology of the dentition, jaws and gill rakers was similar in all three species. Male Holacanthus tricolor defended territories overlapping the foraging areas of two to four females. Within the male's territory, females defended smaller territories against other females of the same size, but tolerated smaller females. In contrast, both Pomacanthus spp. formed pairs which defended intraspecific feeding territories. 相似文献
150.