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At least 883 records · Page 49Linked to original sources
PubMed1987

Chlorpropamide-induced pure white cell aplasia.

We investigated the mechanism for isolated agranulocytosis and marrow pure white cell aplasia in an elderly man receiving 0.5 to 1.0 g per day of chlorpropamide (Chl) without other toxic drug exposure or overt systemic illness. Patient marrow revealed an absence of recognizable granulocytic precursors; megakaryocytes and erythroid precursors were normal. The WBC count was 1800/mm3 on admission with only 2% neutrophils; the absolute neutrophil count first exceeded 500/mm3 on the 17th day following cessation of Chl. A serum Chl level on admission was 100 micrograms/mL (acute phase, AP); no Chl was detected in serum (convalescent phase, CP) assessed on the 22nd hospital day. Antineutrophil antibodies were not detected, and T cell depletion failed to augment patient in vitro granulopoiesis. Patient AP serum produced potent complement-mediated inhibition (87% +/- 7%) of autologous granulocyte progenitors (CFU-GM) with minimal inhibition of erythroid (11% +/- 5%) or multipotent (5% +/- 4%) progenitor cells. Selective inhibition by patient AP serum of CFU-GM (74% +/- 11%) was also seen against two allogeneic marrows. Patient CP serum no longer inhibited (6% +/- 4%) autologous CFU-GM. Addition of Chl (5 to 120 micrograms/mL) to CP serum but not to control serum resulted in potent drug concentration-dependent complement-mediated inhibition of autologous and allogeneic CFU-GM. Inhibition of CFU-GM in the presence of Chl was no longer demonstrable following immunoabsorbent removal of IgG from patient serum. Patient serum in the presence of Chl had limited activity against morphologically recognizable marrow granulocytic precursors in a microimmunofluorescence assay. These results are most consistent with the development of Chl-dependent, selective antibody-mediated immune inhibition of granulopoiesis.

Aged↗
PubMed2003

Adenocarcinoma of the uterine cervix: the presence of human papillomavirus and the method of detection.

BACKGROUND: Effective screening programs have contributed to a decrease in the incidence of cervical squamous cell carcinomas but have had a limited sensitivity in the detection of adenocarcinoma precursor lesions. The aim of our study was to analyze cervical adenocarcinoma in greater detail: symptoms preceding the detection, the method of detection and the prevalence of human papillomavirus (HPV) with respect to age at diagnosis. MATERIAL AND METHODS: Clinical data were abstracted from the medical records of 82 women with pure invasive cervical adenocarcinomas. As diagnostic tools we used polymerase chain reaction (PCR)-based single-strand conformation polymorphism (SSCP) and/or direct DNA sequencing for HPV detection. RESULTS: Age at diagnosis predicting factors were HPV status, positive lymph nodes, histology and stage. HPV-negativity, lymph node metastases, advanced stage and poor differentiation were all associated with a high diagnostic age. In the multivariate analysis only HPV status was shown to have an independent impact on age at diagnosis, while stage showed only borderline significance. Twenty-three percent of the cancers were detected by screening and the remaining were due to different symptoms. Among the women considered, 93% had a normal Papanicolaou (Pap) smear 3 years before diagnosis and 60% within 1 year. There was no significant correlation between smoking, oral contraceptives and HPV-positivity. CONCLUSIONS: The absence of HPV was significantly associated with a high age at diagnosis. Pap screening had a limited effect in detecting adenocarcinoma at an early stage.

Adenocarcinoma↗
PubMed2026

Strategy for enhanced production of A40926B0 in Nonomuraea gerenzanensis using an efficient CRISPR/AsCas12f1 system.

The global emergence of vancomycin-resistant Gram-positive pathogens underscores the urgent need for efficient production of novel lipoglycopeptide antibiotics. Dalbavancin, a last-resort therapeutic agent, relies on its key biosynthetic precursor A40926B0, whose industrial manufacture is severely limited by the low yield of wild-type Nonomuraea gerenzanensis and inefficient genetic tools for this rare actinomycete. Here, we developed a high-efficiency CRISPR/AsCas12f1 genome editing system and applied systematic metabolic engineering to boost A40926B0 biosynthesis. First, conjugation conditions were optimized to elevate the transfer efficiency in N. gerenzanensis D11. The hypercompact AsCas12f1 nuclease showed markedly lower cytotoxicity than SpCas9 and enabled 100% gene deletion efficiency with preferred PAMs (TTTG, CTTG, GTTG). Second, we strengthened the shikimate pathway via multiple genetic strategies: overexpressing feedback-resistant DAHP synthase (aroG fbr ) and chorismate mutase/prephenate dehydrogenase (tyrA fbr ), as well as knocking out pheA. This manipulation blocks the phenylalanine synthetic branch and redirects metabolic flux toward the l-tyrosine branch. Third, we engineered the branched-chain fatty acid (BCFA) pathway via promoter replacement of bkdA2B2C2, LipAB, fabF and deletion of acdH to enhance isododecanoyl side-chain supply. The combinatorial engineering yielded strain B-13, which produced 1740 mg/L A40926B0 in shake flasks. Finally, 50-L fed-batch fermentation with continuous maltodextrin feeding further increased the titer to 1817 mg/L, the highest reported titer to date. This work establishes a robust CRISPR editing tool for N. gerenzanensis and provides valuable engineering references for precursor-oriented strain improvement targeting lipoglycopeptide antibiotics, offering insights for the industrial scale production of A40926B0.

A40926B0↗
PubMedDate not supplied

Enhanced isoamyl acetate production upon manipulation of the acetyl-CoA node in Escherichia coli.

Coenzyme A (CoA) and its thioester derivative acetyl-Coenzyme A (acetyl-CoA) participate in over 100 different reactions in intermediary metabolism of microorganisms. Earlier results indicated that overexpression of upstream rate-limiting enzyme pantothenate kinase with simultaneous supplementation of precursor pantothenic acid to the culture media increased intracellular CoA levels significantly ( approximately 10-fold). The acetyl-CoA levels also increased ( approximately 5-fold) but not as much as that of CoA, showing that the carbon flux from the pyruvate node is rate-limiting upon an increase in CoA levels. In this study, pyruvate dehydrogenase was overexpressed under elevated CoA levels to increase carbon flux from pyruvate to acetyl-CoA. This coexpression did not increase intracellular acetyl-CoA levels but increased the accumulation of extracellular acetate. The production of isoamyl acetate, an industrially useful compound derived from acetyl-CoA, was used as a model reporter system to signify the beneficial effects of this metabolic engineering strategy. In addition, a strain was created in which the acetate production pathway was inactivated to relieve competition at the acetyl-CoA node and to efficiently channel the enhanced carbon flux to the ester production pathway. The synergistic effect of cofactor CoA manipulation and pyruvate dehydrogenase overexpression in the acetate pathway deletion mutant led to a 5-fold increase in isoamyl acetate production. Under normal growth conditions the acetate pathway deletion mutant strains accumulate intracellular pyruvate, leading to excretion of pyruvate. However, upon enhancing the carbon flux from pyruvate to acetyl-CoA, the excretion of pyruvate was significantly reduced.

Acetyl Coenzyme A↗
PubMed2003

Kinetics of proton-coupled electron-transfer reactions to the manganese-oxo "cubane" complexes containing the Mn4O4(6+) and Mn4O4(7+) core types.

The kinetics of proton-coupled electron-transfer (pcet) reactions are reported for Mn(4)O(4)(O(2)PPh(2))(6), 1, and [Mn(4)O(4)(O(2)PPh(2))(6)](+), 1(+), with phenothiazine (pzH). Both pcet reactions form 1H, by H transfer to 1 and by hydride transfer to 1(+). Surprisingly, the rate constants differ by only 25% despite large differences in the formal charges and driving force. The driving force is proportional to the difference in the bond-dissociation energies (BDE >94 kcalmol for homolytic, 1H --> H + 1, vs. approximately 127 kcalmol for heterolytic, 1H --> H(-) + 1(+), dissociation of the OH bond in 1H). The enthalpy and entropy of activation for the homolytic reaction (deltaH = -1.2 kcalmol and deltaS= -32 calmol.K; 25-6.7 degrees C) reveal a low activation barrier and an appreciable entropic penalty in the transition state. The rate-limiting step exhibits no HD kinetic isotope effect (k(H)k(D) = 0.96) for the first H atom-transfer step and a small kinetic isotope effect (1.4) for the second step (1H + pzH --> 1H(2) + pz(*)). These lines of evidence indicate that formation of a reactive precursor complex before atom transfer is rate-limiting (conformational gating), and that little or no NH bond cleavage occurs in the transition state. H-atom transfer from pzH to alkyl, alkoxyl, and peroxyl radicals reveals that BDEs are not a good predictor of the rates of this reaction. Hydride transfer to 1(+) provides a concrete example of two-electron pcet that is hypothesized for the OH bond cleavage step during catalysis of photosynthetic water oxidation.

Calorimetry↗
PubMed1991

In vivo functional clonal deletion of recipient CD4+ T helper precursor cells that can recognize class II MHC on injected donor lymphoid cells.

Intravenous injection of semiallogeneic (C57BL/6XDBA/2)F1 lymphocytes into adult C57BL/6 recipient mice not only, as previously reported, reduces the recipients' cytotoxic T lymphocyte response in a subsequent in vitro mixed lymphocyte reaction against the injected cell type, but also reduces Th cell function in the same MLR. Thus lymphoid cells derived from the injected mice were greatly reduced in their ability to proliferate and to produce IL-2 in response to (C57BL/6XDBA/2)F1 stimulator cells in vitro, whereas third party responses were unaffected. This appears to be due to a reduction in the precursor frequency of IL-2-producing T lymphocytes specific for the injected cells as measured by limiting dilution analysis. Similar donor-specific reduction in the frequency of precursors of IL-2-producing cells was seen after i.v. injection of A.TL lymphocytes into A.TH recipients (differing at class II determinants I-A and I-E, but identical at K and D). Here there also appeared to be a functional clonal deletion of precursors of IL-2-producing Th cells, shown directly to be class II MHC reactive and CD4+. There is strong evidence that the reduction of class I-specific cytotoxic responses in the injected mice is a manifestation of donor cells that function as veto cells, i.e., that function as deletional APC that inactivate class I-reactive CTL precursors that recognize them. Our data in this study show that class II-specific Th responses are similarly reduced in the injected mice and suggest that CD4+ class II-reactive precursors of Th cells may be functionally inactivated in vivo by donor cells via a veto-like mechanism.

Animals↗
PubMed1974

The N-terminal amino-acid sequence of bovine proparathyroid hormone.

Proparathyroid hormone (calcemic fraction-A) is a biosynthetic precursor of parathyroid hormone in bovine glands. Limited amounts of the isolated prohormone have been obtained for the purpose of initial structural studies. The results of automated sequence analysis on two separate preparations indicate that the N-terminal region of the prohormone consists of the sequence Lys-Ser-Val-Lys-Lys-Arg followed by a sequence exactly corresponding to residues 1 to 34 of bovine parathyroid hormone. Also observed was a minor sequence (about 12% of the total) in which the N-terminal lysine was absent. These data suggest that more than one species of prohormone may exist. Due to the small quantities of sample available, the analyses were restricted to the N-terminal portion of the prohormone only. However, because the amino-acid composition of the prohormone indicates it to be a molecule containing more than 100 amino acids, the possibility remains that additional residues occur at the C-terminus. Thus, the prohormone structure based on these data is believed to consist of the hexapeptide sequence above, followed by the known sequence of the 84 residues in parathyroid hormone, possibly followed by an additional sequence of 10-15 residues.

Amino Acid Sequence↗
PubMed1991

Association between leukemic erythroid progenitors and bone marrow macrophages.

Previous ultrastructural investigations have shown that the erythroblastic island is composed of erythroblasts at different stages of maturation which are intimately associated with a central macrophage. However, it is still unclear at which stage of erythroid differentiation this interaction occurs, mainly because of the lack of purified populations of normal erythroid progenitors [erythroid colony-forming units (CFU-E) and erythroid burst-forming units (BFU-E)] and early precursor cells (proerythroblasts) and because of our limited knowledge of their ultrastructural characteristics. In the present work we analyzed the ultrastructure of CFU-E enriched from normal human bone marrow by avidin-biotin immune rosetting and leukemic blasts of erythroid origin from two patients. Normal and leukemic CFU-Es were defined as glycophorin A (GPA)-negative blasts, devoid of rhopheocytosis, containing some ferritin molecules, either free in the cytoplasm or associated with theta-granules (theta-Gr) in the Golgi zone. Peroxidase activity was detected in the endoplasmic reticulum of these blasts. A preproerythroblast stage was identified, which corresponded to an intermediate phenotype with few GPA sites and rhopheocytosis. In contrast to hemoglobin synthesis, which was absolutely dependent on the presence of erythropoietin (Epo) during culture for 24 hours, ferritin molecules accumulated in the absence of Epo. Interestingly, leukemic CFU-E-like blasts were always in contact with bone marrow macrophages and adhesion between these cell types resisted mechanical dissociation. This result suggests that erythroid progenitors may be part of the erythroblastic island. The mechanisms involved in erythroblast-macrophage binding are still unknown, but the expression by macrophages and erythroid progenitors of receptors for fibronectin and thrombospondin (TSP), as well as their respective ligands in the case of macrophages, suggests that these molecules could be involved in the formation of the erythroblastic island.

Bone Marrow Cells↗
PubMed1996

Peer victimization: cause or consequence of school maladjustment?

Past research has shown that peer victimization and school maladjustment are related, but it is unclear whether victimization is a cause or consequence of such difficulties. This study examined whether (a) peer victimization is a precursor of school maladjustment, (b) the effects are limited to the period of victimization, and (c) stable peer victimization experiences compound adjustment difficulties. Toward this end, data were collected on 200 5- and 6-year-old children (105 males, 95 females) in the fall and spring of kindergarten. Findings supported the hypothesis that victimization is a precursor of children's loneliness and school avoidance. Whereas children's feelings of loneliness were more pronounced while victimization was occurring, delayed effects were found for school avoidance. Furthermore, the duration of children's victimization experiences was related to the magnitude of their school adjustment problems.

Adolescent↗
PubMed1993

Potential role of two novel elastase-like enzymes in processing pro-transforming growth factor-alpha.

Transforming growth factor-alpha (TGF-alpha) is a mitogenic peptide produced by tumor cells and by virally and chemically transformed cells in culture. TGF-alpha is almost certainly derived from its precursor protein (pro-TGF-alpha) by limited proteolysis, but the physiologically relevant processing enzyme(s) is(are) unknown. We now report that oncogenically transformed rat liver epithelial cells (known to secrete TGF-alpha) and Schwann cells in culture transfected with SV40 T-antigen (which are now reported to express mRNA encoding pro-TGF-alpha) contain membrane associated, neutral pH, serine proteinases which are elastase-like in their substrate specificity, but elastase is not known to be associated with these cell types. In both cell types, the enzyme is associated with a subcellular fraction enriched for microsomes and plasma membranes. Furthermore, the enzyme appears to be specifically induced 4-fold in the transformed epithelial cells as compared with the level of enzyme present in the nontransformed parental cells. The enzymes have been purified approximately 20,000-fold to near homogeneity (50-60 units/mg) and are virtually identical with regard to their molecular weights (38,000) and other physiochemical properties. Results obtained with numerous synthetic peptide substrates show the enzymes prefer nonpolar residues such as Ala and Val in the P1 and P2 positions, but promiscuity of cleavage specificity observed with long-chain peptide substrates is attributed to the absence of structure in these peptides. Thus, although these enzymes may be involved in processing pro-TGF-alpha at the plasma membrane of the cell, it is just as likely that these enzymes play other physiological roles in the parental and/or transformed cells and that there is no specific endoproteolytic processing enzyme of pro-TGF-alpha.

Amino Acid Sequence↗
PubMed1997

Delta-6-desaturase and delta-5-desaturase in human Hep G2 cells are both fatty acid interconversion rate limiting and are upregulated under essential fatty acid deficient conditions.

Essential fatty acids are interconverted by desaturases and elongases to eicosanoid precursors. In essential fatty acid deficiency (EFAD) an increased hepatic interconversion of linoleic acid (18:2) to arachidonic acid (20:4n-6) has been demonstrated in vivo. We now cultured Hep G2 cells under EFAD conditions. 20:3n-6 appeared in EFAD cells, but also in controls. After adding 14C-18:2 to the medium, interconversion products and their distribution in different lipids were studied by HPLC. When trace amounts 18:2 were incubated, 38% were converted by the EFAD cells after 21 h, vs 6% by controls. 20% was converted to 20:4 by EFAD cells vs 14% by controls. EFAD cells preferentially distributed more 18:2 and conversion products to neutral fats and to phosphatidyl ethanolamine, but less to cardiolipin than controls did, when incubated with trace amount 18:2, but not with 1 mM 18:2. A relative accumulation of radioactivity in 20:3 was observed. In conclusion; in EFAD Hep G2 cells delta-6- and delta-5-desaturase both were found to be upregulated and eicosanoid precursors were distributed more into phosphatidyl ethanolamine. Delta-5-desaturase had a rate limiting property as well as delta-6-desaturase.

Arachidonic Acid↗
PubMed1977

Differentiation of functionally active mouse T-lymphocytes from functionally inactive bone marrow precursors.

An investigation has been made of the development of various T cell functions in lethally irradiated mice reconstituted with anti-0 treated spleen or bone marrow cells. Evidence is presented to show that both organs contain a post-thymic precursor pool able to regenerate by 15 days limited T cell responses in thymectomized recipients. A prethymic pool also exists in each organ able to regenerate, at a later date, first a suppressor T cell population and probably later, mature functional T cells involved in helper functions and cell mediated lympholysis. The spleen is apparently a better source of precursors of the suppressor cells than bone marrow, while a poorer source of precursors of the other T cell functions. All T cell functions investigated apparently first appear in large cells which undergo a reversion to small cells without necessarily maturing to their full potential reactivity. By following the kinetics of appearance of T cell functions, and the physical parameters of the cells with which these functions are associated, it is shown that PHA responding and Con A responding cells, cytotoxic T cell progenitors, helper T cells for antibody production and helper T cells for cytotoxicity induction can all at some stage of differentiation be separated from one another.

Animals↗
PubMed1985

Transfer RNA splicing in Saccharomyces cerevisiae. Secondary and tertiary structures of the substrates.

Secondary and tertiary structures of four yeast tRNA precursors that contain introns have been elucidated using limited digestion with a variety of single-strand- and double-strand-specific nucleases. The pre-tRNAs, representing the variety of intron sizes and potential structures, were: pre-tRNALeuCAA, pre-tRNALeuUAG, pre-tRNAIleUAU, and pre-tRNAPro-4UGG. Conventional tRNA cloverleaf structure is maintained in these precursors except that the anticodon loop is interrupted by the intron. The intron contains a sequence which is complementary to a portion of the anticodon loop and allows the formation of a double helix often extending the anticodon stem. The 5' and 3' splicing cleavage sites are located at either end of this helix and are single-stranded. The intron is the most sensitive region to nuclease cleavage, suggesting that it is on the surface of the molecule and available for interaction with the splicing endonuclease. Absence of Mg2+ or spermidine renders the dihydrouridine and T psi C loops of these precursors highly sensitive to nuclease digestion. These ionic effects mimic those observed for tRNAPhe and suggest that the tRNA portion of these precursors has native tRNA structure. We propose consensus secondary and tertiary structures which may be of significance to eventual understanding of the mechanism of yeast tRNA splicing.

Macromolecular Substances↗
PubMed1986

Rearrangement of immunoglobulin heavy chain genes in human T leukaemic cells shows preferential utilization of the D segment (DQ52) nearest to the J region.

The DNA rearrangements leading to the assembly of genes coding for the immunoglobulin heavy chain (IgH) in B cells and the T cell receptor for antigen in T cells are not completely lineage specific. This probably reflects the use of a common recombinase by IgH and the T cell receptor. This paper describes novel observations on the nature of these cross-lineage rearrangements. A high proportion (though not all) IgH rearrangements in human T leukaemic cells involve the D segment nearest to the J region (DQ52). This same D segment is not involved in B cell IgH rearrangements with one important exception, namely a proportion of B cell leukaemic clones with the most primitive B cell precursor phenotype. These observations have potentially important implications for early lymphoid cell differentiation and in particular support the idea that the 3' D plus J region might lie within a limited window of accessibility of the IgH gene in precursor lymphocytes.

DNA Restriction Enzymes↗
PubMed2001

Coupling of conformational folding and disulfide-bond reactions in oxidative folding of proteins.

The oxidative folding of proteins consists of conformational folding and disulfide-bond reactions. These two processes are coupled significantly in folding-coupled regeneration steps, in which a single chemical reaction (the "forward" reaction) converts a conformationally unstable precursor species into a conformationally stable, disulfide-protected successor species. Two limiting-case mechanisms for folding-coupled regeneration steps are described. In the folded-precursor mechanism, the precursor species is preferentially folded at the moment of the forward reaction. The (transient) native structure increases the effective concentrations of the reactive thiol and disulfide groups, thus favoring the forward reaction. By contrast, in the quasi-stochastic mechanism, the forward reaction occurs quasi-stochastically in an unfolded precursor; i.e., reactive groups encounter each other with a probability determined primarily by loop entropy, albeit modified by conformational biases in the unfolded state. The resulting successor species is initially unfolded, and its folding competes with backward chemical reactions to the unfolded precursors. The folded-precursor and quasi-stochastic mechanisms may be distinguished experimentally by the dependence of their kinetics on factors affecting the rates of thiol--disulfide exchange and conformational (un)folding. Experimental data and structural and biochemical arguments suggest that the quasi-stochastic mechanism is more plausible than the folded-precursor mechanism for most proteins.

Disulfides↗
PubMed1984

Interleukin 2 enhancement of lymphokine secretion by T lymphocytes: analysis of established clones and primary limiting dilution microcultures.

The effect of exogenous interleukin 2 (IL 2) on lymphokine production by T lymphocytes was examined in two systems: the secretion of macrophage-activating factor (MAF) and interferon (IFN) by cloned long-term T cell lines, and a limiting dilution system for estimating the frequency of precursors of MAF-secreting cells in normal spleen. An IL 2-containing, MAF- and IFN-free supernatant from the EL-4 thymoma (EL-4 SN) significantly enhanced release of MAF and IFN by mitogen- or antigen-stimulated, cytolytic or noncytolytic T lymphocyte clones directed against alloantigens or Moloney leukemia virus-associated antigens. Highly purified IL 2 produced equivalent enhancement as EL-4 SN in cultures of alloreactive clones stimulated with concanavalin A. Kinetics experiments showed that EL-4 SN increased both the rate and duration of MAF release by T cell clones. EL-4 SN also increased MAF production when added during restimulation of limiting dilution cultures of positively selected Lyt-2+ and Lyt-2- C57BL/6 splenic T lymphocytes activated against DBA/2 alloantigens. This enhancement resulted in a threefold increase in the apparent precursor frequency of MAF-secreting cells among Lyt-2+ lymphocytes, but did not affect the frequency among Lyt-2- cells. Additional analysis indicated that average MAF production in cultures of Lyt-2-+ cells was sixfold lower than in cultures of Lyt-2- cells, and hence that EL-4 SN allowed detection of a significant proportion of Lyt-2+ cell cultures secreting low levels of MAF. Under these improved conditions, the MAF assay detected the majority of responding Lyt-2+ and Lyt-2- lymphocytes.

Animals↗
PubMed1998

Quantification of metabolites in the indole alkaloid pathways of catharanthus roseus: implications for metabolic engineering

In this article, we present a review of the current state of metabolic engineering in Catharanthus roseus. A significant amount of research has contributed to characterization of several individual steps in the biosynthetic pathway of medicinally valuable alkaloids. However, knowledge of the regulation of these pathways is still sparse. Using hairy root cultures, we studied the responses of alkaloid metabolism to environmental stimulation such as light and elicitation. Through precursor feeding studies, the putative rate-limiting steps of the terpenoid pathway in hairy root cultures also have been examined. Relating this knowledge to specific events at the molecular level, and the cloning of corresponding genes are the next key steps in metabolic engineering of the C. roseus alkaloids. Copyright 1998 John Wiley & Sons, Inc.

Journal Article↗
PubMed1999

Fra-1 potentiates osteoclastic differentiation in osteoclast-macrophage precursor cell lines.

c-Fos, a component of the dimeric transcription factor AP-1, is necessary for osteoclast formation. To determine whether c-Fos can substitute for any or all of the stimuli needed for osteoclast induction, we infected osteoclast precursors with retroviral vectors expressing c-Fos or the Fos-related protein, Fra-1. The infected cells were incubated with or without osteoclast-inductive stimuli. Osteoclast formation from retroviral-infected precursors remained completely dependent on osteoclast-inductive stromal cells. Unexpectedly, infection of bipotential osteoclast-macrophage precursor cell lines with retroviruses expressing Fra-1 but not c-Fos caused a 10-100-fold increase in the number of precursors that developed calcitonin receptors associated with an increase in bone resorption. These observations suggest that, in the precursor cell lines, Fra-1 is a limiting factor for full responsiveness to the osteoclast-inductive environment. Fra-1 is therefore likely to play a role in osteoclast differentiation which is distinct from that of c-Fos.

Autoradiography↗