Biomedical subjects

J Qian

Publications and source records attributed to J Qian.

At least 19 recordsLinked to original sources

PubMed2006

The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer--results from a 4-month pre-radical prostatectomy study.

BACKGROUND: As dihydrotestosterone (DHT) is the most potent androgen in the prostate, inhibition of the 5alpha-reductase isoenzymes, which convert testosterone to DHT, could be an appropriate target for the treatment of prostate cancer. METHODS: Eighty-one men with clinically localized prostate cancer received daily dutasteride 3.5 or 0.5 mg, or no therapy for 4 months before radical prostatectomy. Histopathological assessments were conducted on prostatectomy specimens. RESULTS: Treatment with dutasteride was associated with reductions in serum and intraprostatic DHT of >or=90%, and a decrease in total prostate and tumor volumes. No effect of dutasteride was noted on Gleason grade. Histopathological effects on benign tissue were similar but less prominent than those seen with androgen ablation, whereas there was no significant difference in cancer histology among the groups. CONCLUSIONS: Dutasteride treatment results in similar but less marked changes compared with androgen ablation.

5-alpha Reductase Inhibitors↗

PubMed2006

Toroidal symmetry of the geodesic acoustic mode zonal flow in a tokamak plasma.

The toroidal symmetry of the geodesic acoustic mode (GAM) zonal flows is identified with toroidally distributed three step Langmuir probes at the edge of the HuanLiuqi-2A (commonly referred to as HL-2A) tokamak plasmas for the first time. High coherence of both the GAM and the ambient turbulence for the toroidally displaced measurements along a magnetic field line is observed, in contrast with the high coherence of the GAM but low coherence of the ambient turbulence when the toroidally displaced measurements are not along the same field line. The radial and poloidal features of the flows are also simultaneously determined. The nonlinear three wave coupling between the high frequency turbulent fluctuations and the flows is demonstrated to be a plausible formation mechanism of the flows.

Journal Article↗

PubMed2006

Efficacy of emergent transcatheter transplantation of stem cells for treatment of acute myocardial infarction (TCT-STAMI).

OBJECTIVE: To study whether emergent intracoronary autologous bone marrow cell transplantation (BMT) is applicable for the treatment of acute myocardial infarction (AMI). METHODS: 20 patients admitted within 24 h after the onset of a first AMI were randomly allocated to receive intracoronary autologous BMT (n = 10) or bone marrow supernatant (controls, n = 10) immediately after primary percutaneous coronary intervention. Left ventricular ejection fraction (LVEF), left ventricular end diastolic internal diameter (LVDd) and myocardial perfusion defect scores were examined respectively by echocardiography and single-photon emission computed tomography at one week and six months after AMI. RESULTS: From one week to six months after AMI, LVEF was enhanced from mean 53.8 (SD 9.2)% to 58.6 (9.9)% (p < 0.05) in the BMT group but was unchanged in the control group (58.2 (7.5)% v 56.3 (3.5)%, p > 0.05); LVDd remained unchanged (52.5 (2.8) v 52.1 (3.2) mm, p > 0.05) in the BMT group but was significantly enlarged in the control group (50.4 (6.0) v 55.2 (7.1) mm, p < 0.05). Additionally, myocardial perfusion defect scores decreased from 21 (11) to 13 (10) (p < 0.01) in the BMT group but were unchanged in the control group (20 (14) v 17 (15), p > 0.05). CONCLUSION: Emergent intracoronary transplantation of bone marrow mononuclear cells after AMI is practicable, and it improved cardiac function, prevented myocardial remodelling and increased myocardial perfusion at six months' follow up.

Bone Marrow Transplantation↗

PubMed2006

A frequent partial AZFc deletion does not render an increased risk of spermatogenic impairment in East Asians.

The gene families in the AZFc region of the Y chromosome have been shown to be functionally important in human spermatogenesis. The gr/gr deletion, a partial AZFc deletion that reduces the copy numbers of all the AZFc gene families, was identified as a significant risk factor for spermatogenic impairment in Dutch, Spanish and Italians. However, the presence of this deletion in healthy French and Germans questioned its importance in male infertility. In this study, we have shown that the gr/gr deletion does not render an increased risk in Han Chinese. In fact, the gr/gr deletion is frequent (about 8%) in our survey of 886 East Asians from 8 ethnic groups. Furthermore, the DAZ1/DAZ2 deletion has been detected as the primary subtype of the gr/gr deletion in East Asians, though this doublet has been considered as crucial for normal spermatogenesis in Europeans. The different spermatogenic effects of various types of the partial AZFc deletion suggest that the functional difference between AZFc gene copies is a likely cause of inconsistent associations of the gr/gr deletion with spermatogenic impairment across populations.

Base Sequence↗

PubMed2005

Simultaneous labeling of mast cell proteases and protease mRNAs at the bone-implant interface of aseptically loosened hip implants.

Human mast cells (MC) exhibit two distinct phenotypes based on the protease content of their secretory granules. MC(TC) cells express tryptase, chymase, cathepsin G, and mast cell carboxypeptidase, while MC(T) cells express only tryptase. Both mast cell phenotypes were assessed near regions of osteolysis in uninfected failed joint implants by immunohistochemistry with antibodies to tryptase and chymase, and by in situ hybridization with anti-sense RNA probes for the respective mRNA molecules. Specimens from the interface membrane of 32 aseptically loosened total hip implants were studied, 28 of which had mast cells of the MC(TC) type. Most of these mast cells were aligned along the bone-prosthesis interface adjacent to loosened implants, suggesting involvement in the chronic inflammatory response that leads to bone resorption. Further ultrastructural evidence of mast cells in tissues from failed joint interface membranes was shown by transmission electron microscopy, and detection by staining after magnetic activated cell sorting. The presence of MC at the periprosthetic interface of eroded bone suggests MC degranulation and activity are associated with osteolysis in failed joint prostheses.

Arthroplasty, Replacement, Hip↗

PubMed2005

[Laser-induced Interstitial thermotherapy (LITT) in hepatic metastases of various sizes in an animal model].

PURPOSE: To assess the effect of laser-induced thermotherapy (LITT) on liver metastases of various size from colon carcinoma in an animal model. MATERIALS AND METHODS: Liver metastases were implanted in 20 Wistar Albino Glaxo (WAG) rats by subcapsular injection of cells from a colorectal strain (CC531) (day 0). The animals were divided into two groups with regard to the measured tumor size of 0.05 - 0.06 cm (3) (group A) and 0.10 - 0.12 cm (3) (group B). On day 14 after laparotomy, the tumors were exposed to 1064 nm Nd:YAG laser light at 2 watts for 5 minutes after intratumoral placement of the laser applicator set. The tumor volumes before (V1, at day 13) and after treatment (V2, at day 28) were determined by MRI and the mean tumor growth ratio (V2/V1) was calculated. RESULTS: The mean tumor volumes V1 and V2 were 0.05 +/- 0.003 cm (3) and 0.23 +/- 0.016 cm (3) in group A, and 0.11 +/- 0.006 cm (3) and 0.68 +/- 0.037 cm (3) in group B. The mean tumor growth ratio (V2/V1) was 4.31 +/- 0.19 in group A and 6.11 +/- 0.14 in group B. The mean volume of the induced necrosis (0.15 +/- 0.01 cm (3)) was the same for both groups ( p > 0.05). Compared to group B, liver metastases of group A showed a significant slower tumor growth velocity (paired t-test, p < 0.0001). CONCLUSION: The interventional treatment of large hepatic tumors with LITT leads to faster tumor growth compared to smaller lesions.

Animals↗

PubMed2004

Transarterial chemoembolization alone and in combination with other therapies: a comparative study in an animal HCC model.

The purpose of this study is to compare transarterial chemoembolization (TACE) alone and in combination with other therapies in an animal model. Subcapsular implantation of a solid Morris hepatoma 3924A in the liver was carried out in 50 male ACI rats (day 0). Tumor volume (V1) was measured by MRI (day 13). After laparotomy and retrograde placement of a catheter into the gastroduodenal artery (day 14), the following protocols of the interventional procedure were applied: TACE (mitomycin C + lipiodol) + immunotherapy (group A: TNFalpha + IL-2, group B: OK-432 + IL-2); TACE + antiangiogenesis therapy (group C: TNP-470, group D: endostatin); TACE alone in group E (control group). Tumor volume (V2) was assessed by MRI and the mean ratio of x (V2/V1) was calculated. Data were analyzed using Dunnett's t test (comparing therapeutic groups with the control group) and the Student-Newman-Keuls test (comparing significant therapeutic groups). Multivariate analysis showed a significant reduction in the tumor growth rate (P<0.05) in groups B (x=6.53) and C (x=4.01) compared to the mean ratio of the control group E (x=9.14). Significant results were observed in group C (P<0.05) in comparison with the other therapeutic groups. TACE combined with immunotherapy (OK-432) and antiangiogenesis therapy (TNP-470) retards tumor growth compared with TACE alone in an HCC animal model.

Angiogenesis Inhibitors↗

PubMed2004

Retroviral delivery of GAD-IgG fusion construct induces tolerance and modulates diabetes: a role for CD4+ regulatory T cells and TGF-beta?

Previous studies have demonstrated that antigen-specific tolerance could be induced by lipopolysaccharide (LPS)-stimulated B cells retrovirally transduced with an immunoglobulin-antigen (or epitope-containing peptide) fusion construct. To investigate the mechanism of this gene therapy system, we now adapted this approach to immunotherapy of spontaneous diabetes in nonobese diabetic (NOD) mice, a T-cell-mediated autoimmune disease triggered, in part, by a pathogenic response to glutamate decarboxylase (GAD) 65. We demonstrate that LPS-stimulated splenocytes, retrovirally transfected with GAD-IgG fusion construct, induce a significant antigen-specific hyporesponsiveness at both cellular and humoral levels and reduce the incidence of diabetes in female NOD mice. Parallel with disease protection, we observed a prolonged increase of the numbers of CD4+CD25+ T cells in the periphery of GAD-IgG-treated mice, compared to those treated with a control IgG vector, both in the prediabetic period and persisting even 8 months after gene therapy. This increase appeared to be induced by the repeated stimulation of the antigen in the periphery instead of a result of differentiation of T-cell precursor in the thymus. Moreover, CD4+CD25+ T cells induced by GAD-IgG fusion construct were capable of suppressing the proliferative response of CD4+CD25- T cells in vitro; and ablation of the activity of CD4+CD25+ T cells by blocking antibody against CD25 could reverse GAD-specific T-cell hyporesponsiveness. These results suggested that CD4+CD25+ T-cell subset induced in GAD-IgG-treated NOD mice represented the regulatory or suppressive CD4+CD25+ T cells (Treg) and might play an important role in the induction and maintenance of tolerance in NOD mice. Furthermore, the numbers of splenic CD4+CD62L+ regulatory T cells in GAD-IgG-treated mice during the prediabetic period and serum TGF-beta levels in 34-38-week-old GAD-IgG-protected mice were also increased, compared to control IgG-treated ones. Therefore, we propose that the induction of tolerance and the prevention of diabetes incidence in NOD female mice induced by the GAD-IgG fusion construct may require CD4+ regulatory T cells, and the possible mediation of TGF-beta.

Animals↗

PubMed2003

Protein interaction for an interferon-inducible systemic lupus associated gene, IFIT1.

OBJECTIVE: To identify disease-related genes and immune-regulatory pathways in the pathogenesis of systemic lupus erythematosus (SLE) by using gene expression profiling and protein-protein interaction analysis. METHODS: Peripheral white blood cell gene expression profiles of 10 SLE patients were determined by oligonucleotide microarray analysis. Clustering of the gene expression profile was compared with the clinical immune phenotype. SLE-induced genes that were over- or under-expressed were determined and independently validated using a real-time polymerase chain reaction (PCR) method. To study their potential function and the possible pathways involved, a candidate gene was cloned and a GST (glutathione S-transferase) fusion protein was expressed in Escherichia coli. The fusion protein was further purified using the glutathione Sepharose 4B system, and was treated as bait to capture prey from SLE peripheral white blood cell lysate. MALDI-TOF (matrix-assisted laser desorption/ionization-time-of-flight) mass spectrometry was then performed to determine the prey protein. RESULTS: Similarity was found between the gene expression profile and the immune phenotype clusters of the SLE patients. More than 20 disease-associated genes were identified, some of which have not been related to SLE previously. Of these genes, a cluster of interferon-induced genes were highly correlated. IFIT1 (interferon-induced with tetratricopeptide repeats 1) was one of these genes, and overexpression of its mRNA was confirmed independently by real-time PCR in a larger population (40 SLE patients and 29 normal controls). An IFIT1 protein- protein interaction study showed that IFIT1 may interact with Rho/Rac guanine nucleotide exchange factor. CONCLUSION: The gene expression profile seems to be the molecular basis of the diverse immune phenotype of SLE. On the basis of the SLE-related genes found in this study, we suggest that the interferon-related immune pathway is important in the pathogenesis of SLE. IFIT1 is the first gene described as a candidate gene for SLE, and may function by activating Rho proteins through interaction with Rho/Rac guanine nucleotide exchange factor. IFIT1 and the interferon-related pathway may provide potential targets for novel interventions in the treatment of SLE.

Adaptor Proteins, Signal Transducing↗

PubMed2003

CD95 ligand--death factor and costimulatory molecule?

The CD95 ligand is involved as a death factor in the regulation of activation-induced cell death, establishment of immune privilege and tumor cell survival. In addition, CD95L may serve as a costimulatory molecule for T-cell activation. Alterations in expression or shedding of membrane and soluble CD95L are associated with numerous diseases, and underscore the pathophysiological relevance of the CD95/CD95L system. In most cases, the causal link between altered CD95L expression and pathophysiology is unknown. Given the potency of the molecule to regulate death and survival of many different cell types, the control of CD95L production, transport, storage, shedding and inactivation is of tremendous biological and clinical interest. This review summarizes the current knowledge, hypotheses and controversies about CD95L as a multifunctional ligand and receptor. It considers the different roles of membrane and soluble forms of CD95L and the complex networks of intracellular dynamics of protein trafficking, as well as the potential bidirectional signal transduction capacity of CD95L, with a focus on molecular interactions that have been worked out over the past years.

Animals↗

PubMed2002

GeneCensus: genome comparisons in terms of metabolic pathway activity and protein family sharing.

We present a prototype of a new database tool, GeneCensus, which focuses on comparing genomes globally, in terms of the collective properties of many genes, rather than in terms of the attributes of a single gene (e.g. sequence similarity for a particular ortholog). The comparisons are presented in a visual fashion over the web at GeneCensus.org. The system concentrates on two types of comparisons: (i) trees based on the sharing of generalized protein families between genomes, and (ii) whole pathway analysis in terms of activity levels. For the trees, we have developed a module (TreeViewer) that clusters genomes in terms of the folds, superfamilies or orthologs--all can be considered as generalized 'families' or 'protein parts'--they share, and compares the resulting trees side-by-side with those built from sequence similarity of individual genes (e.g. a traditional tree built on ribosomal similarity). We also include comparisons to trees built on whole-genome dinucleotide or codon composition. For pathway comparisons, we have implemented a module (PathwayPainter) that graphically depicts, in selected metabolic pathways, the fluxes or expression levels of the associated enzymes (i.e. generalized 'activities'). One can, consequently, compare organisms (and organism states) in terms of representations of these systemic quantities. Develop ment of this module involved compiling, calculating and standardizing flux and expression information from many different sources. We illustrate pathway analysis for enzymes involved in central metabolism. We are able to show that, to some degree, flux and expression fluctuations have characteristic values in different sections of the central metabolism and that control points in this system (e.g. hexokinase, pyruvate kinase, phosphofructokinase, isocitrate dehydrogenase and citric synthase) tend to be especially variable in flux and expression. Both the TreeViewer and PathwayPainter modules connect to other information sources related to individual-gene or organism properties (e.g. a single-gene structural annotation viewer).

Animals↗

PubMed2002

Scaling of structure functions in homogeneous shear-flow turbulence.

We apply spectral dynamics and non-Gaussian statistical model of velocity difference to study the scaling of structure functions in homogeneous shear-flow turbulence. Let L(S) be the shear length scale and eta the viscous scale. It is found that, when L(S)/eta is finite, due to a combined effect of viscosity and mean shear, the scaling deviates from normal scaling, and the deviation increases as L(S)/eta decreases. In the presence of a strong shear (L(S)/eta<100), the deviation is substantially larger than the prediction of typical intermittency models, in agreement with recent experiments. As L(S)/eta-->infinity, the normal scaling is valid in the inertial range where viscous and shear effects are negligible.

Journal Article↗

PubMed2002

Haemophilia A: effects of inhibitory antibodies on factor VIII functional interactions and approaches to prevent their action.

Factor VIII (FVIII) is an essential component of the intrinsic pathway of blood coagulation. Normal functioning of FVIII requires its interactions with other components of the coagulation cascade. In the circulation, it exists as a complex with von Willebrand factor (vWF). Upon activation by thrombin or activated factor X (FXa), activated FVIII (FVIIIa) functions as a cofactor for the serine protease factor IXa. Their complex assembled on the phospholipid surface activates FX to FXa, which consequently participates in formation of thrombin, the key protease of the coagulation cascade. Genetic deficiency in FVIII results in a coagulation disorder haemophilia A, which is treated by infusions of FVIII products. Approximately 25-30% of patients develop antibodies inhibiting FVIII activity (FVIII inhibitors). The major epitopes of inhibitors are located within the A2, C2 and A3 domains of the FVIII molecule. The inhibitory effects of antibodies are manifested at various stages of the FVIII functional pathway, including FVIII binding to vWF, activation of FVIII by thrombin, and FVIIIa incorporation into the Xase complex. We summarize the current knowledge of the FVIII sites involved in interaction with its physiological ligands and different classes of inhibitory antibodies and describe their inhibitory mechanisms. We outline the strategies aimed to overcome the effects of inhibitory antibodies such as development of human/porcine FVIII molecules, resistant to inhibitors. We also discuss approaches to modulate the antibody response, as well as efforts to develop a long-term immunotolerance to FVIII protein.

Animals↗

PubMed2002

Differences in the expression of neurokinin receptor in neural and bone marrow mesenchymal cells: implications for neuronal expansion from bone marrow cells.

The neurokinin-1 (NK-1) receptor interacts with peptides that belong to the tachykinin family. NK-1 is inducible in bone marrow (BM) stroma. In neural cells, its expression is high to constitutive. Screening of three cDNA libraries indicated that this different in NK-1 expression in neural and BM cells could not be explained by differences in the cDNA sequence. Analyses the 5' flanking sequence in BM stroma and three neural cell lines indicated that sequence +1/+358 relative to the transcription start (TS) site could account for the differences in NK-1 expression. Particular cytokines could reverse the repressive effects of region +1/+358 in BM stroma. The effects of NF-kappa B and cAMP activators were studied in stromal cells using a dominant negative inhibitor of NF-kappa B (I kappa B) or a repressor of CRE activators (ICERII gamma). The results showed that their effects of these transcription factors depended on the stimulating cytokine. This study provides insight into the tissue-specific differences in the expression of the NK-1 gene.

5' Untranslated Regions↗

PubMed2001

Beyond synexpression relationships: local clustering of time-shifted and inverted gene expression profiles identifies new, biologically relevant interactions.

The complexity of biological systems provides for a great diversity of relationships between genes. The current analysis of whole-genome expression data focuses on relationships based on global correlation over a whole time-course, identifying clusters of genes whose expression levels simultaneously rise and fall. There are, of course, other potential relationships between genes, which are missed by such global clustering. These include activation, where one expects a time-delay between related expression profiles, and inhibition, where one expects an inverted relationship. Here, we propose a new method, which we call local clustering, for identifying these time-delayed and inverted relationships. It is related to conventional gene-expression clustering in a fashion analogous to the way local sequence alignment (the Smith-Waterman algorithm) is derived from global alignment (Needleman-Wunsch). An integral part of our method is the use of random score distributions to assess the statistical significance of each cluster. We applied our method to the yeast cell-cycle expression dataset and were able to detect a considerable number of additional biological relationships between genes, beyond those resulting from conventional correlation. We related these new relationships between genes to their similarity in function (as determined from the MIPS scheme) or their having known protein-protein interactions (as determined from the large-scale two-hybrid experiment); we found that genes strongly related by local clustering were considerably more likely than random to have a known interaction or a similar cellular role. This suggests that local clustering may be useful in functional annotation of uncharacterized genes. We examined many of the new relationships in detail. Some of them were already well-documented examples of inhibition or activation, which provide corroboration for our results. For instance, we found an inverted expression profile relationship between genes YME1 and YNT20, where the latter has been experimentally documented as a bypass suppressor of the former. We also found new relationships involving uncharacterized yeast genes and were able to suggest functions for many of them. In particular, we found a time-delayed expression relationship between J0544 (which has not yet been functionally characterized) and four genes associated with the mitochondria. This suggests that J0544 may be involved in the control or activation of mitochondrial genes. We have also looked at other, less extensive datasets than the yeast cell-cycle and found further interesting relationships. Our clustering program and a detailed website of clustering results is available at http://www.bioinfo.mbb.yale.edu/expression/cluster (or http://www.genecensus.org/expression/cluster).

Algorithms↗

PubMed2001

The dynamics of bone marrow stromal cells in the proliferation of multipotent hematopoietic progenitors by substance P: an understanding of the effects of a neurotransmitter on the differentiating hematopoietic stem cell.

Communication within the hematopoietic-neuroendocrine-immune axis is partly mediated by neurotransmitters (e.g. substance P, SP) and cytokines. SP mediates neuromodulation partly through the stimulation of bone marrow (BM) progenitors. This study shows that SP, through the neurokinin-1 receptor, stimulates the proliferation of primitive hematopoietic progenitors: cobblestone-forming cells (CAFC, CD34+). This effect is optimal when macrophage is included within the fibroblast support. Indirect induction of IL-1 could be important in the proliferation of CAFC colonies by SP. Phenotypic and functional studies suggest that SP might directly interact with the CD34+/CD45(dim) population. These studies indicate that SP can initiate a cascade of biological responses in the BM stroma and stem cells to stimulate hematopoiesis.

Cell Differentiation↗

PubMed2001

Protein family and fold occurrence in genomes: power-law behaviour and evolutionary model.

Global surveys of genomes measure the usage of essential molecular parts, defined here as protein families, superfamilies or folds, in different organisms. Based on surveys of the first 20 completely sequenced genomes, we observe that the occurrence of these parts follows a power-law distribution. That is, the number of distinct parts (F) with a given genomic occurrence (V) decays as F=aV(-b), with a few parts occurring many times and most occurring infrequently. For a given organism, the distributions of families, superfamilies and folds are nearly identical, and this is reflected in the size of the decay exponent b. Moreover, the exponent varies between different organisms, with those of smaller genomes displaying a steeper decay (i.e. larger b). Clearly, the power law indicates a preference to duplicate genes that encode for molecular parts which are already common. Here, we present a minimal, but biologically meaningful model that accurately describes the observed power law. Although the model performs equally well for all three protein classes, we focus on the occurrence of folds in preference to families and superfamilies. This is because folds are comparatively insensitive to the effects of point mutations that can cause a family member to diverge beyond detectable similarity. In the model, genomes evolve through two basic operations: (i) duplication of existing genes; (ii) net flow of new genes. The flow term is closely related to the exponent b and can accommodate considerable gene loss; however, we demonstrate that the observed data is reproduced best with a net inflow, i.e. with more gene gain than loss. Moreover, we show that prokaryotes have much higher rates of gene acquisition than eukaryotes, probably reflecting lateral transfer. A further natural outcome from our model is an estimation of the fold composition of the initial genome, which potentially relates to the common ancestor for modern organisms. Supplementary material pertaining to this work is available from www.partslist.org/powerlaw.

Animals↗

PubMed2001

Negative feedback on the effects of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study.

Hematopoietic regulation is a complex but dynamic process regulated by intercellular and intracellular interactions within the bone marrow (BM) microenvironment. Through neurokinin-1 (NK-1) and NK-2 receptors, peptides (eg, substance P [SP]) encoded by the preprotachykinin-I gene mediate distinct hematopoietic effects. Cytokines, associated with hematopoietic stimulation, and SP regulate the expression of each other in BM mesenchymal and immune cells. Neutral endopeptidase (NEP) uses SP as a substrate to produce SP(1-4), which inhibits the proliferation of matured myeloid progenitor. This study determines whether the degradation of SP to SP(1-4) by endogenous NEP in BM stroma could be a feedback on hematopoietic stimulation by stem cell factor (SCF). SP(1-4) induced the production of transforming growth factor (TGF)-beta and tumor necrosis factor-alpha in BM stroma. TGF-beta production accounted for part of the inhibitory effects by SP(1-4) on the proliferation of early (granulocyte-macrophage colony-forming units) and late (long-term culture-initiating cells) hematopoietic progenitors. Enzyme-linked immunosorbent assays and/or protein-chip arrays indicated a timeline change of SP to SP(1-4) in BM stroma stimulated with SCF, which correlated with increase in NEP messenger RNA. Since SP and its fragment, SP(1-4), interact with the same receptor to mediate opposing hematopoietic effects, 2 interactive studies were done to understand the dual responses of NK-1: (1) a 3-dimensional molecular model of NK-1 and SP and (2) screening of a random dodecapeptide library for SP(1-4) interacting sites. The effects of SP(1-4) on hematopoietic progenitors and the timeline change of SP to SP(1-4), together with the 3-dimensional model, provide a partial explanation for the feedback on the stimulatory effects of SCF and SP on hematopoiesis.

Binding Sites↗