The interdisciplinary approach with nanotechnology and animal tissue culture technique is going to revolutionize biomedical science in the next fifty years. Nanotechnology along with regulated animal tissue culture, makes tissue engineering a realization based on the creation of new tissues in vitro followed by surgical placement in the body or the stimulation of normal repair in situ using bio-artificial constructs or implants of living cells introduced in or near the area of damage at nano level. It makes use of artificially stimulated cell proliferation by using suitable nano-material based scaffolds and growth factors. Nanotechnology can be successfully used to create a tissue or organ that can take the place of one that is terminally diseased, such as an eye, ear, heart, or joint. Implantable prosthetic devices and nano scaffolds are used for growing of artificial organs. The key components of tissue engineering with nanotechnology include: cells, scaffolds, signals and bioreactors. Scaffolds are produced by electrospinning technique. The scaffold acts as an interim synthetic extra cellular matrix (ECM) that cells interact with prior to forming a new tissue. Nano materials such as quantum dots, fluorescent carbon nano tubes and fluorescent magnetic nano particles, etc., are been used for imaging and tracing and for gene or drug delivery. Designed nanostructures have been used to regulate the proliferation and differentiation of stem cells, which will speed up the understanding and controlling the micro environmental signals, helping to solve the current bottleneck problems of tissue -based therapy. In the future, we could imagine a world where medical nano devices are routinely implanted or even injected into the bloodstream to monitor wellness and to automatically participate in the repair of systems that deviate from established norms.

This paper presents a novel approach based on eigen value analyses to predict capacitance required for self excitation of three-phase self-excited induction generator (SEIG). It is based on the d-q axis generalized theory model of electrical machine. It shows the effect of machine parameters (e.g. rotor resistance, stator resistance, rotor reactance and stator reactance) and speed variation on excitation capacitance for self-excitation using eigen value analysis.

Myelofibrosis is an uncommon phenomenon associated with a variety of neoplastic and inflammatory processes. Although there is evidence that cytokines elaborated by clonal malignant hematopoietic cells are implicated in myelofibrosis in primary hematologic disorders, there has been little data to date on the pathophysiology of myelofibrosis in autoimmune disorders. Here we report a case of autoimmune myelofibrosis with pancytopenia. Peripheral blood monocytes and CD4‐positive lymphocytes produced significantly elevated levels of transforming growth factor β (TGF‐β) compared to similar cells from healthy volunteer controls. TGF‐β has been implicated in the pathogenesis of myelofibrosis associated with primary hematological malignancies. Furthermore, substance P, previously linked to myelofibrosis, was also detected in elevated levels in the patient's serum and correlated negatively with the levels of the patient's blood counts. These findings suggest a role for both TGF‐β and substance P in the pathophysiology of autoimmune myelofibrosis. This is the first report of deregulated production of TGF‐β by monocytes in the pathobiology of autoimmune myelofibrosis. Am. J. Hematol. 81:51–58, 2006. © 2005 Wiley‐Liss, Inc.

Neurokinin 1 (NK-1) is a member of seven transmembrane G protein-coupled receptors. NK-1 interacts with peptides belonging to the tachykinin family and showed preference for substance P (SP). NK-1 is induced in bone marrow (BM) stroma. NK-1–SP interactions could lead to changes in the functions of lymphohematopoietic stem cell (LHSC). This report describes the cloning and characterization of a cDNA clone isolated after screening of three cDNA libraries with an NK-1-specific probe. Based on its expression, the cDNA clone was designated hematopoietic growth factor inducible neurokinin-1 type (HGFIN). Computational analyses predicted that HGFIN is transmembrane with the carboxyl terminal extracellular. Proteomic studies with purified HGFIN and SP showed noncovalent interactions. HGFIN–SP interactions were supported by transient expression of HGFIN in CHO cells. Transient expression of HGFIN in unstimulated BM fibroblasts led to the induction of endogenous NK-1. Since NK-1 expression in BM fibroblasts requires cell stimulation, these studies suggest that there might be intracellular crosstalk between NK-1 and HGFIN. Northern analyses with total RNA from different BM cell subsets showed that HGFIN was preferentially expressed in differentiated cells. This suggests that HGFIN might be involved in the maturation of LHSC. HGFIN was detected in several other tissues, but not in brain where NK-1 is constitutively expressed.

In the adult bone marrow (BM), immune cells are replenished through the process of definitive hematopoiesis, which is regulated by a complex process of cellular and humoral interactions. The latter include substance P (SP), a neurotransmitter that is produced by neural and nonneural cells. Neurokinin-1 (NK-1), the high-affinity SP receptor, shares structural similarity with fibronectin, a component of the BM extracellular matrix proteins. This study examines how such similarity could alter the effects of SP on the proliferation of the immature BM progenitors. In vitro studies show that 1 ng fibronectin/mL enhanced the stimulatory effect of SP on the proliferation of primitive BM progenitors. This finding was studied by computational studies: proteomics and three-dimensional molecular modeling. Use of surface-enhanced laser desorption/ionization ProteinChip technology showed that despite the induction of neutral endopeptidase, exogenous fibronectin hindered the degradation of SP to SP(1-4). These findings support a protective role for fibronectin in the digestion of SP. Since SP(1-4) is a negative regulator of hematopoiesis, this report indicates that the structural similarity between fibronectin and NK-1 could be important for maintaining hematopoietic stimulation. These studies could be extrapolated to hematological disorders that are associated with SP-fibronectin complexes.

Bone marrow (BM) fibrosis may occur in myeloproliferative diseases, lymphoma, myelodysplastic syndrome, myeloma, and infectious diseases. In this study, the role of substance P (SP), a peptide with pleiotropic functions, was examined. Some of its functions-angiogenesis, fibroblast proliferation, and stimulation of BM progenitors-are amenable to inducing BM fibrosis. Indeed, a significant increase was found in SP-immunoreactivity (SP-IR) in the sera of patients with BM fibrosis (n = 44) compared with the sera of patients with hematologic disorders and no histologic evidence of fibrosis (n = 46) (140 +/-12 vs 18 +/-3; P <.01). Immunoprecipitation of sera SP indicated that this peptide exists in the form of a complex with other molecule(s). It was, therefore, hypothesized that SP might be complexed with NK-1, its natural receptor, or with a molecule homologous to NK-1. To address this, 3 cDNA libraries were screened that were constructed from pooled BM stroma or mononuclear cells with an NK-1 cDNA probe. A partial clone (clone 1) was retrieved that was 97% homologous to the ED-A region of fibronectin (FN). Furthermore, sequence analyses indicated that clone 1 shared significant homology with exon 5 of NK-1. Immunoprecipitation and Western blot analysis indicated co-migration of SP and FN in 27 of 31 patients with BM fibrosis. Computer-assisted molecular modeling suggested that similar secondary structural features between FN and NK-1 and the relative electrostatic charge might explain a complex formed between FN (negative) and SP (positive). This study suggests that SP may be implicated in the pathophysiology of myelofibrosis, though its role would have to be substantiated in future research. (Blood. 2001;97:3025-3031)

We studied the complex interactions within the neuroendocrine-immune-hematopoietic axis by determining a possible link among ACTH, PRL, PPT-I and the receptors for its peptides, NK-1 and NK-2. Indeed, ACTH and PRL induced the expression of PPT-I and NK-1 in human bone marrow stroma with no effect on NK-2. Consistent with a role for PPT-I in regulating the development of myeloid and erythroid progenitors, we found that ACTH and PRL, through NK-1 stimulated the proliferation of both types of progenitors. Induction of PPT-I was regulated at the transcriptional and post-transcriptional levels. The results showed that ACTH and PRL stimulated the proliferation of bone marrow progenitors, partly through PPT-I and NK-1 induction.

Abstract: Hematopoiesis is maintained by “fine‐tuned” regulation among cytokines, neuropeptides, neurotransmitters, and neurotrophic factors. Neurotransmitters, derived from PPT‐I exert immune and hematopoietic regulation. PPT‐I is also expressed locally in bone marrow (BM) stromal cells. PPT‐I peptides induce the production of cytokines in BM cells, resulting in regulation of both committed progenitors (CFU‐GM) and primitive hematopoietic progenitors (CAFC). Both types of progenitors are regulated differently by the two major PPT‐I peptides, SP and NK‐A. Endopeptidases, present in BM cells, can digest SP to produce SP(1‐4) and SP(4‐11). In this study, we investigated the hematopoietic effects of these fragments on CFU‐GM and CAFC. Similar to the two major intact PPT‐I peptides (SP and NK‐A), we observed different hematopoietic effects by SP(1‐4) and SP(4‐11). Whereas SP(1‐4) exerted inhibitory effects on CFU‐GM and CAFC, SP(4‐11) mediated stimulatory effects. Similar to NK‐A, the inhibitory effects of SP(1‐4) can be partly explained by the induction of suppressive cytokines (TGF‐β, TNF‐α, and INF‐γ). Use of antagonists and screening of a dodecapeptide expression library determined that the effects of SP(1‐4) were mediated by NK‐1. These results show that PPT‐I peptides and their endopeptidase‐derived fragments may add to the fine‐tuned regulation on hematopoiesis. Furthermore, PPT‐I may be exerting autoregulation to protect hematopoietic stem cells. These studies have relevance to stem cell protection and BM transplant.

Neuropeptides are implicated in many tumors, breast cancer (BC) included. Preprotachykinin-I (PPT-I) encodes multiple neuropeptides with pleiotropic functions such as neurotransmission, immune/hematopoietic modulation, angiogenesis, and mitogenesis.PPT-Iis constitutively expressed in some tumors. In this study, we investigated a role forPPT-Iand its receptors, neurokinin-1 (NK-1) andNK-2, in BC by using quantitative reverse transcription–PCR, ELISA, andin situhybridization. Compared with normal mammary epithelial cells (n= 2) and benign breast biopsies (n= 21), BC cell lines (n= 7) and malignant breast biopsies (n= 25) showed increased expression ofPPT-IandNK-1. NK-2 levels were high in normal and malignant cells. Specific NK-1 and NK-2 antagonists inhibited BC cell proliferation, suggesting autocrine and/or intercrine stimulation of BC cells by PPT-I peptides. NK-2 showed no effect on the proliferation of normal cells but mediated the proliferation of BC cells. Cytosolic extracts from malignant BC cells enhanced PPT-I translation whereas extracts from normal mammary epithelial cells caused no change. These enhancing effects may be protein-specific because a similar increase was observed for IL-6 translation and no effect was observed for IL-1α and stem cell factor. The data suggest that PPT-I peptides and their receptors may be important in BC development. Considering that PPT-I peptides are hematopoietic modulators, these results could be extended to understand early integration of BC cells in the bone marrow, a preferred site of metastasis. Molecular signaling transduced by PPT-I peptides and the mechanism that enhances translation of PPT-I mRNA could lead to innovative strategies for BC treatments and metastasis.