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Background: Physical exercise is known to aid stress regulation, however the effects of specific exercise types are under-researched. Dance combines in a unique way several characteristics that are known to have stress regulatory effects, such as music listening. Nonetheless, dance has not received particular attention in investigations of its stress regulatory effects., Objective: We used a multidisciplinary narrative review as a novel approach to explore the complex relationship between dance and stress by integrating psychological, neurobiological, physiological, and socio-cultural findings. In particular, we looked at the effects of music and rhythm; partnering and social contact; and movement and physical activity., Findings: There is strong empirical evidence for the beneficial stress regulatory effects of music, social contact, and movement, illustrating that dance can promote coping and foster resilience. Neurobiological research shows that these findings can be explained by the effects that music, social contact, and movement have on, amongst others, dopamine, oxytocin, and β-endorphin modulation and their interplay with the stress system. Socio-cultural considerations of the significance of dance help to understand why dance might have these unique effects. They highlight that dance can be seen as a universal form of human expression, offering a communal space for bonding, healing and collective coping strategies., Discussion: This review is the first to integrate perspectives from different disciplines on the stress regulatory effects of dance. It shows that dance has a large potential to aid coping and resilience at multiple levels of the human experience. At the same time, we identified that the existing evidence is often still limited by a narrow focus on exercise characteristics like intensity levels. This hinders a more holistic understanding of underlying stress regulatory mechanisms and provides important directions for future research., Competing Interests: Declaration of Competing Interest ☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025. Published by Elsevier Ltd.)

Background & Aims: Cells of hematopoietic origin, including macrophages, are generally radiation sensitive, but a subset of Kupffer cells (KCs) is relatively radioresistant. Here, we focused on the identity of the radioresistant KCs in unmanipulated mice and the mechanism of radioresistance., Methods: We employed Emr1- and inducible CX3Cr1-based fate-mapping strategies combined with the RiboTag reporter to identify the total KCs and the embryo-derived KCs, respectively. The KC compartment was reconstituted with adult bone-marrow-derived KCs (bm-KCs) using clodronate depletion. Mice were lethally irradiated and transplanted with donor bone marrow, and the radioresistance of bone-marrow- or embryo-derived KCs was studied. Gene expression was analyzed using in situ mRNA isolation via RiboTag reporter mice, and the translatomes were compared among subsets., Results: Here, we identified the radioresistant KCs as the long-lived subset that is derived from CX3CR1-expressing progenitor cells in fetal life, while adult bm-KCs do not resist irradiation. While both subsets upregulated the Cdkn1a gene, encoding p21- cip1/WAF1 protein, radioresistant embryo-derived KCs showed a greater increase in response to irradiation. In the absence of this molecule, the radioresistance of KCs was compromised. Replacement KCs, derived from adult hematopoietic stem cells, differed from radioresistant KCs in their expression of genes related to immunity and phagocytosis., Conclusions: Here, we show that, in the murine liver, a subset of KCs of embryonic origin resists lethal irradiation through Cdkn1a upregulation and is maintained for a long period, while bm-KCs do not survive lethal irradiation., Lay Summary: Kupffer cells (KCs) are the tissue-resident macrophages of the liver. KCs can be originated from fetal precursors and from monocytes during the fetal stage and post-birth, respectively. Most immune cells in mice are sensitive to lethal-irradiation-induced death, while a subset of KCs resists radiation-induced death. These radioresistant KCs continue to live in the irradiated mice. We discovered that this relatively radioresistant KC subset are the fetal-derived KCs, and they achieve this through cell-cycle arrest. Understanding the radiobiology of KCs will provide valuable insights into the mechanisms that elicit radiation-induced liver disease., (Published by Elsevier B.V.)

Background & Aims: The liver exhibits a unique capacity for regeneration in response to injury. Lymphotoxin-β receptor (LTβR), a core member of the tumor necrosis factor (TNF)/tumor necrosis factor receptor (TNFR) superfamily is known to play an important role in this process. However, the function of LTβR during pathophysiological alterations and its molecular mechanisms during liver regeneration are so far ill-characterized., Methods: LTβR(-/-) mice were subjected to 70% hepatectomy and liver regeneration capacity, bile acid profiles, and transcriptome analysis were performed., Results: LTβR(-/-) deficient mice suffered from increased and prolonged liver tissue damage after 70% hepatectomy, accompanied by deregulated bile acid homeostasis. Pronounced differences in the expression patterns of genes relevant for bile acid synthesis and recirculation were observed. LTβR and TNFRp55 share downstream signalling elements. Therefore, LTβR(-/-) mice were treated with etanercept to create mice functionally deficient in both signalling pathways. Strikingly, the combined blockade of TNFRp55 and LTβR signalling leads to complete failure of liver regeneration resulting in death within 24 to 48h after PHx. Transcriptome analysis revealed a marked disparity in gene expression programs in livers of LTβR(-/-) and etanercept-treated LTβR(-/-) vs. wild-type animals after PHx. Murinoglobulin 2 was identified as a significantly differentially regulated gene., Conclusions: LTβR is essential for efficient liver regeneration and cooperates with TNFRp55 in this process. Differences in survival kinetics strongly suggest distinct functions for these two cytokine receptors in liver regeneration. Failure of TNFR and LTβR signalling renders liver regeneration impossible., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Janus kinases (Jak) play essential roles in cytokine and growth factor signaling. Conventional gene targeting of Jak2, creating a null allele, leads to a block in definitive erythropoiesis as a result of failing signal transduction at the homomeric erythropoietin receptor (EpoR) and at the heteromeric interferon γ receptor (IFNGR). To investigate the in vivo relevance of the activation loop of Jak2, a Jak2-YY1007/1008FF knockin mutation was introduced into the germline of mice. The phenotype of the Jak2(FF/FF) mouse line reveals that tyrosine residues 1007/1008 are absolutely essential for kinase function and signal transduction at the homomeric EpoR. Detailed studies using the Jak2 activation loop mutant uncover an essential scaffolding function of Jak2 within the IFNGR receptor complex and reveal that Jak1 can mediate a semi-redundant function for IFNGR signal transduction. These studies are highly important for the molecular understanding of cytokine and growth factor signaling and provide new insights for future strategies in the design of pharmacological blockers of Jak2.

The pleiotropic cytokine transforming growth factor-β (TGF-β) signals through different pathways among which the Smad- and the MAP-Kinase pathways are already well characterized. Both pathways utilize adaptor/chaperone molecules that facilitate or modulate the intracellular signaling events. Two of the proteins shown in vitro to play a role in Smad-dependent signaling are the TGF-β Receptor Associated Protein-1 (TRAP1, also TGFBRAP1) and its homologue VPS39, also known as Vam6 and TRAP1-Like-Protein (TLP). We generated mice deficient for TRAP1 and VPS39/TLP, respectively. Absence of TRAP1 protein results in death at either of two defined timepoints during embryogenesis, before the blastula stage or during gastrulation, whereas most of the VPS39 deficient mice die before E6.5. Heterozygous mice show no overt phenotype. In summary, our data indicate that TRAP1 and VPS39 are nonredundant and essentially required for early embryonic development., (Copyright © 2010 Elsevier GmbH. All rights reserved.)

Signaling through tumor necrosis factor receptor 1 (TNFR1) controls bacterial infections and the induction of inflammatory Th1 cell-mediated autoimmune diseases. By dissecting Th1 cell-mediated delayed-type hypersensitivity responses (DTHRs) into single steps, we localized a central defect to the missing TNFR1 expression by endothelial cells (ECs). Adoptive transfer and mast cell knockin experiments into Kit(W)/Kit(W-v), TNF(-/-), and TNFR1(-/-) mice showed that the signaling defect exclusively affects mast cell-EC interactions but not T cells or antigen-presenting cells. As a consequence, TNFR1(-/-) mice had strongly reduced mRNA and protein expression of P-selectin, E-selectin, ICAM-1, and VCAM-1 during DTHR elicitation. In consequence, intravital fluorescence microscopy revealed up to 80% reduction of leukocyte rolling and firm adhesion in TNFR1(-/-) mice. As substitution of TNF(-/-) mice with TNF-producing mast cells fully restored DTHR in these mice, signaling of mast cell-derived TNF through TNFR1-expressing ECs is essential for the recruitment of leukocytes into sites of inflammation.

We have produced and characterised reporter knock-in CD45-YFP and CD45-Cre mice that drive expression of yellow fluorescent protein (YFP) and Cre-recombinase, respectively under control of the haematopoietic CD45 locus. CD45-YFP expression was characterised in various haematopoietic cells populations. The activity of CD45-Cre mice was assessed by crossing with silent GFP reporter mice. Flow cytometry analysis indicated that both CD45-YFP and CD45-Cre were strongly expressed in the CD45(+) compartment of peripheral blood. Expression of these markers in various populations of adult bone marrow, including primitive cell populations was also determined. These mouse models will be useful for the direct visualisation of haematopoietic cells, especially at the periphery, and for gene knockout studies, in the haematopoietic system.

Erythropoiesis requires erythropoietin (Epo) and stem cell factor (SCF) signaling via their receptors EpoR and c-Kit. EpoR, like many other receptors involved in hematopoiesis, acts via the kinase Jak2. Deletion of EpoR or Janus kinase 2 (Jak2) causes embryonic lethality as a result of defective erythropoiesis. The contribution of distinct EpoR/Jak2-induced signaling pathways (mitogen-activated protein kinase, phosphatidylinositol 3-kinase, signal transducer and activator of transcription 5 [Stat5]) to functional erythropoiesis is incompletely understood. Here we demonstrate that expression of a constitutively activated Stat5a mutant (cS5) was sufficient to relieve the proliferation defect of Jak2(-/-) and EpoR(-/-) cells in an Epo-independent manner. In addition, tamoxifen-induced DNA binding of a Stat5a-estrogen receptor (ER)* fusion construct enabled erythropoiesis in the absence of Epo. Furthermore, c-Kit was able to enhance signaling through the Jak2-Stat5 axis, particularly in lymphoid and myeloid progenitors. Although abundance of hematopoietic stem cells was 2.5-fold reduced in Jak2(-/-) fetal livers, transplantation of Jak2(-/-)-cS5 fetal liver cells into irradiated mice gave rise to mature erythroid and myeloid cells of donor origin up to 6 months after transplantation. Cytokine- and c-Kit pathways do not function independently of each other in hematopoiesis but cooperate to attain full Jak2/Stat5 activation. In conclusion, activated Stat5 is a critical downstream effector of Jak2 in erythropoiesis/myelopoiesis, and Jak2 functionally links cytokine- with c-Kit-receptor tyrosine kinase signaling.

The lymphotoxin beta receptor (LTbetaR) mediates crucial signals in host defense against intracellular bacteria and viruses. Mice deficient in LTbetaR readily succumb to infections with Listeria monocytogenes, Mycobacterium tuberculosis and murine cytomegalovirus (mCMV). LTbetaR has been shown to be important for the early induction of interferon (IFN) beta after infection with mCMV. However, up to now, it is not known which host effector molecules are induced in cells of the innate immune system after bacterial infections. In order to address this question, comprehensive transcriptome profiling of LTbetaR-deficient and control splenocytes depleted from T and B lymphocytes was performed and differentially regulated genes were identified. Interestingly, a deficiency in IFNalpha- and IFNgamma-mRNA transcription could be found in LTbetaR-deficient cells leading to a marked failure in the immediate up-regulation of IFN controlled genes. These encompass interferon regulatory factors (IRF1 and IRF7), signal transducer activator of transcription (STAT) proteins (STAT1 and STAT2), chemokines, IFN regulated GTPases (IRGs, GBPs), and IFN-induced protein with tetratricopeptide repeats (IFITs). Thus, the immediate LTbetaR-initiated transcriptional response of innate immune cells carries an IFN signature and is responsible for mounting an effective innate immune response to L. monocytogenes.

The aim of this study was to compare the antimicrobial performance of the Endox Endodontic System (Lysis Srl, Nova Milanese, Italy), MTAD (Dentsply Tulsa Dental, Tulsa, OK), sodium hypochlorite (NaOCl), and HealOzone (Kavo, Biberach, Germany). Seventy instrumented and initially sterile roots with open accesses and containing a paper point were carried by one volunteer in the oral cavity for 1 week. After removal, samples were taken for microbiological analysis. The root canals were then disinfected with the Endox Endodontic System, MTAD, 3% NaOCl, or HealOzone, and, thereafter, samples were repeated for microbiological analysis. The roots were then sealed and incubated for a further week, after which bacterial growth was again determined. After disinfection, there was a significant decrease in the absolute bacterial count between each disinfection method and the positive control group. There was no statistically significant difference between the NaOCl, MTAD, and HealOzone groups. The Endox device showed the least antibacterial effect with significant differences to MTAD and HealOzone. Bacterial regrowth after 1 week of incubation was detected in all samples of the control group, whereas test groups showed several bacteria-free samples.

A crucial step in murine natural killer (NK) cell development, mediated by bone marrow stromal cells, is the induction of Ly49 and CD94/NKG2 receptor expression. The signals that regulate Ly49 receptor expression are still largely undetermined. It has been shown that interaction between lymphotoxin alpha1beta2 (LTalpha1beta2) and LTbeta receptor (LTbetaR), expressed on lymphoid progenitor cells and nonlymphoid bone marrow stromal cells, respectively, is important for both quantitative and functional NK cell development. Therefore, we have investigated the role of LT-LTbetaR-mediated signaling in Ly49 and CD94/NKG2 receptor acquisition. We show that the NK receptor repertoire of LTbetaR-/- mice can only be partially analyzed because of the residual 129/Ola mouse genetic background, due to a physical linkage of the LTbetaR locus and the loci encoding the Ly49 and CD94/NKG2 receptors. Therefore, we transferred wild-type B6 lymphoid-committed progenitor cells into LTbetaR-/- mice, which differentiated into NK cells with a normal NK cell receptor repertoire. Also, administration of LTbetaR-immunoglobulin (Ig), which acts as a soluble receptor for LTalpha1beta2, resulted in reduced NK cell percentages but did not influence the Ly49 and CD94/NKG2 receptor acquisition on remaining NK cells. These results indicate that LTbetaR-mediated signals are not required for Ly49 and CD94/NKG2 receptor acquisition.

Disrupted signaling through lymphotoxin beta receptor (LTbetaR) results in severe defects of the spleen and even loss of all other secondary lymphoid tissues, making mice susceptible to diverse infectious agents. Surprisingly, however, we find that female LTbetaR-deficient mice are even more resistant to blood stages of Plasmodium chabaudi malaria than wild-type C57BL/6 mice. Higher resistance of LTbetaR-deficient mice correlates with an earlier onset of reticulocytosis, and the period of anemia is shorter. After surviving fulminant parasitemias of about 35%, mice develop long-lasting protective immunity against homologous rechallenge, with both spleen and liver acting as anti-malaria effectors. Testosterone suppresses resistance, i.e. all mice succumb to infections during or shortly after peak parasitemia. At peak parasitemia, testosterone does not essentially affect cellularity and apoptosis in the spleen, but aggravates liver pathology in terms of increased cell swelling, numbers of apoptotic and binucleated cells and reduced serum alkaline phosphatase levels, and conversely, reduces inflammatory lymphocytic infiltrates in the liver. In the spleen, hybridization of cDNA arrays identified only a few testosterone-induced changes in gene expression, in particular upregulation of INFgamma and IFN-regulated genes. By contrast, a much larger number of testosterone-affectable genes was observed in the liver, including genes involved in regulation of the extracellular matrix, in chemokine and cytokine signaling, and in cell cycle control. Collectively, our data suggest that testosterone dysregulates the inflammatory response in spleen and liver during their differentiation to anti-malaria effectors in malaria-resistant female LTbetaR-deficient mice, thus contributing to the testosterone-induced lethal outcome of malaria.

TNF/LTalpha/LTbeta (tumor necrosis factor/lymphotoxin-alpha/lymphotoxin-beta) triple knockout (KO) mice show a significant reduction of dendritic cell (DC) number in the spleen, presumably due to defective recruitment and/or production. To distinguish between these possibilities, DCs were generated from bone marrow (BM) cultures prepared from wild-type (wt) and mutant mice in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). The yield of CD11c(+) major histocompatibility complex (MHC) class II(+) DCs generated from TNF/LTalpha/LTbeta(-/-) BM culture was significantly reduced compared with wt BM culture. In order to further dissect the individual pathways responsible for defective DC properties observed in TNF/LTalpha/LTbeta(-/-) mice, the panel of TNF/LT ligand and receptor single KO mice were used. The production of DCs from BM culture was significantly reduced in TNF(-/-) and TNF receptor (TNFR) p55(-/-) mice, but normal in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice. Recombinant TNF (rTNF) exogenously added to TNF/LTalpha/LTbeta(-/-) BM cultures could reverse this defect, and blocking antibodies showed partial effect on BM cultures of wt mice. Conversely, numbers of mature DCs in spleen were significantly decreased in LTalpha(-/-), LTbeta(-/-), LTbetaR(-/-) mice, but not in TNF(-/-) and TNFRp55(-/-) mice. These results reveal 2 distinct contributions of TNF/LT cytokines. First, TNF acting through TNF receptor is involved in the development/maturation of DCs in BM progenitor cultures, but this function appears to be redundant in vivo. Second, the microenvironment in peripheral lymphoid organs associated with LTalpha/LTbeta-LTbetaR signaling and chemokine production is critical for recruitment efficiency of DCs, and this pathway is indispensable.

The receptor-associated protein tyrosine kinase janus-kinase 2 (JAK2) is essential for normal red cell development and for erythropoietin receptor (EpoR) signaling. JAK2(-/-) embryos are severely deficient in erythropoiesis and die at an early stage of development from fetal anemia. The binding of erythropoietin (Epo) to the EpoR triggers the activation of JAK2, the phosphorylation of the EpoR, and the initiation of the EpoR signaling cascade. In addition to Epo binding to its receptor, signaling pathways downstream of the EpoR can also be stimulated by the BCR-ABL oncoprotein. This study explored whether JAK2 is required for BCR-ABL-mediated stimulation of erythropoiesis. Here, it is shown that JAK2 is constitutively tyrosine phosphorylated in cultured and primary erythroid cells expressing BCR-ABL. However, BCR-ABL effectively supports normal erythroid proliferation, differentiation, and maturation in JAK2-deficient fetal liver cells. Using mutants of BCR-ABL, this study shows that certain signaling pathways activated by BCR-ABL segments distinct from its tyrosine kinase domain are essential for rescue of erythropoiesis in JAK2(-/-) progenitors. The consequences of these multiple signaling pathways for normal erythroid development are discussed.

To investigate the role of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the resistance to Paracoccidioides brasiliensis (Pb) infection, mice with homologous disruption of the IFN-gamma (GKO) or TNF-alpha receptor p55 (p55KO) were infected with the parasite. GKO and p55KO, but not wild-type (WT) mice, were unable to control the growth of yeast cells and the mice succumbed to infection by days 16 and 90 after infection, respectively. Typical inflammatory granulomas were found only in WT mice. In contrast, knockout mice presented an inflammatory infiltrate composed of a few neutrophils, mononuclear, epithelioid, and multinuclear giant cells forming incipient granulomas in GKO mice and without granuloma formation in p55KO mice. Besides, both groups of knockout mice exhibited elevated numbers of yeast forms in agreement with colony-forming unit counts in organs. Compared with WT, splenocytes from infected GKO mice cultured with the Pb F1 fraction produced lower TNF-alpha levels, whereas leukocytes from infected p55KO mice produced similar amounts of TNF-alpha but higher levels of IFN-gamma. Moreover, splenocytes from infected WT mice produced higher levels of nitric oxide (NO) resulting in a lower T-cell proliferative response to Con A than uninfected WT, or infected p55KO and GKO mice. On the contrary, the addition of IFN-gamma to splenocytes from infected GKO mice resulted in higher NO production and lower T cell proliferation. Taken together, these findings suggests that endogenous TNF-alpha, acting through the p55 receptor, and IFN-gamma mediate resistance to Pb infection and induce NO production that determines marked T cell unresponsiveness.

The BOB.1/OBF.1/OCAB.1 protein is a lymphocyte-specific transcriptional coactivator. It interacts with the Oct1 and Oct2 transcription factors and contributes to the transcriptional activity of octamer motifs. The analysis of established B cell lines had suggested that BOB.1/OBF.1 is constitutively expressed at all stages of B cell development. Here we show that expression of BOB. 1/OBF.1 is regulated within the B cell lineage. Specifically, germinal center B cells show highly increased BOB.1/OBF.1 levels. We can induce the up-regulation by stimulating primary splenic B cells, eg, by triggering CD40 signaling in the presence of interleukin-4. Expression of BOB.1/OBF.1 is detectable but reduced in spleens from mice unable to undergo the germinal center reaction due to mutations in the TNF receptor p55 or lymphotoxin beta (LTbeta) receptor genes. Furthermore, we demonstrate that BOB.1/OBF.1 expression is highly regulated in human B cell lymphomas. Whereas lymphomas representing pre- and postfollicular B cell developmental stages are negative for BOB.1/OBF.1, high-level expression of BOB.1/OBF.1 is characteristic of germinal center-derived tumors. In these tumors BOB.1/OBF.1 is typically coexpressed with high levels of Bcl6. These results imply that overexpression of BOB.1/OBF.1, like overexpression of Bcl6, might play a role in the pathogenesis of germinal center-derived B cell lymphomas. Furthermore, overexpression of BOB.1/OBF.1 represents a characteristic feature of these tumors that is useful in their identification.

Analysis of the V beta-repertoire of antigen-reactive T cell populations can be approached using either flow-cytometry or PCR-based techniques. While the former method requires a complete set of V beta-specific monoclonal antibodies (mAbs) and large cell numbers for analysis, the latter is both time-consuming and labour-intensive. To circumvent the drawbacks of both these methods we have employed the recently developed technique of TaqManR PCR to analyse the V beta-usage of human T cell populations. TaqManR PCR is based on the 5'-->3' nuclease activity of Taq polymerase. During PCR amplification an internal oligonucleotide probe, that is labelled with a fluorescent reporter and a quencher dye, is cleaved by Taq polymerase. After cleavage, quenching of the reporter dye is lost and reporter fluorescence can be detected with a fluorescence plate reader. Using one C beta-specific fluorogenic probe and a panel of V beta-specific primers, we show that fluorescence-detected amplification of TCR beta cDNA is V beta-specific and linear within a 2-3-log range of template concentration. The sensitivity of TaqManR PCR is comparable to conventional detection of PCR-products by agarose gel staining, while processing time is reduced. Furthermore, superantigen-induced skewing of the V beta-repertoire of human T cells is readily detected with this method. Thus TaqManR PCR is a reliable and fast method for semiquantitative analysis of the V beta-repertoire of human T cell populations.

Intraepithelial intestinal T lymphocytes (IEL) bearing alpha beta or gamma delta T cell receptors (TCR) are positioned to serve as a first line of defense against enteric pathogens. To investigate whether intestinal IEL are subject to antigenic selective forces distinct from that influencing (xp T cells in the peripheral blood (PBL), we performed a comparative analysis of V beta gene segment usage in IEL and PBL of immunologically normal donors by quantitative PCR. Primers for 22 different human TCR V beta gene segments of V beta gene segments families were used to analyze the repertoire of TCR beta chain transcripts in colonic IEL (c-IEL), in corresponding colonic lamina propria lymphocytes (c-LPL), and in peripheral blood lymphocytes. In each of the three individuals examined, a limited number (1-4 out of 22) of TCR V beta families predominated and accounted for more than 50% of the total beta chain transcripts from c-IEL, whereas in PBL and c-LPL a more even distribution of V beta gene families was observed. The dominating V beta gene families were V beta 2, V beta 3, V beta 6, V beta 8 and V beta 14. In one individual, V beta 3 comprised more than 40% of the entire repertoire of c-IEL beta chain transcripts. Sequence analysis of the predominant V beta 3 family in this individual revealed identical sequences in 13 of 17 clones analyzed. Human alpha beta TCR+ c-IEL could not be driven to proliferate or exhibit cytotoxic function in vitro however, PCR analysis for detection of lymphokine mRNA revealed constitutive production of several lymphokines known to exert trophic effects on intestinal epithelial cells and pro-inflammatory activities. Taken together, the striking degree of oligoclonality may indicate that the intraepithelial intestinal immune system is targeted to a limited set of hitherto unknown self- or foreign antigens present in the intestine and orchestrates intramucosal inflammatory and regenerative processes.

Spin-echo sequences with echo times as short as 3.5 msec were implemented on a standard 1.5 T NMR whole-body imager for 1H imaging of polymers in the solid-state. No modification of the NMR hardware designed for clinical usage was made. Beside images of different polymers a "self-portrait" of the polymeric materials of the receiver coil is given as a neat application. Based on imaging experiments the longitudinal and transverse relaxation time of polymers were investigated. The results indicate that using a standard whole-body imager, it is possible to provide additional information to other examination techniques in polymer and materials science.

The FID, DRESS, CRISIS/CODEX, and STEAM techniques for localized 31P NMR spectroscopy were compared using a Siemens Magnetom SP63 1.5 T whole-body imager and a surface-coil, 80 mm in diameter, acting as transmitter and receiver coil. The comparison was performed with phantom experiments and human in vivo investigations on the calf muscle. The phantom experiments which used the same volume size showed a comparable signal-to-noise ratio for FID and DRESS, while the two fully localized techniques showed a reduction in signal-to-noise ratio to 76% for CRISIS/CODEX and 31% for STEAM. The in vivo measurements confirm the phantom results and reveal that CRISIS/CODEX gains a 2.5 fold higher signal-to-noise ratio than STEAM under the same conditions.

Maturation of B cells into immunoglobulin (Ig)-secreting cells is influenced by antigen-nonspecific growth and differentiation factors. In the present study, we have analyzed the effect of several recombinant cytokines (rIL2, rIFN-alpha, rIFN-gamma) on the terminal differentiation of B cells from 10 patients with chronic lymphocytic leukemia (CLL) stimulated with three different B cell activators (phorbolester TPA, staphylococcus aureus Cowan I bacteria, or pokeweed mitogen). Secretion of IgM, as determined by heavy-chain specific ELISA, varied widely among different CLL cell populations, but was induced in all cases by one or several of these activators. Importantly, this response was enhanced 2-10-fold in all patients by at least one of the tested recombinant cytokines alone, or a combination of rIL2 with rIFN-alpha or rIFN-gamma. The results illustrate the clonal heterogeneity of CLL B cell maturation in vitro and demonstrate that rIL2, rIFN-alpha or rIFN-gamma can act as a B cell differentiation factor, depending on the responsiveness (stage of differentiation) of the individual clonal B cell population.