Testicular torsion and subsequent testicular function in young men from the general population.

STUDY QUESTION: Is prior testicular torsion associated with testicular function (semen quality and reproductive hormones) in young men from the general population? SUMMARY ANSWER: In young men from the general population, no differences in semen parameters were observed in those who had experienced testicular torsion compared to controls and observations of higher FSH and lower inhibin B were subtle. WHAT IS KNOWN ALREADY: Testicular function may be impaired after testicular torsion, but knowledge is sparse and based on studies with small sample sizes and no control group or a less than ideal control group. STUDY DESIGN, SIZE, DURATION: A cross-sectional population-based study was carried out including 7876 young Danish men with unknown fertility potential, examined from 1996 to 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: All men (median age 19.0 years) had a physical examination, provided a blood and semen sample, and filled in a questionnaire including information about prior testicular torsion, birth, lifestyle and current and previous diseases. Markers of testicular function, including testis volume, semen parameters and reproductive hormones, were compared between men operated for testicular torsion and controls, using multiple linear regression analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The average participation rate was 24% for the entire study period. In total, 57 men (0.72%) were previously operated for testicular torsion (median age at surgery 13.4 years) of which five had only one remaining testicle. Men with prior testicular torsion were more often born preterm (25% versus 9.5% among controls), and they had significantly higher FSH and lower inhibin B levels, and a lower inhibin B/FSH ratio than controls in crude and adjusted models. The association was mainly driven by the subgroup of men who had undergone unilateral orchiectomy. No differences in semen parameters were observed. LIMITATIONS, REASONS FOR CAUTION: A limitation is the retrospective self-reported information on testicular torsion. Also, results should be interpreted with caution owing to the high uncertainty of the observed differences. WIDER IMPLICATIONS OF THE FINDINGS: Overall, the results of our study are reassuring for men who have experienced testicular torsion, especially when treated with orchiopexy, for whom reproductive hormone alterations were subtle and without obvious clinical relevance. Our study found no differences in semen parameters, but follow-up studies are needed to assess any long-term consequences for fertility. STUDY FUNDING/COMPETING INTEREST(S): Financial support was received from the Danish Ministry of Health; the Danish Environmental Protection Agency; the Research fund of Rigshospitalet, Copenhagen University Hospital; the European Union (Contract numbers BMH4-CT96-0314, QLK4-CT-1999-01422, QLK4-CT-2002-00603, FP7/2007-2013, DEER Grant agreement no. 212844); A.P. Møller and wife Chastine Mckinney Møllers Foundation; Svend Andersens Foundation; the Research Fund of the Capital Region of Denmark; and ReproUnion (EU/Interreg). The authors have nothing to declare. TRIAL REGISTRATION NUMBER: N/A.

A multicenter investigation of reablement in Norway: a clinical controlled trial.

BACKGROUND: Reablement is an emerging approach in rehabilitation services, but evidence for its efficacy is rather weak and inconsistent. The purpose of the present study is therefore to investigate the health effects of reablement in home-dwelling adults. METHODS: A multicenter, clinical controlled trial involving 47 municipalities in Norway, with assessments at baseline, and after 10 weeks and at 6 and 12 months. The sample consisted of 707 persons that received a 4-10 week reablement program and 121 underwent treatment as usual. Primary outcomes were activity performance and satisfaction with performance measured by the Canadian Occupational Performance Measure (COPM, 1-10). Secondary outcomes included the Short Physical Performance Measure Battery (SPPB), the European Quality of Life Scale (EQ-5D-5 L), and the Sense of Coherence Questionnaire (SOC). Overall treatment effects were estimated with mixed-model repeated measures analyses. RESULTS: Significant treatment effects in the rehabilitation group compared with the control group were found in COPM-Performance and COPM-Satisfaction scores at 10 weeks (mean differences between groups (MD), 1.61, 95% confidence interval (CI), 1.13, 2.10 and MD 1.47, CI 0.98, 1.97, respectively), and at 6 months (MD 1.42; CI 0.82,2.02 and MD 1.37; CI 0.77,1.98, respectively). There were also significant treatment effects in the SPPB-subscales for balance and walking after 6 months, in the total SPPB score and in the subscale for sit-to-stand after 12 months. In the EQ-5D-5 L assessment, significant treatment effects were found in the subscales for mobility, and for usual activities and health after 6 months. There was a significant difference in the SOC after six months. CONCLUSION: Reablement seems to be a more effective rehabilitation service for persons with functional decline than traditional home-based services after six months. After 12 months, the differences between the groups decreased. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov on October 24, 2014, (retrospectively registered) identifier: NCT02273934 .

Curcumin and Viscum album Extract Decrease Proliferation and Cell Viability of Soft-Tissue Sarcoma Cells: An In Vitro Analysis of Eight Cell Lines Using Real-Time Monitoring and Colorimetric Assays.

BACKGROUND: The cytostatic effects of the polyphenol curcumin and Viscum album extract (VAE) were assessed in soft-tissue sarcoma (STS) cells. METHODS: Eight human STS cell lines were used: fibrosarcoma (HT1080), liposarcoma (SW872, T778, MLS-402), synovial sarcoma (SW982, SYO1, 1273), and malignant fibrous histiocytoma (U2197). Primary human fibroblasts served as control cells. Cell proliferation, viability, and cell index (CI) were analyzed by BrdU assay, MTT assay, and real-time cell analysis (RTCA). RESULTS: As indicated by BrdU and MTT, curcumin significantly decreased the cell proliferation of five cell lines (HT1080, SW872, SYO1, 1273, and U2197) and the viability of two cell lines (SW872 and SW982). VAE led to significant decreases of proliferation in eight cell lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, 1293, and U2197) and reduced viability in seven STS lines (HT1080, SW872, T778, MLS-402, SW982, SYO1, and 1273). As indicated by RTCA for 160 h, curcumin decreased the CI of all synovial sarcoma cell lines as well as T778 and HT1080. VAE diminished the CI in most of the synovial sarcoma (SW982, SYO1) and liposarcoma (SW872, T778) cell lines as well as HT1080. Primary fibroblasts were not affected adversely by the two compounds in RTCA. CONCLUSION: Curcumin and VAE can inhibit the proliferation and viability of STS cells.

Albumin reduces the antibacterial efficacy of wound antiseptics against Staphylococcus aureus.

OBJECTIVE: The influence of proteins on the efficacy of antiseptic solutions has been rarely investigated even though exudate can contain high levels of protien. The aim of this study was to analyse the antibacterial efficacy of commonly used solutions in the presence of albumin protein. METHOD: Using Staphylococcus aureus in a standardised quantitative suspension assay, the antibacterial effects of poly (1-(2-oxo-1-pyrrolidinyl) ethylene)-iodine (PVP-I) and octenidin-dihydrochloride/phenoxyethanol (OCT/PE) were analysed in the presence of 0-3% bovine serum albumin (BSA). These were compared with previous results obtained with polyhexamethylene biguanide hydrochloride (PHMB). RESULTS: Presence of albumin caused a significant (p<0.001) decrease in antibacterial effect in the analysed solutions. The concentrations of albumin that provoked highly significant decreases in the bacterial reduction factors of the study agents were: 0.01875 % for PVP-I, followed by 0.75 % for OCT/PE. After addition of 3 % albumin, adequate antimicrobial effects were ensured for titrations to 5 % PVP-I and 8 % OCT/PE. As we could show before, it is not possible to titrate PHMB in order to assure adequate potency. CONCLUSION: This study demonstrates that albumin induces a significant decrease of the antibacterial potency of the analysed solutions.

EPHB4 tyrosine-kinase receptor expression and biological significance in soft tissue sarcoma.

Soft tissue sarcomas (STS) are heterogeneous malignant tumors of mesenchymal origin. Due to low incidence and high number of different histological subtypes, their pathogenesis and thus potential targets for their therapy remain barely investigated. Several studies revealed significant higher EPHB4 expression in malignancies such as prostate and colorectal cancer showing survival advantages for these tumor cells. Therefore we studied the expression of EPHB4 in a total of 46 clinical human specimens of different STS and human fibroblasts. EPHB4 mRNA and protein expression were significantly increased in synovial sarcoma. After targeting EPHB4 in fibrosarcoma, synovial sarcoma, liposarcoma and MFH sarcoma cell lines by siRNA or by inhibition of autophosphorylation using the specific EPHB4 kinase inhibitor NVP-BHG712 a decreased proliferation rate/vitality of synovial- and fibrosarcoma cells was observed. Silencing of EPHB4 significantly reduced the transmigration of synovial sarcoma cells towards fibroblasts and endothelial cells. In addition, we assessed the anti-metastatic effect of EPHB4 inhibition in vivo by intraperitoneal administration of the EPHB4 inhibitor in an appropriate sarcoma lung metastasis xenograft model. As result 43% of NVP-BHG712 treated mice (n = 3/7) developed pulmonary metastases whereas all control mice (n = 5) revealed lung metastases. The residual 57% of mice (n = 4/7) showed only small local tumor cell spots. Size measurements of the Vimentin positive area explained significant decrease in lung metastasis formation (p < 0.05) after EPHB4 kinase inhibition. In summary, these data provide first evidence of the importance of EPHB4 in the tumorigenesis of synovial sarcoma and present EPHB4 as a potential target in the therapy of this malignancy.

Efficacy of topically delivered moxifloxacin against wound infection by Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus.

Wound infection is a common risk for patients with chronic nonhealing wounds, causing high morbidity and mortality. Currently, systemic antibiotic treatment is the therapy of choice, despite often leading to several side effects and the risk of an insufficient tissue penetration due to impaired blood supply. If systemically delivered, moxifloxacin penetrates well into inflammatory blister fluid, muscle, and subcutaneous adipose tissues and might therefore be a possible option for the topical treatment of skin and infected skin wounds. In this study, topical application of moxifloxacin was investigated in comparison to mupirocin, linezolid, and gentamicin using a porcine wound infection and a rat burn infection model. Both animal models were performed either by an inoculation with methicillin-resistant Staphylococcus aureus (MRSA) or Pseudomonas aeruginosa. Wound fluid, tissue, and blood samples were taken, and bacterial counts as well as the moxifloxacin concentration were determined for a 14-day follow-up. A histological comparison of the rat burn wound tissues was performed. Both strains were susceptible to moxifloxacin and gentamicin, whereas mupirocin and linezolid were effective only against MRSA. All antibiotics showed efficient reduction of bacterial counts, and except with MRSA, infected burn wounds reached bacterial counts below 10(5) CFU/g tissue. Additionally, moxifloxacin was observed to promote wound healing as determined by histologic analysis, while no induction of bacterial resistance was observed during the treatment period. The use of topical antibiotics for the treatment of infected wounds confers many benefits. Moxifloxacin is therefore an ideal candidate, due to its broad antibacterial spectrum, its high efficiency, and its potential to promote wound healing.

Novel role of interleukin 7 in myelopoiesis: stimulation of primitive murine hematopoietic progenitor cells.

Interleukin 7 (IL-7) has been demonstrated to be an important regulator of the growth of B and T cell precursors as well as mature T cells, whereas IL-7 has been reported to have no direct myeloproliferative effects. Here we show that IL-7 potently and directly enhances colony stimulating factor-induced myeloid colony formation from Lin-Sca-1+ murine bone marrow progenitor cells, increasing the cloning frequency up to ninefold and cell numbers up to 50-fold, without affecting their ability to differentiate along the myeloid lineages In contrast, IL-7 has no effect on proliferation of committed Lin- myeloid progenitors. Thus, in addition to its established lymphopoietic potential, this study implicates a novel role of IL-7 in early myelopoiesis.

Expression of antimicrobial peptides in cutaneous infections after skin surgery.

BACKGROUND: Increasing numbers of antibiotics have lost efficiency because of bacterial resistance. The consequences can be severe when surgical wounds become infected during postoperative care. Natural peptide antibiotics, the so-called host defence peptides (HDPs), have been investigated since the 1990s in a search for alternative treatment strategies. HDPs build up a protection shield against pathological microorganisms, especially in human epithelium. The use of HDPs is currently being discussed as a new antimicrobial therapeutic strategy. Accordingly, a profound knowledge of the quantitative relationships of the effectors is essential. OBJECTIVES: To evaluate differences in HDP expression between postoperatively inflamed and healthy epithelium. METHODS: Expression profiles of the genes encoding HDP human beta-defensin (hBD)-1 (DEFB1, previously known as HBD-1), hBD-2 (DEFB4A, previously known as HBD-2), hBD-3 (DEFB103A, previously known as HBD-3) and psoriasin (S100A7) were assessed in samples of surgical wound healing disorders (n = 27) and healthy epithelium (n = 16) by using real-time polymerase chain reaction. Immunohistochemical staining was performed in the same samples. RESULTS: A significant overexpression of DEFB4A (P < 0.001), DEFB103A (P = 0.001) and S100A7 (P < 0.001) was found in cutaneous surgical site infections. Immunohistochemistry revealed intensely elevated protein levels of psoriasin in infected wounds, and differences in distribution with respect to the epithelial layers. CONCLUSIONS: The study demonstrates upregulated mRNA expression and protein levels of HDPs in postoperatively inflamed epithelium. The results may be a starting point for novel pharmacological treatments.

Germline transmission of exogenous genes in the chicken.

Difficulties associated with in vitro manipulation and culture of the early chicken embryo have restricted generation of transgenic chickens to approaches that use replication-competent retroviruses. The need to produce transgenic chickens in the absence of replicating virus prompted development of a new method of gene transfer into the chicken. Microinjection of the replication-defective reticuloendotheliosis virus (REV) vector ME111 beneath unincubated chicken embryo blastoderms results in infection of germline stem cells. This vector contains genetic information exogenous to the chicken genome, including both the herpes simplex virus type 1 thymidine kinase gene and the Tn5 neomycin phosphotransferase gene. About 8 percent of male birds hatched from injected embryos contained vector DNA in their semen. All four positive males tested passed vector sequences onto their progeny. Analysis of G1 offspring showed that gonads of G0 male birds were mosaic with respect to insertion of vector provirus. Thus, primordial germ cells present in the unincubated chicken embryo blastoderm are susceptible to infection by defective REV vectors.

[A comparative in vitro study of cell toxicity of clinically used antiseptics]. / Vergleichende In-vitro-Studie zur Zytotoxizität klinisch eingesetzter Antiseptika.

PURPOSE: Local skin antiseptics are the standard of care for chronic and non-healing wounds. However, little is known about their potential toxic properties. This study investigates the impact of three commercially available and widely used antiseptics on vitality and proliferation of human cutaneous cells. MATERIAL AND METHODS: Three antiseptics, Lavasept (PHMB), Octenisept (octenidine) and Betaisodona (PVP-iodine) were tested for their cytotoxic effects towards HaCaT cells, primary human keratinocytes and fibroblasts using MTT assay and BrDU ELISA. RESULTS: Lavasept showed only slight to moderate toxic effects on cellular vitality and proliferation. Ocentisept and Betaisodona induced severe reduction of cell vitality (p<0.05) to 0% surviving fibroblasts at 7.5% (Betaisodona) and 12.5% Octenisept, respectively. Furthermore, poliferative activity was reduced to 0% in keratinocytes at 7.5% concentration of Betaisodona and Ocentisept. CONCLUSION: This study shows that frequently used wound- and skin antiseptics show severe cytotoxic effects towards cutaneous cells. Furthermore, antimicrobial efficacy and toxic properties must be included in the clinical decision process for optimal therapy of chronic wounds. The PHMB solution Lavasept showed best results regarding toxicity in this study.

Tumor necrosis factor-alpha inhibits stem cell factor-induced proliferation of human bone marrow progenitor cells in vitro. Role of p55 and p75 tumor necrosis factor receptors.

Stem cell factor (SCF), a key regulator of hematopoiesis, potently synergizes with a number of hematopoietic growth factors. However, little is known about growth factors capable of inhibiting the actions of SCF. TNF-alpha has been shown to act as a bidirectional regulator of myeloid cell proliferation and differentiation. This study was designed to examine interactions between TNF-alpha and SCF. Here, we demonstrate that TNF-alpha potently and directly inhibits SCF-stimulated proliferation of CD34+ hematopoietic progenitor cells. Furthermore, TNF-alpha blocked all colony formation stimulated by SCF in combination with granulocyte colony-stimulating factor (CSF) or CSF-1. The synergistic effect of SCF observed in combination with GM-CSF or IL-3 was also inhibited by TNF-alpha, resulting in colony numbers similar to those obtained in the absence of SCF. These effects of TNF-alpha were mediated through the p55 TNF receptor, whereas little or no inhibition was signaled through the p75 TNF receptor. Finally, TNF-alpha downregulated c-kit cell-surface expression on CD34+ bone marrow cells, and this was predominantly a p55 TNF receptor-mediated event as well.

A novel mammalian protein, p55CDC, present in dividing cells is associated with protein kinase activity and has homology to the Saccharomyces cerevisiae cell division cycle proteins Cdc20 and Cdc4.

A novel protein, p55CDC, has been identified in cycling mammalian cells. This transcript is readily detectable in all exponentially growing cell lines but disappears when cells are chemically induced to fall out of the cell cycle and differentiate. The p55CDC protein appears to be essential for cell division, since transfection of antisense p55CDC cDNA into CHO cells resulted in isolation of only those cells which exhibited a compensatory increase in p55CDC transcripts in the sense orientation. Immunoprecipitation of p55CDC yielded protein complexes with kinase activity which fluctuated during the cell cycle. Since p55CDC does not have the conserved protein kinase domains, this activity must be due to one or more of the associated proteins in the immune complex. The highest levels of protein kinase activity were seen with alpha-casein and myelin basic protein as substrates and demonstrated a pattern of activity distinct from that described for the known cyclin-dependent cell division kinases. The p55CDC protein was also phosphorylated in dividing cells. The amino acid sequence of p55CDC contains seven repeats homologous to the beta subunit of G proteins, and the highest degree of homology in these repeats was found with the Saccharomyces cerevisiae Cdc20 and Cdc4 proteins, which have been proposed to be involved in the formation of a functional bipolar mitotic spindle in yeast cells. The G beta repeat has been postulated to mediate protein-protein interactions and, in p55CDC, may modulate its association with a unique cell cycle protein kinase. These findings suggest that p55CDC is a component of the mammalian cell cycle mechanism.

MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.

The alpha-subunit mRNAs for Gs and Go2 are differentially regulated by protein kinase A and protein kinase C in rat Sertoli cells.

In the present study, we have examined regulatory effects of protein kinase A and protein kinase C activation by 8-CPTcAMP and TPA, respectively, on mRNAs for various G protein alpha-subunits and corresponding immunoreactive proteins in rat Sertoli cells. Gs alpha and Go alpha mRNA levels were transiently increased 1.5-fold and 4-fold, respectively, by 8-CPTcAMP in cultured Sertoli cells. This up-regulation of mRNAs for Gs alpha and Go alpha was also observed when Sertoli cells were incubated in the presence of FSH. When protein synthesis was inhibited by cycloheximide, the cAMP-mediated stimulation of Gs alpha mRNA was abolished, whereas Go alpha mRNA was superinduced to a 50- to 100-fold higher level than basal. Activation of protein kinase C with TPA had a strong, synergistic effect on cAMP-mediated stimulation of Gs alpha mRNA, whereas the cAMP-mediated stimulation of Go alpha mRNA was completely blocked. Surprisingly, changes in mRNA levels were not accompanied by any alterations in the levels of immunoreactive Gs alpha and Go alpha proteins.

Phototherapy of seasonal affective disorder. Time of day and suppression of melatonin are not critical for antidepressant effects.

Seasonal affective disorder is characterized by recurring cycles of fall-winter depression and spring-summer hypomania (or euthymia). In winter, depressed patients with seasonal affective disorder respond to daily treatments with five to six hours of bright artificial light in two to three days. They relapse two to three days after light is withdrawn. In this study carefully controlled experimental conditions were used to determine whether phototherapy acts via a photoperiodic mechanism in which the timing of light is critical for its therapeutic effect. Photoperiodism is a common regulatory mechanism in animal seasonal rhythms and depends for its effect on light-induced changes in the pattern of nocturnal melatonin secretion. The results reported herein of "skeleton photoperiod" experiments indicate that the efficacy of phototherapy may not depend on its timing or its effect on melatonin secretion.

Neuroendocrine response to 5-hydroxytryptophan in seasonal affective disorder.

A double-blind random-ordered comparison of the effects of placebo and 5-hydroxytryptophan (200 mg, orally) in ten depressed patients with seasonal affective disorder (SAD) and ten controls disclosed slightly but significantly higher basal levels of serum prolactin and a trend toward higher basal levels of serum cortisol in the patients with SAD compared with controls. After administration of 5-HTP, the cortisol level significantly increased and the prolactin level significantly decreased in both patients and controls. No differences in the melatonin level, growth hormone level, blood pressure, or pulse rate and no side effects were noted between patients and controls in the two study conditions; the timing of basal and 5-hydroxytryptophan-stimulated hormonal secretions was similar for both groups. These results are discussed with reference to current hypotheses of the cause of SAD.

Use of Trypanosoma equiperdum infected rabbits as a source of splenic mRNA; construction of cDNA clones and identification of a rabbit mu heavy chain clone.

Rabbits were infected by Trypanosoma equiperdum and the splenic mRNA was isolated. In vitro translation of this RNA and immunoprecipitation with anti-light chain, anti-heavy chain, anti-mu and anti-VH antibodies demonstrated that T. equiperdum infection elicits large quantities of splenic mRNA encoding mu and kappa chains. The mu and gamma heavy chains and the kappa light chains synthesized in the cell-free translation system were specifically immunoprecipitated by antisera to heavy chain VHa and light chain kappa b allotypes. In vitro labeling of spleen cells from trypanosome-infected animals demonstrated that the biosynthetically labeled IgM has a mu chain of higher molecular weight than the mu chain synthesized by in vitro translation, a difference that is largely abolished when cellular glycosylation is blocked with the antibiotic tunicamycin. Enrichment for heavy chain or light chain mRNA was achieved by fractionating mRNA from trypanosome-infected animals on a sucrose gradient. cDNA clones carrying mu heavy chain sequences were produced using a 'one tube' protocol and identified by cross species hybridization and hybridization selection. Infection of rabbits with T. equiperdum followed by sucrose gradient enrichment of splenic mRNA has provided sufficient quantities of mRNA encoding mu heavy chain suitable for cDNA cloning.

Platelet factor 4 mRNA expression in human erythroleukemic cells: regulation by phorbol esters and certain cytokines.

Developing megakaryocytes are distinguished from progenitor cells by the appearance of platelet proteins such as platelet factor 4 (PF 4). The human erythroleukemic cell line HEL can also be induced to produce PF 4 by incubation in phorbol esters. HEL cells were used here as a model system in which to study the phenomenon of inducible PF 4 production at both the mRNA and protein levels. The cytokines interleukin 1 beta (IL-1 beta), interleukin 3 (IL-3), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), erythropoietin (EPO), and transforming growth factor-beta (TGF-beta) were also evaluated for their effects on PF 4 mRNA induction in HEL cells.

Direct synergistic effects of IL-4 and IL-11 on proliferation of primitive hematopoietic progenitor cells.

The present studies have investigated, for the first time, the synergistic effects of interleukin-4 (IL-4) and IL-11 on the growth of single murine bone marrow progenitor cells. These studies suggest that IL-4 and IL-11 are synergistic hematopoietic growth factors, enhancing colony formation of bone marrow progenitors from normal mice in the presence of colony-stimulating factors or stem cell factor, whereas neither IL-4 nor IL-11, alone or in combination, resulted in colony formation. However, in the presence of a neutralizing anti-TGF-beta antibody, IL-11 plus IL-4 induced clonal growth of primitive Lin-Sca1+ progenitors. Furthermore, here we report several observations extending the knowledge about IL-4 and IL-11 as synergistic factors. In addition to the established ability of IL-11 to enhance IL-3- and GM-CSF-induced colony formation, IL-11 also enhanced the number of G-CSF- and CSF-1-stimulated colonies of mature (Lin-) and primitive (Lin-Sca-1+) hematopoietic progenitors cultured at the single-cell level. In contrast, IL-4 bifunctionally regulated the growth of Lin- progenitors, whereas the growth of single Lin-Sca=1+ progenitors was unaffected or enhanced in the presence of IL-4. Finally, IL-4 and IL-11, in combination, potently synergized to enhance the high-proliferative-potential colony-forming cell colony formation of Lin-Sca-1+ progenitors in response to all four CSFs and to SCF.