Interleukin-11 inhibits adipogenesis and stimulates myelopoiesis in human long-term marrow cultures

Interleukin-11 (IL-11) is a bone marrow (BM) stromal-derived growth factor that has been shown to stimulate murine myeloid and lymphoid cells both in vitro and in vivo and to inhibit adipogenesis in a murine fibroblast cell line. We have studied the effects of IL-11 on highly purified human BM stem and progenitor cells and on human long-term marrow cultures (LTMC). Adipocyte differentiation is an integral component of murine and human LTMC. IL-11 stimulates myeloid growth as a single cytokine when added to highly enriched CD34+, HLA-DR+ bone marrow cells. IL-11 stimulated no growth in the more primitive CD34+, HLA-DR- population even in the presence of additional cytokines. IL-11 addition to human LTMC resulted in the expansion of myeloid and mixed, but not erythroid, progenitor populations. IL-11 dramatically increased the adherent cell populations, including both stromal cells and macrophages. Treated cultures also showed marked inhibition of fat accumulation in the adherent cells due in part to a block in the differentiation of preadipocytes to adipocytes, as shown by RNA analysis using adipocyte-specific markers. These data show that IL-11 stimulates a more differentiated, although multipotential, progenitor cell in human BM and that LTMC provide a useful model for studying the effects of this cytokine in the context of the hematopoietic microenvironment.     

Critical comparison of laparoscopic, robotic, and open radical prostatectomy: Techniques, outcomes, and cost

Radical prostatectomy has maintained paramount importance in prostate cancer management. Emerging alternative treatments are laparoscopic and robotic prostatectomy. Technical modifications have improved radical prostatectomy outcomes, yet surgery remains difficult to perform regardless of approach. Contemporary series have shown comparable outcomes with operative time, transfusion rates, analgesia, and length of catheterization. Open radical prostatectomy provides excellent long-term oncologic control, but sparse short-term data are available for laparoscopic and robotic prostatectomy. Favorable outcomes also have been reported for urinary control and sexual function, regardless of approach. Additional prospective data collection is needed to evaluate if minimally invasive approaches provide distinct advantages over open surgery.     

High-intensity focused ultrasound extracorporeal ablation of liver tissues in rabbits

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The influence of purified recombinant human heavy-subunit and light- subunit ferritins on colony formation in vitro by granulocyte- macrophage and erythroid progenitor cells

Purified recombinant human heavy subunit (rHF, acidic) and recombinant human light subunit (rLF, basic) ferritins were assessed for their effects in vitro on colony formation by normal human granulocyte- macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells. The purity of the samples was confirmed by electrophoresis in both nondenaturing and denaturing conditions and silver staining. Concentrations of 10(-8) to 10(-10) mol/L rHF caused an approximately 40% significant decrease in colony formation. Some significant activity was detected at 10(-11) mol/L, and activity was lost at 10(-12) mol/L. In contrast, rLF had no significant activity at 10(-8) to 10(-16) mol/L. rHF was significantly active against mouse bone marrow CFU-GM to concentrations as low as 10(- 8) to 10(-9) mol/L. The inhibitory activity of rHF was inactivated with three different monoclonal antibodies recognizing the heavy subunit of ferritin, but not with two monoclonal antibodies recognizing the light subunit of ferritin. The inhibitory activity of rHF was similar in the absence or presence of serum, monocytes, and T lymphocytes. We and others have shown an association of a glycosylated natural acidic isoferritin (AIF) with inhibitory activity, but since the rHF was expressed in Escherichia coli and did not bind to concanavalin A, glycosylation of AIF is not an absolute prerequisite for this activity. These results demonstrate that rHF has suppressive activity in vitro and substantiate our original observations using purified natural acidic isoferritins.     

Effects of in vivo recombinant methionyl human granulocyte colony- stimulating factor on the neutrophil response and peripheral blood colony-forming cells in healthy young and elderly adult volunteers

Recombinant granulocyte colony stimulating factor (G-CSF) was administered daily for 14 days to healthy young (Y) (20 to 30 years) and elderly (O) (70 to 80 years) volunteers to evaluate the effects of age on the neutrophil (polymorphonuclear leukocytes, PMN) responses. Thirty-eight volunteers were randomized to receive 0 micrograms, 30 micrograms, or 300 micrograms per day. Baseline neutrophil counts (ANC), peak ANCs, and the rate of attaining the peak ANC were similar in both age groups at both doses. The peak ANC was increased 5-fold at 30 micrograms and 15-fold at 300 micrograms in both the young and elderly. Daily tests of PMN function, as measured by an automated chemiluminescence system, showed nearly identical responses to several agonists for both age groups. Marrow proliferative activity as reflected by the percentage of cells in the marrow neutrophil mitotic pool also increased similarly for both age groups at both doses. In contrast, there was an age-related change in blood colony formation as measured by the blood CFU-GM assay. Compared with controls at the 30 micrograms dose, mean colony formation was increased 2-fold in the young versus no change in the elderly and at the 300 micrograms dose 24- fold in the young versus 12-fold in the elderly. These studies indicate that neutrophil responses to rhG-CSF are equivalent in healthy young and elderly volunteers but the mobilization of progenitor cells, as measured by the CFU-GM assay appears to differ substantially.     

Inhibition of delayed-type contact hypersensitivity in mice deficient in both E-selectin and P-selectin

Leukocyte rolling and emigration in response to inflammatory stimuli appears to involve both E-selectin- and P-selectin-dependent adhesion, which suggests that these molecules have overlapping functions. To clarify their relative contributions in chronic inflammation, we examined delayed-type contact hypersensitivity (DTH) responses in P- selectin, E-selectin, and E-/P-selectin-deficient mice. Oxazolone- induced increases in ear thickness and ear weight were equivalent in wild-type mice and in P-selectin and E-selectin mutants, but were significantly reduced in E-/P-selectin mutants. The number and area of microabscesses on the ears of E-/P-deficient mice were decreased by 72% and 93%, and the number of leukocytes invading the subdermal ear tissue was reduced. T cells from E-/P-deficient mice transferred oxazolone reactivity into naive wild-type mice. However, when donor T cells from wild-type mice were transferred into E-/P-selectin-deficient mice, the DTH response was significantly impaired. These results show that leukocyte recruitment into a subacute inflammatory reaction can occur when either P-selectin or E-selectin is present, but is significantly reduced when both selectins are absent. Both P- and E-selectin are likely to play important roles in the development and maintenance of inflammatory diseases.     

Hairy cell leukemia: a tumor of pre-plasma cells

Monoclonal antibodies defining B-, T-, and myeloid-restricted cell surface antigens were used to characterize the lineage and state of differentiation of tumor cells isolated from 22 patients with hairy cell leukemia (HCL). These tumors were shown to be of B lineage because they strongly expressed the B cell-restricted antigens B1 and B4 and lacked T cell- and monocyte-restricted antigens. Moreover, the strong expression of the plasma cell-associated PCA-1 antigen on the majority of hairy cells suggested that these tumors correspond to later stages of B cell ontogeny. Dual fluorescence experiments further confirmed that HCL splenocytes that coexpressed B1 and PCA-1 demonstrated both the morphology and tartrate-resistant acid phosphatase positivity of hairy cells. The observation that some hairy cells either spontaneously produce immunoglobulin (Ig) or could be induced to proliferate and secrete Ig provides complementary support for the view that HCL is a pre-plasma cell tumor. However, staining of hairy cells with anti-IL2R1 monoclonal antibody, which is directed to the T cell growth factor receptor and/or with the anti-Mo1 reagent, directed to C3bi complement receptor, distinguish these cells from currently identified B cells.     

O10 The technology behind Colgate® TotalTM toothpaste

In the early 1990s, a break‐through toothpaste, known as Colgate^® Total?, was launched with documented long‐lasting activity against plaque, gingivitis, calculus, tooth decay and bad breath. The technology behind this toothpaste is the combination of triclosan, a polyvinyl methyl ether maleic acid (PVM/MA) copolymer and sodium fluoride (TCF). The function of the copolymer is to ensure optimal oral retention and prolonged release of the antibacterial triclosan. Effective levels of triclosan have been measured in the oral cavity 12 h after brushing the teeth. This allows prolonged control of oral bacteria that can lead to the formation of dental plaque and gingivitis and bad breath. Similarly, the retention of triclosan to oral surfaces during 2 years regular use of the product has led to a significant reduction in incremental coronal caries compared to an ADA‐approved anti‐cavity fluoride toothpaste. Furthermore, significantly less calcium phosphate has been shown to be present in dental plaque after brushing the teeth with the triclosan/copolymer toothpaste, and this has resulted in the reduced formation of tartar. A new variant of the triclosan/copolymer/fluoride toothpaste, having the numerous therapeutic and aesthetic benefits of the original formula, has been made available to consumers. The new dentifrice, which contains an impactful breath freshening flavor, has been documented to be significantly better (P < 0.05) than a control toothpaste in providing sustained control of bad breath over 12 h. After 12 h, breath odor was reduced from 51% compared to the control. The long term retention and subsequent release of triclosan by the copolymer in the TCF formula provide consumers protection against plaque, gingivitis, tartar, caries and bad breath.     

Rearrangement of T-cell delta locus in lymphoproliferative disorders

Studies of lymphoproliferative disorders using immunoglobulin and T- cell receptor genes have contributed to our understanding of clonality and lineages of these disorders. In this study, we examined the rearrangement of the recently discovered T-cell delta chain genes in a variety of lymphoproliferative diseases. We show here that six of 14 T- cell lymphomas and five of 23 B-cell lymphomas or B-cell leukemia cell lines have rearranged the delta loci, while two of two hyperimmune reactions retain germline configuration within these genes. Seven of ten cases of AILD were rearranged, and Lennert's lymphoma, which has been previously described as a T-cell malignancy, also contains rearrangements in the delta chain genes (three of five). Large cell anaplastic lymphomas positive for the activation antigen CD 30 also contain rearrangement in about one-half (five of 11) of the tumors examined. Two of seven of the Hodgkin's lymphomas studied contained a rearrangement for this gene. This study indicates that this newly identified T-cell delta gene is useful in evaluating clonality but is not lineage specific. However, with only one exception (in 28 rearrangements), this gene rearranges in tumors with gamma and beta chain gene rearrangements, indicating that when used in conjunction with the other TcR genes, delta rearrangement may also be useful in evaluating lineages.