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Sample records for autologous mixed lymphocyte

  1. Defective autologous mixed lymphocyte reactivity in multiple sclerosis.

    PubMed Central

    Hirsch, R L

    1986-01-01

    T cells from patients with multiple sclerosis (MS) and normal controls were assessed for their ability to respond in the autologous mixed lymphocyte reaction (AMLR). Cells from stable MS patients demonstrated a significant defect in their proliferative response to non-T cells in comparison to normal controls. Despite the defective AMLR response, T cells from MS patients reacted as well as T cells from normal controls to allogeneic stimuli. Furthermore, MS non-T-cells were fully capable of stimulating allogeneic MLR responses by normal and MS T cells. Since the T4+ cell is the major subpopulation which proliferates in the AMLR, these studies suggest a functional defect in a subpopulation of T4+ cells in MS patients. Since the AMLR may represent an important mechanism by which immune responses are regulated, a defect in the ability of MS T cells to respond to autologous cells could account for several of the autoimmune features of the disease. PMID:2942317

  2. Autologous mixed lymphocyte culture reactions and generation of cytotoxic T cells

    PubMed Central

    1977-01-01

    Autologous mixed lymphocyte culture (MLC) reactions were studied utilizing autologous purified B cells and autologous established B lymphoid cell lines as stimulating cells. Similar results were obtained although somewhat greater stimulation of lymphocyte proliferation was found with the autologous lymphoid cell lines. Cytotoxic T cells were not generated against the stimulating cells in either case when peripheral blood cells were used as targets. A low cytotoxicity was detected when lymphoid cell lines were used both as stimulators and target cells. However this was nonspecific and was always greater for heterologous lines than for the stimulator line. Third-party cell experiments demonstrated that the autologous reaction could serve as a proliferative stimulus for specific cytotoxic lymphocyte generation. Heat-treated allogeneic lymphocytes that alone do not stimulate proliferation ro cytotoxic T-cell generation in MLC reactions when added to the autologous system produced specific cytotoxic cells. The separation of the proliferative phase from the cytotoxic cell generation was especially striking in these experiments. Possible uses of this system for the generation of specific cytotoxic cells to other nonstimulatory cells are discussed. PMID:144772

  3. Autologous rosette-forming T cells as the responding cells in human autologous mixed-lymphocyte reaction.

    PubMed Central

    Palacios, R; Llorente, L; Alarcón-Segovia, D; Ruíz-Arguelles, A; Díaz-Jouanen, E

    1980-01-01

    Autologous rosette-forming cells (Tar cells) have surface and functional characteristics of post-thymic precursors and among these characteristics there are some that have been identified in the responsive cell of the autologous mixed-lymphocyte reaction (AMLR). We therefore did AMLR with circulating mononuclear cells from normal subjects using as responding cells either total T cells, T cells depleted of Tar cells, or purified Tar cells. The response of Tar cells in AMLR was significantly greater than that of total T cells and these responded significantly more than Tar-depleted T cells. Conversely, Tar cells responded less than total T cells or T cells depleted of Tar cells in allogeneic mixed-lymphocyte reactions. Increasing numbers of Tar cells gave significantly greater AMLR responses both alone and when added to diminishing proportions of Tar-depleted T cells to keep the number of T cells constant in the system. Tar cells are the responding cells in AMLR but not in allogeneic mixed-lymphocyte reactions. PMID:6447710

  4. Impaired autologous mixed lymphocyte reaction (AMLR) in patients with ataxia-telangiectasia and their family members.

    PubMed Central

    Lahat, N; Zelnik, N; Froom, P; Kinarty, A; Etzioni, A

    1988-01-01

    We used the autologous mixed lymphocyte reaction (AMLR) to test T cell function in four patients with Ataxia-telangiectasia (AT), in 11 first-degree relatives and in 20 controls. There was a marked reduction of AMLR in the patients and in three relatives compared to the age-matched controls. In the AT patients the defect in AMLR was intrinsic to the CD4 subpopulation, since exogenous IL-2 did not improve the response of isolated CD4 cells. In contrast to normal controls, pre-incubation of autologous B cells with Epstein-Barr virus (EBV) did not enhance the reduced AMLR in the AT patients and the three first-degree relatives. We conclude that in both patients with AT and in some of their family members there is an intrinsic defect in CD4 T cells. This defect leads to diminished reactivity to EBV infected autologous B cells, and may explain in part the high incidence of malignancies observed in such families. PMID:2851398

  5. Inhibition of autologous mixed lymphocyte reaction by monoclonal antibodies specific for the beta chain of HLA-DR antigens.

    PubMed

    Kasahara, M; Ikeda, H; Ogasawara, K; Ishikawa, N; Okuyama, T; Fukasawa, Y; Kojima, H; Kunikane, H; Hawkin, S; Ohhashi, T

    1984-09-01

    Recent studies using rabbit antisera to the separated HLA-DR alpha and beta subunits have suggested that alpha chain-specific, but not beta chain-specific, antisera inhibit T cell proliferative responses in primary and secondary human autologous mixed lymphocyte reaction (AMLR). In the present study, with the aid of sequential co-precipitation assays and Western blotting methods, a monoclonal rat alloantibody 1E4, specific for the beta chain of rat class II molecules carrying an Ia determinant Ba-2.7, was characterized to recognize a monomorphic determinant located on the beta chain of DR antigens. This antibody and a murine monoclonal antibody HU-4, also specific for the beta chain of DR antigens, strongly inhibited both primary and secondary AMLR through a mechanism distinct from an antibody-dependent cell-mediated cytotoxicity reaction. These results indicate that the inhibition of AMLR is not a unique feature of DR alpha-specific antibodies.

  6. Gamma irradiation of human dendritic cells influences proliferation and cytokine profile of T cells in autologous mixed lymphocyte reaction.

    PubMed

    Cao, Meng-De; Chen, Zong-De; Xing, Ying

    2004-01-01

    Dendritic cells (DC) are the most potent antigen-presenting cells (APC); their ability to induce proliferation of T cells in a mixed lymphocyte reaction (MLR) assay is commonly used for the evaluation of their function. It is a general thought that gamma irradiation of APC does not influence their ability to activate T-cell proliferation, but the data from several studies are controversial. To further determine the mechanisms involved in DC-induced T-cell activation in MLR assay, human DC induced from peripheral blood mononuclear cells (PBMC) were gamma-irradiated and determine their effects on the proliferation and cytokine profiles of T cells in an autologous MLR. DC were induced from the PBMC of 11 multiple sclerosis (MS) patients with RMPI 640 medium containing recombinant human GM-CSF (rhGM-CSF; 800 U/ml) and recombinant human IL-4 (rhIL-4; 500 U/ml). DC harvested on day 7 were divided into two equal parts. One part was not irradiated (naive DC); the other was gamma-irradiated at a dose of 30 Gy. Cell surface molecules were analyzed by flow cytometry. T-cell proliferation was determined using a beta-scintillation counter. The levels of IL-2, IL-4, IL-6 and IL-10 in co-culture supernatants were measured by ELISA. The results indicated that gamma irradiation reduced expression of CD86, CD80 and HLA-DR molecules on DC, especially CD86 (P=0.0072). DC, irradiated or non-irradiated, effectively stimulated autologous T-cell proliferation. Compared to naive DC, irradiated DC showed a markedly lower capacity to promote T-cell proliferation (P=0.0073), and strikingly up-regulated secretion of IL-4 (P=0.0145) and IL-2 (P=0.0323) by autologous T cells. No significant differences were noted in IL-6 and IL-10 production between T cells co-cultured with naive DC and irradiated DC (P>0.05). It is concluded that gamma irradiation of DC not only influences the phenotype of DC but also alters their capacity to stimulate the proliferation and the cytokine profiles of autologous T

  7. Deficient autologous mixed lymphocyte reaction in Kaposi's sarcoma associated with deficiency of Leu-3+ responder T cells.

    PubMed Central

    Gupta, S; Safai, B

    1983-01-01

    Autologous mixed lymphocyte reaction (AMLR) and T cell subsets defined with monoclonal antibodies were analyzed in the peripheral blood of homosexual males with Kaposi's sarcoma (KS). All seven patients demonstrated decreased AMLR (P less than 0.001) when compared with age- and sex-matched simultaneously studied controls. These patients also showed decreased proportions of Leu-3+ (helper/inducer phenotype) and an increase in the proportion of Leu-2+ (suppressor/cytotoxic phenotype) T cells. Leu-3+ T cells were purified from two patients by depleting Leu-2+ T cells in complement-dependent cytotoxicity. Leu-3+ T cells from both patients demonstrated poor proliferative response in the AMLR. In allogeneic MLR, patients' T cells were poor responders and their non-T cells were poor stimulators against healthy controls. This study demonstrates deficiency of both AMLR and allogeneic MLR in patients with KS. The decreased AMLR is associated with qualitative and functional deficiency of Leu-3+ responder T cells. Whether the functional deficiency of Leu-3+ responder T cells in the AMLR is a general phenomena or a feature of a subset of patients with KS remains to be determined. PMID:6218186

  8. Inhibition of autologous mixed lymphocyte reaction by monoclonal antibodies specific for the β chain of HLA-DR antigens

    PubMed Central

    Kasahara, M.; Ikeda, H.; Ogasawara, K.; Ishikawa, N.; Okuyama, T.; Fukasawa, Y.; Kojima, H.; Kunikane, H.; Hawkin, S.; Ohhashi, T.; Natori, T.; Wakisaka, A.; Kikuchi, Y.; Aizawa, M.

    1984-01-01

    Recent studies using rabbit antisera to the separated HLA-DR α and β subunits have suggested that α chain-specific, but not β chain-specific, antisera inhibit T cell proliferative responses in primary and secondary human autologous mixed lymphocyte reaction (AMLR). In the present study, with the aid of sequential co-precipitation assays and Western blotting methods, a monoclonal rat alloantibody 1E4, specific for the β chain of rat class II molecules carrying an Ia determinant Ba-2.7, was characterized to recognize a monomorphic determinant located on the β chain of DR antigens. This antibody and a murine monoclonal antibody HU-4, also specific for the β chain of DR antigens, strongly inhibited both primary and secondary AMLR through a mechanism distinct from an antibody-dependent cell-mediated cytotoxicity reaction. These results indicate that the inhibition of AMLR is not a unique feature of DR α-specific antibodies. ImagesFigure 2 PMID:6205985

  9. Spinal fluid lymphocytes responsive to autologous and allogeneic cells in multiple sclerosis and control individuals.

    PubMed Central

    Birnbaum, G; Kotilinek, L; Schwartz, M; Sternad, M

    1984-01-01

    Spinal fluid lymphocytes from multiple sclerosis (MS) patients and controls were stimulated with either autologous non-T cells or with allogeneic non-T cells followed by stimulation with autologous non-T lymphocytes. Cells responding to these stimuli were cloned and their proliferative responses to autologous and allogeneic MS and normal non-T cells were measured. Large numbers of clones with specific patterns of reaction to both autologous and allogeneic cells were obtained from lymphocytes in MS cerebrospinal fluid (CSF), but only occasionally from cells in control CSF. Patterns of responses among clones from a particular CSF were similar and often identical, which suggested that cells in MS CSF were relatively restricted in their specificities. Surface antigen phenotyping of the clones showed them to be predominantly OKT4+, with 13% OKT8+ and 11% OKT4+8+. Peripheral T cells that were stimulated and cultured in parallel with CSF cells were different in that they usually did not give rise to as many clones nor were their patterns of response similar. Many CSF clones were heteroclitic, that is they responded to particular allogeneic cells but not autologous cells. Lymphocytes in MS CSF thus appear to represent a selected population of cells with a high frequency of responsiveness to autologous and allogeneic antigens. Such responses may be evidence for immune regulation within the central nervous system or could represent responses to altered-self antigens. PMID:6237121

  10. T lymphocyte-mediated cytotoxicity against autologous EBV-genome-bearing B cells.

    PubMed

    Tsoukas, C D; Fox, R I; Slovin, S F; Carson, D A; Pellegrino, M; Fong, S; Pasquali, J L; Ferrone, S; Kung, P; Vaughan, J H

    1981-05-01

    We have stimulated human peripheral blood lymphocytes in vitro with autologous EBV-infected or noninfected B cells. A cytotoxic response was obtained only when virally infected cells were used. The activity of the effector cells was restricted by the major histocompatibility complex and was directed against EBV-genome-bearing targets. The highest cytolytic response was obtained when lymphocytes of individuals previously exposed to the virus (EBV-VCA positive) were used. Lymphocytes of noninfected donors (EBV-VCA negative) gave a low response; the relative frequency of their effector cells was at least 4-fold lower. Lymphocytes of newborns did not respond. The cytotoxic activity was mediated by T lymphocytes of the cytotoxic/suppressor subset, as determined by cytofluorographic analysis and antibody plus complement-mediated lysis, using monoclonal antibodies to human lymphocyte surface antigen.

  11. [Apoptosis and necrosis of lymphocytes induced by UV-radiation in the presence of autological plasma].

    PubMed

    Artiukhov, V G; Zemchenkova, O V; Basharina, O V; Riazantsev, S V; Pashkov, M V

    2014-01-01

    The influence of UV-light (240-390 nm) in doses 151-3020 J/m2 on the nature of the death of lymphocytes cells of donor's blood (using markers of apoptotic and necrotic death of cells) and on the level of expression of the marker of apoptotic pre-preparation--CD95-receptor has been investigated. We have shown that UV-radiation increases expression of CD95-receptors which is caused mainly by de novo synthesis of the receptors. It has been revealed that during daily incubation of photo-modified lymphocytes (151 and 755 J/m2) without autological blood cell death occurs by receptor-involved apoptosis. Exposure to high doses of radiation (1510 and 3020 J/m2) causes massive necrotic death of immunocytes. The use of autologous blood plasma during incubation of photo-modified lymphocytes allows decreasing the number of both apoptotic and necrotic cells.

  12. Suppression of mixed lymphocyte reactivity by human chorionic gonadotrophin

    PubMed Central

    Beling, C. G.; Weksler, M. E.

    1974-01-01

    Highly purified human chorionic gonadotrophin inhibits the response of lymphocytes from both male and female subjects to allogeneic cells in mixed lymphocyte culture. Human chorionic gonadotrophin is not cytotoxic for human lymphocytes. PMID:4283122

  13. Disappearance of CD4 lymphocyte circadian cycles after autologous bone marrow transplantation.

    PubMed

    Martini, E; Gorin, N C; Gastal, C; Doinel, C; Roquin, H; Najman, A; Salmon, C

    1988-01-01

    Circadian variations are observed in CD4 lymphocyte count in healthy people. Samples taken of the basal value occurring around 08.00 hr and peak value at midnight made it possible to define the range of cyclic variations. Movement of lymphocytes seems important in accounting for the observed circadian variations. CD4 circadian cycle amplitudes were investigated in 12 patients with autologous bone marrow transplantation. Cycle abnormalities were observed in 7 patients. Two of them had a normal CD4 lymphocyte count. It was therefore possible for functional abnormalities in CD4 lymphocytes to be detected in patients with a normal CD4 count. Because of these results, we are of the opinion that the evaluation of CD4 lymphocyte cycle might be a more sensitive test than the absolute CD4 count itself.

  14. Autologous bone marrow transplantation in chronic lymphocytic leukemia (CLL).

    PubMed

    Mangoni, L; Rizzoli, V

    1996-01-01

    Chronic lymphocytic leukemia (CLL) is an indolent disease characterized by an abnormal proliferation of monoclonal lymphocytes in the bone marrow and lymphoid tissues. Most of the cases (> 90%) belong to the B-lymphocyte lineage and the course of the disease is variable depending on the presence of poor prognostic factors at diagnosis. Therefore optimal treatment is still questioned; presently there are no proven cures for CLL, but the natural history of the disease and the advanced age of the majority of patients makes prolongation of survival a reasonable therapeutic goal in most cases. The traditional therapeutic approach has been based on the activity of alkylating agents and corticosteroid, while patients resistant have been treated with nucleoside analogs. However, patients ultimately relapse and the choice of salvage therapy by conventional methods does not offer many chances. Particularly in younger patients, with poor prognostic factors, the therapeutic options may substantially change in the near future, based on alternative and innovative approaches aimed at achieving cure or long disease-free-survival. The results of high-dose therapy followed by reinfusion of hematopoietic stem cells, either from bone marrow or peripheral blood, will be presented and discussed.

  15. Lysis of fresh human solid tumors by autologous lymphocytes activated in vitro with lectins

    SciTech Connect

    Mazumder, A.; Grimm, E.A.; Zhang, H.Z.; Rosenberg, S.A.

    1982-03-01

    Human peripheral blood lymphocytes (PBL), obtained from patients with a variety of cancers, were incubated in vitro with phytohemagglutinin, concanavalin A, and crude or lectin-free T-cell growth factors. The lectin-activated PBL of nine patients were capable of lysing fresh autologous tumor during a 4-hr 51Cr release assay. Multiple metastases from the same patient were equivalently lysed by these activated autologous PBL. No lysis of fresh PBL or lectin-induced lymphoblast cell targets was seen, although tumor, PBL, and lymphoblast cells were shown to be equally lysable using allosensitized cells. The activated cells could be expanded without loss of cytotoxicity in crude or lectin-free T-cell growth factors. The generation of cells lytic to fresh autologous tumor was dependent on the presence of adherent cells, although the lytic cell itself was not adherent. Proliferation was not involved in the induction of lytic cells since equal lysis was induced in irradiated and nonirradiated lymphocytes. Lectin was not required in the lytic assay, and the addition of alpha-methyl-D-mannoside to concanavalin A-activated lymphoid cells did not increase the lysis of fresh tumor cells. Activation by lectin for 3 days appears to be an efficient and convenient method for generating human cells lytic to fresh autologous tumor. These lytic cells may be of value for studies of the cell-mediated lysis of human tumor and possibly for tumor immunotherapy as well.

  16. Human mixed lymphocyte culture using separated lymphocyte populations.

    PubMed Central

    Potter, M R; Moore, M

    1977-01-01

    The ability of human blood lymphocyte populations enriched with T or B cells to act as responder and stimulator populations in the one-way mixed lymphocyte reaction (MLR) was investigated. T- and B-cell-enriched populations were obtained by separation of rosette-forming and non rosette-forming cells and T-cell-enriched populations were also obtained by nylon-fibre column filtration. Using cells prepared by rosette sedimentation, control unseparated and T-cell-enriched populations responded well when stimulated by mitomycin C-treated unseparated cells from a second individual; and stimulation by T- and B-enriched populations generally produced some response, although the magnitude was variable. B-cell-enriched populations gave virtually no response regardless of the composition of the stimulating populations. Nylon-column-enriched T-cell populations responded to stimulation by control unseparated cells but not to T cells purified by the same procedure. T-cell enriched populations prepared by the two methods thus had different activities in the MLR despite containing similar numbers of T cells suggesting that other factors, such as the presence of small numbers of accessory cells, are important in determining the magnitude of the MLR. PMID:139361

  17. Modulation of Mitogen-Induced Proliferation of Autologous Peripheral Blood Lymphocytes by Human Alveolar Macrophages

    PubMed Central

    Yeager, Henry; Sweeney, Jan A.; Herscowitz, Herbert B.; Barsoum, Ibrahim S.; Kagan, Elliott

    1982-01-01

    Experiments were carried out to determine the effect of cocultivation of T-cell-enriched human peripheral blood lymphocytes with autologous alveolar macrophages on mitogen-induced proliferation as determined by [3H]thymidine uptake. Cells obtained by fiberoptic bronchoscopy and saline bronchial lavage from 14 normal volunteers were enriched for macrophages by adherence in plastic dishes for 1 h in RPMI 1640 medium supplemented with 10% fetal calf serum. Nonadherent mononuclear cells were prepared from heparinized venous blood after Ficoll-Hypaque sedimentation by passage over nylon wool columns. T-cell-enriched populations were incubated with and without alveolar macrophages, either in the presence or absence of phytohemagglutinin. In these experiments, the number of lymphocytes was held constant (105 per well), while the number of alveolar macrophages was varied (0.1 × 105 to 4.0 × 105 per well). Alveolar macrophages generally tended to stimulate phytohemagglutinin-induced lymphoproliferation at lymphocyte/macrophage ratios of 10:1 but consistently and significantly suppressed proliferation at ratios which approach those usually observed in recovered human bronchial lavage fluid, namely, 1:4. The suppressive effect of alveolar macrophages was observed as early as 48 h after culture initiation, while the magnitude of suppression increased with time. Suppression did not appear to be due to alteration in lymphocyte viability, nor was it sensitive to indomethacin. These results indicate that human alveolar macrophages can modulate the in vitro proliferative response of autologous peripheral blood lymphocytes. This observation may have relevance to interactions between alveolar macrophages and bronchial lymphocytes in the human lung in vivo. PMID:6982862

  18. Mixed lymphocyte culture stimulatory and responding capacity of lymphocytes from patients with lymphoproliferative diseases.

    PubMed Central

    Rühl, H; Vogt, W; Bochert, G; Schmidt, S; Moelle, R; Schaoua, H

    1975-01-01

    Lymphocyte reactivity in vitro was studied in patients with Hodgkin's disease, chronic lymphocytic leukaemia and lymphosarcoma. The responding capacity to phytohaemagglutinin (PHA) was markedly depressed and delayed in all three groups of patients compared with the PHA response observed in lymphocyte cultures from normal individuals. In one-way mixed lymphocyte culture experiments a significant decrease in responding capacity of the patients' lymphocytes to lymphocytes from normal donors could be demonstrated. In contrast, the stimulatory capacity of the patients' lymphocytes was found to be intact, or only slightly reduced. PMID:128426

  19. Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients

    PubMed Central

    Radvanyi, Laszlo G.; Bernatchez, Chantale; Zhang, Minying; Fox, Patricia S.; Miller, Priscilla; Chacon, Jessica; Wu, Richard; Lizee, Gregory; Mahoney, Sandy; Alvarado, Gladys; Glass, Michelle; Johnson, Valen E.; McMannis, John D.; Shpall, Elizabeth; Prieto, Victor; Papadopoulos, Nicholas; Kim, Kevin; Homsi, Jade; Bedikian, Agop; Hwu, Wen-Jen; Patel, Sapna; Ross, Merrick I.; Lee, Jeffrey E.; Gershenwald, Jeffrey E.; Lucci, Anthony; Royal, Richard; Cormier, Janice N.; Davies, Michael A.; Mansaray, Rahmatu; Fulbright, Orenthial J.; Toth, Christopher; Ramachandran, Renjith; Wardell, Seth; Gonzalez, Audrey; Hwu, Patrick

    2012-01-01

    Purpose Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing Phase II clinical trial testing the efficacy of ACT using TIL in metastatic melanoma patients and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. Experimental Design Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL followed by two cycles of high-dose (HD) IL-2 therapy. The effects of patient clinical features and the phenotypes of the T-cells infused on clinical response were determined. Results Overall, 15/31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC), with two patients (6.5%) having a complete response. Progression-free survival of >12 months was observed for 9/15 (60%) of the responding patients. Factors significantly associated with objective tumor regression included a higher number of TIL infused, a higher proportion of CD8+ T-cells in the infusion product, a more differentiated effector phenotype of the CD8+ population and a higher frequency of CD8+ T-cells co-expressing the negative costimulation molecule “B- and T-lymphocyte attenuator” (BTLA). No significant difference in telomere lengths of TIL between responders and non-responders was identified. Conclusion These results indicate that immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in metastatic melanoma patients and that CD8+ T-cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression. PMID:23032743

  20. Modulation of MUC1 mucin as an escape mechanism of breast cancer cells from autologous cytotoxic T-lymphocytes

    PubMed Central

    Kontani, K; Taguchi, O; Narita, T; Izawa, M; Hiraiwa, N; Zenita, K; Takeuchi, T; Murai, H; Miura, S; Kannagi, R

    2001-01-01

    MUC1 mucin is known to serve as a target molecule in the killing of breast cancer cells by cytotoxic T-lymphocytes (CTLs). We searched for a possible mechanism allowing tumour cells to escape from autologous CTLs. When the killing of breast cancer cells by autologous lymphocytes was examined in 26 patients with breast cancer, significant tumour cell lysis was observed in 8 patients, whereas virtually no autologous tumour cell lysis was detected in as many as 18 patients. In the patients who showed negligible tumour cell lysis, the autologous tumour cells expressed MUC1-related antigenic epitopes much more weakly than the tumour cells in the patients who exhibited strong cytotoxicity (significant statistically at P< 0.0005–0.0045), suggesting that the unresponsiveness of cancer cells to CTLs observed in these patients was mainly due to loss of MUC1 expression or modulation of its antigenicity. A breast cancer cell line, NZK-1, established from one of the cytotoxicity-negative patients, did not express MUC1 and was resistant to killing by CTLs, while control breast cancer cell lines expressing MUC-1 were readily killed by CTLs. Transfection of NZK-1 cells with MUC1 cDNA induced significant lysis by autologous T-lymphocytes. These results supported the importance of MUC1 mucin in autologous anti-tumour immunity, but suggested that the major escape mechanism of tumour cells from autologous T-lymphocytes is the loss and/or modulation of MUC1 antigenicity on tumour cells, which would limit the effectiveness of possible immunotherapy designed to target the MUC1 mucin. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11336479

  1. Behavior of autologous indium-114m-labeled lymphocytes in patients with lymphoid cell malignancy

    SciTech Connect

    Hamilton, D.; Cowan, R.A.; Sharma, H.L.; Drayson, M.; Nuttall, P.M.; Wagstaff, J.; Deakin, D.P.; Crowther, D.

    1988-04-01

    It has been shown that radioactive material can be localized to lymphocyte traffic areas using radiolabeled autologous lymphocytes and that /sup 114m/In deposited in such a way in rats produces a lymphopoenia by establishing a selective internal irradiation of circulating lymphocytes. The study reported here was undertaken to investigate the feasibility of using this technique in patients with lymphoid cell malignancy. Up to 22.7 MBq was administered to seven patients with active non-Hodgkin's lymphoma involving the spleen and the behavior of the radioactive material was followed over subsequent months. Estimates of the activity in peripheral blood, bone marrow, excreta samples, and of the variation in the whole-body distribution were obtained. The administered radioactive material cleared rapidly from the blood, 85% being removed within the first 30 min. There was an almost immediate uptake of most of this by the spleen and liver with less than 5% of administered activity accumulating in the bone marrow. After 48 hr, the whole-body distribution changed only slowly and there was a regular decrease of the activity in the spleen. Excretion of radioactive material occurred via both the urine and feces and amounted to less than 1% of administered activity per day. This pharmacokinetic data was used to calculate radiation absorbed doses to various organs for a standard man. It is concluded that this represents a feasible technique for the targeting of radioactive material for the treatment of lymphoid malignancy.

  2. Treatment of solid organ transplant recipients with autologous Epstein Barr virus–specific cytotoxic T lymphocytes (CTLs)

    PubMed Central

    Savoldo, Barbara; Goss, John A.; Hammer, Markus M.; Zhang, Lan; Lopez, Teresita; Gee, Adrian P.; Lin, Yu-Feng; Quiros-Tejeira, Ruben E.; Reinke, Petra; Schubert, Stephan; Gottschalk, Stephen; Finegold, Milton J.; Brenner, Malcolm K.; Rooney, Cliona M.; Heslop, Helen E.

    2006-01-01

    We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)–specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive of lysis of EBV-infected cells, although there was no consistent decrease in virus load in peripheral-blood mononuclear cells. Interferon-γ enzyme-linked immunospot (ELISPOT) assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to preinfusion levels after 2 to 6 months. None of the treated patients developed PTLD. One patient with liver PTLD showed a complete response, and one with ocular disease has had a partial response stable for over one year. These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity. PMID:16835376

  3. QUANTITATIVE STUDIES ON THE MIXED LYMPHOCYTE INTERACTION IN RATS

    PubMed Central

    Wilson, Darcy B.; Blyth, Janet L.; Nowell, Peter C.

    1968-01-01

    The proliferative interaction of cultured rat lymphocytes of immunogenetically disparate origin—the mixed lymphocyte interaction—was employed as an experimental model to examine the initial stages of the immune response mechanism. Using mixed cultures of cells derived from parental strain and F1 hybrid rats, in which only the parental lymphocytes respond, the following observations were made on the magnitude and kinetics of the reaction. After initiation of the cultures, there was a latent period of approximately 40 hours during which time no mitotic activity was detected. This inactive phase was followed by a period of proliferation in which previously nondividing cells entered the mitotic cycle for the first time. Activity in the cultures, as detected by incorporation of radioactive thymidine and measured by radioautography or scintillation spectrometry, increased exponentially with a doubling time (T2) of 9–10 hr. In this exponential proliferative phase, lasting approximately 100 hr, the dividing cells underwent a series of rapid sequential divisions with a generation time (Tc) of 8 hr, and few, if any, dropped out of the mitotic cycle. In addition to the cells which first entered mitosis at the beginning of the proliferative phase and then proceeded through multiple divisions, significant numbers of new, previously nondividing cells continued to enter the mitotic cycle during the entire exponential growth phase. The total number of these newly responsive, first division cells throughout the total culture period amounted to 1–3% of the original parental cell inoculum. This is a surprisingly large proportion of peripheral blood lymphocytes with demonstrable reactivity to a particular antigen system, if it is assumed that these first division cells in vitro are functionally related to the hypothetical antigen-sensitive cells which proliferate and differentiate into immunological effector cells. At present there is no entirely satisfactory explanation for

  4. Transferrin receptor expression by stimulated cells in mixed lymphocyte culture.

    PubMed Central

    Salmon, M; Bacon, P A; Symmons, D P; Walton, K W

    1985-01-01

    Transferrin receptor (TRFr) expression by cells in mixed lymphocyte culture increases steadily for the first 5 days, but then reaches a plateau. By the sixth day in culture, about 20% of viable cells express TRFr in two-way mixed lymphocyte reactions. This subpopulation of TRFr-positive cells represents the proliferating population; it is heterogeneous, containing T-cell blasts and smaller cells which are a mixture of T and non-T cells. A small group of non-T cells have phenotypic similarity to natural killer (NK) cells. T cells appear to divide earlier in the course of the response than non-T cells. The biphasic nature of this response and the slower non-T reactivity may be due to a secondary stimulation of non-T cells by factors released from activated T cells (such as interleukin-2). PMID:2982734

  5. [Computer-assisted histocompatibility assessment in mixed lymphocyte culture (MLC)].

    PubMed

    Schwartz, D; Hajek-Rosenmayr, A

    1987-02-20

    Analysis of the results of mixed lymphocyte culture (MLC) for compatibility testing preceding transplantation of bone marrow and other organs has so far required a vast input, both in terms of laboratory staff and work hours. We have developed a computer programme which performs this work rapidly. Graphics of the reaction patterns can be obtained, moreover, and these can prove a helpful tool in interpretation of the results.

  6. Bifunctional major histocompatibility-linked genetic regulation of cell- mediated lympholysis to trinitrophenyl-modified autologous lymphocytes

    PubMed Central

    1975-01-01

    Murine thymus-derived lymphocytes can be sensitized in vitro to trinitrophenyl (TNP)-modified autologous spleen cells (1, 2). Cytotoxic effector cells were generated which were specific for TNP-modified target cells expressing the same H-2K and H-2D serological regions as the modified stimulator cells (3, 7). Spleen cells from two C57BL/10 congenic strains of mice sharing common I-C, S, and D regions, but differing at K, I-A, and I-B regions, generated different levels of lytic responses to the shared modified H-2Dd products upon sensitization with auto logous TNP-modified cells. Lymphocytes from an F1 between responder and nonresponder strain generated a level of cytolysis toward the H-2Dd modified specificity which was of the same order of magnitude as that obtained with the high responder, irrespective of whether F 1 or either parental strain of modified stimulator cell was used. These results suggest that the modification of H-2Dd products resulted in formation of new antigenic determinants in both parental strains. However, the difference observed in responsiveness appeared to be due to a gene or genes mapping in the K, I-A, or I-B region which influenced the ability of the responding lymphocytes to react to these modified H-2Dd products. Responsiveness was expressed as a dominant trait in the F1. PMID:52685

  7. Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells

    PubMed Central

    Fei, Fei; Lim, Min; George, Aswathi A.; Kirzner, Jonathan; Lee, Dean; Seeger, Robert; Groffen, John; Abdel-Azim, Hisham; Heisterkamp, Nora

    2014-01-01

    Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3- cells had spontaneous and anti-BAFF-R mAb-stimulated ADCC activity against autologous ALL cells, which could be further enhanced by IL15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B-ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants. PMID:25134458

  8. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts

    PubMed Central

    Mehta, Rohtesh S.; Chen, Xiaohua; Antony, Jeyaraj; Boyiadzis, Michael; Szabolcs, Paul

    2015-01-01

    Expanding on our prior studies with cord blood T-cells, we hypothesized that primary AML-reactive autologous T-cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T-cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T-cells were stimulated with IFN-γ treated autologous AML weekly X 3, IL-15 and agonistic anti-CD28 antibody. CTL and ELISpot assays tested functionality; RT-qPCR tested AML and T-cell gene expression profiles. Based on combined positive ELIspot and CTL assays, T-cells reactive against AML were generated in 5/8 patients. Treg proportion declined post-co-cultures in reactive T-cell samples. AML-reactive T-cells displayed an activated gene expression profile. “Resistant” AML blasts displayed genes associated with immunosuppressive MDSC. We discuss our approach to creating primary AML-reactive autologous T-cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia reactive T-cells. PMID:26849076

  9. Generating Peripheral Blood Derived Lymphocytes Reacting Against Autologous Primary AML Blasts.

    PubMed

    Mehta, Rohtesh S; Chen, Xiaohua; Antony, Jeyaraj; Boyiadzis, Michael; Szabolcs, Paul

    2016-01-01

    Expanding on our prior studies with cord blood T cells, we hypothesized that primary acute myeloid leukemia (AML)-reactive autologous T cells could be generated ex vivo under immunomodulatory conditions. We purified AML and T cells from 8 newly diagnosed high-risk patients. After 2 weeks expansion, T cells were stimulated with interferon-γ-treated autologous AML weekly × 3, interleukin-15, and agonistic anti-CD28 antibody. Cytotoxic T cells and ELISpot assays tested functionality; reverse transcriptase quantitative polymerase chain reaction tested AML and T-cell gene expression profiles. On the basis of combined positive ELIspot and cytotoxic T cells assays, T cells reactive against AML were generated in 5 of 8 patients. Treg proportion declined after cocultures in reactive T-cell samples. AML-reactive T cells displayed an activated gene expression profile. "Resistant" AML blasts displayed genes associated with immunosuppressive myeloid-derived suppressor cells. We discuss our approach to creating primary AML-reactive autologous T cell and limitations that require further work. Our study provides a platform for future research targeting on generating autologous leukemia-reactive T cells.

  10. The clinical implications of mixed lymphocyte reaction with leukemic cells.

    PubMed

    Kim, Hee-Je; Kim, Tai-Gyu; Cho, Hyun Il; Han, Hoon; Min, Woo-Sung; Kim, Chun-Choo

    2002-11-01

    To evaluate the clinical implications of a mixed lymphocyte reaction between leukemic cells and lymphocytes from HLA-matched sibling donors, we attempted to generate donor-derived, graft-versus-leukemia-effective cells and to define their characteristics. We studied 8 patients with chronic myelogenous leukemia (CML), including 5 patients in the chronic phase (CP), 3 patients in the accelerated phase (AP), and 2 patients with acute myelogenous leukemia (AML) in their first complete remission. Cells from these patients were used as stimulators in a mixed lymphocyte reaction.The effects of natural killer (NK) cells and cytotoxic T-lymphocytes (CTLs) were separated by observing tests for cytotoxicity to target cells, including K562 cells, the patient's leukemic cells, and phytohemagglutinin (PHA) blasts. Donor-derived antileukemic CTLs againstthe patient's own leukemic cells are productive in vitro. The efficacy of generating CTLs against leukemic target cells was (in decreasing order) AML, CML-CP, and CML-AP. Cytotoxic activity against leukemic targets was prominent in 4 cases--2 CML-CP and the 2 AML cases. On the contrary, the 3 cases of CML-AP showed low CTL activity. In cases showing 1 positive result among 3 targets (K562 cells, the patient's leukemic cells, and PHA blasts), the relapse rate was significantly lower (P = .022) on follow-up (median, 33 months; 7-40 months) after hematopoietic stem cell transplantation. By a combined analysis of the cytotoxicity effects for all 3 target cells, we were able to demonstrate a correlation between leukemic relapse and the variable degree of the cytotoxicity test results. Although the total sample numbers for this study were low, we speculate that these results may come from differences in the individual characteristics of the leukemic cells that are in line with their clinical disease status.

  11. Cytotoxicity of CD56-positive lymphocytes against autologous B-cell precursor acute lymphoblastic leukemia cells.

    PubMed

    Fei, F; Lim, M; George, A A; Kirzner, J; Lee, D; Seeger, R; Groffen, J; Abdel-Azim, H; Heisterkamp, N

    2015-04-01

    Precursor B-lineage acute lymphoblastic leukemia (pre-B ALL) affects hematopoietic development and therefore is associated with immune deficiencies that can be further exacerbated by chemotherapy. It is unclear if and when monoclonal antibodies (mAbs) that stimulate antibody-mediated cellular cytotoxicity (ADCC) can be used for treatment because this depends on the presence of functional effector cells. Here, we used flow cytometry to determine that patient samples at diagnosis, post-induction and relapse contain detectable numbers of CD56+ cells. We were able to selectively expand CD56+ immune effector cells from bone marrow and peripheral blood samples at diagnosis and at various stages of treatment by co-culture with artificial antigen-presenting K562 clone 9.mbIL-21 cells. Amplified CD56+CD3- cells had spontaneous and anti-B cell-activating factor receptor mAb-stimulated ADCC activity against allogeneic ALL cells, which could be further enhanced by IL-15. Importantly, matched CD56+ effector cells also killed autologous ALL cells grown out from leukemia samples of the same patient, through both spontaneous as well as antibody-dependent cellular cytotoxicity. Since autologous cell therapy will not be complicated by graft-versus-host disease, our results show that expanded CD56+ cells could be applied for treatment of pre-B ALL without transplantation, or for purging of bone marrow in the setting of autologous bone marrow transplants.

  12. Thymus cells in myasthenia gravis selectively enhance production of anti-acetylcholine-receptor antibody by autologous blood lymphocytes

    SciTech Connect

    Newsom-Davis, J.; Willcox, N.; Calder, L.

    1981-11-26

    We investigated the role of the thymus in 16 patients with myasthenia gravis without thymoma by studying the production of anti-acetylcholine-receptor antibody by thymic and blood lymphocytes cultured alone or together. In 10 responders (with the highest receptor-antibody titers in their plasma), cultured thymic cells spontaneously produced measurable receptor antibody. Receptor-antibody production by autologous blood lymphocytes was enhanced by the addition of responder's thymic cells, irradiated to abrogate antibody production and suppression (P<0.01). This enhancement was greater and more consistent than that by pokeweed mitogen; it depended on viable thymic cells, appeared to be selective for receptor antibody, and correlated with the ratio of thymic helper (OKT4-positive or OKT4+) to suppressor (OKT8+) T cells (P<0.01). These results suggest that myasthenic thymus contains cell-bound acetylcholine-receptor-like material or specific T cells (or both) that can aid receptor-antibody production. This may be relevant to the benefits of thymectomy in myasthenia and to the breakdown in self-tolerance in this and other autoimmune diseases.

  13. Sustained Complete Responses in Patients With Lymphoma Receiving Autologous Cytotoxic T Lymphocytes Targeting Epstein-Barr Virus Latent Membrane Proteins

    PubMed Central

    Bollard, Catherine M.; Gottschalk, Stephen; Torrano, Vicky; Diouf, Oumar; Ku, Stephanie; Hazrat, Yasmin; Carrum, George; Ramos, Carlos; Fayad, Luis; Shpall, Elizabeth J.; Pro, Barbara; Liu, Hao; Wu, Meng-Fen; Lee, Daniel; Sheehan, Andrea M.; Zu, Youli; Gee, Adrian P.; Brenner, Malcolm K.; Heslop, Helen E.; Rooney, Cliona M.

    2014-01-01

    Purpose Tumor cells from approximately 40% of patients with Hodgkin or non-Hodgkin lymphoma express the type II latency Epstein-Barr virus (EBV) antigens latent membrane protein 1 (LMP1) and LMP2, which represent attractive targets for immunotherapy. Because T cells specific for these antigens are present with low frequency and may be rendered anergic by the tumors that express them, we expanded LMP–cytotoxic T lymphocytes (CTLs) from patients with lymphoma using autologous dendritic cells and EBV-transformed B–lymphoblastoid cell lines transduced with an adenoviral vector expressing either LMP2 alone (n = 17) or both LMP2 and ΔLMP1 (n = 33). Patients and Methods These genetically modified antigen-presenting cells expanded CTLs that were enriched for specificity against type II latency LMP antigens. When infused into 50 patients with EBV-associated lymphoma, the expanded CTLs did not produce infusional toxicities. Results Twenty-eight of 29 high-risk or multiple-relapse patients receiving LMP-CTLs as adjuvant therapy remained in remission at a median of 3.1 years after CTL infusion. None subsequently died as a result of lymphoma, but nine succumbed to complications associated with extensive prior chemoradiotherapy, including myocardial infarction and secondary malignancies. Of 21 patients with relapsed or resistant disease at the time of CTL infusion, 13 had clinical responses, including 11 complete responses. T cells specific for LMP as well as nonviral tumor-associated antigens (epitope spreading) could be detected in the peripheral blood within 2 months after CTL infusion, but this evidence for epitope spreading was seen only in patients achieving clinical responses. Conclusion Autologous T cells directed to the LMP2 or LMP1 and LMP2 antigens can induce durable complete responses without significant toxicity. Their earlier use in the disease course may reduce delayed treatment-related mortality. PMID:24344220

  14. Morphologic studies of lymphocyte nuclei in follicular and diffuse mixed small- and large-cell (lymphocytic-histiocytic) lymphoma.

    PubMed

    Dardick, I; Caldwell, D R; Moher, D; Jabi, M

    1988-08-01

    Twelve examples of mixed small- and large-cell lymphoma (eight follicular, one follicular and diffuse, and three diffuse) were investigated morphometrically using plastic-embedded tissue in order to study nuclear characteristics of lymphocyte populations in this form of non-Hodgkin's lymphoma (NHL) and to test morphologic bases for current NHL classification systems. This study illustrates that there are many inaccuracies, illusions, and misconceptions in the morphologic criteria currently used to classify mixed small- and large-cell lymphoma. A principal finding was that lymphocyte nuclear profiles in mixed-cell lymphomas tend to be smaller in size (P less than .005) and more irregular in shape (P = .0001) than the morphologically similar counterparts in germinal centers of lymph nodes with reactive hyperplasia. Intercase comparison of mixed small- and large-cell lymphomas revealed a considerable range of mean nuclear area values, some of which were within the size range of normal, small lymphocytes. At the magnifications used for morphometric assessment, a high proportion of lymphocyte nuclear profiles had shallow invaginations, but only a limited number of profiles (4% to 14%) had deep (cleaved) indentations. Contrary to current definitions for this subtype of NHL, lymphocytes with "small" nuclei had the same proportion of the nuclear diameter occupied by nuclear invaginations as lymphocytes with "large" nuclei and, in fact, mean nuclear invagination depth was shallower in "small" nuclei than in "large" nuclei. Furthermore, regardless of whether it is nuclear area or shape that is evaluated, lymphocytes in mixed-cell lymphoma do not separate into two populations of small-cleaved and large noncleaved cells. Morphometry reveals that only four of the 12 examples of mixed small- and large-cell lymphoma had a proportion of the lymphocytes in the size range of fully transformed germinal center lymphocytes that exceeded 25%, and none of the cases approached 50% even

  15. Absolute lymphocyte count as predictor of overall survival for patients with multiple myeloma treated with single autologous stem cell transplant.

    PubMed

    Jimenez-Zepeda, Victor H; Reece, Donna E; Trudel, Suzanne; Chen, Christine; Franke, Norman; Winter, Andrew; Tiedemann, Rodger; Kukreti, Vishal

    2015-01-01

    Post-autologous stem cell transplant (ASCT) studies have demonstrated that absolute lymphocyte count (ALC) recovery is associated with prolonged survival in some hematological malignancies. To assess whether ALC recovery has prognostic significance in patients with multiple myeloma (MM) undergoing single ASCT, we conducted a retrospective analysis of ALC at different time-points in patients with MM. In total 769 consecutive patients who underwent single ASCT from January 2000 to December 2007 were evaluated. An ALC of ≥ 1400 cells/μL at day 0, day 15 and day 90 significantly correlated with a better overall survival (OS) (median OS of 111, 90.7 and 84 months vs. 74, 70.5 and 65 months, respectively, p < 0.001 for all time-points). Multivariate analysis showed that ALC is an independent prognostic factor for OS after ASCT. In conclusion, ALC is a surrogate marker of the host immune system that correlates with better survival in patients with MM undergoing single ASCT. Immunomodulatory drugs, vaccination strategies and cellular therapies in MM should be investigated.

  16. Manufacturing of gene-modified cytotoxic T lymphocytes for autologous cellular therapy for lymphoma.

    PubMed

    Cooper, L J N; Ausubel, L; Gutierrez, M; Stephan, S; Shakeley, R; Olivares, S; Serrano, L M; Burton, L; Jensen, M C V; Forman, S J; DiGiusto, D L

    2006-01-01

    The production of therapeutic T-cell populations for adoptive immunotherapy of cancer requires extensive ex vivo cell processing, including the isolation or creation of Ag-specific T cells and their subsequent propagation to clinically relevant numbers. These procedures must be performed according to the principles of current good manufacturing practices (cGMP) for phase I clinical trials to ensure the identity, purity potency and safety of the cellular product. In this report we describe our approach to manufacturing and characterizing bulk populations of gene-modified autologous T cells for use in treating follicular lymphoma. PBMC from healthy donors, obtained after informed consent, were stimulated in vitro with Ab to CD3epsilon (OKT3) and recombinant human IL-2 and then electroporated with plasmid DNA containing a human CD19-specific chimeric Ag receptor (CAR) gene and HSV-1 thymidine kinase (TK) gene. Stably transfected cells were selected in cytocidal concentrations of hygromycin B over multiple 14-day stimulation culture cycles and then cryopreserved. Vials of cryopreserved/selected T cells were used to initiate T-cell expansion cultures to produce cell products for clinical infusion. These cultures were characterized for phenotype, function and suitability for use in adoptive immunotherapy studies. Our results demonstrate that bulk populations of gene-modified T cells derived from peripheral blood of healthy donors express CD19+ chimeric Ag receptor at low levels and can specifically lyse CD19+ target cells in vitro. These cells display a differentiated T-effector phenotype, are sensitive to ganciclovir-mediated killing and display a non-transformed phenotype. TCR Vbeta usage indicated that all populations tested were polyclonal. Ex vivo cell expansion from cryopreserved cell banks is sufficient to produce doses of between 5 x 10(9) and 1 x 10(10) cells/run. One of three transductions resulted in a population of cells that was not suitable for infusion but

  17. Adoptive immunotherapy with donor lymphocyte infusions and interleukin-2 after high-dose therapy and autologous stem cell rescue for multiple myeloma.

    PubMed

    Ballester, O F; Fang, T; Raptis, A; Ballester, G; Wilcox, P; Hiemenz, J; Tan, B

    2004-09-01

    In an attempt to induce a graft-versus-myeloma effect, we administered donor lymphocyte infusions (DLI) after high-dose therapy with autologous stem cell transplant rescue to seven patients with refractory or relapsed multiple myeloma. High-dose therapy consisted of melphalan, idarubicin and etoposide (days -9 to -6) followed by autologous stem cell infusion on day 0. DLI (five of seven donors with two or three HLA antigens mismatched) were administered on days +1, +5 and +10 along with IL-2 (from day +1 through +12). Six of the seven patients developed acute graft-versus-host disease (GVHD), which resolved spontaneously, coincidentally with autologous hematopoietic reconstitution. One patient failed to engraft and received a second autologous graft. One patient died from complications of a pulmonary hemorrhage after experiencing GVHD. With a minimum follow-up of 38 months, five patients remain without disease progression in complete remission or with minimal residual disease. In this setting, DLI/IL-2 is biologically active resulting in GVHD. A graft-versus-myeloma effect is suggested by the improved outcome of our small cohort of high-risk patients. The use of partially mismatched related donors makes this approach potentially available to nearly all patients.

  18. Adoptive T-cell Therapy Using Autologous Tumor-infiltrating Lymphocytes for Metastatic Melanoma: Current Status and Future Outlook

    PubMed Central

    Wu, Richard; Forget, Marie-Andree; Chacon, Jessica; Bernatchez, Chantale; Haymaker, Cara; Chen, Jie Qing; Hwu, Patrick; Radvanyi, Laszlo

    2012-01-01

    Immunotherapy using autologous T-cells has emerged to be a powerful treatment option for patients with metastatic melanoma. These include the adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL), T-cells transduced with high-affinity T-cell receptors (TCR) against major melanosomal tumor antigens, and T cells transduced with chimeric antigen receptors (CAR) composed of hybrid immunoglobulin light chains with endo-domains of T-cell signaling molecules. Among these and other options for T-cell therapy, TIL together with high-dose IL-2 has had the longest clinical history with multiple clinical trials in centers across the world consistently demonstrating durable clinical response rates near 50% or more. A distinct advantage of TIL therapy making it still the T-cell therapy of choice is the broad nature of the T-cell recognition against both defined as well as un-defined tumors antigens against all possible MHC, rather than the single specificity and limited MHC coverage of the newer TCR and CAR transduction technologies. In the past decade, significant inroads have been made in defining the phenotypes of T cells in TIL mediating tumor regression. CD8+ T cells are emerging to be critical, although the exact subset of CD8+ T cells exhibiting the highest clinical activity in terms of memory and effector markers is still controversial. We present a model in which both effector-memory and more differentiated effector T cells ultimately may need to cooperate to mediate long-term tumor control in responding patients. Although TIL therapy has shown great potential to treat metastatic melanoma, a number of issues have emerged that need to be addressed to bring it more into the mainstream of melanoma care. First, we have a reached the point where a pivotal phase II or phase III trials are needed in an attempt to gain regulatory approval of TIL as standard-of-care. Second, improvements in how we expand TIL for therapy are needed, that minimize the time the T

  19. Mesenchymal stromal cells improve early lymphocyte recovery and T cell reconstitution after autologous hematopoietic stem cell transplantation in patients with malignant lymphomas.

    PubMed

    Batorov, Egor V; Shevela, Ekaterina Ya; Tikhonova, Marina A; Batorova, Dariya S; Ushakova, Galina Yu; Sizikova, Svetlana A; Sergeevicheva, Vera V; Gilevich, Andrey V; Kryuchkova, Irina V; Ostanin, Alexandr A; Chernykh, Elena R

    2015-10-01

    Mesenchymal stromal cells (MSCs) possess a multi-lineage potential and immunoregulatory activities and provide a great potential in cell-based technologies. However, MSC suppressive activity raises concerns regarding the possible adverse effect of MSCs on the immune recovery. The influence of autologous MSC co-transplantation on recovery of T cell subsets in patients receiving autologous hematopoietic stem cell transplantation (AHSCT) for malignant lymphomas and multiple myeloma were characterized. Co-transplantation of MSCs improved lymphocyte recovery most effectively in patients with low input of hematopoietic stem cells or low absolute lymphocyte count in apheresis product. MSC co-transplantation improved early recovery of both memory and naive T cells with more prominent effect on naive CD4(+) T cells. Patients with MSC co-transplantation showed more effective reconstitution of recent thymic emigrants. These data indicate the positive impact of MSCs on immune reconstitution and note MSC co-transplantation is feasible to optimize the outcomes of AHSCT in malignant lymphoma patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Chronic lymphocytic leukemia B cells inhibit spontaneous Ig production by autologous bone marrow cells: role of CD95-CD95L interaction.

    PubMed

    Sampalo, A; Navas, G; Medina, F; Segundo, C; Cámara, C; Brieva, J A

    2000-11-01

    A variable degree of humoral immunodeficiency is a common feature in patients with B-cell chronic lymphocytic leukemia (B-CLL). The aim of this study was to explore the possibility that B-CLL cells play a direct role in this phenomenon. To this end, patients' bone marrow (BM) immunoglobulin (Ig)-secreting cells were cocultured with autologous purified B-CLL cells. The results show that tumoral cells inhibited the spontaneous IgG secretion by BM plasma cells, and this effect increased after PMA-induction of B-CLL cells. This inhibitory process was proportional to the number of B-CLL cells added and depended on cellular contact. Adhesion molecules did not appear to be involved in the cellular interaction, because the inclusion of blocking antibody to a variety of these proteins did not reverse the inhibitory phenomenon. However, the addition of monoclonal antibody that blocked the function of either CD95 or CD95L clearly reversed B-CLL cell inhibition on autologous BM plasma cells. These latter cells were shown to express CD95, and B-CLL cells contained detectable quantities of CD95L at the level of messenger RNA and protein. Annexin V-binding experiments revealed increased apoptosis of BM Ig-secreting cells when cocultured with autologous B-CLL cells. Finally, this inhibitory phenomenon might be operative in vivo because (a) there was a good correlation between the intensity of the inhibitory effect in vitro and the serum IgG level exhibited by every patient and (b) B-CLL cells also inhibited in vivo antigen-induced IgG-tetanus toxoid-secreting cells obtained from normal immunized subjects. Collectively, these data suggest that B-CLL cells inhibit autologous CD95-bearing Ig-secreting cells by the interaction with CD95L present on B-CLL cells and, hence, contribute to the state of humoral immunodeficiency that occurs in these patients.

  1. Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDC-MEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma.

    PubMed

    Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; van Baren, Nicolas; Lucas, Sophie; Kvistborg, Pia; Thielemans, Kris; Neyns, Bart

    2016-04-20

    Autologous monocyte-derived dendritic cells (DCs) electroporated with synthetic mRNA (TriMixDC-MEL) are immunogenic and have antitumor activity as a monotherapy in patients with pretreated advanced melanoma. Ipilimumab, an immunoglobulin G1 monoclonal antibody directed against the cytotoxic T-lymphocyte-associated protein 4 receptor that counteracts physiologic suppression of T-cell function, improves the overall survival of patients with advanced melanoma. This phase II study investigated the combination of TriMixDC-MEL and ipilimumab in patients with pretreated advanced melanoma. Thirty-nine patients were treated with TriMixDC-MEL (4 × 10(6) cells administered intradermally and 20 × 10(6) cells administered intravenously) plus ipilimumab (10 mg/kg every 3 weeks for a total of four administrations, followed by maintenance therapy every 12 weeks in patients who remained progression free). Six-month disease control rate according to the immune-related response criteria served as the primary end point. The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post-DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event. The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma. © 2016 by American Society of Clinical Oncology.

  2. B- and T-lymphocyte number and function in HIV(+)/HIV(-) lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation.

    PubMed

    Bertoli, Diego; Re, Alessandro; Chiarini, Marco; Sottini, Alessandra; Serana, Federico; Giustini, Viviana; Roccaro, Aldo M; Cattaneo, Chiara; Caimi, Luigi; Rossi, Giuseppe; Imberti, Luisa

    2016-12-01

    Combination of anti-retroviral therapy, high-dose chemotherapy (HCT) and autologous stem cell transplantation (ASCT) has led to an improved survival of HIV(+) non-Hodgkin lymphoma (NHL) patients. We compared T- and B-cell subset recovery and related capability to respond to in-vitro stimulation, as well as T-cell repertoire modifications of HIV(+) and HIV(-) NHL patients undergoing HCT and ASCT as first-line consolidation or salvage treatment, using sequential blood samples obtained before and at 3, 6, 12 and 24 months after ASCT. B lymphocyte recovery occurred earlier, reaching higher levels in HIV(+) patients as compared to HIV(-) patients and healthy controls; in particular, immature and naïve B cells were significantly higher in HIV(+) patients who had received rituximab in the pre-ASCT period. These lymphocytes equally responded to in-vitro stimulation. Newly produced T cells similarly increased in HIV(+) and HIV(-) NHL patients, but their levels remained constantly lower than in healthy controls. T lymphocytes showed a reduced proliferative capacity, but their repertoire was reassorted by the treatment. The functional and numeric B-cell recovery and the qualitative modifications of T-cell receptor repertoire may explain, at least in part, the success of this aggressive therapeutic approach in HIV(+) patients.

  3. B- and T-lymphocyte number and function in HIV+/HIV− lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation

    PubMed Central

    Bertoli, Diego; Re, Alessandro; Chiarini, Marco; Sottini, Alessandra; Serana, Federico; Giustini, Viviana; Roccaro, Aldo M.; Cattaneo, Chiara; Caimi, Luigi; Rossi, Giuseppe; Imberti, Luisa

    2016-01-01

    Combination of anti-retroviral therapy, high-dose chemotherapy (HCT) and autologous stem cell transplantation (ASCT) has led to an improved survival of HIV+ non-Hodgkin lymphoma (NHL) patients. We compared T- and B-cell subset recovery and related capability to respond to in-vitro stimulation, as well as T-cell repertoire modifications of HIV+ and HIV− NHL patients undergoing HCT and ASCT as first-line consolidation or salvage treatment, using sequential blood samples obtained before and at 3, 6, 12 and 24 months after ASCT. B lymphocyte recovery occurred earlier, reaching higher levels in HIV+ patients as compared to HIV− patients and healthy controls; in particular, immature and naïve B cells were significantly higher in HIV+ patients who had received rituximab in the pre-ASCT period. These lymphocytes equally responded to in-vitro stimulation. Newly produced T cells similarly increased in HIV+ and HIV− NHL patients, but their levels remained constantly lower than in healthy controls. T lymphocytes showed a reduced proliferative capacity, but their repertoire was reassorted by the treatment. The functional and numeric B-cell recovery and the qualitative modifications of T-cell receptor repertoire may explain, at least in part, the success of this aggressive therapeutic approach in HIV+ patients. PMID:27905485

  4. Immunoglobulin secretion in the human autologous mixed leukocyte reaction. Definition of a suppressor-amplifier circuit using monoclonal antibodies.

    PubMed

    Gatenby, P A; Kotzin, B L; Kansas, G S; Engleman, E G

    1982-07-01

    The induction of immunoglobulin (Ig) synthesis in the autologous MLR has an absolute requirement for helper/inducer (Leu-3) T cells, whereas an excess of suppressor/cytotoxic (leu-2) cells suppresses the response. The current study was an effort to assess the immunoregulatory potential to T cells activated in the autologous mixed-leukocyte response (MLR). T cells were cultured with autologous non-T cells for 8-9 d, after which the activated T cells were fractionated into subsets with monoclonal antibodies to T cell markers and HLA-DR antigen. Each population was co-cultured in fresh autologous MLR, and on the 8th day of culture, Ig-secreting cells were measured in a reverse hemolytic plaque assay. The results show that activated Leu-2, DR+ T cells, but neither Leu-2, DR- nor Leu-3 T cells, were at least 50 times more potent as suppressors of IgM and IgG synthesis than fresh Leu-2 cells alone. The activation of this Leu-2, DR+ subpopulation required Leu-3 cells in the primary culture. Furthermore, in the absence of Leu-2 cells in the second culture, little or no suppression was observed, suggesting that the Leu-2, DR+ cells act to amplify or induce suppressor effects of fresh Leu-2 cells. This indicates that at least two distinct subpopulations of Leu-2 cells are required for maximal suppression of an immune response, and that immunoregulatory circuits analogous to those described in the mouse exist in man.

  5. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes

    SciTech Connect

    Grimm, E.A.; Mazumder, A.; Zhang, H.Z.; Rosenberg, S.A.

    1982-06-01

    Activation in lectin-free interleukin 2 (IL-2) containing supernatants of peripheral blood mononuclear leukocytes (PBL) from cancer patients or normal individuals resulted in expression of cytotoxicity toward 20 of 21 natural killer (NK)-resistant fresh solid tumor cells tested. Fresh solid tumor cells were resistant to NK-mediated lysis in 10 autologous patients' PBL-tumor interactions, and from 17 normal individuals tested against 13 allogeneic fresh tumors. Culture of PBL in IL-2 for 2-3 d was required for the lymphokine activated killers (LAK) to be expressed, and lytic activity toward a variety of NK-resistant fresh and cultured tumor targets developed in parallel. Autologous IL-2 was functional in LAK activation, as well as interferon-depleted IL-2 preparations. Irradiation of responder PBL before culture in IL-2 prevented LAK development. Precursors of LAK were present in PBL depleted of adherent cells and in NK-void thoracic duct lymphocytes, suggesting that the precursor is neither a monocyte nor an NK cell. LAK effectors expressed the serologically defined T cell markers of OKT.3, Leu-1, and 4F2, but did not express the monocyte/NK marker OKM-1. Lysis of autologous fresh solid tumors by LAK from cancer patients' PBL was demonstrated in 85% of the patient-fresh tumor combinations. Our data present evidence that the LAK system is a phenomenon distinct from either NK or CTL systems that probably accounts for a large number of reported nonclassical cytotoxicities. The biological role of LAK cells is not yet known, although it is suggested that these cells may be functional in immune surveillance against human solid tumors.

  6. Limitations of G-banding Karyotype Analysis with Peripheral Lymphocytes in Diagnosing Mixed Gonadal Dysgenesis

    PubMed Central

    Takahashi, Ikuko; Miyamoto, Junko; Hasegawa, Yukihiro

    2006-01-01

    Mixed gonadal dysgenesis (MGD) is an abnormal sexual differentiation syndrome usually presenting with ambiguous genitalia. Karyotype analysis is one of the essential components in the diagnosis of MGD and is conventionally done with peripheral lymphocytes by the G-banding technique. It is speculated that this conventional karyotype analysis has limitations since there are often difference in gonadal tissue analysis. Here we present four cases of MGD, in which karyotype analysis were performed by peripheral lymphocytes fluorescence in situ hybridization (FISH), gonad fibroblasts FISH and gonad fibroblasts G-banding technique, in addition to the conventional peripheral lymphocytes G-banding technique. In Case 1, the percentage of the 45,X cell line in lymphocytes decreased after birth and detection of mosaicism could only be done by karyotype of gonads at 7 mo of age. In Case 2, FISH analysis with peripheral lymphocytes was more useful for detecting low frequency mosaicism. In all cases, phenotype of gonads and external genitalia were more consistent with karyotype of gonads than that of the peripheral lymphocytes G-banding technique. In conclusion, conventional G-banding karyotype analysis with peripheral lymphocytes has limitations in the diagnosis and evaluation of MGD. Karyotype analysis by FISH or by using gonads is useful for diagnosing MGD and understanding of the phenotype of gonadal tissue. PMID:24790330

  7. Surface immunoglobulins on blood lymphocytes of normal and immunodeficient persons studied by the mixed antiglobulin method

    PubMed Central

    Litwin, S. D.; Ochs, H.; Pollara, B.

    1973-01-01

    Surface immunoglobulins on human peripheral blood lymphocytes were investigated by the mixed antiglobulin technique—using the single layer mixed antiglobulin method as originally described (SLMA), and a modification employing a double layer of antibody (DLMA). Lymphocytes isolated from the blood of normal individuals had a mean of 7.8 and 18.4 per cent Ig + cells by the SLMA and DLMA techniques respectively. The DLMA data are similar to results obtained by other methods of detecting membrane Igs indicating that the mixed antiglobulin method is comparable in sensitivity. When the total numbers of Ig + cells, obtained by separate κ and λ testing, were compared with results obtained using single anti-light chain antisera, there was no significant difference, suggesting that most positive lymphocytes carry a single variety of light chain. Lymphocytes from the blood of seventeen patients with primary immunodeficiency were analysed. Four patients with variable immunodeficiency and four others with absent serum IgA all had normal surface Igs including α chains. All members of a family having an X-linked immunodeficiency had normal surface Igs including the affected members and a presumed carrier. Four cases of immunodeficiency associated with thymoma proved to have disparate findings. One patient exhibited a selective absence of μ antigens on the membranes of blood lymphocytes of over 2800 tested cells. Two other cases had normal surface Igs while a fourth patient, previously reported, lacked all surface Igs. PMID:4796276

  8. Induction of anti-leukemic cytotoxic T lymphocytes by fusion of patient-derived dendritic cells with autologous myeloblasts.

    PubMed

    Gong, Jianlin; Koido, Shigeo; Kato, Yoko; Tanaka, Yasuhiro; Chen, Dongshu; Jonas, Anna; Galinsky, Ilene; DeAngelo, Daniel; Avigan, David; Kufe, Donald; Stone, Richard

    2004-12-01

    Presentation of AML antigens by dendritic cells (DC) could potentially induce a T cell-mediated anti-leukemic immune response. In the present study, we generated DC from adherent (AD-DC) and non-adherent (NAD-DC) myeloblasts obtained from bone marrows of AML patients. Both cell populations displayed morphological, phenotypic and functional properties of DC. The functions of NAD-DC were compared to AD-DC that had been fused with autologous AML blasts (FC/AML). The FC/AML induced greater T cell proliferation and CTL activity against autologous AML blasts (9/10 cases) as compared to NAD-DC. FC/AML may thus represent a promising strategy for DC-based immunotherapy of patients with AML.

  9. Autologous hematopoietic stem cell transplantation in lymphoma patients is associated with a decrease in the double strand break repair capacity of peripheral blood lymphocytes

    PubMed Central

    Lacoste, Sandrine; Bhatia, Smita; Chen, Yanjun; Bhatia, Ravi; O’Connor, Timothy R.

    2017-01-01

    Patients who undergo autologous hematopoietic stem cell transplantation (aHCT) for treatment of a relapsed or refractory lymphoma are at risk of developing therapy related- myelodysplasia/acute myeloid leukemia (t-MDS/AML). Part of the risk likely resides in inherent interindividual differences in their DNA repair capacity (DRC), which is thought to influence the effect chemotherapeutic treatments have on the patient’s stem cells prior to aHCT. Measuring DRC involves identifying small differences in repair proficiency among individuals. Initially, we investigated the cell model in healthy individuals (primary lymphocytes and/or lymphoblastoid cell lines) that would be appropriate to measure genetically determined DRC using host-cell reactivation assays. We present evidence that interindividual differences in DRC double-strand break repair (by non-homologous end-joining [NHEJ] or single-strand annealing [SSA]) are better preserved in non-induced primary lymphocytes. In contrast, lymphocytes induced to proliferate are required to assay base excision (BER) or nucleotide excision repair (NER). We established that both NHEJ and SSA DRCs in lymphocytes of healthy individuals were inversely correlated with the age of the donor, indicating that DSB repair in lymphocytes is likely not a constant feature but rather something that decreases with age (~0.37% NHEJ DRC/year). To investigate the predictive value of pre-aHCT DRC on outcome in patients, we then applied the optimized assays to the analysis of primary lymphocytes from lymphoma patients and found that individuals who later developed t-MDS/AML (cases) were indistinguishable in their DRC from controls who never developed t-MDS/AML. However, when DRC was investigated shortly after aHCT in the same individuals (21.6 months later on average), aHCT patients (both cases and controls) showed a significant decrease in DSB repair measurements. The average decrease of 6.9% in NHEJ DRC observed among aHCT patients was much

  10. Expression Profiles of Cloned Channel Catfish (Ictalurus punctatus) Lymphoid Cell Lines and Mixed Lymphocyte Cultures

    USDA-ARS?s Scientific Manuscript database

    Clonal channel catfish lymphoid cell lines and mixed lymphocyte cultures (MLC) have proven extremely useful in examining immune responses at the cellular and molecular levels. To date clonal catfish cell lines and MLC have been biologically and phenotypically characterized using a variety of techniq...

  11. The importance of the number of transplanted cells with dipeptidyl peptidase-4 expression on the haematopoietic recovery and lymphocyte reconstitution in patients with multiple myeloma after autologous haematopoietic stem-cell transplantation.

    PubMed

    Kopinska, Anna; Krawczyk-Kulis, Małgorzata; Dziaczkowska-Suszek, Joanna; Bieszczad, Katarzyna; Jagoda, Krystyna; Kyrcz-Krzemien, Slawomira

    2017-06-01

    Autologous haematopoietic stem cell transplantation (AHSCT) remains recommended treatment in the first remission in multiple myeloma (MM). In earlier research it has been suggested that there is an influence of the expression of dipeptidyl peptidase-4 (CD26) on both the homing and lymphocyte reconstitution after AHSCT. The aim of the study is to investigate the influence of transplanted cells CD26+ on the haematopoietic recovery and lymphocyte reconstitution after AHSCT in MM. Forty eight patients with MM underwent AHSCT in our centre. Number of all CD26+ cells, CD26+ lymphocytes, CD26+ monocytes and CD26+ and CD34+ cells were measured in the harvested material. Number of lymphocyte's subpopulations (all lymphocytes CD3+, helpers, suppressors, natural killer (NK), cytotoxic NK and lymphocytes B) were measured in peripheral blood during regeneration after AHSCT. In both flow cytometry was used. On the basis of the analysis there was, as regards regeneration of haematopoietic cells after AHSCT, it was shown that a higher number of monocytes CD26+ improves the reconstitution of helper, suppressor and NK lymphocytes. A higher number of transplanted CD26+ lymphocytes accelerates the reconstitution of NK lymphocytes, whereas a higher number of all the cells CD26+ has a positive impact on the regeneration of cytotoxic NK lymphocytes. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  12. Primary cicatricial alopecia: Other lymphocytic primary cicatricial alopecias and neutrophilic and mixed primary cicatricial alopecias.

    PubMed

    Bolduc, Chantal; Sperling, Leonard C; Shapiro, Jerry

    2016-12-01

    Primary cicatricial alopecias can be frustrating for both patients and physicians. Proper diagnosis guides more successful management of these challenging conditions. Part II will cover the remaining lymphocytic primary cicatricial alopecias, which include pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa, and keratosis follicularis spinulosa decalvans. It will also discuss the neutrophilic and mixed primary cicatricial alopecias, namely folliculitis decalvans, dissecting cellulitis, folliculitis keloidalis, folliculitis (acne) necrotica, and erosive pustular dermatosis.

  13. [T-cell large granular lymphocyte leukemia after autologous peripheral blood stem cell transplantation for malignant lymphoma-report of three cases and a review of the literature].

    PubMed

    Kuroda, Hiroyuki; Sakurai, Tamaki; Yamada, Michiko; Abe, Tomoyuki; Fujii, Shigeyuki; Maeda, Masahiro; Kohda, Kyuhei; Hirayama, Yasuo; Jyomen, Wataru; Uemura, Naoki; Ono, Michihiro; Fujimi, Yuko; Iyama, Satoshi; Sato, Tsutomu; Kato, Junji

    2011-10-01

    There have been only three reports in the literature of T-cell large granular lymphocyte (T-LGL) leukemia occurring after autologous peripheral stem cell transplantation (APBSCT). We describe 3 patients in whom a transient monoclonal T-LGL developed after APBSCT for malignant lymphoma. Case 1: A 58-year-old man with peripheral T-cell lymphoma in second complete remission (CR) who underwent APBSCT. Case 2: A 51-year-old man with follicular lymphoma in second CR who underwent APBSCT. Case 3: A 65-year-old man with diffuse large B-cell lymphoma in second CR who underwent tandem APBSCT. One month after transplant, fever followed by the proliferation of CD8+/CD57+ T-LGL in peripheral blood occurred in all three cases. Because clonal rearrangements of the T-cell receptor were detected in peripheral blood samples, T-LGL leukemia was diagnosed. The first patient had episodes of Epstein-Barr virus viremia. The other patients suffered from cytomegalovirus colitis after APBSCT. These data show that T-LGL leukemia can occur after viral infection followed by APBSCT.

  14. Autologous stem cell transplantation as a first-line treatment strategy for chronic lymphocytic leukemia: a multicenter, randomized, controlled trial from the SFGM-TC and GFLLC.

    PubMed

    Sutton, Laurent; Chevret, Sylvie; Tournilhac, Olivier; Diviné, Marine; Leblond, Véronique; Corront, Bernadette; Leprêtre, Stéphane; Eghbali, Houchingue; Van Den Neste, Eric; Michallet, Mauricette; Maloisel, Frédéric; Bouabdallah, Krimo; Decaudin, Didier; Berthou, Christian; Brice, Pauline; Gonzalez, Hugo; Chapiro, Elise; Radford-Weiss, Isabelle; Leporrier, Nathalie; Maloum, Karim; Nguyen-Khac, Florence; Davi, Frédéric; Lejeune, Julie; Merle-Béral, Hélène; Leporrier, Michel

    2011-06-09

    Long-term responses have been reported after autologous stem cell transplantation (ASCT) for chronic lymphocytic leukemia (CLL). We conducted a prospective, randomized trial of ASCT in previously untreated CLL patients. We enrolled 241 patients < 66 years of age with Binet stage B or C CLL. They received 3 courses of mini-CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisone/prednisolone) and then 3 courses of fludarabine. Patients in complete response (CR) were then randomized to ASCT or observation, whereas the other patients were randomized to dexamethasone, high-dose aracytin, cisplatin (DHAP) salvage followed by either ASCT or 3 courses of fludarabine plus cyclophosphamide (FC). The primary end point was event-free survival (EFS). After up-front treatment, 105 patients entered CR and were randomized between ASCT (n = 52) and observation (n = 53); their respective 3-year EFS rates were 79.8% and 35.5%; the adjusted hazard ratio was 0.3 (95% CI: 0.1-0.7; P = .003). Ninety-four patients who did not enter CR were randomized between ASCT (n = 46) and FC (n = 48); their respective 3-year EFS rates were 48.9% and 44.4%, respectively; the adjusted hazard ratio was 1.7 (95% CI: 0.9-3.2; P = .13). No difference in overall survival was found between the 2 response subgroups. In young CLL patients in CR, ASCT consolidation markedly delayed disease progression. No difference was observed between ASCT and FC in patients requiring DHAP salvage.

  15. Neoplastic cells obtained from Hodgkin's disease are potent stimulators of human primary mixed lymphocyte cultures.

    PubMed

    Fisher, R I; Bostick-Bruton, F; Sauder, D N; Scala, G; Diehl, V

    1983-06-01

    Neoplastic cells obtained from the pleural effusion of a patient with Hodgkin's disease have been maintained in culture since 1978. These tumor cells have been shown to have the cytologic features, cytochemical staining, and cell surface markers of Reed-Sternberg cells. In this study we demonstrate that the cell line termed L428 is a potent stimulator of the primary human mixed lymphocyte reaction. Significant proliferation occurred when mononuclear leukocytes obtained from normal donors were stimulated with radiated L428 cells at responder:stimulator ratios varying from 200:1 to 20:1. Proliferative responses occurred between days 3 and 6 of the cultures with maximal proliferation on day 5. Under optimal culture conditions, mean net proliferative response of 14 normal donors was 51,000 +/- 10,600 dpm. The mixed lymphocyte response was totally blocked by concentrations of monoclonal anti-Ia antibody that had no effect on concanavalin A-induced proliferation. However, the mixed lymphocyte response was not blocked by an anti-K562 cell monoclonal antibody of the same immunoglobulin subclass that binds to the L428 cells. Antigen processing by responder monocytes or Ia-positive cells was not required for the MLC. When responder T cells from two normals were depleted of Ia-bearing cells and monocytes, the mixed lymphocyte reaction between the two normals was eliminated, yet the stimulation of each normal by the L428 cells was not reduced. The cells that proliferated in response to stimulation by the L428 cells were T cells, primarily of the helper subset. No IL 1 activity could be detected in concentrated supernatants of L428 cultures after stimulation of L428 cells by mitogens, phorbol esters, or muramyl dipeptide, or in the MLC. All of these cultures contain fetal calf serum. However, the L428 cells are capable of producing IL 1, because IL 1 was detected when the L428 cells were stimulated with LPS in the absence of fetal calf serum. These neoplastic cells, obtained

  16. Adoptive cell therapy with autologous tumor-infiltrating lymphocytes and high-dose interleukin-2 for metastatic melanoma: The surgeon’s perspective

    PubMed Central

    ZIPPEL, DOUGLAS B.; BESSER, MICHAL; SHAPIRA, RONI; BEN-NUN, ALON; GOITEIN, DAVID; DAVIDSON, TIMA; TREVES, ABRAHAM J.; MARKEL, GAL; SCHACHTER, JACOB; PAPA, MOSHE Z.

    2012-01-01

    Tumor-infiltrating lymphocytes (TILs) are produced by resecting tumor tissue and growing and expanding ex vivo large quantities of autologous T cells. Once the TILs are ready for infusion, the patient undergoes a non-myeloablative lympho-depleting course of chemotherapy and subsequent TIL infusion with high-dose bolus IL-2. This study reviews the surgical experience of the TIL program at the Chaim Sheba Cancer Research Center in Israel. Eligible patients underwent surgical consultation to determine what tumorectomy would be beneficial for harvesting appropriate tissue. Factors involved in the decision included tumor mass size, location and morbidity of the procedure. Between January 2006 and May 2010, 44 patients underwent 47 procedures of adoptive transfer of TILs. Three patients underwent the procedure twice for recurrence after initial good responses, including an additional surgical procedure to produce fresh tumor. Thirty-seven excisions were with general anesthesia and 10 were with local anesthesia. Of the 37 general anesthesia procedures, 27 were open procedures involving a thoracotomy, a laparotomy or dissection of a major lymph node basin. Ten used minimally invasive techniques such as thorascopy or laparoscopy. Tumorectomy sites included 18 lymph node metastasis, 13 subcutaneous nodules, 11 lung specimens and 5 abdominal visceral metastasis including 2 liver lesions. Surgical mortality and major morbidity was 0%. Minor morbidity included only wound complications. Maximal number of TILs were derived from lymph node specimens, while liver metastasis procured the fewest TILs. Adoptive cell transfer technology affords a maximal tumor response with minimal surgical morbidity in metastatic patients. PMID:22969990

  17. In vivo distribution of recombinant interleukin-2-activated autologous lymphocytes administered by intra-arterial infusion in patients with renal cell carcinoma

    SciTech Connect

    Morita, T.; Yonese, Y.; Minato, N.

    1987-03-01

    Recombinant interleukin-2 (RIL 2)-activated autologous peripheral blood lymphocytes (PBL) were infused directly into the renal arteries of 3 patients with renal cell carcinoma, and the in vivo distribution of the infused cells was investigated. In vitro studies to define the optimal culture conditions indicated that maximal lymphokine-activated killer activity was observed at around 10-20 days in culture, as judged by the cytotoxicity against fresh allogenic tumor cells. Maximal expression of the interleukin-2 receptor was also obtained at around 10 days. PBL collected by leukopheresis from each patient were thus cultured for 10 days with RIL 2, labeled with /sup 111/In-oxine, and then infused directly into the renal artery of the affected kidney via a catheter. Radioactivity in the infused side of the kidneys increased immediately after the infusion but then gradually decreased. Radioactivity in the lungs also rapidly increased within the first hour but then cleared gradually, whereas that in the liver and spleen tended to increase steadily. Nevertheless, at 48 hours, the infused side of the kidneys retained levels of radioactivity comparable to those seen in the liver and spleen, while the levels seen in the lungs were already close to background levels. The radioactivity in the areas corresponding to tumors remained consistently higher than that in the normal parts of the affected kidneys. The direct comparison of the radioactivity distribution pattern with the macroscopic appearance of surgically resected kidneys indicated that the accumulation of radioactivity was indeed selectively associated with the tumor tissues in the kidneys, except for a case in which the tumor was quite necrotic and hypovascular.

  18. Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by H-2K and H-2D serological regions of the murine major histocompatibility complex

    PubMed Central

    1975-01-01

    Splenic lymphocytes from four C57BL/10 congenic resistant mouse strains were sensitized in vitro with trinitrophenyl (TNP)-modified autologous spleen cellsmthe effector cells generated were incubated with 51-Cr- labeled unmodified or TNP-modified spleen or tumor target cells, and the percentage of specific lympholysis determined. The results obtained using syngeneic-, congenic-, recombinante, and allogeneic-modified target cells indicated that TNP modification of the target cells was a necessary but insufficient requirement for lympholysis. Intra-H-2 homology either between modified stimulating cells and modified target cells or between responding lymphocytes and modified target cells was also important in the specificity for lysis. Homology at the K serological region or at K plus I-A in the B10.A and B10BR strains, and at either the D serological region or at some other region (possibly K) in the B10.D2 and C57BL/10 strains were shown to be necessary in order to detect lympholysis. Experiments using (B10itimes C57BL/10)F1 responding lymphocytes sensitized and assayed with TNP-modified parental cells indicated that the homology required for lympholysis was between modified stimulating and modified target cellsmthe possibility is raised that histocompatibility antigens may serve in the autologous system as cell surface components which are modified by viruses or autoimmune complexes to form cell-bound modified-self antigens, which are particularly suited for cell-mediated immune reactions. Evidence is presented suggesting that H-2-linked Ir genes are expressed in the TNP- modified autologous cytotoxic system. These findings imply that the major histocompatibility complex can be functionally involved both in the response potential to and in the formation of new antigenic determinants involving modified-self components. PMID:47900

  19. Enhancement of murine mixed lymphocyte response by 1,1-dimethylhydrazine: characterization and possible mechanism.

    PubMed

    Tarr, M J; McKown, B J; Olsen, R G

    1988-01-01

    Treatment of mice with 1,1-dimethylhydrazine (UDMH) resulted in enhancement of the one-way mixed lymphocyte response (MLR); this effect was seen when both responder and stimulator mice were treated as well as when just the stimulator or just the responder mice were treated. Experiments in which splenocytes were exposed to UDMH in vitro indicated that exposure of the stimulator cells alone resulted in an enhanced MLR; exposure of the responder cells alone had no effect; and addition of UDMH to the assay (exposure of both populations) resulted in suppression of the response at higher concentrations. A possible mechanism for the enhancement of the MLR by UDMH was suggested by further experiments showing that UDMH inhibited prostaglandin E2 production by adherent splenocytes.

  20. Mixed lymphocyte reactivity against normal cells by splenic lymphocytes from tumor-bearing mice : ii. Studies of autoimmune-like activity in completely syngeneic and semisyngeneic systems.

    PubMed

    Devlin, R G; McCurdy, J D; Baronowsky, P E

    1974-01-01

    A possible consequence of an antilymphocytic autoimmune process would be serious impairment of an animal's ability to destroy tumor cells. One measure of autoimmune reactivity of this type would be the demonstration of cellular immune responsiveness by cells from tumor-bearing mice against syngeneic normal cells. These experiments demonstrate that spleen cells from mice bearing a lymphocytic leukemia of identical histocompatability type as the host mounted a vigorous immune response against normal syngeneic cells in a mixed lymphocyte reaction (MLR). Moreover, ascitic cells from leukemic mice responded significantly to normal syngeneic spleen cells in MLR's. The former reactions are usually much more vigorous than the responses of normal to malignant cells. These results are discussed in terms of the relationship between autoimmunity and neoplasia. Alternative explanations necessitated by the dangers involved in the interpretation of the immunology of transplantable tumors are considered.

  1. Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Confirmation of genetic control of response to trinitrophenyl-modified H-2 antigens by the use of anti-H-2 and anti-Ia antibodies

    PubMed Central

    1976-01-01

    Splenic lymphocytes from B10.A and B10.D2 mice were sensitized in vitro to trinitrophenyl (TNP)-modified autologous spleen cells. The effector cells generated were assayed in a 51Cr-release assay on TNP-modified syngeneic or congenic spleen target cells. Effector cells from B10.A donors lysed TNP-modified H-2Kk- but not H-2Dd-region products, whereas B10.D2 effectors reacted with modified products of both the H-2Kd and H- 2Dd regions. As an independent confirmation that this selective K-end lysis by B10.A effector cells is due to an H-2-linked responder cell defect (4), anti-H-2Kk but not anti-H-2Dd sera were shown to inhibit the lysis of B10.A-TNP targets by B10.A effectors. In contrast, anti-H- 2Dd sera inhibited the lysis of B10.A-TNP targets by B10.D2 effectors. Anti-Ia antibodies had no detectable effect on lysis. Anti-TNP-keyhole limpet hemocyanin sera blocked the lysis of TNP-modified targets, irrespective of whether the effector cells were directed against TNP- modified autologous H-2 products or H-2 alloantigens. These results independently verify that B10. A responding lymphocytes do not generate effector cells to TNP-modified H-2Dd products, whereas B10.D2 lymphocytes do (4), and suggest that some TNP groups are sterically close to (or part of) the serologically defined H-2K- and H-2D-region antigens. PMID:1244419

  2. Locoregional immunotherapy of malignant effusion from colorectal cancer using the streptococcal preparation OK-432 plus interleukin-2: induction of autologous tumor-reactive CD4+ Th1 killer lymphocytes.

    PubMed

    Yamaguchi, Y; Miyahara, E; Ohshita, A; Kawabuchi, Y; Ohta, K; Shimizu, K; Minami, K; Hihara, J; Sawamura, A; Toge, T

    2003-11-17

    In total, 16 patients with cytologically proven malignant effusion from colorectal cancer were treated by locoregional administration of the streptococcal preparation OK-432 alone or OK-432 plus the T-cell growth factor interleukin (IL)-2, and the action mechanism of the treatment was studied. A positive clinical response, showing a cytologic disappearance of cancer cells and decrease of effusion, was observed in nine of 11 (82%) patients treated with OK-432 alone and in all five patients treated with OK-432 plus IL-2. Flow cytometric analysis revealed that OK-432 plus IL-2 locally induced acute inflammation-like responses, including serial cellular infiltrations of granulocyte migration within a matter of hours, and activation of macrophages and T lymphocyte involvement within the following days, and that a predominant expansion of CD3+CD4+ lymphocytes (CD: cluster of differentiation) was induced by in vitro stimulation with IL-2 of locoregional cells after the OK-432 administration (OK/IL-2AK cells). The OK/IL-2AK cells produced tumour necrosis factor-alpha and interferon-gamma, but these cells did not produce IL-4 and IL-6. The OK/IL-2AK cells expressed potent killing activity against autologous tumour cells. This activity was abrogated by treatment of the lymphocytes with anti-CD3, -CD4, -TCRalphabeta antibody, and by the treatment of target cells with anti-human leukocyte antigen (HLA)-DR antibody. The OK/IL-2AK cells expressed Fas-L gene, and flow cytometric analysis demonstrated HLA-DR expression in approximately 75% of CEA+ or cytokeratin+ effusion cells. TCRVbeta gene analysis of the OK/IL-2AK cells showed an oligoclonal usage of TCRbeta20, which was also involved in the cytotoxic mechanism of the OK/IL-2AK cells. Single-strand conformational polymorphism analysis demonstrated the clonotypes for the TCRVbeta20 gene, and the CDR3s of the gene were sequenced. The clonotypic PCR using the TCRVbeta20-CDR3 sequences could detect the CDR3-identical TCRs in

  3. Human Ly9 (CD229) as novel tumor-associated antigen (TAA) in chronic lymphocytic leukemia (B-CLL) recognized by autologous CD8+ T cells.

    PubMed

    Bund, Dagmar; Mayr, Christine; Kofler, David M; Hallek, Michael; Wendtner, Clemens-Martin

    2006-07-01

    CD229, a cell-surface molecule being involved in cell adhesion, is overexpressed in B-CLL cells. In this study we wanted to explore whether CD229 might function as B-CLL-specific tumor-associated antigen (TAA). Autologous, CD229-specific HLA-A2-restricted T cells were identified using IFN-gamma-ELISPOT assays and HLA-A2/dimer-peptide staining after 4 weeks of in vitro culture. We were able to expand autologous T cells from 9/11 B-CLL patients using native B-CLL cells as antigen presenting cells (APCs) in 5 cases, whereas for 4 samples an autologous T-cell response could only be evoked by use of CD40L-stimulated B-CLL cells as APCs. The number of CD8+ T cells could be expanded during 4 weeks of in vitro culture with native or CD40L-activated B-CLL cells while the amount of specific T cells recognizing CD229 peptides bound to HLA-A2 dimers increased on average 12-fold (native CLL) and 13-fold (CD40L-activated CLL), respectively. Using IFN-gamma-ELISPOT assays we could demonstrate that the expanded T cells were able to secrete IFN-gamma upon recognition of the antigen. These T cells not only recognized HLA-A0201-binding CD229-derived peptides presented by T2 cells, but also CD229-overexpressing autologous B-CLL cells in an MHC-I-restricted manner. In summary, CD229 was shown to be naturally processed and presented as TAA in primary B-CLL cells, enabling the expansion of autologous tumor-specific T cells.

  4. Alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following alemtuzumab, fludarabine, and melphalan RIC HCT.

    PubMed

    Marsh, Rebecca A; Lane, Adam; Mehta, Parinda A; Neumeier, Lisa; Jodele, Sonata; Davies, Stella M; Filipovich, Alexandra H

    2016-01-28

    Reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT) with alemtuzumab, fludarabine, and melphalan is an effective approach for patients with nonmalignant disorders. Mixed chimerism and graft-versus-host-disease (GVHD) remain limitations on success. We hypothesized that higher levels of alemtuzumab at day 0 would result in a low risk of acute GVHD, a higher risk of mixed chimerism, and delayed early lymphocyte recovery and that alemtuzumab level thresholds for increased risks of these outcomes would be definable. We collected data from 105 patients to examine the influence of peritransplant alemtuzumab levels on acute GVHD, mixed chimerism, and lymphocyte recovery. The cumulative incidences of initial grades I-IV, II-IV, and III-IV acute GVHD in patients with alemtuzumab levels ≤0.15 vs ≥0.16 μg/mL were 68% vs 18% (P < .0001), 47% vs 13% (P = .0002), and 32% vs 8%, respectively (P = .005). The cumulative incidence of mixed chimerism in patients with an alemtuzumab level ≤0.15 μg/mL was 21%, vs 42% with levels of 0.16 to 4.35 μg/mL, and 100% with levels >4.35 μg/mL (P = .003). Patients with alemtuzumab levels ≤0.15 or 0.16 to 0.56 μg/mL had higher lymphocyte counts at day +30 and higher T-cell counts at day +100 compared with patients with levels ≥0.57 μg/mL (all P < .05). We conclude that peritransplant alemtuzumab levels impact acute GVHD, mixed chimerism, and lymphocyte recovery following RIC HCT with alemtuzumab, fludarabine, and melphalan. Precision dosing trials are warranted. We recommend a day 0 therapeutic range of 0.2 to 0.4 μg/mL. © 2016 by The American Society of Hematology.

  5. Mixed Chimerism, Lymphocyte Recovery and Evidence for Early Donor-Specific Unresponsiveness in Patients Receiving CKBMT to Induce Tolerance

    PubMed Central

    LoCascio, Samuel A.; Morokata, Tatsuaki; Chittenden, Meredith; Preffer, Frederic I.; Dombkowski, David M.; Andreola, Giovanna; Crisalli, Kerry; Kawai, Tatsuo; Saidman, Susan L.; Spitzer, Thomas R.; Tolkoff-Rubin, Nina; Cosimi, A. Benedict; Sachs, David H.; Sykes, Megan

    2011-01-01

    Background We have previously reported operational tolerance in patients receiving HLA-mismatched combined kidney and bone marrow transplantation (CKBMT). We now report on transient multilineage hematopoietic chimerism and lymphocyte recovery in five patients receiving a modified CKBMT protocol, and evidence for early donor-specific unresponsiveness in one of these patients. Methods Five patients with end-stage renal disease received CKBMT from HLA-mismatched, haploidentical living related donors following modified non-myeloablative conditioning. Polychromatic flow cytometry (FCM) was used to assess multilineage chimerism where evaluable and lymphocyte recovery post-transplant. Limiting dilution analysis was used to assess helper-T-lymphocyte reactivity to donor antigens. Results Transient multilineage mixed chimerism was observed in all patients but chimerism became undetectable by 2 weeks post-CKBMT. A marked decrease in T and B lymphocyte counts immediately following transplant was followed by gradual recovery. Initially recovering T cells were depleted of CD45RA+/CD45RO− “naïve-like” cells, which have shown strong recovery in two patients and CD4/CD8 ratios increased immediately following transplant but then declined markedly. NK cells were enriched in the peripheral blood of all patients following transplant. For Subject 2, a pre-transplant limiting dilution assay revealed T helper cells recognizing both donor and third-party PBMCs. However, the anti-donor response was completely undetectable by Day 24, while third-party reactivity persisted. Conclusion These results characterize the transient multilineage mixed hematopoietic chimerism and recovery of lymphocyte subsets in patients receiving a modified CKBMT protocol. The observations are relevant to the mechanisms of donor-specific tolerance in this patient group. PMID:21085064

  6. Values of apoptosis of lymphocytes and granulocytes in peripheral blood of Polish mixed-breed rabbits in the annual cycle.

    PubMed

    Tokarz-Deptuła, B; Hukowska-Szematowicz, B; Niedźwiedzka-Rystwej, P; Trzeciak-Ryczek, A; Deptuła, W

    2017-03-28

    The objective of the study was to determine values of apoptosis for peripheral blood lymphocytes and granulocytes, including dependency on the season of the year, in Polish mixed-breed rabbits and in mixed-breed rabbits with the addition of blood of meat-breed rabbits. The study was carried out in four seasons of the year (spring, summer, autumn, winter) involving 120 Polish mixed-breed rabbits - group I, and 120 Polish mixed-breed rabbits with addition of meat-breed rabbit blood - group II. Assessment of apoptosis of lymphocytes and granulocytes was performed using as FACScan cytometer by Becton Dickinson with FACSDiva software (USA), using as ApoFluor® Green Caspase reagent kit (MP Biomedicals, USA) to detect the activity of the total caspase pool 1, 3, 4, 5, 6, 7, 8, 9 in granulocytes and lymphocytes of rabbit peripheral blood. The results for apoptosis of lymphocytes and granulocytes in peripheral blood in the animals investigated (group I and II) were subjected to statistical analysis with the t'Student test at p=0.05. It was noted that, in rabbits from group I, the values for apoptosis of lymphocytes were the highest in winter and autumn (36.02% and 31.24%, respectively), and the lowest in spring and summer (26.73% and 22.72%, respectively), whereas in the case of granulocytes the highest values were in summer and spring (14.69% and 12.95%, respectively), and the lowest in winter and autumn (8.16% and 8.57%, respectively). In mixed-breed rabbits with the addition of meat-breed blood (group II), the values for apoptosis of lympocytes were the highest in spring (29.13%), and the lowest in summer (25.43%); whereas in the case of granulocytes the highest values were in summer and spring (14.0% and 11.15%, respectively), and the lowest in autumn and winter (7.46% and 7.64%, respectively).

  7. Cytokine Release Patterns in Mixed Lymphocyte Culture (MLC) of T-Cells with Dendritic Cells (DC) Generated from AML Blasts Contribute to Predict anti-Leukaemic T-Cell Reactions and Patients' Response to Immunotherapy.

    PubMed

    Fischbacher, Dorothea; Merle, Marion; Liepert, Anja; Grabrucker, Christine; Kroell, Tanja; Kremser, Andreas; Dreyßig, Julia; Freudenreich, Markus; Schuster, Friedhelm; Borkhardt, Arndt; Kraemer, Doris; Koehne, Claus-Henning; Kolb, Hans-Jochem; Schmid, Christoph; Schmetzer, Helga Maria

    To enlighten interactions between autologous, allogeneic or T-cells from patients after stem cell transplantation with leukaemia-derived-dendritic-cells containing dendritic cells or blast containing mononuclear cells (n = 21, respectively), we determined cytokine-concentrations (interleukin 2, 4, 6, 10, tumor-necrosis-factor-α, interferon-γ) in supernatants of mixed-lymphocyte-culture and in serum (n = 16) of 20 patients with acute myeloid leukaemia and three patients with myelodysplastic syndromes by cytometric-bead-assay. We correlated our data with lytic capabilities of stimulated T-cells in a fluorolysis-assay and clinical data: Dendritic-cell-/mononuclear-cell-stimulation of T-cells resulted in increased cytokine-levels in culture-medium compared to serum. There were no significant differences between cytokine-patterns of cases with/without lytic T-cell-activity, response to immunotherapy (stem cell transplantation/donor-lymphocyte-infusion) or graft-versus-host-disease. However, some predictive cytokine-cut-off-values for antileukaemic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease could be defined. Cytokine-profiles alone, without functional assays, are no useful tool to predict antileukaemic T-cell-function, although they can indicate lytic T-cell-activity, patients' response to immunotherapy and graft-versus-host-disease.

  8. T-lymphocyte induction of human monocyte angiotensin converting enzyme (ACE) is not dependent upon T-lymphocyte proliferation

    SciTech Connect

    Vuk-Pavlovic, Z.; Rohrbach, M.S.

    1986-03-05

    Human peripheral blood monocytes cultured in serum free media for seven days show a basal activity of the ectoenzyme ACE which is augmented 2-3 times by the presence of autologous peripheral blood T-lymphocytes. Since these two cell types are also involved in autologous mixed lymphocyte reaction if serum is present, the authors compared the ability of T-cells to stimulate ACE activity in the presence or absence of proliferation (measured by /sup 3/H-thymidine incorporation). By the seventh day, cultures with 5% AB/sup +/ serum showed significant increase in proliferation but no increase in ACE activity compared to the serum free cultures. Even higher proliferation rate achieved by co-culturing T-lymphocytes with allogeneic monocytes did not increase ACE production; on the contrary, ACE activity remained at the basal level. Monocyte-T-cell co-cultures stimulated with increasing concentrations of ConA or PHA showed dose dependent increases in proliferation but parallel decreases in ACE activity. Addition of soluble antigen (Candida albicans) also enhanced proliferation but not ACE synthesis. They conclude that T-lymphocyte induction of monocyte ACE is a result of cooperation between autologous cells which is not dependent upon T-cell proliferation.

  9. Chromosomal aberrations in peripheral blood lymphocytes exposed to a mixed beam of low energy neutrons and gamma radiation.

    PubMed

    Wojcik, A; Obe, G; Lisowska, H; Czub, J; Nievaart, V; Moss, R; Huiskamp, R; Sauerwein, W

    2012-09-01

    Cells exposed to thermal neutrons are simultaneously damaged by radiations with high and low linear energy transfer (LET). A question relevant for the assessment of risk of exposure to a mixed beam is whether the biological effect of both radiation types is additive or synergistic. The aim of the present investigation was to calculate whether the high and low LET components of a thermal neutron field interact when damaging cells. Human peripheral blood lymphocytes were exposed to neutrons from the HB11 beam at the Institute for Energy and Transport, Petten, Netherlands, in a 37 °C water phantom at varying depths, where the mix of high and low LET beam components differs. Chromosomal aberrations were analysed and the relative biological effectiveness (RBE) values as well as the expected contributions of protons and photons to the aberration yield were calculated based on a dose response of aberrations in lymphocytes exposed to (60)Co gamma radiation. The RBE for 10 dicentrics per 100 cells was 3 for mixed beam and 7.2 for protons. For 20 dicentrics per 100 cells the respective values were 2.4 and 5.8. Within the limitations of the experimental setup the results indicate that for this endpoint there is no synergism between the high and low LET radiations.

  10. A pilot study of autologous cancer cell vaccination and cellular immunotherapy using anti-CD3 stimulated lymphocytes in patients with recurrent grade III/IV astrocytoma.

    PubMed

    Wood, G W; Holladay, F P; Turner, T; Wang, Y Y; Chiga, M

    2000-06-01

    The study objectives were to determine; (1) whether activated T cells could be generated from peripheral blood of patients immunized with their own cancer cells, (2) whether adoptive transfer of the activated T cells to patients had toxic effects and (3) whether the infused cells produced clinical responses. Study patients had recurrent, surgically accessible grade III/IV astrocytomas. The patients were tapered off steroids after total surgical resection and immunized with autologous cancer cells plus Bacillus, Calmette and Guerin (BCG). Peripheral blood mononuclear cells were activated with anti-CD3, expanded with interleukin-2 (IL-2) and reinfused to patients. The number of activated T cells that was given back to patients varied between 10(10) and 10(11). Side effects that were observed following immunization and adoptive cell transfer included mainly transient flu-like symptoms. One patient's tumor partially regressed, but there was no effect on survival. Two other patients' tumors regressed, and the patients are apparently disease-free more than 5 and 4 years later. The other six patients' tumors were apparently unaffected by the treatment. Patient age, tumor grade and CD4/CD8 composition of infused cells were positively correlated with clinical responses. Cellular immunotherapy is feasible and is associated with minimal toxicity. Additional appropriately controlled studies will be required to determine whether cellular immunotherapy could be used as a treatment for central nervous system malignancy. Additional studies also will be required to determine the underlying immunological mechanisms.

  11. Complex aberrations in lymphocytes exposed to mixed beams of (241)Am alpha particles and X-rays.

    PubMed

    Staaf, Elina; Deperas-Kaminska, Marta; Brehwens, Karl; Haghdoost, Siamak; Czub, Joanna; Wojcik, Andrzej

    2013-08-30

    Modern radiotherapy treatment modalities are associated with undesired out-of-field exposure to complex mixed beams of high and low energy transfer (LET) radiation that can give rise to secondary cancers. The biological effectiveness of mixed beams is not known. The aim of the investigation was the analysis of chromosomal damage in human peripheral blood lymphocytes (PBL) exposed to a mixed beam of X-rays and alpha particles. Using a dedicated exposure facility PBL were exposed to increasing doses of alpha particles (from (241)Am), X-rays and a mixture of both. Chromosomal aberrations were analysed in chromosomes 2, 8 and 14 using fluorescence in situ hybridisation. The found and expected frequencies of simple and complex aberrations were compared. Simple aberrations showed linear dose-response relationships with doses. A higher than expected frequency of simple aberrations was only observed after the highest mixed beam dose. A linear-quadratic dose response curve for complex aberrations was observed after mixed-beam exposure. Higher than expected frequencies of complex aberrations were observed for the two highest doses. Both the linear-quadratic dose-response relationship and the calculation of expected frequencies show that exposure of PBL to mixed beams of high and low LET radiation leads to a higher than expected frequency of complex-type aberrations. Because chromosomal changes are associated with cancer induction this result may imply that the cancer risk of exposure to mixed beams in radiation oncology may be higher than expected based on the additive action of the individual dose components.

  12. Serine protease detection in mixed lymphocyte cultures: a histochemical method for possible prediction of graft-versus-host disease.

    PubMed

    Maiocchi, M A; Nano, R; Capelli, E; Bonfichi, M; Alessandrino, E P; Bernasconi, P

    1998-08-01

    Graft-versus-host disease (GVHD) presents an important complication of allogeneic bone marrow transplantation. A method to predict GVHD might be the analysis of cytotoxic T lymphocyte precursors, but the technique requires the use of radioactive elements not suitable in all laboratories. Serine esterase (SE) activity was studied by a cytochemical method in donor-recipient mixed lymphocytes cultures (MLC). Twelve patients, affected by acute or chronic leukemia, and 20 donors were studied. MLC incubated with and without growth factors (IGF-1 or IL-2), were analyzed. The relationship between positivity of MLC and GVHD in transplanted patients was evaluated. The data obtained showed that the percentage of SE positive cells was higher in MLC compared to negative control MLC. The highest percentage of positive cells was found in the MLC obtained from unrelated subjects. These results show that serine protease expression in MLC may be a predictive marker of GVHD and could be used as an additional early test associated with cytotoxicity.

  13. Micronuclei in human peripheral blood lymphocytes exposed to mixed beams of X-rays and alpha particles.

    PubMed

    Staaf, Elina; Brehwens, Karl; Haghdoost, Siamak; Nievaart, Sander; Pachnerova-Brabcova, Katerina; Czub, Joanna; Braziewicz, Janusz; Wojcik, Andrzej

    2012-08-01

    The purpose of this study was to analyse the cytogenetic effect of exposing human peripheral blood lymphocytes (PBL) to a mixed beam of alpha particles and X-rays. Whole blood collected from one donor was exposed to different doses of alpha particles ((241)Am), X-rays and a combination of both. All exposures were carried out at 37 °C. Three independent experiments were performed. Micronuclei (MN) in binucleated PBL were scored as the endpoint. Moreover, the size of MN was measured. The results show that exposure of PBL to a mixed beam of high and low linear energy transfer radiation led to significantly higher than expected frequencies of MN. The measurement of MN size did not reveal any differences between the effect of alpha particles and mixed beam. In conclusion, a combined exposure of PBL to alpha particles and X-rays leads to a synergistic effect as measured by the frequency of MN. From the analysis of MN distributions, we conclude that the increase was due to an impaired repair of X-ray-induced DNA damage.

  14. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF

    PubMed Central

    Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

    2017-01-01

    Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients. PMID:28798878

  15. Treatment of Knee Osteochondral Lesions Using a Novel Clot of Autologous Plasma Rich in Growth Factors Mixed with Healthy Hyaline Cartilage Chips and Intra-Articular Injection of PRGF.

    PubMed

    Cugat, Ramón; Alentorn-Geli, Eduard; Steinbacher, Gilbert; Álvarez-Díaz, Pedro; Cuscó, Xavier; Seijas, Roberto; Barastegui, David; Navarro, Jordi; Laiz, Patricia; García-Balletbó, Montserrat

    2017-01-01

    Knee cartilage or osteochondral lesions are common and challenging injuries. To date, most symptomatic lesions warrant surgical treatment. We present two cases of patients with knee osteochondral defects treated with a one-step surgical procedure consisting of an autologous-based matrix composed of healthy hyaline cartilage chips, mixed plasma poor-rich in platelets clot, and plasma rich in growth factors (PRGF). Both patients returned to playing soccer at the preinjury activity level and demonstrated excellent defect filling in both magnetic resonance imaging and second-look arthroscopy (in one of them). The use of a clot of autologous plasma poor in platelets with healthy hyaline cartilage chips and intra-articular injection of plasma rich in platelets is an effective, easy, and cheap option to treat knee cartilage injuries in young and athletic patients.

  16. A comparison of irradiation and mitomycin as blocking agents in the mixed lymphocyte reaction

    SciTech Connect

    Anderson, R.E.; Pogue, L.; Troup, G.M.; Standefer, J.C.

    1984-05-01

    In comparison with administration of mitomycin, lethal irradiation (2,000 rad) of the stimulator cells in a one-way mixed leukocyte culture results in a reduced response due at least in part to the release of inhibitory materials by the irradiated cells. These inhibitory molecules may be partially removed by washing and possess differential reactivity with respect to phytohemagglutinin, concanavalin A, lipopolysaccharide, and pokeweed mitogen.

  17. Improved renal allograft survival using the mixed lymphocyte culture for selection of nonidentical living related donors.

    PubMed

    Riggio, R R; Saal, S D; Katz, E B; Tapia, L; White, R; Chami, J; Sheigh, J S; Sullivan, J F; Stenzel, K H; Stubenbord, W T; Whitsell, J C; Rubin, A L

    1975-01-01

    Our results concur with earlier published work, by other groups, showing that LRD-recipient pairs with low MLC stimulation usually have better and more prolonged graft success than do those with higher stimulation. Specific HL-A compatibilities or incompatibilities did not seem to affect these results, nor did the presence of an increased number of common loci, short of increasing the apparent chromosome compatibility. The presence of pre-transplant cytotoxic antibodies, in patients with a high MI, however, may unfavorably affect the LRD transplant. The overall results of our LRD transplant experience is shown in Figure 1, and superimposed upon Figure 2, is the current extrapolation of data showing MLC stimulation and haplotype success. Thus, it appears that graft survival may be improved and more closely approach the levels seen in a full-house, diplotype match, by using the MLC results in considering patients for transplantation. Not all patients with a high MLC, however, (see table) reject their grafts and it is impossible to predict pre-transplant who will develop specific allograft enhancement. Before the MI becomes a specific criteria for transplant selection, additional studies of patient stimulation in MLC should be done. Suppression of stimulation by donor cells in autologous serum, as compared to the response to unrelated controls, might provide pre-transplant clues to the presence of enhancing factors. Such studies could provide an index that would be more meaningful than the MI in AB sera alone. Since overall results from both our series and from the Transplant Registry continue to indicate better long term graft survival for LRD than for cadaver transplants, and since the evidence suggests that a successful transplant offers a patient a better quality of life, as well as decreased morbidity and mortality compared to concomitant time spent on hemodialysis, continued LRD transplants with high MI is warranted in some circumstances with the patient

  18. THE IN VITRO TRANSFORMATION OF FROZEN-STORED LYMPHOCYTES IN THE MIXED LYMPHOCYTE REACTION AND IN CULTURE WITH PHYTOHEMAGGLUTININ AND SPECIFIC ANTIGENS

    PubMed Central

    Mangi, Richard J.; Mardiney, Michael R.

    1970-01-01

    We have investigated the in vitro transformation of lymphocytes that have been frozen and stored at low temperatures. Cells frozen at different times and stored for various times do transform in a reproducible manner when placed in culture with PHA or as one population of the two-way or the one-way MLR. When frozen-stored lymphocytes are cultured with specific antigen or as both partners in the MLR the response is minimal. The freezing process destroys neutrophils, and the remaining population transforms in a manner similar to cultures of purified lymphocytes. Practical aspects of the technique are discussed and we have suggested possible practical applications for future investigation. PMID:5523965

  19. Human T-Cell Clones from Autoimmune Thyroid Glands: Specific Recognition of Autologous Thyroid Cells

    NASA Astrophysics Data System (ADS)

    Londei, Marco; Bottazzo, G. Franco; Feldmann, Marc

    1985-04-01

    The thyroid glands of patients with autoimmune diseases such as Graves' disease and certain forms of goiter contain infiltrating activated T lymphocytes and, unlike cells of normal glands, the epithelial follicular cells strongly express histocompatability antigens of the HLA-DR type. In a study of such autoimmune disorders, the infiltrating T cells from the thyroid glands of two patients with Graves' disease were cloned in mitogen-free interleukin-2 (T-cell growth factor). The clones were expanded and their specificity was tested. Three types of clones were found. One group, of T4 phenotype, specifically recognized autologous thyroid cells. Another, also of T4 phenotype, recognized autologous thyroid or blood cells and thus responded positively in the autologous mixed lymphocyte reaction. Other clones derived from cells that were activated in vivo were of no known specificity. These clones provide a model of a human autoimmune disease and their analysis should clarify mechanisms of pathogenesis and provide clues to abrogating these undesirable immune responses.

  20. Induction of PD-L1 on monocytes: a new mechanism by which IVIg inhibits mixed lymphocyte reactions.

    PubMed

    Padet, Lauriane; Loubaki, Lionel; Bazin, Renée

    2014-09-01

    Allograft rejection and graft-versus-host disease (GvHD) are frequent complications following solid organ or stem cell transplantation in which T cell activation plays a central role. Despite the development of new immunosuppressive drugs that improve the success rate of transplantation, allograft survival continues to be a challenge. Recently, intravenous immunoglobulin (IVIg) has been proposed as prophylaxis and post-transplant treatment to reduce acute rejection episodes. IVIg is a therapeutic agent that is known to down-modulate T cell functions in patients with autoimmune disorders. To test the hypothesis that this immunomodulatory effect could be beneficial in the context of transplantation, we used mixed lymphocyte reactions (MLR) as an in vitro model of allograft rejection and GvHD. Our results show that IVIg strongly inhibits the MLR as evaluated by IL-2 secretion, a well-known marker of T cell activation. IVIg also modulates the secretion of other pro-(IL-6, IFN-γ) and anti-inflammatory (IL-1RA) cytokines. More importantly, we show that IVIg induces monocytes with a CD80(low) PD-L1(high) phenotype and that blockade of PD-L1 partially abrogates the inhibitory effect of IVIg. We have thus identified a new mechanism by which IVIg inhibits T cell functions in the context of transplantation, supporting the potential usefulness of IVIg in the prevention or treatment of graft rejection and GvHD.

  1. Lymphocyte function in myasthenia gravis.

    PubMed Central

    Kawanami, S; Kanaide, A; Itoyama, Y; Kuroiwa, Y

    1979-01-01

    Mitogen-induced blastoid transformation of peripheral blood lymphocytes from patients with myasthenia gravis was studied using a microplate culture technique and evaluated with 3H-thymidine incorporation. It was found that both phytohaemagglutinin and pokeweed mitogen responses decreased significantly in patients with myasthenia gravis. In myasthenic crisis, indices of stimulation by phytohaemagglutination became very low. The autologous plasma neither inhibited nor facilitated mitogenic responses of lymphocytes. The decreased mitogen responsiveness of lymphocytes suggests that part of the T lymphocyte function is subnormal in myasthenia. PMID:490180

  2. Mixed lymphocyte reactivity against normal cells by splenic lymphocytes from tumor-bearing mice : I. Studies of vigorous immune responsiveness induced in f(1) mice by parental strain tumor cells.

    PubMed

    Devlin, R G; McCurdy, J D; Baronowsky, P E

    1974-01-01

    The establishment of an intimate connection between autoimmunity and neoplasia would require the demonstration of an experimentally induced, tumor-dependent autoimmune process. For this reason, we have studied cellular immune reactions of mice bearing a transplantable leukemia (L1210). Spleen cells from hybrid BDF(1) mice bearing the L1210 tumor (BDFt) reacted vigorously in mixed lymphocyte culture with mitomycin-treated, normal spleen cells from mice of the parental strain from which the L1210 tumor was derived (DBA/2). Spleen cells from nontumor-bearing BDF(1) mice reacted only weakly with these parental cells. The BDFt cells likewise did not respond when cultured with mitomycin-treated spleen cells from the other parental strain (C57B1/6). The vigorous mixed lymphocyte reaction (MLR) by BDFt cells against normal parental cells of the same strain as the tumor was not due to a double exposure of the reacting cells to histocompatibility antigens shared by tumor cells and normal parental cells. The response of cells from tumor-bearing F(1) mice against normal parental cells seen in these experiments suggests the possibility of the induction of an autoimmune-like process against host lymphocytes by spleen cells from leukemic mice. Theoretically such a phenomenon would considerably reduce an animal's ability to mount an immune attack against malignant cells.

  3. Mixed T Lymphocyte Chimerism after Allogeneic Hematopoietic Transplantation Is Predictive for Relapse of Acute Myeloid Leukemia and Myelodysplastic Syndromes.

    PubMed

    Lee, Hans C; Saliba, Rima M; Rondon, Gabriela; Chen, Julianne; Charafeddine, Yasmeen; Medeiros, L Jeffrey; Alatrash, Gheath; Andersson, Borje S; Popat, Uday; Kebriaei, Partow; Ciurea, Stefan; Oran, Betul; Shpall, Elizabeth; Champlin, Richard

    2015-11-01

    Chimerism testing after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represents a promising tool for predicting disease relapse, although its precise role in this setting remains unclear. We investigated the predictive value of T lymphocyte chimerism analysis at 90 to 120 days after allo-HSCT in 378 patients with AML/MDS who underwent busulfan/fludarabine-based myeloablative preparative regimens. Of 265 (70%) patients with available T lymphocyte chimerism data, 43% of patients in first or second complete remission (CR1/CR2) at the time of transplantation had complete (100%) donor T lymphocytes at day +90 to +120 compared with 60% of patients in the non-CR1/CR2 cohort (P = .005). In CR1/CR2 patients, donor T lymphocyte chimerism ≤ 85% at day +90 to +120 was associated with a higher frequency of 3-year disease progression (29%; 95% confidence interval [CI], 18% to 46% versus 15%; 95% CI, 9% to 23%; hazard ratio [HR], 2.1; P = .04). However, in the more advanced, non-CR1/CR2 cohort, mixed T lymphocyte chimerism was not associated with relapse (37%; 95% CI, 20% to 66% versus 34%; 95% CI, 25% to 47%; HR, 1.3; P = .60). These findings demonstrate that early T lymphocyte chimerism testing at day +90 to +120 is a useful approach for predicting AML/MDS disease recurrence in patients in CR1/CR2 at the time of transplantation.

  4. Comparison of microtitre plates with flat-bottomed and round-bottomed wells for mixed lymphocyte culture (MLC).

    PubMed

    Herva, E

    1977-04-01

    To compare microtitre plates with flat-bottomed and round-bottomed wells and to standardize a method for mixed lymphocyte culture (MLC), the effects of cell number, culture time, 3H-thymidine concentration and labelling time were studied. On both plates, allogeneic cells induced increased RNA synthesis beginning at about 30 hours and increased DNA synthesis beginning at about 50 hours, if suitable cell numbers were used. On plates with flat-bottomed wells, 1.5 X 10(5) responding and stimulating cells per well had near-exponential growth on day four and five, often through day six; on plates with round-bottomed wells the corresponding cell number was 0.25-1.0 (optimally 0.5) X 10(5). Near these cell numbers, the response depended closely on the number of responding cells. On plates with flat-bottomed wells, stimulating cells had a dose-dependent effect on the response, whereas on plates with round-bottomed wells, increasing the stimulating cell dose did not consistently strengthen the response. Both plate types proved suitable for MLC experiments; plates with round-bottomed wells have the obvious advantage of requiring smaller cell numbers. 3H-thymidine (spec, act 2000 mCi/mmol) self-suppressed its incorporation, which increased only slightly or even decreased if labelling time exceeded 12-18 hours. Relative responses remained virtually unaltered, however, with 3H-concentrations of 0.5 and 2.0 micronCi/ml and with labelling times of 8 and 24 hours.

  5. Mechanism of augmentation of the antibody response in vitro by 2-mercaptoethanol in murine lymphocytes. II. A major role of the mixed disulfide between 2-mercaptoethanol and cysteine.

    PubMed

    Ohmori, H; Yamamoto, I

    1983-07-01

    Five thiol compounds including 2-mercaptoethanol (2-ME) were examined for their augmenting effects on in vitro antibody response to sheep erythrocytes. Three compounds were effective with the following order of activity; 2-ME greater than dithiothreitol greater than cysteamine. Glutathione and thioglycollate failed to enhance the response. The same order or effectiveness was seen in the stimulation of [35S]cystine uptake by murine lymphocytes by these thiols. Murine lymphocytes took up cysteine five to six times more rapidly than cystine. It is, however, unlikely that 2-ME stimulation of cystine uptake is solely due to the reduction of cystine into cysteine, because 2-ME was still stimulatory after free thiol groups had disappeared in the medium containing 2-ME and [35S]cystine. The mixed disulfide of cysteine with 2-ME (Cys-2-ME) was found to be an only product after free thiols had been oxidized. [35S]Cys-2-ME was taken up by the lymphocytes with a comparable rate to cysteine via a transport system common to that of leucine and phenylalanine. Cysteine was, however, transported via a different route. It was observed that Cys-2-ME was readily metabolized to cysteine and glutathione after the uptake. Cys-2-ME added to cystine-free RPMI 1640 medium could support the antibody response as efficiently as cystine plus 2-ME. These observations strongly suggest that 2-Me stimulates cystine uptake and, therefore, enhances the antibody response through the formation of the mixed disulfide with cysteine.

  6. Mechanism of augmentation of the antibody response in vitro by 2-mercaptoethanol in murine lymphocytes. II. A major role of the mixed disulfide between 2-mercaptoethanol and cysteine

    SciTech Connect

    Ohmori, H.; Yamamoto, I.

    1983-07-01

    Five thiol compounds including 2-mercaptoethanol (2-ME) were examined for their augmenting effects on in vitro antibody response to sheep erythrocytes. Three compounds were effective with the following order of activity; 2-ME greater than dithiothreitol greater than cysteamine. Glutathione and thioglycollate failed to enhance the response. The same order or effectiveness was seen in the stimulation of (/sup 35/S)cystine uptake by murine lymphocytes by these thiols. Murine lymphocytes took up cysteine five to six times more rapidly than cystine. It is, however, unlikely that 2-ME stimulation of cystine uptake is solely due to the reduction of cystine into cysteine, because 2-ME was still stimulatory after free thiol groups had disappeared in the medium containing 2-ME and (/sup 35/S)cystine. The mixed disulfide of cysteine with 2-ME (Cys-2-ME) was found to be an only product after free thiols had been oxidized. (/sup 35/S)Cys-2-ME was taken up by the lymphocytes with a comparable rate to cysteine via a transport system common to that of leucine and phenylalanine. Cysteine was, however, transported via a different route. It was observed that Cys-2-ME was readily metabolized to cysteine and glutathione after the uptake. Cys-2-ME added to cystine-free RPMI 1640 medium could support the antibody response as efficiently as cystine plus 2-ME. These observations strongly suggest that 2-Me stimulates cystine uptake and, therefore, enhances the antibody response through the formation of the mixed disulfide with cysteine.

  7. Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2017-01-06

    B-Cell Prolymphocytic Leukemia; Hypodiploidy; Loss of Chromosome 17p; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; t(14;16); t(4;14); T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  8. B-Lymphocyte stimulator (BLyS) up-regulation in mixed cryoglobulinaemia syndrome and hepatitis-C virus infection.

    PubMed

    Fabris, M; Quartuccio, L; Sacco, S; De Marchi, G; Pozzato, G; Mazzaro, C; Ferraccioli, G; Migone, T S; De Vita, S

    2007-01-01

    To investigate the role of B-Lymphocyte stimulator (BLyS) in mixed cryoglobulinaemia syndrome (MCsn), a systemic vasculitis associated with a high risk to develop lymphoma, since BLyS up-regulation may favour both autoimmunity and lymphoproliferation. BLyS serum levels were analysed by enzyme-linked immunosorbent assay (positive when >0.85 ng/ml) in 66 patients with MCsn, 54 (81.8%) of whom were positive for hepatitis-C virus (HCV) infection. Thirty-three HCV-positive patients without MCsn were also studied. Patients were compared with 48 healthy blood donors (HBDs). BLyS modifications after antiviral therapy were also studied. A significantly higher frequency of BLyS serum positivity was detected both in MCsn patients and in HCV-positive patients without MCsn (37.9 and 30.3%, respectively) when compared with HBDs (4.2%) (P < 0.0001 vs MCsn and P = 0.0026 vs HCV-positive patients without MCsn, respectively). BLyS appeared significantly higher in MCsn (3.70 +/- 2.97 ng/ml) than in HCV-positive patients without MCsn (1.56 +/- 0.63 ng/ml; P = 0.0044). BLyS expression did not correlate with rheumatoid factor levels, cryoglobulin levels or definite MCsn-related systemic features. High BLyS levels were significantly associated only with MCsn-related overt lymphoproliferative disorder. Finally, antiviral treatment significantly increased BLyS levels, independently from HCV-RNA negativization. However, BLyS normalization was noticed after both HCV-RNA negativization and suspension of antiviral therapy by preliminary data. BLyS is up-regulated and may play a pathogenetic role in a fraction of patients with MCsn, similarly to other autoimmune diseases. HCV infection likely represents the early event leading to BLyS up-regulation in this setting. BLyS is up-regulated during antiviral treatment. Overall, these data provide new insights for BLyS and virus-related autoimmunity, lymphoproliferation and possible treatment strategies.

  9. T cell receptor variable β gene repertoire in liver and peripheral blood lymphocytes of chronically hepatitis C virus-infected patients with and without mixed cryoglobulinaemia

    PubMed Central

    Russi, S; Lauletta, G; Serviddio, G; Sansonno, S; Conteduca, V; Sansonno, L; De Re, V; Sansonno, D

    2013-01-01

    To characterize the repertoire of T lymphocytes in chronically hepatitis C virus (HCV)-infected patients with and without mixed cryoglobulinaemia (MC). T cell receptor (TCR) variable (V) β clonalities in portal tracts isolated from liver biopsy sections with a laser capture microdissection technique in 30 HCV-positive MC patients were studied by size spectratyping. Complementarity-determining region 3 (CDR3) profiles of liver-infiltrating lymphocytes (LIL) were also compared with those circulating in the blood. The representative results of TCR Vβ by CDR3 were also obtained from liver tissues and peripheral blood lymphocytes (PBL) of 21 chronically HCV-infected patients without MC. LIL were highly restricted, with evidence of TCR Vβ clonotypic expansions in 23 of 30 (77%) and in 15 of 21 (71%) MC and non-MC patients, respectively. The blood compartment contained TCR Vβ expanded clones in 19 (63%) MC and 12 (57%) non-MC patients. The occurrence of LIL clonalities was detected irrespective of the degree of liver damage or circulating viral load, whereas it correlated positively with higher levels of intrahepatic HCV RNA. These results support the notion that TCR Vβ repertoire is clonally expanded in HCV-related MC with features comparable to those found in chronically HCV-infected patients without MC. PMID:23574322

  10. The immunosuppressive compound 2-acetyl-4-tetrahydroxybutyl imidazole inhibits the allogeneic mixed lymphocyte reaction by sequestration of a recirculating subpopulation of T cells.

    PubMed Central

    Bradbury, M G; Doherty, K V; Parish, C R; Lyons, A B

    1996-01-01

    2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole (THI) is an immunosuppressive component of caramel food colouring that causes lymphopenia in mice and rats by an unknown mechanism. In this study we investigated some of the affects of THI on the murine immune system. Initially we showed that splenic T lymphocytes from mice treated with 50 mg/l THI in their drinking water were unable to launch a mixed lymphocyte reaction (MLR) against allogeneic stimulator cells, and had decreased and delayed interleukin-2 (IL-2) production. However, these T cells exhibited a normal proliferative response to concanavalin A (Con A), immobilized anti-CD3 monoclonal antibody (mAb) and anti-CD3 plus anti-CD28 mAb. Furthermore, the MLR response could be restored by the addition of IL-2 to the MLR culture. Homing studies using intravenous injection of fluorescence-labelled splenocytes showed that THI treatment decreased absolute numbers of labelled T and B lymphocytes in the blood and the spleen. Furthermore, these labelled cells reappeared in the blood and the spleen when mice were taken off THI, indicating that lymphocyte recirculation and splenic homing were modified reversibly by THI treatment. Cessation of THI treatment also resulted in a rapid reappearance of MLR responsiveness in the spleen, indicating that THI treatment does not functionally impair recirculating T cells. Collectively these data are compatible with the concept that a rapidly recirculating population of T cells, which produce IL-2 in an allogeneic MLR, are lost from the blood and spleen following THI treatment, and are sequestered in other, yet to be identified, tissues. PMID:8666439

  11. Autologous and Allogeneic Equine Mesenchymal Stem Cells Exhibit Equivalent Immunomodulatory Properties In Vitro.

    PubMed

    Colbath, Aimée C; Dow, Steven W; Phillips, Jennifer N; McIlwraith, C Wayne; Goodrich, Laurie R

    2017-04-01

    The use of allogeneic bone marrow-derived mesenchymal stem cells (BMDMSCs) may provide an effective alternative to autologous BMDMSCs for treatment of equine musculoskeletal injuries. However, concerns have been raised regarding the potential safety and effectiveness of allogeneic BMDMSCs. We conducted studies to assess the immunological properties of equine allogeneic BMDMSCs compared with those of autologous BMDMSCs. For assessment of inherent immunogenicity, the relative ability of allogeneic and autologous BMDMSCs to stimulate spontaneous proliferation of equine lymphocytes was compared. The immunosuppressive activity of the two cell types was evaluated by adding autologous or allogeneic BMDMSCs to activated lymphocytes and assessing suppression of lymphocyte proliferation and IFNγ production. Fifty-six allogeneic and 12 autologous combinations were evaluated. Studies were also done to elucidate mechanisms by which equine mesenchymal stem cells (MSCs) suppress lymphocyte function. Potential mechanisms evaluated included production of prostaglandin E2 (PGE2), nitric oxide, transforming growth factor-beta, and indoleamine 2,3-dioxygenase. We found that autologous and allogeneic BMDMSCs both induced mild but equivalent levels of spontaneous lymphocyte activation in vitro. In in vitro assays assessing the ability of BMDMSCs to suppress activated lymphocytes, both allogeneic and autologous BMDMSCs suppressed T cell proliferation and IFNγ production to an equal degree. The primary mechanism of equine BMDMSC suppression of T cells was mediated by PGE2. We concluded that allogeneic and autologous BMDMSCs are equivalent in terms of their immunomodulatory properties, and stimulated peripheral blood mononuclear cells appear to trigger the immunosuppressive properties of MSCs. Therefore, both cell types appear to have equal potency in modulating inflammatory processes related to acute or chronic musculoskeletal injuries in the horse.

  12. Autologous Therapies in Dermatology

    PubMed Central

    Kumar, Sumir; Mahajan, Bharat Bhushan; Singh, Amarbir

    2014-01-01

    Autologous therapy is a therapeutic intervention that uses an individual’s cells or tissues, which are processed outside the body, and reintroduced into the donor. This emerging field presently represents a mere tip of the iceberg with much knowledge and applications yet to be discovered. It, being free from risks of hypersensitivity reactions and transmission of infectious agents, has been explored in various fields, such as plastic surgery, orthopedics, and dermatology. This review article focuses on various forms of autologous therapies used in dermatology along with their applications and mechanisms of action. PMID:25584137

  13. Cryptococcal meningitis post autologous stem cell transplantation.

    PubMed

    Chaaban, S; Wheat, L J; Assi, M

    2014-06-01

    Disseminated Cryptococcus disease occurs in patients with defective T-cell immunity. Cryptococcal meningitis following autologous stem cell transplant (SCT) has been described previously in only 1 patient, 4 months post SCT and while off antifungal prophylaxis. We present a unique case of Cryptococcus meningitis pre-engraftment after autologous SCT, while the patient was receiving fluconazole prophylaxis. A 41-year-old man with non-Hodgkin's lymphoma underwent autologous SCT. Post-transplant prophylaxis consisted of fluconazole 400 mg daily, levofloxacin 500 mg daily, and acyclovir 800 mg twice daily. On day 9 post transplant, he developed fever and headache. Peripheral white blood cell count (WBC) was 700/μL. Magnetic resonance imaging of the brain showed lesions consistent with meningoencephalitis. Cerebrospinal fluid (CSF) analysis revealed a WBC of 39 with 77% lymphocytes, protein 63, glucose 38, CSF pressure 20.5 cmH2 O, and a positive cryptococcal antigen. CSF culture confirmed Cryptococcus neoformans. The patient was treated with liposomal amphotericin B 5 mg/kg intravenously daily, and flucytosine 37.5 mg/kg orally every 6 h. He was switched to fluconazole 400 mg daily after 3 weeks of amphotericin therapy, with sterilization of the CSF with negative CSFCryptococcus antigen and negative CSF culture. Review of the literature revealed 9 cases of cryptococcal disease in recipients of SCT. Median time of onset was 64 days post transplant. Only 3 meningitis cases were described; 2 of them after allogeneic SCT. Fungal prophylaxis with fluconazole post autologous SCT is recommended at least through engraftment, and for up to 100 days in high-risk patients. A high index of suspicion is needed to diagnose and treat opportunistic infections, especially in the face of immunosuppression and despite adequate prophylaxis. Infection is usually fatal without treatment, thus prompt diagnosis and therapy might be life saving.

  14. Cannabinoids inhibit T-cells via cannabinoid receptor 2 in an in vitro assay for graft rejection, the mixed lymphocyte reaction.

    PubMed

    Robinson, Rebecca Hartzell; Meissler, Joseph J; Breslow-Deckman, Jessica M; Gaughan, John; Adler, Martin W; Eisenstein, Toby K

    2013-12-01

    Cannabinoids are known to have anti-inflammatory and immunomodulatory properties. Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes. This study tested the capacity of Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ(9)-THC significantly suppressed the MLR in a dose dependent fashion. The inhibition was via CB2, as suppression could be blocked by pretreatment with a CB2-selective antagonist, but not by a CB1 antagonist, and none of the compounds suppressed the MLR when splenocytes from CB2 deficient mice were used. The CB2 agonists were shown to act directly on T-cells, as exposure of CD3(+) cells to these compounds completely inhibited their action in a reconstituted MLR. Further, the CB2-selective agonists completely inhibited proliferation of purified T-cells activated by anti-CD3 and anti-CD28 antibodies. T-cell function was decreased by the CB2 agonists, as an ELISA of MLR culture supernatants revealed IL-2 release was significantly decreased in the cannabinoid treated cells. Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients.

  15. Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an in vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction

    PubMed Central

    Robinson, Rebecca Hartzell; Meissler, Joseph J.; Breslow-Deckman, Jessica M.; Gaughan, John; Adler, Martin W.; Eisenstein, Toby K.

    2013-01-01

    Cannabinoids are known to have anti-inflammatory and immunomodulatory properties. Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes. This study tested the capacity of Δ9-tetrahydrocannabinol (Δ9-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ9-THC significantly suppressed the MLR in a dose dependent fashion. The inhibition was via CB2, as suppression could be blocked by pretreatment with a CB2-selective antagonist, but not by a CB1 antagonist, and none of the compounds suppressed the MLR when splenocytes from CB2 deficient mice were used. The CB2 agonists were shown to act directly on T-cells, as exposure of CD3+ cells to these compounds completely inhibited their action in a reconstituted MLR. Further, the CB2-selective agonists completely inhibited proliferation of purified T-cells activated by anti-CD3 and anti-CD28 antibodies. T-cell function was decreased by the CB2 agonists, as an ELISA of MLR culture supernatants revealed IL-2 release was significantly decreased in the cannabinoid treated cells. Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients. PMID:23824763

  16. Transplantation in chronic lymphocytic leukemia.

    PubMed

    Le Dieu, Rifca; Gribben, John G

    2007-02-01

    Although there have been no randomized trials comparing the outcome of stem cell transplantation (SCT) with standard chemotherapy for patients with chronic lymphocytic leukemia (CLL), increasingly, both autologous and allogeneic SCT approaches are being explored in this disease. Clinical trials have demonstrated that these approaches are feasible, but current data suggest that autologous transplantation is not curative and myeloablative SCT, although offering the potential for cure, is associated with high treatment-related mortality. There is a clear demonstration of a graft-versus-leukemia effect in CLL, with encouraging results seen after SCT with reduced-intensity conditioning. Because no other treatment modalities are currently capable of improving survival in this disease, the treatment of choice for younger patients with poor-risk CLL may well be SCT, but continued enrollment of appropriate patients into well-designed clinical trials is vital to compare advances in SCT with the advances occurring in chemoimmunotherapy in CLL.

  17. Autologous Costochondral Microtia Reconstruction.

    PubMed

    Patel, Sapna A; Bhrany, Amit D; Murakami, Craig S; Sie, Kathleen C Y

    2016-04-01

    Reconstruction with autologous costochondral cartilage is one of the mainstays of surgical management of congenital microtia. We review the literature, present our current technique for microtia reconstruction with autologous costochondral graft, and discuss the evolution of our technique over the past 20 years. We aim to minimize donor site morbidity and create the most durable and natural appearing ear possible using a stacked framework to augment the antihelical fold and antitragal-tragal complex. Assessment of outcomes is challenging due to the paucity of available objective measures with which to evaluate aesthetic outcomes. Various instruments are used to assess outcomes, but none is universally accepted as the standard. The challenges we continue to face are humbling, but ongoing work on tissue engineering, application of 3D models, and use of validated questionnaires can help us get closer to achieving a maximal aesthetic outcome. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  18. Anaphylactic reaction after autologous blood transfusion: A case report and review of the literature

    PubMed Central

    Kumar, Shailendra; Goyal, Keshav; Dubey, Surya; Bindra, Ashish; Kedia, Shweta

    2015-01-01

    Autologous blood transfusion as a cause of intraoperative anaphylaxis is very rare. We encountered one such life-threatening event in a 72-year-old patient undergoing laminectomy and pedicle screw fixation. The probable cause identified was the floseal mixed autologous blood transfusion. Review of literature has been done, and measures to avoid such an event in the future are discussed. PMID:25972952

  19. Transfer of antigenic macromolecules from macrophages to lymphocytes

    PubMed Central

    Bona, C.; Anteunis, A.; Robineaux, R.; Astesano, A.

    1972-01-01

    In an in vitro autologous system, studies were carried out on the transfer of either biosynthetically-labelled [14C]Salmonella enteritidis endotoxin or [125I]Maia squinado haemocyanin from macrophages to lymphocytes. When cultured 1 hour in vitro, lymphocytes adhered to autologous macrophages, forming lymphocyte-macrophage islands (LMI). Quantitative data obtained from stained thick sections showed that 1.8 per cent of the lymphocytes had adhered to macrophages with ingested [14C]endotoxin while 0.6 per cent of the lymphocytes adhered to macrophages with ingested [125I]haemocyanin. The presence of antigen macromolecules was observed mainly within lymphocytes adhering to macrophages with ingested antigens, i.e. at the level of LMI. On the other hand, autoradiography carried out on the same thick sections, showed that 0.20 per cent of the lymphocyte population in LMI possess silver grains. High resolution autoradiographic pictures of thin sections, showed a peculiar localization of silver grains in LMI lymphocytes: about 80 per cent of the radioactivity was found within lymphocytic nuclei and the remainder either on the cellular membrane or free in the cytoplasm. The disappearance of radioactivity from the LMI-located macrophage membranes (where lymphocytes contain silver grains) as well as the regular inhibition of antigen transfer occurring after pronase treatment of the macrophage which contained ingested antigen, strongly suggest that antigen bound to macrophage membrane was transferred to lymphocytes. As pretreatment of lymphocytes with anti-Ig serum resulted in regular inhibition of antigen transfer, it appears that the Ig receptors of lymphocyte membranes play an important role in the transfer mechanism. Combined technique, i.e. autoradiography and the peroxidase method for revealing Ig bound to lymphocyte membranes, showed that silver grains occurred only within lymphocytes displaying peroxidase-positive membrane. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5 PMID

  20. Mechanical and chemical characteristics of an autologous glue.

    PubMed

    De Somer, Filip; Delanghe, Joris; Somers, Pamela; Debrouwere, Maarten; Van Nooten, Guido

    2008-09-15

    The study evaluates the mechanical and chemical characteristics of autologous surgical glue made by mixing ultrafiltered plasma with glutaraldehyde (GTA). Human albumin 200 g/L mixed with different concentrations of GTA (25, 50, 75, or 100 g/L) was used as a single protein set-up for testing tensile strength, elasticity, and rate of crosslinking. Subsequently, ultrafiltered canine or human plasma to obtain autologous glue replaced human albumin. BioGlue, a surgical glue, and Tissucol Duo, a fibrin sealant, were used as controls. Tensile strength of human albumin 200 g/L mixed with 75 g/L GTA is 825 +/- 109 N versus 672 +/- 167 N for BioGlue. Ultrafiltered canine plasma showed a maximum tensile strength of 634 +/- 137 N when mixed with GTA 75 g/L. For human plasma, the maximum tensile strength of 436 +/- 69 N was reached after mixing with GTA 25 g/L. Autologous glue had a higher elasticity of 144 +/- 66 N versus 322 +/- 104 N for BioGlue at maximum load. Autologous glues for vascular repair can be easily prepared out of the patient's plasma. The optimal characteristics, compared to BioGlue, are obtained for ultrafiltered canine and human plasma by mixing with a GTA concentration of 50-75 g/L and 25-50 g/L, respectively. The autologous glue will exert less tensile strength than BioGlue but has a better compliance. In case where no plasma can obtained from the patient, mixing human albumin 200 g/L with GTA 75 g/L can be an alternative to BioGlue.

  1. Tumor-Infiltrating Lymphocyte Therapy and Neoantigens.

    PubMed

    Robbins, Paul F

    The adoptive cell transfer (ACT) of autologous tumor-infiltrating lymphocytes has been shown to be effective at mediating tumor regression in more than half of patients with metastatic melanoma and in mediating long-term complete regression in approximately one fourth of all patients with this cancer. The success of this approach in patients with cholangiocarcinoma and colon cancer supports efforts to expand ACT therapies to treatment of patients bearing a wide array of cancer types. Recent improvements in deep sequencing of the patient cancers, combined with extensive immunological testing of autologous tumor-infiltrating lymphocytes, indicate that T cells targeting epitopes arising from nonsynonymous somatic mutations, termed neoantigens, play important roles in mediating many of the effective cancer immunotherapies seen in response to ACT.

  2. A receptor for 'self' on lymphocytes.

    PubMed Central

    Kolb, H

    1977-01-01

    A large population of lymphocytes is able to form rosettes with syngeneic, allogeneic or closely related xenogeneic erythrocytes. Similar results were found with spleen cells from mice, rats and rabbits. The highest numbers were found in mice where up to 30% of lymphocytes bound autologous erythrocytes. Rosette formation is probably due to stereospecific cell surface receptors since erythrocytes of distant xenogeneic origin were not recognized. Rosette forming cells do not seem to be restricted to the B-cell or T-cell compartment since mouse thymus cells as well as spleen cells from congenitally athymic (nude) mice bound erythrocytes to a similar degree. PMID:73501

  3. Cell-mediated lympholysis of N-(3-nitro-4-hydroxy-5-iodophenylacetyl)- beta-anaylglycylglycyl-modified autologous lymphocytes. Effector cell specificity to modified cell surface components controlled by the H-2K and H-2D serological regions of the murine major histocompatibility complex

    PubMed Central

    1976-01-01

    Splenic lymphocytes from four C57BL/10 congenic mouse strains were sensitized in vitro to N(-3-nitro-4-hydroxy-5-iodophenylacetyl)-beta- alanylglycylglycyl-(N) modified autologous lymphoctyes. The effector cells generated after 5 days of culture were assayed on a series of either N-modified phytohemagglutinin-stimulated spleen cells or N- modified tumor cells. The results indicated inall cases that both N modification of the targets and H-2 homology between the modified stimulating and target cells are required for lysis to occur. In each case the effector cells were found to lyse N-modified target cells only when there was homology at either or both ends of the major histocompatibility complex (MHC) between the stimulator and target cells. B10.BR lysed targets sharing alleles at K (or K plus I-A) and/or at D. B10.A effector cell specificity was mapped to K (or K plus I-A) and/or the D half of the MHC (D or D plus I-C and/or S). The two regions of specificity determined for B10.D2 effector cells were D (or D plus S plus I-C) and a region not including D of the MHC. C57BL/10 effector cells lysed N-modified targets only if there was target cell H- 2 homology at K, I-A, and I-B or at the D serological region. As in the trinitrophenyl (TNP) system (6) B10.BR and B10.A effector cells lysed targets sharing K end H-2 serological regions greater than target cells sharing D-end serological regions. The C57BL/10 effector cells were shown to react to the K end greater than the D end, which differed from the equal reactivity seen in the TNP system for this strain. The data are consistent with the hypothesis that the antigen recognized by the effector cell includes an altered H-2 serological cell surface product. That the reaction is not "hapten specific" and the H-2 homology is required only for effector:target cell interaction was excluded by the use of two F1 combinations in which lysis of only N-modified target cells sharing the H-2 haplotype with the stimulating parental

  4. Is Autologous or Heterologous Pericardium Better for Valvuloplasty? A Comparative Study of Calcification Propensity

    PubMed Central

    Jiang, Wen-Jian; Cui, Yong-Chao; Li, Jin-Hua; Zhang, Xiu-Hui; Ding, Huan-Huan; Zhang, Hong-Jia

    2015-01-01

    Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium. We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at 4 months in group C, and at 6 months in group D. Each collected sample was divided into 2 parts, one for calcium-content measurement by means of atomic-absorption spectroscopy, and one for morphologic and histopathologic examinations. When compared with the autologous pericardium, calcium levels in the heterologous pericardium were higher in groups B, C, and D (P <0.0001, P <0.0002, and P <0.0006, respectively). As embedding time increased, calcium levels in the heterologous pericardium increased faster than those in the autologous, especially in group D. Disorganized arrangements of collagenous fibers, marked calculus, and ossification were seen in the heterologous pericardium. Inflammatory cells—mainly lymphocytes and small numbers of macrophages—infiltrated the heterologous pericardium. The autologous pericardium showed a stronger ability to resist calcification. Our results indicate that autologous pericardium might be a relatively better choice for valvuloplasty. PMID:26175630

  5. Is autologous or heterologous pericardium better for valvuloplasty? A comparative study of calcification propensity.

    PubMed

    Jiang, Wen-Jian; Cui, Yong-Chao; Li, Jin-Hua; Zhang, Xiu-Hui; Ding, Huan-Huan; Lai, Yong-Qiang; Zhang, Hong-Jia

    2015-06-01

    Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium. We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at 4 months in group C, and at 6 months in group D. Each collected sample was divided into 2 parts, one for calcium-content measurement by means of atomic-absorption spectroscopy, and one for morphologic and histopathologic examinations. When compared with the autologous pericardium, calcium levels in the heterologous pericardium were higher in groups B, C, and D (P <0.0001, P <0.0002, and P <0.0006, respectively). As embedding time increased, calcium levels in the heterologous pericardium increased faster than those in the autologous, especially in group D. Disorganized arrangements of collagenous fibers, marked calculus, and ossification were seen in the heterologous pericardium. Inflammatory cells-mainly lymphocytes and small numbers of macrophages-infiltrated the heterologous pericardium. The autologous pericardium showed a stronger ability to resist calcification. Our results indicate that autologous pericardium might be a relatively better choice for valvuloplasty.

  6. CD8+ Lymphocytes Can Control HIV Infection in vitro by Suppressing Virus Replication

    NASA Astrophysics Data System (ADS)

    Walker, Christopher M.; Moody, Dewey J.; Stites, Daniel P.; Levy, Jay A.

    1986-12-01

    Lymphocytes bearing the CD8 marker were shown to suppress replication of human immunodeficiency virus (HIV) in peripheral blood mononuclear cells. The effect was dose-dependent and most apparent with autologous lymphocytes; it did not appear to be mediated by a cytotoxic response. This suppression of HIV replication could be demonstrated by the addition of CD8+ cells at the initiation of virus production as well as after several weeks of virus replication by cultured cells. The observations suggest a potential approach to therapy in which autologous CD8 lymphocytes could be administered to individuals to inhibit HIV replication and perhaps progression of disease.

  7. Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia: mixed T-cell chimerism is associated with high relapse risk and inferior survival.

    PubMed

    Thompson, Philip A; Stingo, Francesco; Keating, Michael J; Wierda, William G; O'Brien, Susan M; Estrov, Zeev; Ledesma, Celina; Rezvani, Katayoun; Qazilbash, Muzaffar; Shah, Nina; Parmar, Simrit; Popat, Uday; Anderlini, Paolo; Yago, Nieto; Ciurea, Stefan O; Kebriaei, Partow; Champlin, Richard; Shpall, Elizabeth J; Hosing, Chitra M

    2017-05-01

    There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P < 0·001] and survival (HR 1·66, P = 0·05 and HR 2·17, P < 0·001), independent of baseline patient characteristics, and a lower rate of grade II-IV acute graft-versus-host disease (GHVD) (16% vs. 52%, P < 0·001). Thirty-three patients were treated with immunomodulation for relapse post-alloSCT (immunosuppression withdrawal, n = 6, donor lymphocyte infusion, n = 27); 17 achieved complete response (CR), which predicted superior PFS (53 months vs. 10 months, P < 0·001) and survival (117 months vs. 30 months, P = 0·006). Relapsed patients with mixed chimerism had inferior response to immunomodulation; conversion to full donor chimerism was highly correlated both with CR and with the development of severe acute GVHD, which was fatal in 3/8 patients. Novel therapeutic strategies are required for patients with mixed T-cell chimerism post-alloSCT for CLL. © 2017 John Wiley & Sons Ltd.

  8. Cell-mediated immunity in operable bronchial carcinoma: the effect of injecting irradiated autologous tumour cells and BCG.

    PubMed

    Stack, B H; McSwan, N; Stirling, J M; Hole, D J; Parratt, D; Spilg, W G; Gillis, C R; McHattie, I; Green, A G; White, R G; Turner, M A

    1979-02-01

    In 52 patients undergoing tests of cell-mediated immunity before surgical resection of bronchial carcinoma a positive tuberculin test result was found in 71% compared with 68% of age- and sex-matched controls. Sensitisation to DNCB occurred in 52% of 37 patients but in 78% of controls. There was depression of lymphocyte transformation by PPD in 19 patients compared with controls (P=0.001), but there was no difference in lymphocyte transformation by PHA or pokeweed mitogen between 34 patients and controls. In a pilot study patients were randomly allocated to autograft (eight) or non-autograft (seven) groups. The autograft group were given an intradermal injection of a suspension of irradiated autologous tumour-cells mixed with intradermal BCG on the day of operation. Tests of cell-mediated immunity were repeated two weeks after operation. Five patients in each group received a course of radiotherapy to the mediastinum three weeks after operation. There was a rise in cutaneous tuberculin reactivity (P=0.08) and total leucocyte count (P=0.09) in the autograft group postoperatively with a fall in total lymphocyte and T lymphocyte counts in the non-autograft group (P less 0.05). These differences, however, were not followed by any difference in the frequency of tumour recurrence or the survival rate two years after operation. The results show that the immunological surveillance mechanism is impaired even in patients with early bronchial carcinoma and that it is possible to overcome postoperative immunological depression with specific immunotherapy combined with BCG. This treatment did not produce any clinical advantage in this small number of patients and the skin lesions caused the patients considerable discomfort.

  9. Expression of costimulatory molecule CD86 in HL-60 cells induced by MG132 and its effect on allogeneic mixed lymphocyte reaction.

    PubMed

    Yu, Mei-Xia; Liu, Xun; Zhou, Yong-Ming; Cheng, Yan-Xiang; Cheng, Jing; Qiu, Yu-Zhen; Xing, Xiao-Lei; Yao, Chun-Hong; Bai, Ru-Jun

    2014-10-01

    This study was aimed to elucidate the expression of costimulatory molecule CD80 and CD86 in HL-60 cells induced by proteasome inhibitor MG132 and its effect on allogeneic mixed lymphocyte reaction. Acute myelocytic leukemia cell line HL-60 and chronic myelocytic leukemia cell line K562 were cultured. The viability of the cells was measured by flow cytometry. Proteasome inhibitor MG132 at the concentrations of 2 or 3 µmol/L was used to stimulate the HL-60 cell cultured for 24 h and 48 h respectively, and the Annexin V/7-AAD staining and flow cytomotry were used to detect the apoptosis of the HL-60 cells. HL-60 and K562 cells were treated with 1 µmol/L MG132 for 24 h and 48 h respectively, then CD80 and CD86 antibodies were added, finally the expression of CD80 and CD86 was analysed by flow cytomery. The mRNA expression of CD86 in the HL-60 cells treated with 1 µmol/L MG132 was detected by RT-PCR. HL-60 and K562 cells were treated by 1 µmol/L MG132 and then underwent irradiation of 75 Gy (60)Co to kill the cells with their antigenicity preserved. Peripheral blood mononuclear cells (PBMNCs) of healthy volunteers, as reactive cells, were isolated and inoculated into the (60)Co irradiated HL-60 cells of different concentrations, as stimulating cells, CCK-8 was added and then the A value of absorbance was measured at the wave length of 450 nm in an enzyme labeling instrument. The results showed that the cell viability of the HL-60 cells treated with 1 µmol/L MG132 for 24 h an d 48 h was 92.95% and 85.87% respectively. The apoptotic rates of the HL-60 cells treated with MG132 increased in dose-and time-dependent manner. High-concentration of MG132 directly killed HL-60 cells. Before MG132 treatment K562 cells did not express CD86, but the CD86 expression of the HL-60 cells was up-regulated time-dependently after MG132 treatment (P < 0.01). The mRNA expression of CD86 in the HL-60 treated with MG132 was up-regulated time-dependently (P < 0.01). CCK-8 test showed that

  10. What is autologous blood transfusion?

    PubMed

    Sansom, A

    1993-07-01

    The word autologous is Greek in origin. The definition is exact 'autos' means self and 'logus' means relation. Thus, the meaning is 'related to self'. Autologous blood transfusion, which also is referred to frequently but incorrectly and imprecisely as auto transfusion, designates the reinfusion of blood or blood components to the same individual from whom they were taken. Homologous blood is blood or blood components, from another human donor, taken and stored for later transfusion as required.

  11. Subsets of T lymphocytes in relation to T lymphocyte function in multiple sclerosis.

    PubMed Central

    Craig, J C; Hawkins, S A; Swallow, M W; Lyttle, J A; Patterson, V H; Merrett, J D; Haire, M

    1985-01-01

    T lymphocyte control of Epstein-Barr virus (EBV) infection of autologous B lymphocytes was examined in parallel to the enumeration of subpopulations of mononuclear cells in 22 multiple sclerosis (MS) patients and in 22 healthy individuals. All were seropositive for EBV. The incidence of lack of T cell control was significantly higher in patients than in controls, confirming previous published work. In the present study, we have shown in addition a significantly reduced proportion of OKT8+ cells and a significantly increased ratio of OKT4/OKT8 cells in the group of patients with lack of control. The findings point to abnormal immunoregulation in MS. PMID:3000660

  12. No mixing of granulocytes and other lymphocytes in the inflamed joints of parabiosis mice with collagen-induced arthritis: possible in situ generation

    PubMed Central

    Nishizawa, Tetsuro; Kawamura, Toshihiko; Izumi, Nakao; Kawamura, Hiroki; Fujii, Katsuyuki; Abo, Toru

    2005-01-01

    Collagen-induced arthritis was evoked by an injection of lipopolysaccharide and anti-type II collagen antibody in mice. In parallel with the onset of arthritis, granulocytes with large light scatter and a Mac-1+ Gr-1+ phenotype expanded in the joints of these mice. Lymphocytes with a CD3− B220+ phenotype (i.e. B220+ B cells) were the major population among lymphocyte subsets in the joints, irrespective of disease. To determine the origin of these leucocyte populations in the joints and other organs, parabiotic experiments using CBF1Ly5.1 and CBF1Ly5.2 mice were conducted in mice with and without collagen-induced arthritis. As expected, leucocyte populations in the liver and spleen became a half-and-half mixture of their own cells and partner cells (e.g. ∼45% of Ly5.1+ cells in Ly5.2+ partner mice). However, such a mixture was extremely delayed in the joints and bone marrow, even in mice with arthritis. These results suggest that, because circulatory blood is not exchanged in the joints, granulocytes and other lymphocytes are generated in situ in the inflamed joints of mice with collagen-induced arthritis or are possibly supplied by the bone marrow. It is of interest that granulocytes in the joints expanded, even without a supply from another site, namely, the synovium. PMID:15606803

  13. Detection of autologous blood transfusions in athletes: a historical perspective.

    PubMed

    Mørkeberg, Jakob

    2012-07-01

    Autologous blood transfusions (ABTs) has been used by athletes for approximately 4 decades to enhance their performance. Although the method was prohibited by the International Olympic Committee in the mid 1980s, no direct detection method has yet been developed and implemented by the World Anti-Doping Agency (WADA). Several indirect methods have been proposed with the majority relying on changes in erythropoiesis-sensitive blood markers. Compared with the first methods developed in 1987, the sensitivity of subsequent tests has not improved the detection of blood doping. Nevertheless, the use of sophisticated statistical algorithms has assured a higher level of specificity in subsequent detection models, which is a crucial aspect of antidoping testing particularly to avoid "false positives." Today, the testing markers with the best sensitivity/specificity ratio are the Hbmr model (an algorithm based on the total amount of circulating hemoglobin level [hemoglobin level mass] and percentage of reticulocytes, 4.51·ln(Hbmass)-√%ret) and the OFF-hr model (algorithm based on hemoglobin level concentration and percentage of reticulocytes, Hb(g/L)-60·√%ret). Only the OFF-hr model is currently approved by WADA. Recently, alternative indirect strategies for detecting blood doping have been proposed. One method is based upon a transfusion-induced immune-response resulting in specific changes in gene expression related to leukocytes such as T lymphocytes. Another method relies on detecting increased plasticizer metabolite levels in the urine caused by the leakage of plasticizers from the blood bags used during the blood storage. These methods need further development and validation across different types of transfusion regimes before they can be implemented. In addition, several research projects have been funded by WADA in recent years and are now under development including "Detection of Autologous Blood Transfusions Using Activated Red Blood Cells (the red blood cells

  14. Human T-cell heterogeneity as delineated with a specific human thymus lymphocyte antiserum. In vitro effects on mitogen response mixed leukocyte culture, cell-mediated lymphocytotoxicity, and lymphokine production.

    PubMed Central

    Woody, J N; Ahmed, A; Knudsen, R C; Strong, D M; Sell, K W

    1975-01-01

    Human peripheral blood lymphocytes (PBL) were evaluated by their responses to phytohemmagglutinin (PHA-P), concanavallin A (con-A), and pokeweed mitogen (PWM), both before and after treatment with an antiserum against human thymic lymphocyte antigens (HTLA) that had been made T-cell-specific by multiple absorptions with immunoglobulin EAC-positive lymphoblast cell lines (B cells). Cells treated with HTLA were examined for their ability to react in a mixed lymphocyte culture (MLC) and to form killer cells in a cell-mediated lymphocytotoxicity (CML) system. Sensitized cells were also examined for their ability to respond to purified protein derivative (PPD) by blastogenesis, migration inhibitory factor release (MIP), and lymphotoxin (LT) production, both before and after treatment with HTLA and complement. The HTLA was in itself highly stimulatory to PBL. However, with the addition of complement and subsequent cell destruction, a marked decrease in its stimulatory response was noted. PBL treated with HTLA and complement exhibited marked inhibition of responsiveness to con-A with little decrease in PHA-P -OR PWM stimulation except at very high concentration of HTLA. MLC reaction was inhibited only when responder cells were treated with HTLA + C'. Treatment of stimulator cells with HTLA + C' did not significantly alter the MLC response. The HTLA + C'-treated cells failed to form killer cells in the CML reaction and inhibited PPD-induced blasto-genesis from PPD-sensitized individuals; however, treatment of sensitized cells with HTLA + C' had little effects on the release of MIF and LT. It is suggested that subpopulations of T-cells carry surface antigens that bind with this specific antisera, and that the con-A-responsive cells, the responder cells in the MLC, and killer T-cells comprise a separate subset from cells responding to PHA-P or PWM, OR THE MIF-and LT-producing cells. PMID:1091657

  15. T-cell subsets in autologous and allogeneic peripheral blood stem cell concentrates.

    PubMed

    Strobel, J; Moellmer, I; Zingsem, J; Hauck-Dlimi, B; Eckstein, R; Strasser, E

    2015-11-01

    Regulatory T cells (Tregs) and other T-cell subsets are of importance in the setting of autologous and allogeneic stem cell transplantations. We conducted a study to assess the content of peripheral blood stem cell concentrates and related apheresis parameters in the autologous and allogeneic setting. We characterized 53 donors, patients and peripheral blood stem cell concentrates (PBSC) regarding the content of CD45(+) cells, lymphocytes, CD3(+) cells, CD3(+) CD4(+) T cells, CD3(+) CD4(+) CD25(+) T cells, CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs and CD34(+) cells and calculated cell yields, recruitment factors and collection efficiency for all cell types. We compared allogeneic data with autologous data. Autologous PBSC show significantly lower concentrations of T-cell subsets compared to allogeneic PBSC (17,112/μl CD4(+), 14,858/μl CD4(+) CD25(+) and 1579/μl CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in autologous compared to 65,539/μl CD4(+), 44,208(+) /μl CD4(+) CD25(+) and 5040/μl CD3(+) CD4(+) CD25(+) CD127(low/negative) Tregs in allogeneic PBSC, respectively), in contrast to CD34(+) concentrations (5342/μl CD34(+) in autologous compared to 2367/μl CD34(+) in allogeneic PBSC, respectively). Accordantly, all T-cell yields are lower in the autologous setting compared to allogeneic PBSC. However, recruitment factor and collection efficiency of all cell types are higher in autologous compared to allogeneic PBSC, but not all parameters differ significantly when groups are compared. T-cell subsets and especially Tregs are a substantial part of PBSC transplantation, as considerable recruitment during apheresis occurs. In large volume apheresis, the collection efficiency of Treg is comparable to that of CD34(+) cells, while recruitment factors are even higher. © 2015 International Society of Blood Transfusion.

  16. Rebooting autoimmunity with autologous HSCT.

    PubMed

    Snowden, John A

    2016-01-07

    Autologous hematopoietic stem cell transplantation (HSCT) is increasingly used for severe autoimmune and inflammatory diseases, but the mechanisms involved have yet to be elucidated. In this issue of Blood, Delemarre et al report their findings in both animal and human models which provide insights into restoration of functionality and diversity within the regulatory T-cell (Treg) compartment following HSCT.

  17. Evidence for immune complexes involving anti-lymphocyte antibodies associated with hypocomplementaemia in chronic lymphocytic leukaemia (CLL).

    PubMed Central

    Day, N K; Winfield, J B; Gee, T; Winchester, R; Teshima, H; Kunkel, H G

    1976-01-01

    Unmeasurable total haemolytic complement (C) was observed in serum of a patient with untreated chronic lymphocytic leukaemia and recurrent non-hereditary angioedema. Analysis of C components immunochemically demonstrated a marked reduction of C1q and C1s inhibitor, undetectable C1r, C1s and an elevated B. Haemolytic C1, C4 and C2 were less than 5 percent of normal, functional C1s inhibitor was absent. Cryoglobulin and C1q precipitins were present in the serum. Of special interest was the presence of high levels of cold-reactive antilymphocyte antibody, determined by both C-dependent cytotoxicity and indirect immunofluorescence. The antibody exhibited specificities for both autologous lymphocytes and lymphocytes from normal donors; cytotoxic activity for autologous leukaemia cells was removed by absorption with normal isologous tonsil lymphocytes. Specific enrichment of this antibody relative to the serum level was demonstrated in the cryoglobulin and its isolated 19S fractions. Free lymphocyte surface antigen was also demonstrated by gel diffusion using specific rabbit antilymphocyte antiserum. These data strongly suggest the presence of pathogenetically significant circulating complexes of lymphocyte surface antigen and specific antibody in certain patients with CLL. Images Fig. 1 PMID:136325

  18. Increased lymphocyte death by neglect-apoptosis is associated with lymphopenia and autoantibodies in lupus patients presenting with neuropsychiatric manifestations.

    PubMed

    Silva, Lucienir M; Garcia, Aglair B; Donadi, Eduardo A

    2002-08-01

    To evaluate lymphocyte death by neglect-apoptosis features in systemic lupus erythematosus (SLE) patients presenting with neuropsychiatric (NPSLE) involvement we studied 40 SLE patients with active disease, 20 with and 20 without neuropsychiatric manifestations, and 20 control individuals. Lymphocyte apoptosis was evaluated by means of DNA staining using flow cytometry, immediately after cell isolation and after incubation with culture medium or autologous serum. Compared with controls, NPSLE and non-NPSLE patients exhibited increased rates of neglect-apoptosis immediately after cell isolation. Only NPSLE patients exhibited an increased neglect-apoptosis rate after incubation with culture medium; however, the neglect-apoptosis rate was associated with lymphopenia in both series of patients. After lymphocyte incubation with autologous serum, only NPSLE patients exhibited a significant negative correlation between the neglect-apoptosis rate and the number of peripheral lymphocytes. The incubation of lymphocytes with autologous serum containing antiphospholipid or anti-SSA/Ro antibodies significantly increased the neglect-apoptosis in NPSLE when compared with non-NPSLE patients with a similar autoantibody profile. In conclusion, NPSLE and non-NPSLE patients shared several abnormalities in terms of lymphocyte neglect-apoptosis. Peculiar findings were observed in NPSLE patients particularly after incubation with autologous serum, such as the fact that the increased lymphocyte death by neglect-apoptosis was associated with lymphopenia and with the presence of antiphospholipid and anti-SSA/Ro antibodies.

  19. Natural killer cell-mediated lysis of autologous cells modified by gene therapy.

    PubMed

    Liberatore, C; Capanni, M; Albi, N; Volpi, I; Urbani, E; Ruggeri, L; Mencarelli, A; Grignani, F; Velardi, A

    1999-06-21

    This study investigated the role of natural killer (NK) cells as effectors of an immune response against autologous cells modified by gene therapy. T lymphocytes were transduced with LXSN, a retroviral vector adopted for human gene therapy that carries the selectable marker gene neo, and the autologous NK response was evaluated. We found that (i) infection with LXSN makes cells susceptible to autologous NK cell-mediated lysis; (ii) expression of the neo gene is responsible for conferring susceptibility to lysis; (iii) lysis of neo-expressing cells is clonally distributed and mediated only by NK clones that exhibit human histocompatibility leukocyte antigen (HLA)-Bw4 specificity and bear KIR3DL1, a Bw4-specific NK inhibitory receptor; and (iv) the targets are cells from HLA-Bw4(+) individuals. Finally, neo peptides anchoring to the Bw4 allele HLA-B27 interfered with KIR3DL1-mediated recognition of HLA-B27, i.e., they triggered NK lysis. Moreover, neo gene mutations preventing translation of two of the four potentially nonprotective peptides reduced KIR3DL1(+) NK clone-mediated autologous lysis. Thus, individuals expressing Bw4 alleles possess an NK repertoire with the potential to eliminate autologous cells modified by gene therapy. By demonstrating that NK cells can selectively detect the expression of heterologous genes, these observations provide a general model of the NK cell-mediated control of viral infections.

  20. A phase I clinical study of autologous dendritic cell therapy in patients with relapsed or refractory multiple myeloma

    PubMed Central

    Jung, Sung-Hoon; Lee, Hyun-Ju; Lee, Youn-Kyung; Yang, Deok-Hwan; Kim, Hyeoung-Joon; Rhee, Joon Haeng; Emmrich, Frank; Lee, Je-Jung

    2017-01-01

    Cellular immunotherapy is emerging as a potential immunotherapeutic modality in multiple myeloma (MM). We have developed potent immunotherapeutic agent (VAX-DC/MM) generated by dendritic cells (DCs) loaded with autologous myeloma cells irradiated with ultraviolet B. In this study, we evaluated the safety and efficacy of VAX-DC/MM in patients with relapsed or refractory MM. This trial enrolled relapsed or refractory MM patients who had received both thalidomide- and bortezomib-based therapies. Patients received the intradermal VAX-DC/MM injection every week for 4 weeks. Patients were treated with 5 × 106 or 10 × 106 cells, with nine patients treated at a higher dose. The median time from diagnosis to VAX-DC/MM therapy was 56.6 months (range, 28.5–130.5). Patients had received a median of five prior treatments, and 75% had received autologous stem cell transplantation. VAX-DC therapy was well-tolerated, and the most frequent adverse events were local reactions at the injection site and infusion-related reactions. In seven of nine patients who received 10×106 cells, an immunological response (77.8%) was observed by interferon-gamma ELISPOT assay or a mixed lymphocyte reaction assay for T-cell proliferation. The clinical benefit rate was 66.7% including one (11.1%) with minor response and five (55.6%) with stable disease; three (33.3%) patients showed disease progression. In conclusion, VAX-DC/MM therapy was well-tolerated, and had disease-stabilizing activity in heavily pretreated MM cases. Further studies are needed to increase the efficacy of VAX-DC/MM in patients with MM. PMID:28088784

  1. Autologous umbilical cord blood transfusion.

    PubMed Central

    Ballin, A.; Arbel, E.; Kenet, G.; Berar, M.; Kohelet, D.; Tanay, A.; Zakut, H.; Meytes, D.

    1995-01-01

    The purpose of this study was to examine some aspects of umbilical cord blood collection for autologous transfusion in premature infants. All 120 microbacterial cultures (aerobic and anaerobic) of cord blood samples as well as 30 cultures of mycoplasma were treated. Cord prothrombin fragment (F 1 + 2) concentrations were quantified at one and 10 minutes after clamping of the cord. F 1 + 2 concentrations assessed on 25 newborn infants were similar and no linear association with time of clamping could be drawn. This means that cord blood thrombosis is not activated for at least 10 minutes following clamping of the cord. As far as is known, the first newborn infant to benefit from this method of transfusion is reported here. The premature infant received two portions of autologous blood (on days 5 and 7). No untoward effects were noted. Blood, collected from the umbilical cord, is a safe source for autotransfusion, provided that bacteriological testing has been carried out. PMID:8535878

  2. Characterization of CD8+ T-cell responses in the peripheral blood and skin injection sites of melanoma patients treated with mRNA electroporated autologous dendritic cells (TriMixDC-MEL).

    PubMed

    Benteyn, Daphné; Van Nuffel, An M T; Wilgenhof, Sofie; Corthals, Jurgen; Heirman, Carlo; Neyns, Bart; Thielemans, Kris; Bonehill, Aude

    2013-01-01

    Treatment of melanoma patients with mRNA electroporated dendritic cells (TriMixDC-MEL) stimulates T-cell responses against the presented tumor-associated antigens (TAAs). In the current clinical trials, melanoma patients with systemic metastases are treated, requiring priming and/or expansion of preexisting TAA-specific T cells that are able to migrate to both the skin and internal organs. We monitored the presence of TAA-specific CD8(+) T cells infiltrating the skin at sites of intradermal TriMixDC-MEL injection (SKILs) and within the circulation of melanoma patients treated in two clinical trials. In 10 out of fourteen (71%) patients screened, CD8(+) T cells recognizing any of the four TAA presented by TriMixDC-MEL cellular vaccine were found in both compartments. In total, 30 TAA-specific T-cell responses were detected among the SKILs and 29 among peripheral blood T cells, of which 24 in common. A detailed characterization of the antigen specificity of CD8(+) T-cell populations in four patients indicates that the majority of the epitopes detected were only recognized by CD8(+) T cells derived from either skin biopsies or peripheral blood, indicating that some compartmentalization occurs after TriMix-DC therapy. To conclude, functional TAA-specific CD8(+) T cells distribute both to the skin and peripheral blood of patients after TriMixDC-MEL therapy.

  3. Rhinoplasty using autologous costal cartilage.

    PubMed

    Miranda, Nancy; Larocca, Carlos Gil; Aponte, Ciro

    2013-06-01

    Most Latin American patients looking to have a primary septorhinoplasty share common characteristics in relation to an incorrect projection of the nasal tip complex and a low dorsal line. Thus, the frequent use of structural techniques and of surgical enhancement techniques becomes necessary to improve the nasal contour. In cases of secondary septorhinoplasty, it is also usual in our practice not to have sufficient septal cartilage available or with the required quality to give structure and support to the nasal tip complex, handle the nasal dorsum, and simultaneously correct postseptorhinoplasty deformities. For these reasons, in our practice costal cartilage represents an excellent option as autologous graft material. We present our experience using autologous costal cartilage for structural and nonstructural purposes in 286 selected patients who underwent open rhinoplasty between 2004 and 2011. We emphasize preoperative analyses, we discuss the criteria for selecting costal graft as graft material, we show key aspects of the dynamic of the surgery, and we consider the possibility of using autologous costal graft in combination with heterologous grafts. In this work we also establish the disadvantages of costal cartilage as graft material in specific areas of the surgical anatomy of the nose.

  4. PRODUCTS OF ACTIVATED LYMPHOCYTES

    PubMed Central

    Sorg, Clemens; Bloom, Barry R.

    1973-01-01

    General methods were developed and applied to the biosynthesis and purification of products of activated lymphocytes available in minute quantities. The activity studied here was the migration inhibitory factor (MIF) produced by purified protein derivative (PPD)- or concanavalin A (Con A)-stimulated lymphocytes obtained from one guinea pig or less. The methods selected yielded results in terms of two chemical parameters characteristic of the molecules involved, namely Kd on Sephadex G-75 and isoionic point, pI, on isoelectric focusing. When supernatants were fractionated on G-75 columns, there were several areas even in control supernatants which produced migration inhibition relative to medium controls. However, in PPD- and Con A-stimulated supernatants, at least one peak of MIF activity was found solely in the stimulated cultures, with a Kd of 0.15. A double-labeling technique was used to characterize the proteins of this peak. Control, unstimulated cultures were labeled with [14C]leucine and stimulated cultures were labeled with [3H]leucine. After mixing the supernatants and G-75 filtration, a major "ratiolabeled" broad peak. i.e. one with increased 3H/14C ratio, was found. When a narrow portion of this peak about Kd 0.15, containing most of the MIF activity, was subjected to analytical isoelectric focusing, all of the label was associated with proteins of lower net charge than albumin. A unique ratiolabeled peak was found in PPD- and Con A-stimulated fractions with a pI of approx. 5.3. A micropreparative isoelectric focusing technique was developed and yielded MIF activity in the same region as the major ratiolabeled peak. Further study will be required to ascertain whether the ratiolabeled protein is MIF. By following the Kd, pI, and 3H/14C labeling ratio, at least 14 products of activated lymphocytes, synthesized either de novo or in increased amounts, could be distinguished. PMID:4688317

  5. [Use of heparinized autologous blood for intraoperative rinsing and storage of vascular grafts].

    PubMed

    Kimura, Hidehito; Hosoda, Kohkichi; Kohmura, Eiji

    2015-02-01

    In cerebral revascularization surgery in Japan, the preferred solution for rinsing and intraoperative storage of saphenous vein or radial artery grafts is a heparinized saline solution with albumin. On the other hand, most cardiac surgeons routinely use solutions of heparinized autologous blood during surgery. Here we used the latter type of solution for cerebral revascularization surgery and evaluated its efficacy. Since December 2011, we have used heparinized autologous blood for saphenous vein grafts during cerebral revascularization surgery. For this, 20mL of the whole blood was obtained from an arterial line;this blood was then mixed with 20mL of a heparinized saline solution containing 500IU of heparin and 40mg of papaverine hydrochloride. The saphenous vein was harvested using standard procedures and immersed in the autologous blood solution just before implantation. Between December 2011 and March 2013, six revascularizations using saphenous vein grafts were performed using this solution. None of the anastomoses presented complications related to revascularization procedures, and all grafts were clearly present postoperatively. There is still no evidence that the storage in autologous blood is superior to the use of a saline solution with albumin. However, the national health insurance does not cover the use of albumin products, which carries an additional cost. Furthermore, the autologous blood medium is a red-colored solution that indicates the presence of unfavorable graft leaks when the wall of the graft turns red. We recommend the use of heparinized autologous blood for intraoperative rinsing and storage grafts.

  6. Reduced recognition of metastatic melanoma cells by autologous MART-1 specific CTL: relationship to TAP expression.

    PubMed

    Murray, J L; Hudson, J M; Ross, M I; Zhang, H Z; Ioannides, C G

    2000-01-01

    Class I expression in context with T-cell receptor expression is crucial for peptide presentation and induction of CD8+ cytotoxic T lymphocytes (CTL). Presentation of class I bound peptides is dependent on transporter-associated proteins (TAP) expression and function. Tumor infiltrating lymphocytes from a patient with melanoma were isolated, expanded in vitro in the presence of interleukin-2, and tested for cytotoxicity against HLA-A2 positive, MART-1 positive autologous tumor cells, an HLA-A2-positive, MART-1 positive melanoma cell line (Mel-501), and HLA-A2-negative melanoma cells. Significant killing occurred against both A2-positive cell lines (63% and 65%, respectively), but not against the A2-negative line (18%) or A2-positive autologous tumor (1.5%). These CTL preferentially recognized the MART-1 peptide F119, 27-35, and gp100 peptide F125, 280-288, resulting in a 30% to 60% enhancement of lysis when autologous tumor or major histocompatibility complex class I "empty" T2 cells were pulsed with either peptide. To address whether the deficiency in autologous tumor recognition might be related to a deficiency in Ag presentation, we screened for the presence of TAP1 and TAP2 transcripts by polymerase chain reaction, Southern blotting, and scanning densitometry using sequence-specific primers and probes. Both TAP1 and TAP2 expression levels in the autologous tumor were minimal, yet were upregulated 7- to 18-fold, respectively, by interferon-gamma. Despite this increase, a similar increase in cytotoxicity did not occur. In short, deficiencies in TAP presentation may have functional significance for tumor escape from immunosurveillance and with respect to impending vaccine trials.

  7. Autologous white blood cell transfusion: toward a younger immunity.

    PubMed

    Charron, Dominique

    2007-10-01

    More and more cells and tissues of human origin are considered as unique medical bio-resources and are instrumental in the ongoing development of regenerative medicine. Although a better understanding of the genetic complexity of the major histocompatibility complex has contributed to develop allogeneic hematopoietic stem cell transplantation, the autologous setting was viewed early on only as a means to overcome myelodepression. The contribution of the immune system for adoptive immunotherapy was recognized in the 1990s, when donor lymphocyte infusion demonstrated an antileukemic effect of the transfused T cells. This led to the foundation and development of adoptive immunotherapy in the treatment and prevention of infectious diseases and cancer. The recognition that the immune system is undergoing a progressive decline and deterioration with age introduces a new challenge. Immunosenescence results in a well-documented increase in incidence and severity of infections, impaired responses to vaccines, and development of cancer. We propose and argue that autologous white blood cells collected and cryopreserved at a young age will represent a valuable bio-resource for the restoration of immunity and the successful development of adoptive immunotherapies in treating infections and cancer, and will pave the way to anticipatory medicine.

  8. Lymphocyte activation by purified HLA-DR molecules fused into autochthonous "stimulating cells".

    PubMed

    Diu, A; Abikar, K; Rode, H N; Gordon, J

    1985-08-01

    Affinity-purified Ia molecules derived from the Daudi cell line were reconstituted into vesicles with Sendai virus envelope glycoproteins. These vesicles inserted into human peripheral leukocytes could induce stimulation of autologous lymphocytes, as measured by thymidine uptake, 6 days later. It is suggested that this method could provide a means to study allostimulation at the molecular level.

  9. Autologous stem cell transplantation for adult acute leukemia.

    PubMed

    Gorin, Norbert-Claude

    2002-03-01

    Autologous stem cell transplantation using marrow or peripheral blood is routinely used to consolidate patients with acute myelocytic leukemia in complete remission. The situation is less clear for adult acute lymphocytic leukemia in which results achieved with all strategies are disappointing. In acute myelocytic leukemia, autografts should be done in patients with good and standard risk factors. Patients with high-risk acute myelocytic leukemia defined by poor cytogenetics or failure to achieve remission with the first induction course, should proceed to allogeneic stem cell transplantation with the best available human leukocyte antigen-identical donor (family or unrelated), and the nature of the conditioning regimen (myelo-ablative or non-myelo-ablative) should be decided in relation to age, and the patient's clinical condition. Results of autografting in acute myelocytic leukemia rely strongly on the quality of the graft. Higher doses of infused stem cells translate into lower relapse rates. Marrow purging with cyclophosphamide derivatives also diminishes the relapse incidence. Autologous stem cell transplantations using peripheral blood are presently preferred to marrow as the source of stem cells, but an aggressive prior in vivo purge (high-dose consolidation course(s) before cytaphereses) is then mandatory. In good-risk acute myelocytic leukemia, autografting is superior to high-dose ARA-C; in standard-risk acute myelocytic leukemia, both are supposedly equivalent. There is no prospective randomized study testing the two approaches in the good-standard-risk population. We presently test the combination of marrow and blood both purged by mafosfamide. In adult acute lymphocytic leukemia, good-risk patients get the best benefit from autografting over conventional chemotherapy. Maintenance chemotherapy after transplant is likely to bring benefit. Research in progress aims at facilitating access of the largest number of patients to autografting and at

  10. Regeneration of Cartilage in Human Knee Osteoarthritis with Autologous Adipose Tissue-Derived Stem Cells and Autologous Extracellular Matrix

    PubMed Central

    Pak, Jaewoo; Lee, Jung Hun; Park, Kwang Seung; Jeong, Byeong Chul; Lee, Sang Hee

    2016-01-01

    Abstract This clinical case series demonstrates that percutaneous injections of autologous adipose tissue-derived stem cells (ADSCs) and homogenized extracellular matrix (ECM) in the form of adipose stromal vascular fraction (SVF), along with hyaluronic acid (HA) and platelet-rich plasma (PRP) activated by calcium chloride, could regenerate cartilage-like tissue in human knee osteoarthritis (OA) patients. Autologous lipoaspirates were obtained from adipose tissue of the abdominal origin. Afterward, the lipoaspirates were minced to homogenize the ECM. These homogenized lipoaspirates were then mixed with collagenase and incubated. The resulting mixture of ADSCs and ECM in the form of SVF was injected, along with HA and PRP activated by calcium chloride, into knees of three Korean patients with OA. The same affected knees were reinjected weekly with additional PRP activated by calcium chloride for 3 weeks. Pretreatment and post-treatment magnetic resonance imaging (MRI) data, functional rating index, range of motion (ROM), and pain score data were then analyzed. All patients' MRI data showed cartilage-like tissue regeneration. Along with MRI evidence, the measured physical therapy outcomes in terms of ROM, subjective pain, and functional status were all improved. This study demonstrates that percutaneous injection of ADSCs with ECM contained in autologous adipose SVF, in conjunction with HA and PRP activated by calcium chloride, is a safe and potentially effective minimally invasive therapy for OA of human knees. PMID:27588219

  11. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  12. Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

    PubMed

    Nair, Velu; Sharma, Ajay; Sharma, Sanjeevan; Das, Satyaranjan; Bhakuni, Darshan S; Narayanan, Krishnan; Nair, Vivek; Shankar, Subramanian

    2015-03-01

    Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  13. Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes

    NASA Astrophysics Data System (ADS)

    Morgan, Richard A.; Dudley, Mark E.; Wunderlich, John R.; Hughes, Marybeth S.; Yang, James C.; Sherry, Richard M.; Royal, Richard E.; Topalian, Suzanne L.; Kammula, Udai S.; Restifo, Nicholas P.; Zheng, Zhili; Nahvi, Azam; de Vries, Christiaan R.; Rogers-Freezer, Linda J.; Mavroukakis, Sharon A.; Rosenberg, Steven A.

    2006-10-01

    Through the adoptive transfer of lymphocytes after host immunodepletion, it is possible to mediate objective cancer regression in human patients with metastatic melanoma. However, the generation of tumor-specific T cells in this mode of immunotherapy is often limiting. Here we report the ability to specifically confer tumor recognition by autologous lymphocytes from peripheral blood by using a retrovirus that encodes a T cell receptor. Adoptive transfer of these transduced cells in 15 patients resulted in durable engraftment at levels exceeding 10% of peripheral blood lymphocytes for at least 2 months after the infusion. We observed high sustained levels of circulating, engineered cells at 1 year after infusion in two patients who both demonstrated objective regression of metastatic melanoma lesions. This study suggests the therapeutic potential of genetically engineered cells for the biologic therapy of cancer.

  14. Histocompatible chicken inbred lines: homogeneities in the major histocompatibility complex antigens of the GSP, GSN/1, PNP/DO and BM-C inbred lines assessed by hemagglutination, mixed lymphocyte reaction and skin transplantation.

    PubMed

    Valdez, Marcos B; Mizutani, Makoto; Fujiwara, Akira; Yazawa, Hajime; Yamagata, Takahiro; Shimada, Kiyoshi; Namikawa, Takao

    2007-10-01

    Chicken inbred lines of the GSP, GSN/1, PNP/DO and BM-C have been established by selection of a specific allele at the B blood group locus (MHC B-G region) and other polymorphic loci through pedigree mating. To extend the potential of these inbred lines as experimental animals in Aves, we assessed the antigenic homogeneities of the MHC antigens by three immunological methods. Antigenic variations of red blood cells (RBCs) were surveyed in the inbred lines and a random-bred line (NG) derived from the Nagoya breed by using ten kinds of intact antisera produced in the inbred line of chickens against RBCs of a red junglefowl and hybrids. In the hemagglutination test, no individual variations were found within the inbred line at all, while all the ten antisera detected highly heterogeneous reactions in individuals of the NG. The reciprocal one-way mixed lymphocyte reactions gave constantly higher stimulation responses (P<0.01) between individual pairs from the inbred lines having different B alleles compared to pairs within the inbred line, while lower stimulation was observed between pairs of the GSP and GSN/1 inbred lines both having the B(21) allele. In reciprocal skin transplantation, the transplanted skingrafts within the inbred line and between individuals from the GSP and GSN/1 inbred lines survived more than 100 days, while all the skingrafts showed signs of rejection within 7 days among the inbred lines having different B alleles. The results obtained by the three practical methods coincidentally indicated that the individuals in the respective four inbred lines were histocompatible, and further, that the GSP and GSN/1 individuals were histocompatible.

  15. Differentiation of human B lymphocyte subpopulations induced by an alloreactive helper T-cell clone

    SciTech Connect

    Anderson, S.J.; Hummell, D.S.; Lawton, A.R.

    1988-07-01

    We have used cloned alloreactive helper T cells to determine if direct T cell-B cell interaction can induce differentiation of human peripheral blood B cells which do not respond to pokeweed mitogen (PWM). T-cell clone 2F8 was derived from a one-way mixed lymphocyte reaction. 2F8 cells are T3+T4+T8-IL-2R+ and proliferate in response to irradiated stimulator cells, but not autologous cells, in the absence of exogenous interleukin-2. 2F8 cells provide allospecific help for polyclonal proliferation and differentiation of B cells in the absence of any other stimulus. The magnitude of this response is comparable to that of the response of the same B cells to PWM and fresh autologous T cells. 2F8 cells could also provide nonspecific help for unrelated donor B cells in the presence of PWM, with no requirement for costimulation by irradiated stimulator cells. Allospecific stimulation of B cells was completely inhibited by antibodies to class II major histocompatibility complex (MHC) framework determinants and was abrogated by 1000-rad irradiation. Cloned 2F8 T cells stimulated differentiation of both small, high-density B cells and larger B cells, generating up to 30% plasma cells with either fraction. B cells forming rosettes with mouse erythrocytes were also induced to differentiate by the helper T cell clone. As found previously, neither small, high-density B cells nor mouse rosette+ B cells responded well to PWM. Direct interaction with allospecific T cells induces differentiation of a broader spectrum of B cells than soluble growth and differentiation factors in conjunction with polyclonal activators such as PWM and protein A containing staphylococci.

  16. Purification and partial characterization of a shed 66 kDa melanoma-associated antigen identified by autologous antibody.

    PubMed

    Vlock, D R; Aul, D J; Toporowicz, A; McCoy, J P; Brown, W E

    1991-10-11

    We have previously reported the isolation of a 66 kDa melanoma-associated antigen, identified by autologous antibody, in serum and unfractionated spent tissue culture media by Western blot analysis. The antigen, detected by autologous serum S150, was found to be broadly represented on melanoma, glioma, renal cell carcinoma, neuroblastoma and head and neck carcinoma cell lines. S150 did not react with bladder or colon carcinoma, fetal fibroblasts, pooled platelets, lymphocytes and red blood cells, autologous cultured lymphocytes or fetal calf serum. To further characterize the antigen, spent tissue culture media, obtained from autologous melanoma cell line, Y-Mel 84:420, was separated by an isoelectric focusing column. Unabsorbed control serum S150 was noted to have a maximum titer of 1:2040 against autologous melanoma cells as measured by protein A hemadsorption. Following isoelectric focusing the greatest decrease in autologous antibody titer (30-fold) occurred with fractions having a pI between 2 and 3. Further resolution of the antigen was accomplished with high-pressure ion-exchange chromatography. One of these fractions showed a significantly higher concentration of antigen and was distinctly resolved from bulk serum albumin. Subsequent Western blot analysis, with autologous antibody, of the isolated antigen-containing fraction, confirmed the presence of a single 66 kDa band. Exposure of the antigen, purified by high-pressure ion-exchange chromatography, to neuraminidase ablated recognition by autologous antibody and suggests that sialic acid is present on the protein and may be part of the antigenic epitope. Binding of antigen, obtained following DEAE anion exchange chromatography, was noted to lectins derived from Triticum vulgaris, Dolichos biflorus and Lycopersicon esculentum. Preparative purification of the antigen was accomplished by anion exchange followed by lectin affinity chromatography with a Dolichos biflorus column. Antigen obtained following

  17. Autologous bone marrow transplanation for extramedullary plasmacytoma presenting as adrenal incidentaloma

    PubMed Central

    Ahmed, Mohammed; Al-Ghamdi, Abduallah; Al-Omari, Mohammed; Aljurf, Mahmoud; Al-Kadhi, Yusuf

    2009-01-01

    Extramedullary adrenal plasmacytoma (EMP) involving the adrenal glands is rarely encountered clinicaly. We report a A 47-year-old male who presented with bilateral adrenal incidentalomas. After confirming EMP, the patient received two consecutive autologous hematopoietic stem cell transplants (HSCT) using high-dose melphalan. Following HSCT, a serial follow-up helical CT revealed a substantial decrease in the size of both adrenal masses. Serial periodic serum protein and urine electrophoresis and immunofixation showed abrogation of a previously noted monoclonal band. At 50 months follow-up the patient was alive and well. Our patient is the first with EMP to have received an autologous HSCT, which may prove to have a role in therapy due to the immunological effect of the infused donor marrow T-lymphocytes against the clonal proliferation of abnormal plasma cells in extrammedullary sites. This case indicates that an EMP should be added to the differential diagnosis of adrenal incidentalomas. PMID:19448366

  18. Detection of cardiac transplant rejection with radiolabeled lymphocytes. [Rats

    SciTech Connect

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-03-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy.

  19. Simplified enrollment for autologous transfusion: automatic referral of presurgical patients for assessment for autologous blood collections.

    PubMed

    Moore, S B; Swenke, P K; Foss, M L; Rand, J A; Cabanela, M E; Kavanagh, B; Taswell, H F

    1992-04-01

    We implemented a pilot program at our institution for automatic referral of patients for presurgical assessment for preoperative and intraoperative collection of autologous blood. Although patients and clinicians support the use of autologous transfusion, often a request for collection of autologous blood is not initiated. During 11 months, 269 patients (82%) of three orthopedic surgeons entered the program, and 218 underwent operation and were dismissed from the hospital. A total of 940 units of autologous blood (675 preoperatively and 265 intraoperatively) was collected from these 218 patients, and 84% of the units were transfused. Throughout hospitalization, 86% of the patients received only autologous blood, whereas 14% received various proportions of homologous and autologous blood. In contrast, only 26% of a concomitant control group of 220 consecutive orthopedic surgical patients not participating in the automatic-referral program received only autologous blood. Thus, the automatic-referral program increased the percentage of elective orthopedic surgical patients who received only autologous blood from 26% to 86% (P less than 0.001). This study also showed that the same amount of blood was used for autologous transfusions as was routinely used for homologous transfusions in similar cases. The automatic-referral system was convenient for physicians and patients and offered the benefits of reduction of transfusion-associated risks and amelioration of patient anxieties.

  20. Apolizumab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-15

    Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Small Lymphocytic Lymphoma

  1. Lymphocyte Functions in Microgravity

    NASA Technical Reports Server (NTRS)

    Pellis, Neal R.; Risin, Diane; Sundaresan, A.; Cooper, D.; Dawson, David L. (Technical Monitor)

    1999-01-01

    To understand the mechanism of immunity impairment in space it is important to analyze the direct effects of space-related conditions on different lymphocytes functions. Since 1992, we are investigating the effect of modeled and true microgravity (MG) on numerous lymphocyte functions. We had shown that modeled (MMG) and true microgravity inhibit lymphocyte locomotion through type I collagen. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. Polyclonal activation of lymphocytes prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. The relationship between activation deficits and the loss of locomotion in MG was investigated using PKC activation by phorbol ester (PMA) and calcium ionophore (ionomycin). Direct activation of PKC by PMA substantially restored the MMG-inhibited lymphocyte locomotion and PHA-induced lymphocyte activation lonomycin by itself did not restore either locomotion or activation of the lymphocytes, indicating that these changes are not related to the impairment in the calcium flux in MMG. Treatment of lymphocytes with PMA before exposure to MMG prevented the loss of locomotion. It was observed that DNA synthesis is not necessary for restoration of locomotion since mitomicin C treated and untreated cells recovered their locomotion to the same level after PKC activation. Our recent data indicate that microgravity may selectively effect the expression of novel Ca2+ independent isoforms of PKC, in particularly PKC sigma and delta. This provides a new insight in understanding of the mechanisms of MG-sensitive cellular functions.

  2. Lymphocyte Functions in Microgravity

    NASA Technical Reports Server (NTRS)

    Pellis, Neal R.; Risin, Diane; Sundaresan, A.; Cooper, D.; Dawson, David L. (Technical Monitor)

    1999-01-01

    To understand the mechanism of immunity impairment in space it is important to analyze the direct effects of space-related conditions on different lymphocytes functions. Since 1992, we are investigating the effect of modeled and true microgravity (MG) on numerous lymphocyte functions. We had shown that modeled (MMG) and true microgravity inhibit lymphocyte locomotion through type I collagen. Modeled microgravity also suppresses polyclonal and antigen-specific lymphocyte activation. Polyclonal activation of lymphocytes prior to exposure to MMG abrogates the MG-induced inhibition of lymphocyte locomotion. The relationship between activation deficits and the loss of locomotion in MG was investigated using PKC activation by phorbol ester (PMA) and calcium ionophore (ionomycin). Direct activation of PKC by PMA substantially restored the MMG-inhibited lymphocyte locomotion and PHA-induced lymphocyte activation lonomycin by itself did not restore either locomotion or activation of the lymphocytes, indicating that these changes are not related to the impairment in the calcium flux in MMG. Treatment of lymphocytes with PMA before exposure to MMG prevented the loss of locomotion. It was observed that DNA synthesis is not necessary for restoration of locomotion since mitomicin C treated and untreated cells recovered their locomotion to the same level after PKC activation. Our recent data indicate that microgravity may selectively effect the expression of novel Ca2+ independent isoforms of PKC, in particularly PKC sigma and delta. This provides a new insight in understanding of the mechanisms of MG-sensitive cellular functions.

  3. Ofatumumab, Pentostatin, and Cyclophosphamide in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2014-10-30

    Hematopoietic/Lymphoid Cancer; B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  4. Generation of cytotoxic T lymphocytes and cytostatic acting cells in T. annulata-immune cattle.

    PubMed

    Ahmed, J S; Wiegers, P; Ritz, H; Hartwig, H; Schein, E; Schnittger, L

    2000-01-01

    Cattle immunized against Theileria annulata with schizont containing autologous cell lines are immune to challenge with a homologous parasite strain. Two cell types have been detected in the peripheral blood of the immunized animals: cytotoxic T lymphocytes (CTL) and cytostatic acting cells (CAC). Killing the target cells by CTL is infection associated and is MHC class I restricted. Hence, no cytotoxicity was observed against target cells that were treated with the theilericidal drug buparvaquone or autologous Con A-blasts. The growth inhibition of CAC is MHC unrestricted, and not mediated by cytokine interferon gamma (IFN-gamma).

  5. Chronic Lymphocytic Leukemia

    PubMed Central

    Motta, Marina; Wierda, William G.; Ferrajoli, Alessandra

    2015-01-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL. PMID:19536902

  6. Brain pathology of a patient 7years after autologous hematopoietic stem cell transplantation for multiple sclerosis.

    PubMed

    Wundes, Annette; Bowen, James D; Kraft, George H; Maravilla, Kenneth R; McLaughlin, Bernadette; von Geldern, Gloria; Georges, George; Nash, Richard A; Lu, Jian-Qiang

    2017-02-15

    Aggressive immunosuppression followed by autologous hematopoietic stem cell transplantation (aHSCT) can be an effective treatment for severe multiple sclerosis (MS), but not all stages of disease may benefit equally. The case of a 49-year-old woman with advanced secondary-progressive MS whose clinical course was not improved by aHSCT and who seven years after transplantation succumbed to complications of severe MS disease-related disability is presented. Autopsy findings of ongoing neurodegeneration despite only rare infiltrating T-lymphocytes illustrate that late MS disease may not represent a suitable disease stage for aHSCT. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Restimulation of tumour-specific immunity in a patient with AML following injection with B7-1 positive autologous blasts.

    PubMed

    Hicks, Christine; Cheung, Carol; Lindeman, Robert

    2003-11-01

    Leukaemic blast cells lack co-stimulatory molecules such as B7, necessary for T-lymphocyte activation. We have used modified CD80+ (B7-1+) tumour cells, with autologous, IL-2 producing, stromal marrow cells in a series of subcutaneous vaccinations to provide a localised environment for the enhancement of cytotoxic T-lymphocytes (CTL) in a patient with acute myeloid leukaemia (AML). Localised inflammation was evident after the fifth and sixth injections with a reduction in the number of circulating blasts in the following 2 weeks. Peripheral blood in vitro CTL activity increased 36-47% after five injections.CD4 T-lymphocytes (5.7%) expanded from post-injection skin biopsies, expressed intracellular IFNgamma and perforin when exposed to autologous B7-1+ blasts and when co-cultured with either B7-1+ or unmanipulated autologous blast cells showed proliferative responses. In this patient, co-injection of B7-1+ tumour cells, together with a local source of sustained IL-2, resulted in an autologous anti-leukaemic in vitro immune response.

  8. FATE OF THE LYMPHOCYTE

    PubMed Central

    Bunting, C. H.; Huston, John

    1921-01-01

    Although the count of circulating lymphocytes in the blood stream remains constant, more lymphocytes enter the blood from the thoracic duct during 24 hours than are present in the blood at any one time. This excess of lymphocytes is not destroyed in the blood stream. The cells migrate from the blood vessels into the mucous membranes and through them to their surface. This occurs chiefly in the gastrointestinal tract, and it is apparently in the mucosa and especially within the intestinal lumen that the function of the lymphocyte is normally performed. PMID:19868519

  9. [Autologous fat grafting and rhinoplasty].

    PubMed

    Nguyen, P S; Baptista, C; Casanova, D; Bardot, J; Magalon, G

    2014-12-01

    Revision rhinoplasty can be very challenging especially in cases of thin skin. Autologous fat graft is utilized in numerous applications in plastic surgery; however, its use relative to the nasal region remains uncommon. Adipose tissue, by virtue of its volumetric qualities and its action on skin trophicity, can be considered to be a gold standard implant. From 2006 until 2012, we have treated patients by lipofilling in order to correct sequelae of rhinoplasty. The mean quantity of adipose tissue injected was 2.1cm(3) depending on the importance of the deformity and the area of injection: irregularity of the nasal dorsum, visible lateral osteotomies, saddle nose. Following the course of our practice, we conceived micro-cannulas that allow a much greater accuracy in the placement of the graft and enable to perform interventions under local anesthesia. These non-traumatic micro-cannulas do not cause post-operative ecchymosis and swelling which shorten the recovery time for the patient. On patients who have undergone multiple operations, lipofilling can be a simple and reliable alternative to correct imperfections that may take place after a rhinoplasty.

  10. Generation of cytotoxic T lymphocytes (CTL) with phorbol ester and calcium ionophore

    SciTech Connect

    Tuttle, T.M.; Bear, H.D. )

    1991-03-15

    Stimulation of lymphocytes with viable tumor cells can induce cytotoxic T lymphocytes (CTL) against autologous tumor. However, sufficient numbers of tumor cells are not always available for such stimulation, and high dose interleukin-2 (IL-2) is often required for growth. Using the weakly immunogenic methylcholanthrene-induced sarcoma MCA105, the authors demonstrate here that CTLs can be expected by pharmacologic manipulation of protein kinase C (PKC) and intracellular calcium with phorbol dibutyrate (PD-Bu) and ionomycin (Io), respectively. Lymphocytes were obtained from the spleens and ipsilateral popliteal draining lymph nodes (DLN) 10 days after the footpad injection of viable MCA105 tumor cells. The cells were stimulated with autologous tumor and 20U/ml IL-2 for 7 days and then treated with PDBu and Io and expanded in culture with 20U/ml IL-2 for an additional 14 days. The lymphocytes from the spleens and DLNs demonstrated significant expansion and marked cytotoxicity against MCA105. In another regimen, lymphocytes from the DLNs of tumor-bearing mice were stimulated directly with PDBu and Io without prior in vitro exposure to autologous tumor and expanded in culture with 20U/ml IL-2. The expansion of these lymphocytes was 500 fold and the cytotoxicity against MCA 105 remained high. Lymphocytes expanded with PDBu and Io also killed MCA102, but normal spleen cells expanded in the same way had no cytotoxic activity. The authors conclude that PKC activators coupled with calcium ionophores and low-dose IL-2 can generate CTL when little or no antigen is available.

  11. Efficient nonviral Sleeping Beauty transposon-based TCR gene transfer to peripheral blood lymphocytes confers antigen-specific antitumor reactivity

    PubMed Central

    Peng, PD; Cohen, CJ; Yang, S; Hsu, C; Jones, S; Zhao, Y; Zheng, Z; Rosenberg, SA; Morgan, RA

    2012-01-01

    Genetically engineered lymphocytes hold promise for the treatment of genetic disease, viral infections and cancer. However, current methods for genetic transduction of peripheral blood lymphocytes rely on viral vectors, which are hindered by production and safety-related problems. In this study, we demonstrated an efficient novel nonviral platform for gene transfer to lymphocytes. The Sleeping Beauty transposon-mediated approach allowed for long-term stable expression of transgenes at ~50% efficiency. Utilizing transposon constructs expressing tumor antigen-specific T-cell receptor genes targeting p53 and MART-1, we demonstrated sustained expression and functional reactivity of transposon-engineered lymphocytes on encountering target antigen presented on tumor cells. We found that transposon- and retroviral-modified lymphocytes had comparable transgene expression and phenotypic function. These results demonstrate the promise of nonviral ex vivo genetic modification of autologous lymphocytes for the treatment of cancer and immunologic disease. PMID:19494842

  12. A method for following human lymphocyte traffic using indium-111 oxine labelling.

    PubMed Central

    Wagstaff, J; Gibson, C; Thatcher, N; Ford, W L; Sharma, H; Benson, W; Crowther, D

    1981-01-01

    A method is described whereby large numbers of human lymphocytes are separated from peripheral blood and labelled in vitro with indium-111 oxine. Following autologous reinjection, the distribution within the body is followed by means of serial blood samples, surface-probe counting and gamma camera imaging. The distribution of radioactivity following reinjection of heat-damaged labelled lymphocytes and free indium-111 oxine is different from that of 'normal' lymphocytes. The results suggest that the separation and labelling procedure does not cause significant physical damage to the lymphocytes The importance of restricting the specific lymphocyte activity to 20-40 microCi per 10(8) cells in order to minimize radiation damage to the lymphocytes is emphasized. Good resolution of lymphoid structures is obtained using gamma camera imaging and the changes recorded in organ distribution correlate well with data from animal models of lymphocyte migration. Thus, indium-111 oxine labelling of human lymphocytes provides a non-invasive method whereby the migratory properties of human lymphocytes can be followed. Images Fig. 2 Fig. 3 Fig. 4 PMID:7285387

  13. Autologous fat injection therapy including a high concentration of adipose-derived regenerative cells in a vocal fold paralysis model: animal pilot study.

    PubMed

    Nishio, N; Fujimoto, Y; Suga, K; Iwata, Y; Toriyama, K; Takanari, K; Kamei, Y; Yamamoto, T; Gotoh, M

    2016-10-01

    To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy. Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted. Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site. The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.

  14. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    ClinicalTrials.gov

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  15. T cells from the tumor microenvironment of patients with progressive myeloma can generate strong, tumor-specific cytolytic responses to autologous, tumor-loaded dendritic cells

    NASA Astrophysics Data System (ADS)

    Dhodapkar, Madhav V.; Krasovsky, Joseph; Olson, Kara

    2002-10-01

    Most untreated cancer patients develop progressive tumors. We tested the capacity of T lymphocytes from patients with clinically progressive, multiple myeloma to develop killer function against fresh autologous tumor. In this malignancy, it is feasible to reproducibly evaluate freshly isolated tumor cells and T cells from the marrow tumor environment. When we did this with seven consecutive patients, with all clinical stages of disease, we did not detect reactivity to autologous cancer cells. However, both cytolytic and IFN--producing responses to autologous myeloma were generated in six of seven patients after stimulation ex vivo with dendritic cells that had processed autologous tumor cells. The antitumor effectors recognized fresh autologous tumor but not nontumor cells in the bone marrow, myeloma cell lines, dendritic cells loaded with tumor-derived Ig, or allogeneic tumor. Importantly, these CD8+ effectors developed with similar efficiency by using T cells from both the blood and the bone marrow tumor environment. Therefore, even in the setting of clinical tumor progression, the tumor bed of myeloma patients contains T cells that can be activated readily by dendritic cells to kill primary autologous tumor.

  16. Investigation of the immune response to autologous, allogeneic, and xenogeneic mesenchymal stem cells after intra-articular injection in horses.

    PubMed

    Pigott, John H; Ishihara, Akikazu; Wellman, Maxey L; Russell, Duncan S; Bertone, Alicia L

    2013-11-15

    Mesenchymal stem cells have demonstrated immunomodulatory capabilities as well as modest efficacy in animal models of joint injury, warranting further study as a potential treatment of joint disease. The goal of the study was to investigate the blood and synovial immune and histologic response to intra-articular injection of autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year-old Thoroughbred mares that had been injected previously with 15 million, genetically modified autologous, allogeneic, or xenogeneic MSC into the fetlock joints. One group of autologous cells was genetically modified to permit MSC biolocalization in the synovium. To assess response to the injection, synovial biopsies were obtained via arthroscopy 60 days after MSC injection for gross, histologic and molecular analyses. Peripheral blood mononuclear cells were isolated from each horse 120 days after MSC injection and co-cultured with a monolayer of each MSC group to permit quantification of activated CD4+ lymphocytes and cytokine release (ELISA) upon re-exposure to MSC. Arthroscopic examination revealed normal synovium with no grossly detrimental effect to the synovium or cartilage. Intra-articular MSC produced a persistent mononuclear infiltrate for at least 60 days, mostly perivascular, identified as CD3+ lymphocytes. An immune response (significant increase in CD4+ lymphocytes) was detected upon re-exposure to xenogeneic but not to allogeneic or autologous MSC. An inflammatory cytokine release from peripheral blood mononuclear cell/MSC co-cultures was present in all MSC groups but was significantly greater in the xenogeneic group. In conclusion, intra-articular injection of MSC, regardless of cell origin, incited a persistent mononuclear synovitis demonstrating a sustained biologic influence of these cells. Allogeneic cells did not elicit a detectable immune response upon re-exposure using our methods

  17. Transabdominal sacrocolpopexy with autologous rectus fascia graft.

    PubMed

    Abraham, Nitya; Quirouet, Adrienne; Goldman, Howard B

    2016-08-01

    Extrusion and infection are potential postoperative complications when using synthetic mesh for abdominal sacrocolpopexy. Long-term follow-up in the Colpopexy and Urinary Reduction Efforts (CARE) trial revealed an estimated 9.9 % risk of mesh extrusion. There are 26 reports of spondylodiscitis after sacrocolpopexy with synthetic mesh. These surgical risks may be decreased by using autologous fascia. To date, there have been no reports of extrusion or spondylodiscitis after using autologous fascia for sacrocolpopexy. This video demonstrates transabdominal sacrocolpopexy with an autologous rectus fascia graft. A 76-year-old woman with symptomatic stage 3 prolapse also had a history of diverticulitis and sigmoid abscess requiring sigmoid colectomy with end colostomy and incidental left ureteral transection with subsequent left nephrostomy tube placement. She presented for colostomy reversal, ureteral reimplantation, and prolapse repair. Given the need for concomitant colon and ureteral reconstruction, the risk of infection was potentially higher if synthetic mesh were used. The patient therefore underwent transabdominal sacrocolpopexy with autologous rectus fascia graft. At 4 months' follow-up the patient reported resolution of her symptoms and on examination she had no pelvic organ prolapse. Transabdominal sacrocolpopexy using autologous rectus fascia graft is a feasible option, especially in cases in which infection and synthetic mesh extrusion risks are potentially higher.

  18. Alvocidib in Treating Patients With B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2013-07-01

    B-cell Chronic Lymphocytic Leukemia; Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  19. Autoclaved bone autograph reconstituted with autologous bone marrow.

    PubMed

    Granados-García, Martín; Cabrera-Rojas, Jesús; Guzmán-Flores, Gerardo; Estrada-Lobato, Enrique; Cano-Valdés, Ana María; Santamaría-Linares, Erik

    2011-01-01

    Bone reconstruction is a common problem in the oncological setting. Mandibular reconstruction is done with microvascularized free flaps, but noticeable differences in shape and size exist in relation to the normal mandible; consequently, new reconstructive methods are desirable. We explored the feasibility of recovering osseous viability using a sterilized mandibular segment reconstituted with autologous bone marrow. A 6- to 7-cm mandibular segment was excised in three Creole dogs. The segment was autoclaved for 40 min. The bone was then drilled, producing 3-mm holes every 10-mm. Bone was reconstituted with autologous bone marrow from the iliac spine mixed with particulated bone. Bone autograph was installed underneath the latissimus dorsi muscle. On week four after surgery, dogs received colloidal rhenium and were placed in a gamma camera. The study showed uptake of the radiotracer in the bone graft, demonstrating viability of bone marrow. One hour later, the autograph was excised in two dogs and a histopathological study corroborated the viability of the bone marrow and the formation of new vessels and osteoid. On week twelve, the third dog was administered MDP-99Tc and placed in a gamma camera. Results proved production of new bone. Osseous reconstruction with microvascularized flaps may cause problems, but sterilized bone reconstituted with bone marrow becomes viable. This observation eventually would allow osseous reconstruction, including the mandibule, easily and reliably in patients with osseous tumors. Autoclaved bone reconstituted with bone marrow recovers its viability.

  20. Lymphocyte emperipolesis revisited

    PubMed Central

    Sandilands, G. P.; Reid, Fiona M.; Gray, Kathleen G.; Anderson, J. R.

    1978-01-01

    A surprisingly high proportion of antibody (IgG) sensitized Chang liver cells apparently contained one or more intracytoplasmic human peripheral blood lymphocytes following a period of contact at 37°. Since various technical factors were found to influence this phenomenon of lymphocyte `emperipolesis', optimum conditions were selected for use in a standard quantitative in vitro assay. Lymphocytes from normal individuals varied considerably in their ability to participate in emperipolesis; an observation which suggested that a particular lymphocyte subpopulation may be involved. Preliminary characterization of emperipoletic cells indicated that they are Fc receptor bearing, non-T lymphocytes. The significance of these findings in relation to immune mechanisms is discussed. ImagesFigure 1Figure 2 PMID:312253

  1. Lenalidomide and Vaccine Therapy in Treating Patients With Early-Stage Asymptomatic Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2017-04-24

    Chronic Lymphocytic Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma

  2. Effective activity of cytokine-induced killer cells against autologous metastatic melanoma including cells with stemness features.

    PubMed

    Gammaitoni, Loretta; Giraudo, Lidia; Leuci, Valeria; Todorovic, Maja; Mesiano, Giulia; Picciotto, Franco; Pisacane, Alberto; Zaccagna, Alessandro; Volpe, Maria Giuseppa; Gallo, Susanna; Caravelli, Daniela; Giacone, Elena; Venesio, Tiziana; Balsamo, Antonella; Pignochino, Ymera; Grignani, Giovanni; Carnevale-Schianca, Fabrizio; Aglietta, Massimo; Sangiolo, Dario

    2013-08-15

    We investigate the unknown tumor-killing activity of cytokine-induced killer (CIK) cells against autologous metastatic melanoma and the elusive subset of putative cancer stem cells (mCSC). We developed a preclinical autologous model using same patient-generated CIK cells and tumor targets to consider the unique biology of each patient/tumor pairing. In primary tumor cell cultures, we visualized and immunophenotypically defined a putative mCSC subset using a novel gene transfer strategy that exploited their exclusive ability to activate the promoter of stemness gene Oct4. The CIK cells from 10 patients with metastatic melanoma were successfully expanded (median, 23-fold; range, 11-117). Primary tumor cell cultures established and characterized from the same patients were used as autologous targets. Patient-derived CIK cells efficiently killed autologous metastatic melanoma [up to 71% specific killing (n = 26)]. CIK cells were active in vivo against autologous melanoma, resulting in delayed tumor growth, increased necrotic areas, and lymphocyte infiltration at tumor sites. The metastatic melanoma cultures presented an average of 11.5% ± 2.5% putative mCSCs, which was assessed by Oct4 promoter activity and stemness marker expression (Oct4, ABCG2, ALDH, MITF). Expression was confirmed on mCSC target molecules recognized by CIK cells (MIC A/B; ULBPs). CIK tumor killing activity against mCSCs was intense (up to 71%, n = 4) and comparable with results reported against differentiated metastatic melanoma cells (P = 0.8). For the first time, the intense killing activity of CIK cells against autologous metastatic melanoma, including mCSCs, has been shown. These findings move clinical investigation of a new immunotherapy for metastatic melanoma, including mCSCs, closer. ©2013 AACR.

  3. Pituitary abscess after autologous bone marrow transplantation.

    PubMed

    Leff, R S; Martino, R L; Pollock, W J; Knight, W A

    1989-05-01

    The first case of pituitary abscess arising in a patient during recovery from autologous bone marrow transplantation is reported. A 31-year-old man with a 9 month history of T-cell lymphoma died suddenly more than 60 days after successful treatment with high-dose cyclophosphamide, total body irradiation, and autologous bone marrow infusion. Autopsy revealed a pituitary abscess associated with clinically silent sphenoid sinusitis. Unique aspects of this case are presented and clinical and pathologic features of pituitary abscess are reviewed. Although rare, pituitary abscess may complicate recovery from bone marrow transplantation.

  4. Autologous fibrin adhesive in experimental tubal anastomosis.

    PubMed

    Rajaram, S; Rusia, U; Agarwal, S; Agarwal, N

    1996-01-01

    To evaluate autologous fibrin in rabbit oviduct anastomosis versus 7-0 vikryl, a conventional suture material used in tubal anastomosis. Thrombin was added to the autologous fibrinogen at the site of anastomosis to obtain a tissue adhesive. The anastomotic time, pregnancy rate, and litter size were evaluated. Three months later, a relaparotomy was done to evaluate patency and degree of adhesions, and a tubal biopsy was taken from the site of anastomosis. Analysis of results showed a statistically significant (P < .001) shortened anastomotic time and superior histopathological union in the tissue adhesive group. Patency rate, pregnancy rate, and degree of adhesions were comparable in both groups.

  5. Elutriated lymphocytes for manufacturing chimeric antigen receptor T cells.

    PubMed

    Stroncek, David F; Lee, Daniel W; Ren, Jiaqiang; Sabatino, Marianna; Highfill, Steven; Khuu, Hanh; Shah, Nirali N; Kaplan, Rosandra N; Fry, Terry J; Mackall, Crystal L

    2017-03-16

    Clinical trials of Chimeric Antigen Receptor (CAR) T cells manufactured from autologous peripheral blood mononuclear cell (PBMC) concentrates for the treatment of hematologic malignancies have been promising, but CAR T cell yields have been variable. This variability is due in part to the contamination of the PBMC concentrates with monocytes and granulocytes. Counter-flow elutriation allows for the closed system separation of lymphocytes from monocytes and granulocytes. We investigated the use of PBMC concentrates enriched for lymphocytes using elutriation for manufacturing 8 CD19- and 5 GD2-CAR T cell products. When compared to PBMC concentrates, lymphocyte-enriched elutriation fractions contained greater proportions of CD3+ and CD56+ cells and reduced proportions of CD14+ and CD15+ cells. All 13 CAR T cell products manufactured using the elutriated lymphocytes yielded sufficient quantities of transduced CAR T cells to meet clinical dose criteria. The GD2-CAR T cell products contained significantly more T cells and transduced T cells than the CD19-CAR T cell products. A comparison of the yields of CAR T cells produced from elutriated lymphocytes with the yields of CAR T cells previous produced from cells isolated from PBMC concentrates by anti-CD3/CD28 bead selection or by anti-CD3/CD28 bead selection plus plastic adherence found that greater quantities of GD2-CAR T cells were produced from elutriated lymphocytes, but not CD19-CAR T cells. Enrichment of PBMC concentrates for lymphocytes using elutriation increased the quantity of GD2-CAR T cells produced. These results provide further evidence that CAR T cell expansion is inhibited by monocytes and granulocytes.

  6. Influence of Immunotherapy with Autologous Dendritic Cells on Innate and Adaptive Immune Response in Cancer

    PubMed Central

    Matias, Bruna F.; de Oliveira, Tânia M.; Rodrigues, Cláudia M.; Abdalla, Douglas R.; Montes, Letícia; Murta, Eddie F.C.; Michelin, Márcia A.

    2013-01-01

    The objective of this study was to evaluate some of the mechanisms involved in the activation of the immune system in patients with advanced-stage cancer (n = 7) who received an autologous dendritic cell vaccine. We examined the immune response mediated by macrophages (CD14+), natural killer cells (CD56+), and B lymphocytes (CD19+) by flow cytometry and assessed the expression of Th1 (IFN-γ, TNF-α, IL-2, and IL-12), Th2 (IL-4), and Treg (TGF-β) cytokines by flow cytometry and an enzyme-linked immunosorbent assay. The CD14+ TNF-α+ population was significantly increased (P < 0.04) when patients received the vaccine; IL-2 expression in both NK cells and in B lymphocytes was increased after a transient initial increase showed a nearly significant decrease (P < 0.07 and P < 0.06 respectively), whereas the CD19+ and CD56+ populations did not show significant changes. Dendritic cell-based immunotherapy led to increased secretion of IFN-γ and IL-12 and reduced secretion of TGF-β. In conclusion, it is likely that the autologous dendritic cell vaccine stimulated the immune cells from the peripheral blood of patients with cancer and generally increased the production of Th1 cytokines, which are related to immunomodulatory responses against cancer. PMID:23926442

  7. Targeted Therapy for Acute Lymphocytic Leukemia

    MedlinePlus

    ... Adults Treating Acute Lymphocytic Leukemia Targeted Therapy for Acute Lymphocytic Leukemia In recent years, new drugs that target specific ... Typical Treatment of Acute Lymphocytic Leukemia More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  8. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... Adults About Acute Lymphocytic Leukemia (ALL) What Is Acute Lymphocytic Leukemia? Cancer starts when cells in the body begin ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  9. Supportive Care for Chronic Lymphocytic Leukemia

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Supportive Care for Chronic Lymphocytic Leukemia Supportive care for chronic lymphocytic leukemia (CLL) is ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  10. Purified plasminogen activating factor produced by malignant lymphoid cells abrogates lymphocyte cytotoxicity.

    PubMed Central

    Sundar, S K; Bergeron, J; Menezes, J

    1984-01-01

    Immunosuppression is a generally observed phenomenon in patients with malignancies. Here we report that plasminogen activating factor (PAF) produced by human (P3HR-1) and simian (B95-8) lymphoid cells of malignant origin abrogates lymphocyte cytotoxicity. PAF has been purified from Epstein-Barr (EB) virus genome carrying lymphocyte cytotoxicity. PAF has been purified from Epstein-Barr (EB) virus genome carrying lymphoid lines by affinity chromatography using lysine-Sepharose columns. Purified PAF consistently inhibited Killer cell activity against the following targets: K-562, EB virus superinfected Raji cells and in vitro EB virus transformed autologous B lymphocytes. Furthermore PAF also inhibited the antibody-dependent cellular cytotoxicity. The results presented also indicate that PAF affects the effector lymphocytes and not the target cells. Taken together, these observations emphasize the importance of factors such as PAF, released by malignant cells, as inhibitors/modulators of immune mechanisms effective against tumour cells. PMID:6430612

  11. Autologous and allogeneic hematopoietic stem cell transplantation in follicular lymphoma.

    PubMed

    Bhatt, V R; Armitage, J O

    2016-01-01

    High-dose chemotherapy and autologous stem cell transplantation (ASCT) improve survival in follicular lymphoma; however, relapse remains the most common cause of death. The lower risk of relapse with allogeneic SCT (alloSCT) is offset by a high transplant-related mortality (TRM). English articles indexed in the MEDLINE database were reviewed to discuss the role of graft purging, rituximab maintenance after ASCT, reduced-intensity conditioning (RIC) alloSCT, T-cell depletion, donor lymphocyte infusion (DLI) and alternate donor sources. Optimal salvage consolidation strategy may utilize ASCT following non-total body irradiation-based conditioning regimen in second remission. Rituximab maintenance after ASCT may improve molecular remission but is not yet shown to improve overall survival. RIC alloSCT permits its use in older and less-fit patients. Studies with T-cell depleted graft failed to reduce TRM despite a decline in graft-versus-host disease; however, these studies did demonstrate a therapeutic role of DLI in post-transplant relapses. In recent years, haploidentical and umbilical cord blood donors have emerged as alternative donor sources, with outcomes comparable to matched unrelated donor SCT. In the future, incorporation of novel therapeutic agents, improved risk-adapted treatment strategies, and advancement of transplant techniques may provide a better chance of survival.

  12. Helper activity by human large granular lymphocytes in in vitro immunoglobulin synthesis.

    PubMed

    Rodriguez, M A; Blanca, I; Baroja, M L; Arama, S; Leon-Ponte, M; Abadi, I; Bianco, N E

    1987-09-01

    In the present study we have examined the effect of human large granular lymphocytes (LGL) from healthy donors on Ig synthesis by autologous B lymphocytes. The results showed that this cell population has a consistent helper activity in pokeweed mitogen-activated cultures even when added at very low numbers. LGL can mediate their effect by secreting soluble helper factors capable of modulating B-cell responses as evidenced by the enhancement of IgG and IgM production by supernatants obtained from LGL cultures. Preincubation with interferon gamma further potentiated the helper activity by LGL.

  13. The use of decompression to simulate the effect of extravehicular activity on human lymphocyte transformation

    NASA Technical Reports Server (NTRS)

    Meehan, R. T.; Duncan, U.; Neale, L.; Waligora, J.; Taylor, G. R.

    1986-01-01

    Lymphocytes from 35 subjects participating in a chamber study simulating extravehicular activity (EVA) conditions were studied. No significant differences in H3 thymidine uptake between pre chamber and post chamber response to any mitogens autologous plasma, or among circulating mononuclear cells by flow cytometry are observed. The studies could not identify the subjects who developed venous bubbles. Data from eight subjects suggests that acute stress associated with participating in the study augments in vitro lymphocyte proliferation. Results indicate EVA exposure does not greatly influence space-flight induced alterations in immune effector cell function.

  14. Cord Blood Banking Standards: Autologous Versus Altruistic.

    PubMed

    Armitage, Sue

    2015-01-01

    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as "biological insurance" should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards.

  15. Cord Blood Banking Standards: Autologous Versus Altruistic

    PubMed Central

    Armitage, Sue

    2016-01-01

    Cord blood (CB) is either donated to public CB banks for use by any patient worldwide for whom it is a match or stored in a private bank for potential autologous or family use. It is a unique cell product that has potential for treating life-threatening diseases. The majority of CB products used today are for hematopoietic stem cell transplantation and are accessed from public banks. CB is still evolving as a hematopoietic stem cell source, developing as a source for cellular immunotherapy products, such as natural killer, dendritic, and T-cells, and fast emerging as a non-hematopoietic stem cell source in the field of regenerative medicine. This review explores the regulations, standards, and accreditation schemes that are currently available nationally and internationally for public and private CB banking. Currently, most of private banking is under regulated as compared to public banking. Regulations and standards were initially developed to address the public arena. Early responses from the medical field regarding private CB banking was that at the present time, because of insufficient scientific data to support autologous banking and given the difficulty of making an accurate estimate of the need for autologous transplantation, private storage of CB as “biological insurance” should be discouraged (1, 2, 3). To ensure success and the true realization of the full potential of CB, whether for autologous or allogeneic use, it is essential that each and every product provided for current and future treatments meets high-quality, international standards. PMID:26779485

  16. Autologous Diced Cartilage in Nasal Septoplasty

    PubMed Central

    Sersar, Sameh Ibrahim; Yassin, Ibrahim; Eldin Aly, Mohammed Saad

    2016-01-01

    Diced rib cartilage is an acceptable option in severe nasal deformities. We present our preliminary experience in KAMC in nasal septoplasties using the autologous diced costal cartilage. This is a retrospective study of the 22 cases who needed the autologous diced costal cartilage in our centre in 4 years. All our patients needed autologous diced rib cartilages. Twelve were wrapped with temporalis fascia, eight needed rectus fascia and perichondrium was used in only 2 cases. The naso-frontal angle for the whole series decreased by a mean of 4.41° (p=0.008) for the group using the rectus fascia diced cartilage graft. From the aesthetic point of view, all cases were satisfied except 3 (13.6%); two in the group of diced cartilage temporalis fascia; group 1. From the functional breathing view, only 1 case was not satisfied. He was in group 1. Autologous rib cartilage was shown to be a good graft in nasal septoplasty especially if wrapped with rectus fascia. PMID:27853694

  17. Autologous blood products in rotator cuff repair.

    PubMed

    Mei-Dan, Omer; Carmont, Michael R

    2012-01-01

    We review the management of rotator cuff tears, the mechanism of action of autologous blood products, principally platelet-rich plasma, and the current evidence for effective use of platelet-rich plasma, particularly in relation to the shoulder and chronic rotator cuff tears, for biological augmentation of rotator cuff repair.

  18. Autologous collagen induced chondrogenesis (ACIC: Shetty-Kim technique) - A matrix based acellular single stage arthroscopic cartilage repair technique.

    PubMed

    Shetty, Asode Ananthram; Kim, Seok Jung; Shetty, Vishvas; Jang, Jae Deog; Huh, Sung Woo; Lee, Dong Hwan

    2016-01-01

    The defects of articular cartilage in the knee joint are a common degenerative disease and currently there are several established techniques to treat this problem, each with their own advantages and shortcomings. Autologous chondrocyte implantation is the current gold standard but the technique is expensive, time-consuming and most versions require two stage procedures and an arthrotomy. Autologous collagen induced chondrogenesis (ACIC) is a single-stage arthroscopic procedure and we developed. This method uses microfracture technique with atelocollagen mixed with fibrin gel to treat articular cartilage defects. We introduce this ACIC techniques and its scientific background.

  19. Vaccination with Irradiated Autologous Melanoma Cells Engineered to Secrete Human Granulocyte--Macrophage Colony-Stimulating Factor Generates Potent Antitumor Immunity in Patients with Metastatic Melanoma

    NASA Astrophysics Data System (ADS)

    Soiffer, Robert; Lynch, Thomas; Mihm, Martin; Jung, Ken; Rhuda, Catherine; Schmollinger, Jan C.; Hodi, F. Stephen; Liebster, Laura; Lam, Prudence; Mentzer, Steven; Singer, Samuel; Tanabe, Kenneth K.; Benedict Cosimi, A.; Duda, Rosemary; Sober, Arthur; Bhan, Atul; Daley, John; Neuberg, Donna; Parry, Gordon; Rokovich, Joseph; Richards, Laurie; Drayer, Jan; Berns, Anton; Clift, Shirley; Cohen, Lawrence K.; Mulligan, Richard C.; Dranoff, Glenn

    1998-10-01

    We conducted a Phase I clinical trial investigating the biologic activity of vaccination with irradiated autologous melanoma cells engineered to secrete human granulocyte--macrophage colony-stimulating factor in patients with metastatic melanoma. Immunization sites were intensely infiltrated with T lymphocytes, dendritic cells, macrophages, and eosinophils in all 21 evaluable patients. Although metastatic lesions resected before vaccination were minimally infiltrated with cells of the immune system in all patients, metastatic lesions resected after vaccination were densely infiltrated with T lymphocytes and plasma cells and showed extensive tumor destruction (at least 80%), fibrosis, and edema in 11 of 16 patients examined. Antimelanoma cytotoxic T cell and antibody responses were associated with tumor destruction. These results demonstrate that vaccination with irradiated autologous melanoma cells engineered to secrete granulocyte--macrophage colony-stimulating factor stimulates potent antitumor immunity in humans with metastatic melanoma.

  20. COMPARATIVE STUDY OF BONE NEOFORMATION USING AUTOLOGOUS GRAFTING AND THREE REPLACEMENTS: BONE DEFECTS IN RATS

    PubMed Central

    Stein, Rodrigo Steffen; Silva, Jefferson Braga; Silva, Vinicius Duval da

    2015-01-01

    Objective: Compare the percentage of bone neoformation promoted by autologous bone grafting and three kinds of replacement materials with different characteristics in rats' femoral holes. Methods: Two holes measuring 5.4×2.7mm, were produced on each femur (right and left) of 14 isogenic Wistar rats. Each of the four defects produced was filled by autologous bone or by one of three tested materials-hydroxyapatite (HA), Genphos® (HA+ β-TCP) and GenMix® (a combined bovine bone graft). In the end of the 6-week (n = 6) and 12-week (n = 8) periods, the animals were sacrificed. The sections (stained with Picro-Sirius) were assessed by optical microscopy and specific software. Results: The groups with autologous bone were shown to be significantly superior to the others at both assessed times, showing a mean bone formation rate ± SD of 90.6 ± 10.8% in six weeks, and 98 ± 9.2% in 12 weeks (p > 0.0001 for both assessed times). In six weeks, the results for the other groups were the following: Genphos®, 46 ± 7.1%; HA, 43.1 ± 8.4%; and GenMix®, 57.3 ± 4.5%. In 12 weeks: Genphos®, 47.8 ± 11.1%; HA, 39.9 ± 5.4%; GenMix®, 59.7 ± 4.8%, significant (p = 0.007). Conclusions: In both assessed times, the three bone replacement materials tested in the study showed to be inferior to autologous bone graft for bone neoformation percentage. PMID:27022515

  1. Autologous lysate-pulsed dendritic cell vaccination followed by adoptive transfer of vaccine-primed ex vivo co-stimulated T cells in recurrent ovarian cancer.

    PubMed

    Kandalaft, Lana E; Powell, Daniel J; Chiang, Cheryl L; Tanyi, Janos; Kim, Sarah; Bosch, Marnix; Montone, Kathy; Mick, Rosemarie; Levine, Bruce L; Torigian, Drew A; June, Carl H; Coukos, George

    2013-01-01

    Novel strategies for the therapy of recurrent ovarian cancer are warranted. We report a study of a combinatorial approach encompassing dendritic cell (DC)-based autologous whole tumor vaccination and anti-angiogenesis therapy, followed by the adoptive transfer of autologous vaccine-primed CD3/CD28-co-stimulated lymphocytes. Recurrent ovarian cancer patients for whom tumor lysate was available from prior cytoreductive surgery underwent conditioning with intravenous bevacizumab and oral metronomic cyclophosphamide, sequentially followed by (1) bevacizumab plus vaccination with DCs pulsed with autologous tumor cell lysate supernatants, (2) lymphodepletion and (3) transfer of 5 × 10(9) autologous vaccine-primed T-cells in combination with the vaccine. Feasibility, safety as well as immunological and clinical efficacy were evaluated. Six subjects received this vaccination. Therapy was feasible, well tolerated, and elicited antitumor immune responses in four subjects, who also experienced clinical benefits. Of these, three patients with residual measurable disease received outpatient lymphodepletion and adoptive T-cell transfer, which was well tolerated and resulted in a durable reduction of circulating regulatory T cells and increased CD8(+) lymphocyte counts. The vaccine-induced restoration of antitumor immunity was achieved in two subjects, who also demonstrated clinical benefits, including one complete response. Our findings indicate that combinatorial cellular immunotherapy for the treatment of recurrent ovarian cancer is well tolerated and warrants further investigation. Several modifications of this approach can be envisioned to optimize immunological and clinical outcomes.

  2. Monitoring of cardiac antirejection therapy with /sup 111/In lymphocytes

    SciTech Connect

    Lerch, R.A.; Bergmann, S.R.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-06-01

    To determine whether lymphocytes labeled with /sup 111/In permit noninvasive assessment of antirejection therapy, we performed 40 allogeneic heterotopic cardiac transplants in rats. Antirejection therapy with azathioprine (30 mg/kg) and sodium salicylate (200 mg/kg) prolonged contractile function of the graft from 7.5 +/- 1.5 (s.d.) days in controls to 19.4 +/- 3.7 days in treated animals. Six to seven days after transplantation, autologous lymphocytes labeled with /sup 111/In were injected intravenously in seven untreated and eight treated rats. Scintigraphy and organ counting were performed 24 hr after administration of labeled cells. At sacrifice all grafts in untreated rats exhibited contractile failure, whereas grafts in all treated rats were beating well. Transplants in untreated recipients exhibited marked accumulation of /sup 111/In lymphocytes detectable scintigraphically, with ratios of 7.7 +/- 1.9 for the activity in the transplant over that in the native heart (HT/HO), as obtained by well counting. In contrast, accumulation was not scintigraphically detectable in transplants of treated rats, with HT/HO ratios of 2.6 +/- 1.8 (p less than 0.005). The results suggested that imaging with /sup 111/In-labeled lymphocytes will permit noninvasive assessment of antirejection therapy.

  3. Human lymphocyte sorting by gravitational field-flow fractionation.

    PubMed

    Roda, Barbara; Reschiglian, Pierluigi; Zattoni, Andrea; Tazzari, Pier Luigi; Buzzi, Marina; Ricci, Francesca; Bontadini, Andrea

    2008-09-01

    Interest in biological studies on various cell types for many biomedical applications, from research to patient treatments, is constantly increasing. The ability to discriminate (sort) and/or quantify distinct subpopulations of cells has become increasingly important. For instance, not only detection but also the highest depletion of neoplastic cells from normal cells is an important requisite in the autologous transplantation of lymphocytes for blood cancer treatments. In this work, gravitational field-flow fractionation (GrFFF) is shown to be effective for sorting a heterogeneous mixture of human, living lymphocytes constituted of neoplastic B cells from a Burkitt lymphoma cell line and healthy T and B lymphocytes from blood samples. GrFFF does not require the use of fluorescent immunotags for sorting cells, and the sorted cells can be collected for their further characterization. Flow cytometry was used to assess the viability of the cells collected, and to evaluate the cell fractionation achieved. A low amount of neoplastic B lymphocytes (less than 2%) was found in a specific fraction obtained by GrFFF. The high depletion from neoplastic cells (more than 98%) was confirmed by a clonogenicity test.

  4. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients.

    PubMed

    Gros, Alena; Parkhurst, Maria R; Tran, Eric; Pasetto, Anna; Robbins, Paul F; Ilyas, Sadia; Prickett, Todd D; Gartner, Jared J; Crystal, Jessica S; Roberts, Ilana M; Trebska-McGowan, Kasia; Wunderlich, John R; Yang, James C; Rosenberg, Steven A

    2016-04-01

    Detection of lymphocytes that target tumor-specific mutant neoantigens--derived from products encoded by mutated genes in the tumor--is mostly limited to tumor-resident lymphocytes, but whether these lymphocytes often occur in the circulation is unclear. We recently reported that intratumoral expression of the programmed cell death 1 (PD-1) receptor can guide the identification of the patient-specific repertoire of tumor-reactive CD8(+) lymphocytes that reside in the tumor. In view of these findings, we investigated whether PD-1 expression on peripheral blood lymphocytes could be used as a biomarker to detect T cells that target neoantigens. By using a high-throughput personalized screening approach, we identified neoantigen-specific lymphocytes in the peripheral blood of three of four melanoma patients. Despite their low frequency in the circulation, we found that CD8(+)PD-1(+), but not CD8(+)PD-1(-), cell populations had lymphocytes that targeted 3, 3 and 1 unique, patient-specific neoantigens, respectively. We show that neoantigen-specific T cells and gene-engineered lymphocytes expressing neoantigen-specific T cell receptors (TCRs) isolated from peripheral blood recognized autologous tumors. Notably, the tumor-antigen specificities and TCR repertoires of the circulating and tumor-infiltrating CD8(+)PD-1(+) cells appeared similar, implying that the circulating CD8(+)PD-1(+) lymphocytes could provide a window into the tumor-resident antitumor lymphocytes. Thus, expression of PD-1 identifies a diverse and patient-specific antitumor T cell response in peripheral blood, providing a novel noninvasive strategy to develop personalized therapies using neoantigen-reactive lymphocytes or TCRs to treat cancer.

  5. Interaction of Choriocarcinoma Cells and Human Peripheral Blood Lymphocytes

    PubMed Central

    August, Charles S.; Cox, Sheila T.; Naughton, Michael A.

    1979-01-01

    Cultured choriocarcinoma (Be Wo) cells exist that share many of the morphologic and bio-synthetic properties of normal human trophoblasts. In an attempt to develop a model for the immunologic relationship between a sensitized mother and fetus, we mixed Be Wo cells with mitogen-activated cytotoxic lymphocytes in vitro. Be Wo cells were resistant to the cytolytic effects of the activated lymphocytes despite 24-h exposure and intimate cell-to-cell contact as determined by microscopy. Control target cells, a line of human hepatoma cells, were readily destroyed. Cytotoxicity was measured by determining residual radioactivity of [3H]thymidine-labeled target cells after exposure to activated lymphocytes. Employing the quantitative assay, we confirmed the morphologic results and showed that Be Wo and a number of other choriocarcinoma cell lines were resistant to the cytotoxic effects of lymphocytes activated by phytohemagglutinin, pokeweed mitogen, and allogeneic cells in mixed lymphocyte cultures. Moreover, Be Wo cells were resistant to injury over a wide range of killer to target cell ratios. Significant killing of the Be Wo cells occurred only after prolonged exposure (48 and 72 h) to the activated lymphocytes. We suggest that one mechanism that may assist the fetus (or a choriocarcinoma) in its immunologic survival is the intrinsic resistance of trophoblast cells to lymphocyte-mediated cytotoxicity. Images PMID:570981

  6. B-1 cells promote immunosurveillance against murine melanoma in host absence of CCR5: new perspective in autologous vaccination therapy.

    PubMed

    Vivanco, Bruno C; Viana, Jacqueline D; Perez, Elisabeth C; Konno, Fabiana T C; Guereschi, Marcia G; Xander, Patricia; Keller, Alexandre C; Lopes, José D

    2014-11-01

    Autologous vaccination with tumor-primed dendritic cells increases immune response against tumor, which seems to be improved in host absence of CCR5. Because B-1 lymphocytes modulate the activity of different immune cells, we decided to study their influence in the resistance against murine B16F10 melanoma in a CCR5 deprived environment. Adoptive transfer of peritoneal B-1 CCR5(+/+) lymphocytes to CCR5(-/-) animals inhibited the establishment of lung metastasis and melanoma cell growth, in comparison to saline-treated CCR5(-/-) mice. In loco cell analysis demonstrated that the adoptive transfer of B-1 CCR5(+/+) lymphocytes to CCR5 deficient host was associated with a more intense influx of T CD8(+) to tumor site, indicating that the presence of CCR5(+/+) B-1 cells in the tumor environment induces the migration of T CD8 CCR5(-/-) cells to the implantation site. To corroborate this idea, CCR5(-/-) mice were injected with non B-1 peritoneal cells from wild type (WT) mice before B16F10 inoculation. In this regimen, CCR5(-/-) mice were not protected from tumor growth reinforcing the idea that, in host absence of CCR5, B-1 cells are essential to confer tumor resistance. This work indicates that, in the host absence of CCR5, naive B-1 cells may activate CD8T lymphocytes thereby promoting tumor resistance. Our results strongly suggest that autologous vaccination with B-1 lymphocytes in combination with CCR5 antagonists can be an alternative approach to tumor therapy. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. Intravenous administration of auto serum-expanded autologous mesenchymal stem cells in stroke.

    PubMed

    Honmou, Osamu; Houkin, Kiyohiro; Matsunaga, Takuya; Niitsu, Yoshiro; Ishiai, Sumio; Onodera, Rie; Waxman, Stephen G; Kocsis, Jeffery D

    2011-06-01

    Transplantation of human mesenchymal stem cells has been shown to reduce infarct size and improve functional outcome in animal models of stroke. Here, we report a study designed to assess feasibility and safety of transplantation of autologous human mesenchymal stem cells expanded in autologous human serum in stroke patients. We report an unblinded study on 12 patients with ischaemic grey matter, white matter and mixed lesions, in contrast to a prior study on autologous mesenchymal stem cells expanded in foetal calf serum that focused on grey matter lesions. Cells cultured in human serum expanded more rapidly than in foetal calf serum, reducing cell preparation time and risk of transmissible disorders such as bovine spongiform encephalomyelitis. Autologous mesenchymal stem cells were delivered intravenously 36-133 days post-stroke. All patients had magnetic resonance angiography to identify vascular lesions, and magnetic resonance imaging prior to cell infusion and at intervals up to 1 year after. Magnetic resonance perfusion-imaging and 3D-tractography were carried out in some patients. Neurological status was scored using the National Institutes of Health Stroke Scale and modified Rankin scores. We did not observe any central nervous system tumours, abnormal cell growths or neurological deterioration, and there was no evidence for venous thromboembolism, systemic malignancy or systemic infection in any of the patients following stem cell infusion. The median daily rate of National Institutes of Health Stroke Scale change was 0.36 during the first week post-infusion, compared with a median daily rate of change of 0.04 from the first day of testing to immediately before infusion. Daily rates of change in National Institutes of Health Stroke Scale scores during longer post-infusion intervals that more closely matched the interval between initial scoring and cell infusion also showed an increase following cell infusion. Mean lesion volume as assessed by magnetic

  8. Autologous serum eye drops for dry eye.

    PubMed

    Pan, Qing; Angelina, Adla; Marrone, Michael; Stark, Walter J; Akpek, Esen K

    2017-02-28

    Theoretically, autologous serum eye drops (AS) offer a potential advantage over traditional therapies on the assumption that AS not only serve as a lacrimal substitute to provide lubrication but contain other biochemical components that allow them to mimic natural tears more closely. Application of AS has gained popularity as second-line therapy for patients with dry eye. Published studies on this subject indicate that autologous serum could be an effective treatment for dry eye. We conducted this review to evaluate the efficacy and safety of AS given alone or in combination with artificial tears as compared with artificial tears alone, saline, placebo, or no treatment for adults with dry eye. We searched CENTRAL (which contains the Cochrane Eyes and Vision Trials Register) (2016, Issue 5), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to July 2016), Embase (January 1980 to July 2016), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to July 2016), the ISRCTN registry (www.isrctn.com/editAdvancedSearch), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We also searched the Science Citation Index Expanded database (December 2016) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 5 July 2016. We included randomized controlled trials (RCTs) that compared AS versus artificial tears for treatment of adults with dry eye. Two review authors independently screened all titles and abstracts and assessed full-text reports of potentially eligible trials. Two review authors extracted data and assessed risk of bias and characteristics of included trials. We contacted investigators to ask for missing data. For both primary and

  9. Buparvaquone but not cyclosporin A prevents Theileria annulata-infected bovine lymphoblastoid cells from stimulating uninfected lymphocytes.

    PubMed

    Rintelen, M; Schein, E; Ahmed, J S

    1990-06-01

    The influence of Buparvaquone on the morphology, proliferation, and stimulation with T and B cell mitogens of Theileria annulata-infected cells was studied. In addition, the stimulatory capacity of the infected cells before and after treatment with Buparvaquone or cyclosporin A (CsA) was also examined and compared to that of ConA-stimulated bovine peripheral blood cells (PBL). After incubation of the cells for 4 days with Buparvaquone only few schizonts were detectable in the cells. Prolongation of the incubation time to 8, 12, or 14 days eliminated completely the parasites. Despite the elimination of the parasites, the cells were still unable to undergo a proliferative response to Con A or PWM. However, the drug did not interfere with the response of normal PBL to these mitogens. Furthermore, Buparvaquone but not CsA inhibits the generation of mixed lymphocyte reaction (MLR). None of the drugs could prevent ConA-blasts from stimulating autologous PBL. These results suggest that the antigen expressed by the infected cells and recognised by the responder PBL was induced by the schizonts.

  10. Autologous antibodies that bind neuroblastoma cells.

    PubMed

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies.

  11. [Cartilage biopsy for autologous chondrocyte implantation (ACI)].

    PubMed

    Pestka, J M; Salzmann, G M; Südkamp, N P; Niemeyer, P

    2013-06-01

    Autologous chondrocyte implantation (ACI) is an established two-step procedure for the treatment of full-thickness cartilage defects of the knee. Cartilage harvest from the affected knee joint represents the first step of this procedure and is essential for further in vitro expansion of autologous chondrocytes. Nevertheless, the cartilage biopsy process itself is underrepresented in the scientific literature and currently there is only a limited amount of data available addressing this process. Biopsy location as well as the technique itself and instruments used for cartilage collection are not well defined and only little standardisation can be found. The article describes the relevant aspects of the biopsy in the context of ACI with regard to the literature available. Follow-up studies to better define and standardise the cartilage biopsy process are thus required.

  12. Autologous split peroneus longus lateral ankle stabilization.

    PubMed

    Budny, Adam M; Schuberth, John M

    2012-01-01

    Lateral ankle instability is a common clinical entity, and a variety of surgical procedures are available for stabilization after conservative management fails. Herein the authors reviewed outcomes after performing autologous split peroneus longus lateral ankle stabilization, using a previously described surgical technique to anatomically recreate the anterior talofibular and calcaneofibular ligaments. Twenty-five consecutive patients from 2 surgeons' practices underwent reconstruction between March 2007 and January 2011 with a minimum follow-up of 12 (range 12 to 51) months (mean 29.5 months). Follow-up interviews demonstrated 92.0% good or excellent outcomes with only 8.0% rating the outcome as fair and none as poor; 92.0% had no recurrent sprains or difficulty going up or down hills; 88.0% related no difficulty with uneven ground. The authors conclude that the autologous split peroneus longus lateral ankle stabilization results in a stable ankle with a low rate of complications and high patient satisfaction.

  13. [Integrated autologous fat graft in face recontouring].

    PubMed

    Xie, Yun; Zheng, Dan-Ning; Liu, Kai; Gu, Bin; Li, Qing-Feng

    2010-05-01

    To discuss the integrated autologous fat graft technique in face recontouring. In this study we treated 83 cases of face recontouring with 3L3M technique (low pressure suction, low speed centrifugation, low volume, multi-plane, multi-tunnel, multi-point injection). Each case was treated 1-3 times and the interval period is 3-6 months. The result was based on comparing the photos taken from pre-operation and post operation, observing the expression recovery, cysts, local absorption, and patients self evaluation. Long time follow up showed that fat graft can be alive in the recipient site for long time after 1-3 times autologous fat injection. More than 73.5% patients were satisfactory with the curative effect while less than 4.8% patients were unsatisfactory. 3L3M integrated fat graft technique is an effective and safe treatment in face recontouring.

  14. Pyoderma gangrenosum following autologous breast reconstruction

    PubMed Central

    Tuffaha, Sami H.; Robbins, Sanford H.; Bonawitz, Steven C.

    2017-01-01

    Pyoderma gangrenosum (PG) is an uncommon disorder characterized by the development of painful cutaneous ulceration, commonly precipitated by dermal injury at surgical sites. It is a diagnostic challenge as it manifests as necrotizing wounds which are commonly misdiagnosed as postoperative wound infection or ischemia. We discuss the clinical features and histopathological findings that allow for rapid identification of PG following autologous breast reconstruction and suggest an algorithm to aid diagnosis. PMID:28210559

  15. Pyoderma gangrenosum following autologous breast reconstruction.

    PubMed

    Singh, Prateush; Tuffaha, Sami H; Robbins, Sanford H; Bonawitz, Steven C

    2017-02-01

    Pyoderma gangrenosum (PG) is an uncommon disorder characterized by the development of painful cutaneous ulceration, commonly precipitated by dermal injury at surgical sites. It is a diagnostic challenge as it manifests as necrotizing wounds which are commonly misdiagnosed as postoperative wound infection or ischemia. We discuss the clinical features and histopathological findings that allow for rapid identification of PG following autologous breast reconstruction and suggest an algorithm to aid diagnosis.

  16. Recovery of autologous erythrocytes in transfused patients.

    PubMed

    Wallas, C H; Tanley, P C; Gorrell, L P

    1980-01-01

    A microcapillary method utilizing phthalate esters or an ultracentrifuge method are both capable of separating autologous from homologous erythrocytes in polytransfused patients. The microcapillary technique which is readily adaptable to blood bank laboratories provides a previously unavailable method for defining blood group antigen typings in transfused patients. Such typings are of vital importance in the laboratory evaluation of transfused patients with multiple or weak blood group antibodies.

  17. Autologous fat graft in postmastectomy pain syndrome.

    PubMed

    Caviggioli, Fabio; Maione, Luca; Forcellini, Davide; Klinger, Francesco; Klinger, Marco

    2011-08-01

    Mastectomy with axillary dissection is still one of the most common procedures in oncologic surgery. Unfortunately, a condition of neuropathic pain, termed postmastectomy pain syndrome, can appear after mastectomy. Although evidence regarding the epidemiology of postmastectomy pain syndrome is well researched, an effective therapy is still unknown. The aim of this study was to assess the clinical effectiveness of lipoaspirate graft in the treatment of postmastectomy pain syndrome. From February of 2006 to August of 2008, a total of 113 patients affected by postmastectomy pain syndrome and severe scar retractions were enrolled for this clinical study. Seventy-two patients were treated with autologous fat grafted in painful scars, and 41 patients did not undergo any further surgical procedure. Pain assessment was performed using a visual analogue scale before and after treatment, with a mean follow-up of 13 months. In addition, antalgic drug intake was recorded in the 34 patients who received a surgical treatment. Results were analyzed using the Wilcoxon rank sum test. A significant decrease in pain according to the visual analogue scale was detected in patients treated with autologous fat graft (3.23-point reduction, p = 0.0005). Twenty-eight of 34 patients stopped their analgesic therapy with a significant follow-up (13 months). Autologous fat grafting is a safe, relatively noninvasive, and rapid surgical procedure. The authors' results suggest its effectiveness for treatment of postmastectomy pain syndrome. Therapeutic, II.

  18. Development of autologous blood cell therapies.

    PubMed

    Kim, Ah Ram; Sankaran, Vijay G

    2016-10-01

    Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are performed commonly in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce the desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. Such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  19. Autologous platelet-labeling in thrombocytopenia

    SciTech Connect

    Sinzinger, H.; Virgolini, I.; Vinazzer, H. )

    1990-11-01

    Field studies performed with peripheral platelets obtained from 6 male volunteers aged 23 to 29 years revealed an extraordinary dependence of labeling efficiency on incubation time and platelet concentration after {sup 111}In-oxine platelet labeling. Since the monitoring of in vivo-platelet function in patients with thrombocytopenia may cause problems due to insufficient labeling results and homologous platelets may show a different in vivo behaviour to autologous ones, we have searched for the minimal amount of platelets necessary to allow appropriate labeling and imaging in patients with thrombocytopenia. In 15 patients with untreated thrombocytopenia aged 14 to 79 years demonstrating a mean peripheral platelet count of 2.509 +/- 1.45 x 10(4) cells/microliters autologous {sup 111}In-oxine platelet labeling was performed. The results indicate that approximately 1 x 10(8) (concentrated) platelets/ml are necessary to obtain an adequate labeling efficiency and recovery. This platelet concentration can be easily achieved by drawing one more Monovette of whole blood per each 5 x 10(4) platelets/microliter peripheral platelet count less than 2 x 10(5)/microliter. It is concluded, that calculation of the required number of platelets in advance, variation of the blood volume drawn and the volume of incubation buffer allow informative, qualitative and quantitative results using autologous platelets. The method presented effectively circumvents the requirement of homologous platelets for radiolabeling in thrombocytopenia.

  20. [Effects of recombinant interleukin-2 on several characteristics of functional activity of lymphocytes from the lymph nodes regional to tumor and mononuclear cells of peripheral blood in cancer patients].

    PubMed

    Semenova-Kobzar', R A; Kushko, L Ia; Iakhimovich, L V; Protsyk, V S; Tolstopiatov, B A; Konovalenko, V F; Berezhnaia, N M

    1990-01-01

    The level of endogenous production of IL-2 by lymphocytes of lymph nodes regional to tumour and by mononuclear cells of peripheral blood, proliferative response of these cell to recombinant IL-2, as well as a modifying influence of autologous serum and actively proliferating bioptats of autologous tumours on enumerated parameters have been studied in cancer patients (tumours of the head and neck and locomotor system). Regional IL-2-dependent immunotherapy of malignant tumors with obligatory preliminary testing for individual sensitivity of the tumor bioptat to the influence of the RIL-2 and RIL-2 activated lymphocytes is shown to be promising.

  1. Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2015-11-10

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  2. What Is Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells in the body begin ... the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts in the ...

  3. Dystrophic calcifications after autologous fat injection on face.

    PubMed

    Kim, Dai Hyun; Jang, Hee Won; Kim, Hee Joo; Son, Sang Wook

    2014-06-01

    Autologous fat injection is widely used procedure for various functional and aesthetic purposes. However, it could result in many immediate or delayed complications including dystrophic calcifications. Almost all of the case reports about dystrophic calcification after autologous fat injection were result from the iatrogenic tissue trauma of breast augmentation. This is a report of a 30-year-old patient who developed pathologically proven multiple dystrophic calcifications on the face after autologous fat injection.

  4. Autologous Chondrocytes and Next-Generation Matrix-Based Autologous Chondrocyte Implantation.

    PubMed

    Hinckel, Betina B; Gomoll, Andreas H

    2017-07-01

    Focal chondral defects of the knee are common and can significantly impair quality of life. The autologous chondrocyte implantation technique has evolved over the past 20 years; the newest third-generation technique is matrix-induced autologous chondrocyte implantation. Physical examination is important to characterize location and source of pain and identify associated injuries. Imaging studies allow characterization of the lesions, identification of associated lesions, and alignment. Conservative measures should be exhausted before proceeding with surgical treatment. Steps of surgical treatment are diagnostic arthroscopy and biopsy, chondrocyte culture, and chondrocyte implantation. The techniques and their outcomes are discussed in this article. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Autologous Growth Factor Injections in Chronic Tendinopathy

    PubMed Central

    Sandrey, Michelle A.

    2014-01-01

    Reference: de Vos RJ, van Veldhoven PLJ, Moen MH, Weir A, Tol JL. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull. 2010;95:63–77. Clinical Question: The authors of this systematic review evaluated the literature to critically consider the effects of growth factors delivered through autologous whole-blood and platelet-rich–plasma (PRP) injections in managing wrist-flexor and -extensor tendinopathies, plantar fasciopathy, and patellar tendinopathy. The primary question was, according to the published literature, is there sufficient evidence to support the use of growth factors delivered through autologous whole-blood and PRP injections for chronic tendinopathy? Data Sources: The authors performed a comprehensive, systematic literature search in October 2009 using PubMed, MEDLINE, EMBASE, CINAHL, and the Cochrane library without time limits. The following key words were used in different combinations: tendinopathy, tendinosis, tendinitis, tendons, tennis elbow, plantar fasciitis, platelet rich plasma, platelet transfusion, and autologous blood or injection. The search was limited to human studies in English. All bibliographies from the initial literature search were also viewed to identify additional relevant studies. Study Selection: Studies were eligible based on the following criteria: (1) Articles were suitable (inclusion criteria) if the participants had been clinically diagnosed as having chronic tendinopathy; (2) the design had to be a prospective clinical study, randomized controlled trial, nonrandomized clinical trial, or prospective case series; (3) a well-described intervention in the form of a growth factor injection with either PRP or autologous whole blood was used; and (4) the outcome was reported in terms of pain or function (or both). Data Extraction: All titles and abstracts were assessed by 2 researchers, and all relevant articles were obtained. Two researchers independently read the full text of

  6. Autologous growth factor injections in chronic tendinopathy.

    PubMed

    Sandrey, Michelle A

    2014-01-01

    de Vos RJ, van Veldhoven PLJ, Moen MH, Weir A, Tol JL. Autologous growth factor injections in chronic tendinopathy: a systematic review. Br Med Bull. 2010;95:63-77. The authors of this systematic review evaluated the literature to critically consider the effects of growth factors delivered through autologous whole-blood and platelet-rich-plasma (PRP) injections in managing wrist-flexor and -extensor tendinopathies, plantar fasciopathy, and patellar tendinopathy. The primary question was, according to the published literature, is there sufficient evidence to support the use of growth factors delivered through autologous whole-blood and PRP injections for chronic tendinopathy? The authors performed a comprehensive, systematic literature search in October 2009 using PubMed, MEDLINE, EMBASE, CINAHL, and the Cochrane library without time limits. The following key words were used in different combinations: tendinopathy, tendinosis, tendinitis, tendons, tennis elbow, plantar fasciitis, platelet rich plasma, platelet transfusion, and autologous blood or injection. The search was limited to human studies in English. All bibliographies from the initial literature search were also viewed to identify additional relevant studies. Studies were eligible based on the following criteria: (1) Articles were suitable (inclusion criteria) if the participants had been clinically diagnosed as having chronic tendinopathy; (2) the design had to be a prospective clinical study, randomized controlled trial, nonrandomized clinical trial, or prospective case series; (3) a well-described intervention in the form of a growth factor injection with either PRP or autologous whole blood was used; and (4) the outcome was reported in terms of pain or function (or both). All titles and abstracts were assessed by 2 researchers, and all relevant articles were obtained. Two researchers independently read the full text of each article to determine if it met the inclusion criteria. If opinions differed on

  7. The production of lymphocyte mitogenic factor and migration–inhibition factor by antigen-stimulated lymphocytes of subjects with grass pollen allergy

    PubMed Central

    Maini, R. N.; Dumonde, D. C.; Faux, J. A.; Hargreave, F. E.; Pepys, J.

    1971-01-01

    Peripheral blood lymphocytes of twenty-three subjects with grass pollen allergy were cultured with grass pollen antigen for 3 days. After harvesting, the culture supernatants were added to fresh autologous lymphocytes which were maintained in culture for 6 days. Cellular uptake of [3H]thymidine was measured during the sixth day of culture, and revealed that the lymphocyte culture supernatants stimulated greater thymidine uptake than expected from the lymphocyte transformation response to corresponding amounts of antigen. The supernatant factor which mediated this effect was termed `lymphocyte mitogenic factor' by analogy with a similar response of lymphocytes in clinical and experimental delayed hypersensitivity. Lymphocyte culture supernatants were also tested for migration–inhibition factor by their ability to inhibit the migration of guinea-pig macrophages. The majority of `allergic' supernatants contained a lymphocyte mitogenic factor active at 1/3 dilution (14/22) and 1/12 dilution (19/21) in contrast to supernatants derived from non-allergic subjects (2/16 and 1/17 respectively). The production of lymphocyte mitogenic factor corresponded to the occurrence of antigen-induced lymphocyte transformation (allergic: 18/22; non-allergic: 1/14); but only a minority of allergic supernatants contained a migration–inhibition factor (6/20). Clinical analysis revealed that migration–inhibition factor was particularly associated with the milder forms of allergy and with a past history of desensitization by depot injection of emulsified pollen antigen. In contrast, lymphocyte transformation and the production of mitogenic factor were uniformly distributed among the various categories of allergic subjects, all of whom had immediate (reaginic) hypersensitivity, but only three of whom had delayed hypersensitivity. The demonstration of lymphocyte mitogenic factor in a clinical state dominated by immediate hypersensitivity supported the view that antigen

  8. Lymphocytic hypophysitis in a dog with diabetes insipidus.

    PubMed

    Meij, B P; Voorhout, G; Gerritsen, R J; Grinwis, G C M; Ijzer, J

    2012-11-01

    An 8-year-old male German longhaired pointer was referred for diabetes insipidus responsive to treatment with desmopressin. The dog had polyuria and polydipsia, exercise intolerance and a dull hair coat. Plasma concentrations of thyroid-stimulating hormone, thyroxine, growth hormone (GH) and insulin-like growth factor-1 were decreased; plasma adrenocorticotropic hormone (ACTH) was slightly elevated and plasma α-melanocyte-stimulating hormone (MSH) was within the reference range. Computed tomography revealed a heterogeneously contrast-enhancing pituitary mass compressing the hypothalamus. Transsphenoidal hypophysectomy was performed and microscopical examination of the surgical biopsy samples revealed hypophysitis without evidence of pituitary adenoma. The hypophysitis was characterized by marked lymphocytic infiltration of the adenohypophysis that contained a mixed population of neuroendocrine cells expressing GH, ACTH or α-MSH. The lymphocytes were identified as T cells, resulting in a final diagnosis of lymphocytic hypophysitis strongly resembling human primary lymphocytic hypophysitis.

  9. Autologous CLL cell vaccination early after transplant induces leukemia-specific T cells.

    PubMed

    Burkhardt, Ute E; Hainz, Ursula; Stevenson, Kristen; Goldstein, Natalie R; Pasek, Mildred; Naito, Masayasu; Wu, Di; Ho, Vincent T; Alonso, Anselmo; Hammond, Naa Norkor; Wong, Jessica; Sievers, Quinlan L; Brusic, Ana; McDonough, Sean M; Zeng, Wanyong; Perrin, Ann; Brown, Jennifer R; Canning, Christine M; Koreth, John; Cutler, Corey; Armand, Philippe; Neuberg, Donna; Lee, Jeng-Shin; Antin, Joseph H; Mulligan, Richard C; Sasada, Tetsuro; Ritz, Jerome; Soiffer, Robert J; Dranoff, Glenn; Alyea, Edwin P; Wu, Catherine J

    2013-09-01

    Patients with advanced hematologic malignancies remain at risk for relapse following reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT). We conducted a prospective clinical trial to test whether vaccination with whole leukemia cells early after transplantation facilitates the expansion of leukemia-reactive T cells and thereby enhances antitumor immunity. We enrolled 22 patients with advanced chronic lymphocytic leukemia (CLL), 18 of whom received up to 6 vaccines initiated between days 30 and 45 after transplantation. Each vaccine consisted of irradiated autologous tumor cells admixed with GM-CSF-secreting bystander cells. Serial patient PBMC samples following transplantation were collected, and the impact of vaccination on T cell activity was evaluated. At a median follow-up of 2.9 (range, 1-4) years, the estimated 2-year progression-free and overall survival rates of vaccinated subjects were 82% (95% CI, 54%-94%) and 88% (95% CI, 59%-97%), respectively. Although vaccination only had a modest impact on recovering T cell numbers, CD8+ T cells from vaccinated patients consistently reacted against autologous tumor, but not alloantigen-bearing recipient cells with increased secretion of the effector cytokine IFN-γ, unlike T cells from nonvaccinated CLL patients undergoing allo-HSCT. Further analysis confirmed that 17% (range, 13%-33%) of CD8+ T cell clones isolated from 4 vaccinated patients by limiting dilution of bulk tumor-reactive T cells solely reacted against CLL-associated antigens. Our studies suggest that autologous tumor cell vaccination is an effective strategy to advance long-term leukemia control following allo-HSCT. Clinicaltrials.gov NCT00442130. NCI (5R21CA115043-2), NHLBI (5R01HL103532-03), and Leukemia and Lymphoma Society Translational Research Program.

  10. Evidence for the presence of a low molecular-weight activator of suppressor monocytes (LASM) in dialysates of T lymphocytes.

    PubMed

    Nekam, K; Strelkauskas, A J; Fudenberg, H H; Donnan, G G; Goust, J M

    1981-05-01

    Lysates of peripheral blood T lymphocytes from healthy individuals were found to contain a low molecular-weight peptide that inhibited phytohaemagglutinin-induced DNA synthesis in vitro by autologous or allogeneic peripheral blood mononuclear cells. The peptide was dialysable, partially heat stable, resistant to trypsin, RNase, and DNase but not to pronase, and was not part of the membrane receptor involved in rosette formation by T lymphocytes with sheep erythrocytes. It was found to act through monocytes, inducing the synthesis of second mediator responsible for the inhibition of lymphocyte DNA synthesis. This inducer of inhibition, designated as "low molecular-weight activator of suppressor monocytes' (LASM), may have a role in the depression of cellular immune response seen in various pathological conditions involving the destruction of T lymphocytes.

  11. Evidence for the presence of a low molecular-weight activator of suppressor monocytes (LASM) in dialysates of T lymphocytes.

    PubMed Central

    Nekam, K; Strelkauskas, A J; Fudenberg, H H; Donnan, G G; Goust, J M

    1981-01-01

    Lysates of peripheral blood T lymphocytes from healthy individuals were found to contain a low molecular-weight peptide that inhibited phytohaemagglutinin-induced DNA synthesis in vitro by autologous or allogeneic peripheral blood mononuclear cells. The peptide was dialysable, partially heat stable, resistant to trypsin, RNase, and DNase but not to pronase, and was not part of the membrane receptor involved in rosette formation by T lymphocytes with sheep erythrocytes. It was found to act through monocytes, inducing the synthesis of second mediator responsible for the inhibition of lymphocyte DNA synthesis. This inducer of inhibition, designated as "low molecular-weight activator of suppressor monocytes' (LASM), may have a role in the depression of cellular immune response seen in various pathological conditions involving the destruction of T lymphocytes. PMID:6972906

  12. General method for the detection and in vitro expansion of equine cytolytic T lymphocytes.

    PubMed

    Hammond, S A; Issel, C J; Montelaro, R C

    1998-04-01

    Equine immunological research is hindered by the lack of a simple yet reliable general protocol by which to assay CTL activity specific for viral or parasitic antigens. We present here the first comprehensive analysis of the parameters necessary to reliably culture equine T cells and to analyze the antigen specific cytolytic activity of T lymphocytes utilizing the equine infectious anemia virus (EIAV) infection of outbred ponies as a source for in vivo primed T lymphocytes. Effective long-term in vitro culture of equine T cells was determined to require minimally 200 U/ml of recombinant human IL-2. We demonstrated that pokeweed mitogen (PWM) stimulated PBMC generated large quantities of MHC class I and MHC class II expressing autologous lymphoblasts that were used initially to activate and expand antigen specific T lymphocytes and later to serve as a source of target cells in standard chromium release assays. The source of antigen expressed by the PWM lymphoblasts was a recombinant vaccinia virus vector which carried sequences encoding various antigens of interest, but most specifically, the envelope glycoprotein of EIAV. Secondary in vitro stimulation of the T lymphocytes by autologous PWM lymphoblasts expressing EIAV envelope glycoprotein was maximal using a ratio of 10 T cells to one stimulator cell. After antigen stimulation, responding T lymphocytes had antigen specific cytolytic activity and were of both the CD4 and CD8 lineage. The methodology presented here should provide an effective and reliable means by which to analyze the cytolytic activity of equine T lymphocytes to other foreign antigens. Furthermore, we suggest that this method derived for the equine animal model should be applicable to other mammalian and avian model systems that currently lack an effective means by which to analyze antigen specific CTL activity.

  13. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

    SciTech Connect

    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-07-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

  14. Reprogramming of Melanoma Tumor-Infiltrating Lymphocytes to Induced Pluripotent Stem Cells

    PubMed Central

    Saito, Hidehito; Okita, Keisuke; Fusaki, Noemi; Sabel, Michael S.; Chang, Alfred E.; Ito, Fumito

    2016-01-01

    Induced pluripotent stem cells (iPSCs) derived from somatic cells of patients hold great promise for autologous cell therapies. One of the possible applications of iPSCs is to use them as a cell source for producing autologous lymphocytes for cell-based therapy against cancer. Tumor-infiltrating lymphocytes (TILs) that express programmed cell death protein-1 (PD-1) are tumor-reactive T cells, and adoptive cell therapy with autologous TILs has been found to achieve durable complete response in selected patients with metastatic melanoma. Here, we describe the derivation of human iPSCs from melanoma TILs expressing high level of PD-1 by Sendai virus-mediated transduction of the four transcription factors, OCT3/4, SOX2, KLF4, and c-MYC. TIL-derived iPSCs display embryonic stem cell-like morphology, have normal karyotype, express stem cell-specific surface antigens and pluripotency-associated transcription factors, and have the capacity to differentiate in vitro and in vivo. A wide variety of T cell receptor gene rearrangement patterns in TIL-derived iPSCs confirmed the heterogeneity of T cells infiltrating melanomas. The ability to reprogram TILs containing patient-specific tumor-reactive repertoire might allow the generation of patient- and tumor-specific polyclonal T cells for cancer immunotherapy. PMID:27057178

  15. Autologous stem cell transplantation for systemic sclerosis.

    PubMed

    Farge, Dominique; Nash, Richard; Laar, Jacob M

    2008-12-01

    Systemic sclerosis (SSc) is a generalised autoimmune disease, of yet unknown origin, with two major clinical subsets: the limited (lcSSc) and the diffuse cutaneous (dcSSc) forms, which can be distinguished by the extent of skin involvement, the autoantibody profile and the pattern of organ involvement. With an incidence of 1/10(5), SSc affects around 250,000 people in Europe and is responsible for significant morbidity with a 5-year mortality rate of at least 30% of all patients. In patients with rapidly progressive dcSSc, the 5-year mortality is estimated to be 40-50%. Hematopoietic stem cell transplantation (HSCT), mostly autologous but also allogeneic in some specific cases, has been employed worldwide since 1996 as a new therapeutic strategy in patients with a poor prognosis. In 2007, 150 HSCT procedures have been reported in the EBMT data base. We review herein both the short and the long-term reports from the various European and North American phase I-II studies, which have shown that autologous HSCT in selected patients with severe dcSSc results in sustained improvement of skin thickening and stabilisation of organ function up to seven years after transplantation. Based on these promising results, ongoing phase III trials have been designed in parallel, both in Europe (ASTIS) and in North America (SCOTT) aiming to analyse the respective benefits from autologous HSCT respectively without or with high dose irradiation. This review reports the current data concerning the effects of HSCT on survival, skin, and major organ function in patients with severe dcSSc.

  16. HIV infection of monocytes inhibits the T-lymphocyte proliferative response to recall antigens, via production of eicosanoids.

    PubMed Central

    Foley, P; Kazazi, F; Biti, R; Sorrell, T C; Cunningham, A L

    1992-01-01

    Human monocytes infected in vitro with human immunodeficiency virus (HIV) soon after adherence to plastic substrate demonstrated a significantly decreased ability to restimulate autologous immune T-lymphocyte proliferation after exposure to soluble (tetanus toxoid) and particulate [herpes simplex virus (HSV)] antigen. Incubation with the cyclo-oxygenase inhibitor, indomethacin (2-5 microM), prevented inhibition of antigen-stimulated lymphocyte proliferation. The inhibitory activity was identified in ultrafiltrates containing the low molecular weight fraction (less than 3000 MW) of supernatants from HIV-infected monocyte cultures. This activity was significantly and markedly reduced in similar ultrafiltrates prepared from indomethacin-treated cultures. Increased concentrations of prostaglandin E2 (PGE2) were detected in ultrafiltrates from HIV-infected monocyte cultures compared with uninfected cultures and cultures preincubated with indomethacin. Ultrafiltrates were inhibitory when added during the presentation of antigen to T lymphocytes but not when removed from monocyte cultures prior to the addition of lymphocytes. In addition, ultrafiltrates inhibited antigen-stimulated lymphocyte proliferation and PHA-induced lymphocyte proliferation to the same extent. These data indicate that cyclo-oxygenase products of arachidonic acid, including PGE2, are produced in excess by HIV-infected monocytes and that PGE2 and perhaps other cyclo-oxygenase products are implicated in the inhibition of antigen-stimulated lymphocyte proliferation via a direct effect on T lymphocytes. PMID:1572689

  17. Heated tumour cells of autologous and allogeneic origin elicit anti-tumour immunity.

    PubMed

    Todryk, Stephen M; Eaton, Jonathan; Birchall, Lindsay; Greenhalgh, Rebecca; Soars, Diane; Dalgleish, Angus G; Melcher, Alan A; Pandha, Hardev S

    2004-04-01

    Vaccination with established tumour cell lines may circumvent the problem of obtaining autologous tumour cells from patients, but may also need immunological adjuvants. Up-regulation of heat shock proteins within tumour cell vaccines has resulted in increased immunogenicity in some models, but this has yet to be demonstrated for allogeneic (MHC-disparate) cell vaccines. This was investigated here using a rat model for prostate tumour cell vaccination. Heating of tumour cells (42 degrees C, 1 h) elicited significant increases in HSP70 expression. Vaccination with heated autologous PAIII cells elicited protection against PAIII challenge in 60% of rats >50 days compared to 0% with unheated vaccine and was associated with an increased Th1 (IFNgamma) immune response. Heated allogeneic MLL cells elicited significant protection against PAIII challenge, in contrast to unheated cells. The principle was confirmed in two mouse models, although the allogeneic melanoma vaccine K1735 elicited the best protection when heated and administered mixed with autologous dendritic cells. Thus, while heating of vaccine cells in some models is highly beneficial, and is a means of enhancing immunogenicity without genetic modification or inclusion of potentially toxic adjuvants, additional immune enhancement may be required.

  18. In vivo traffic of indium-111-oxine labeled human lymphocytes collected by automated apheresis

    SciTech Connect

    Read, E.J.; Keenan, A.M.; Carter, C.S.; Yolles, P.S.; Davey, R.J. )

    1990-06-01

    The in vivo traffic patterns of autologous lymphocytes were studied in five normal human volunteers using lymphocytes obtained by automated apheresis, separated on Ficoll-Hypaque gradients, and labeled ex vivo with {sup 111}In-oxine. Final lymphocyte infusions contained 1.8-3.1 X 10(9) cells and 270-390 microCi (9.99-14.43 MBq) {sup 111}In, or 11-17 microCi (0.41-0.63 MBq) per 10(8) lymphocytes. Gamma imaging showed transient lung uptake and significant retention of radioactivity in the liver and spleen. Progressive uptake of activity in normal, nonpalpable axillary and inguinal lymph nodes was seen from 24 to 96 hr. Accumulation of radioactivity also was demonstrated at the forearm skin test site, as well as in its associated epitrochlear and axillary lymph nodes, in a subject who had been tested for delayed hypersensitivity with tetanus toxoid. Indium-111-oxine labeled human lymphocytes may provide a useful tool for future studies of normal and abnormal lymphocyte traffic.

  19. Autologous bone marrow transplantation by photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Gulliya, Kirpal S.

    1992-06-01

    Simultaneous exposure of Merocyanine 540 dye containing cultured tumor cells to 514-nm laser light (93.6 J/cm2) results in virtually complete cell destruction. Under identical conditions, 40% of the normal progenitor (CFU-GM) cells survive the treatment. Laser- photoradiation treated, cultured breast cancer cells also were killed, and living tumor cells could not be detected by clonogenic assays or by anti-cytokeratin monoclonal antibody method. Thus, laser photoradiation therapy could be useful for purging of contaminating tumor cells from autologous bone marrow.

  20. Detection of accessory spleens with indium 111-labeled autologous platelets

    SciTech Connect

    Davis, H.H., II; Varki, A.; Heaton, W.A.; Siegel, B.A.

    1980-01-01

    In two patients with recurrent immune thrombocytopenia, accessory splenic tissue was demonstrated by radionuclide imaging following administration of indium 111-labeled autologous platelets. In one of these patients, no accessory splenic tissue was seen on images obtained with technetium 99m sulfur colloid. This new technique provides a simple means for demonstrating accessory spleens and simultaneously evaluating the life-span of autologous platelets.

  1. Traffic and proliferative responses of recirculating lymphocytes in fetal calves.

    PubMed Central

    Hein, W R; Shelton, J N; Simpson-Morgan, M W; Morris, B

    1988-01-01

    The thoracic duct or efferent prescapular duct was cannulated in four fetal calves aged 121-259 days post-conception. The duration of lymph flow ranged from 2 to 20 days and the mean flow rates sustained over these collection periods varied from 5.4 to 48.8 ml/hr. Lymphocyte output ranged from 4.4 x 10(6) cells/hr in thoracic duct lymph from a 121-day fetus to 3.9 x 10(8) cells/hr in efferent prescapular lymph from a 259-day fetus. The circulating lymphocyte pool in fetal calves of about 120 and 190 days gestational age was calculated to contain, respectively, 4 x 10(8) cells and 2 x 10(10) cells. The proportion of lymphocytes bearing surface immunoglobulin detected in fetal lymph ranged from 2.1% to 8.7%. Recirculating lymphocytes from fetal calves produced strong proliferative responses when stimulated by T-cell mitogens but responded poorly to B-cell mitogens. Fetal lymphocytes also responded to stimulation by allogeneic cells and stimulated other cells to proliferate during mixed lymphocyte culture. When stimulated with Con A, fetal lymphocytes secreted IL-2 to a degree that was indistinguishable from the secretory behaviour of lymphocytes from adult animals. The results presented in this paper show that chronic lymphatic fistulae can be established successfully in fetal calves to give access to recirculating lymphocytes. This provides a new experimental approach for studying the development of the bovine immune system. PMID:2971606

  2. Immunization of cancer patients with autologous cancer-derived heat shock protein gp96 preparations: a pilot study.

    PubMed

    Janetzki, S; Palla, D; Rosenhauer, V; Lochs, H; Lewis, J J; Srivastava, P K

    2000-10-15

    Heat shock protein (HSP)-peptide complexes isolated from murine cancers elicit protective immunity and T lymphocytes specific for the cancer from which the HSPs are isolated. A pilot study was designed to test the feasibility, immunogenicity and toxicity of such treatment in cancer patients. Sixteen patients with assorted advanced malignancies, which had become refractory to established therapies, were recruited. The gp96 vaccine was prepared for each patient from tumor obtained from that patient. Anti-tumor immune responses were evaluated using Elispot assays of T cells in peripheral blood after minimal in vitro stimulation. No unacceptable vaccine-related toxicities or auto-immune reactions were observed. Immunization with autologous gp96 elicited MHC I-restricted, tumor-specific CD8(+) T lymphocytes in 6/12 patients immunized. In addition, expansion of the NK cell population was seen in 8/13 of patients immunized. These observations are entirely consistent with the murine experience and form a firm basis for future trials with clinical end points, using autologous, patient-specific HSP-peptide vaccines. Copyright 2000 Wiley-Liss, Inc.

  3. Antitumor effects obtained by autologous Lewis lung cancer cell vaccine engineered to secrete mouse interleukin 27 by means of cationic liposome.

    PubMed

    Zhang, Junfeng; Tian, Hongwei; Li, Can; Cheng, Lin; Zhang, Shuang; Zhang, Xiaomei; Wang, Ruibo; Xu, Fen; Dai, Lei; Shi, Gang; Chen, Xiaolei; Li, Yiming; Du, Tao; Deng, Jie; Liu, Yu; Yang, Yang; Wei, Yuquan; Deng, Hongxin

    2013-10-01

    Interleukin-27 (IL-27), a novel IL-6/IL-12 family cytokine, plays an important role in the early regulation of Th1 responses. The cytokine IL-27 can exert a variety of immune-regulatory functions including cytotoxic T lymphocyte (CTL), CD4+, CD8+ T lymphocytes activation and interferon-γ (IFN-γ) production. In this study, we developed an effective and gene modified tumor cell vaccine. Lewis lung cancer cell LL/2 transfected with the DOTAP:cholesterol cationic liposome could express the mouse IL-27 (mIL-27) gene at a relative high level. The resultant transfectants were then irradiated with X-ray and used as a tumor cell vaccine. This tumor cell vaccine not only contained tumor associated antigen (TAA) of LL/2 cells but also secreted mIL-27 which could induce immune response in mice. The mice vaccinated with LL/2-mIL-27 performed strong tumor inhibiting effect accompanied with a high IFN-γ production. Both CD4+ and CD8+ T lymphocytes were significantly elevated in these mice vaccinated with LL/2-mIL-27 cell vaccine. Moreover, after depletion of CD4+, CD8+ T lymphocytes by injection of antibodies against CD4 and CD8, the vaccinated mice inoculated with autologous LL/2 cells were not protected from tumor challenge. In contrast, vaccinated mice inoculated with autologous LL/2 cells were treated with antibody against natural killer (NK)cells or normal rat IgG still possessed strong antitumor activity. Our data suggested that DOTAP:cholesterol cationic liposome was quite useful in generating an autologous tumor cell vaccine and mIL-27 could be therapeutically used to potentiate the host antitumor immunity.

  4. Detection methods for autologous blood doping.

    PubMed

    Segura, J; Monfort, N; Ventura, R

    2012-11-01

    The use of blood doping is forbidden by the World Anti-Doping Agency. Several practices, such as blood transfusions are used to increase oxygen delivery to muscles and all of them are highly pursued. In this regard, the development of accurate methodologies for detecting these prohibited practices is one of the current aims of the anti-doping control laboratories. Flow cytometry methods are able to detect allogeneic blood transfusions but there is no official methodology available to detect autologous blood transfusions. This paper reviews protocols, including the Athlete Biological Passport, that use indirect markers to detect misuse of blood transfusions, especially autologous blood transfusions. The methods of total haemoglobin mass measurements and the detection of metabolites of blood bags plasticizers in urine are reviewed. The latter seems to be an important step forward because it is a fast screening method and it is based on urine, a fluid widely available for doping control. Other innovative approaches to blood transfusion detection are also mentioned. A combination of the reported methodologies and the implementation of the Athlete Biological Passport is becoming a promising approach.

  5. Hyaline cartilage degenerates after autologous osteochondral transplantation.

    PubMed

    Tibesku, C O; Szuwart, T; Kleffner, T O; Schlegel, P M; Jahn, U R; Van Aken, H; Fuchs, S

    2004-11-01

    Autologous osteochondral grafting is a well-established clinical procedure to treat focal cartilage defects in patients, although basic research on this topic remains sparse. The aim of the current study was to evaluate (1) histological changes of transplanted hyaline cartilage of osteochondral grafts and (2) the tissue that connects the transplanted cartilage with the adjacent cartilage in a sheep model. Both knee joints of four sheep were opened surgically and osteochondral grafts were harvested and simultaneously transplanted to the contralateral femoral condyle. The animals were sacrificed after three months and the received knee joints were evaluated histologically. Histological evaluation showed a complete ingrowth of the osseous part of the osteochondral grafts. A healing or ingrowth at the level of the cartilage could not be observed. Histological evaluation of the transplanted grafts according to Mankin revealed significantly more and more severe signs of degeneration than the adjacent cartilage, such as cloning of chondrocytes and irregularities of the articular surface. We found no connecting tissue between the transplanted and the adjacent cartilage and histological signs of degeneration of the transplanted hyaline cartilage. In the light of these findings, long-term results of autologous osteochondral grafts in human beings have to be followed critically.

  6. Rapid cell separation with minimal manipulation for autologous cell therapies

    PubMed Central

    Smith, Alban J.; O’Rorke, Richard D.; Kale, Akshay; Rimsa, Roberts; Tomlinson, Matthew J.; Kirkham, Jennifer; Davies, A. Giles; Wälti, Christoph; Wood, Christopher D.

    2017-01-01

    The ability to isolate specific, viable cell populations from mixed ensembles with minimal manipulation and within intra-operative time would provide significant advantages for autologous, cell-based therapies in regenerative medicine. Current cell-enrichment technologies are either slow, lack specificity and/or require labelling. Thus a rapid, label-free separation technology that does not affect cell functionality, viability or phenotype is highly desirable. Here, we demonstrate separation of viable from non-viable human stromal cells using remote dielectrophoresis, in which an electric field is coupled into a microfluidic channel using shear-horizontal surface acoustic waves, producing an array of virtual electrodes within the channel. This allows high-throughput dielectrophoretic cell separation in high conductivity, physiological-like fluids, overcoming the limitations of conventional dielectrophoresis. We demonstrate viable/non-viable separation efficacy of >98% in pre-purified mesenchymal stromal cells, extracted from human dental pulp, with no adverse effects on cell viability, or on their subsequent osteogenic capabilities. PMID:28150746

  7. Rapid cell separation with minimal manipulation for autologous cell therapies

    NASA Astrophysics Data System (ADS)

    Smith, Alban J.; O'Rorke, Richard D.; Kale, Akshay; Rimsa, Roberts; Tomlinson, Matthew J.; Kirkham, Jennifer; Davies, A. Giles; Wälti, Christoph; Wood, Christopher D.

    2017-02-01

    The ability to isolate specific, viable cell populations from mixed ensembles with minimal manipulation and within intra-operative time would provide significant advantages for autologous, cell-based therapies in regenerative medicine. Current cell-enrichment technologies are either slow, lack specificity and/or require labelling. Thus a rapid, label-free separation technology that does not affect cell functionality, viability or phenotype is highly desirable. Here, we demonstrate separation of viable from non-viable human stromal cells using remote dielectrophoresis, in which an electric field is coupled into a microfluidic channel using shear-horizontal surface acoustic waves, producing an array of virtual electrodes within the channel. This allows high-throughput dielectrophoretic cell separation in high conductivity, physiological-like fluids, overcoming the limitations of conventional dielectrophoresis. We demonstrate viable/non-viable separation efficacy of >98% in pre-purified mesenchymal stromal cells, extracted from human dental pulp, with no adverse effects on cell viability, or on their subsequent osteogenic capabilities.

  8. Dermal Mesenchymal Stem Cells (DMSCs) Inhibit Skin-Homing CD8+ T Cell Activity, a Determining Factor of Vitiligo Patients’ Autologous Melanocytes Transplantation Efficiency

    PubMed Central

    Wu, Ji-long; Lin, Fu-quan; Fu, Li-fang; Wang, Sui-quan; Guan, Cui-ping; Wang, Hong-lin; Xu, Aie

    2013-01-01

    We here investigated the efficiency of autologous melanocyte transplantation of 23 vitiligo patients by focusing on perilesional skin homing CD8+ T lymphocytes, and studied the potential effect of dermal mesenchymal stem cells (DMSCs) on CD8+ T cell activities in vitro. Out of 23 patients with the autologous melanocyte transplantation, 12 patients (52.17%) had an excellent re-pigmentation, 6 patients (26.09%) had a good re-pigmentation, 5 patients (21.74%) had a fair or poor re-pigmentation. CD8+ T cells infiltrating was observed in the perilesional vitiligo area of all patients. Importantly, the efficiency of the transplantation was closely associated with skin-homing CD8+ T cell activities. The patients with high number of perilesional CD8+ T cells or high level of cytokines/chemokines were associated with poor re-pigmentation efficiency. For in-vitro experiments, we successfully isolated and characterized human DMSCs and skin-homing CD8+ T cells. We established DMSCs and CD8+ T cell co-culture system, where DMSCs possessed significant inhibitory effects against skin homing CD8+ T lymphocytes. DMSCs inhibited CD8+ T cells proliferation, induced them apoptosis and regulated their cytokines/chemokines production. Our results suggest that vitiligo patients’ autologous melanocytes transplantation efficiency might be predicted by perilesional skin-homing CD8+ T cell activities, and DMSCs might be used as auxiliary agent to improve transplantation efficacy. PMID:23577097

  9. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    PubMed Central

    Lotem, Michal; Merims, Sharon; Frank, Stephen; Hamburger, Tamar; Nissan, Aviram; Kadouri, Luna; Cohen, Jonathan; Straussman, Ravid; Eisenberg, Galit; Frankenburg, Shoshana; Carmon, Einat; Alaiyan, Bilal; Shneibaum, Shlomo; Ozge Ayyildiz, Zeynep; Isbilen, Murat; Mert Senses, Kerem; Ron, Ilan; Steinberg, Hanna; Smith, Yoav; Shiloni, Eitan; Gure, Ali Osmay; Peretz, Tamar

    2016-01-01

    Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH) response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p = 0.0001) 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2), MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p = 0.007). Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity. PMID:27294163

  10. Tositumomab and Iodine I 131 Tositumomab in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in First Remission

    ClinicalTrials.gov

    2015-08-04

    Lymphoid Leukemia in Remission; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  11. Curcumin and Cholecalciferol in Treating Patients With Previously Untreated Stage 0-II Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2016-10-04

    Contiguous Stage II Small Lymphocytic Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia

  12. Autologous versus allogeneic transfusion: patients' perceptions and experiences

    PubMed Central

    Graham, I D; Fergusson, D; Dokainish, H; Biggs, J; McAuley, L; Laupacis, A

    1999-01-01

    BACKGROUND: Preoperative autologous donation is one way to decrease a patient's exposure to allogeneic blood transfusion. This study was designed to determine patients' perceptions about the autologous blood donation process and their experiences with transfusion. METHODS: To assess patient perception, a questionnaire was administered a few days before surgery to patients undergoing elective cardiac and orthopedic surgery in a Canadian teaching hospital. All patients attending the preoperative autologous donation clinic during a 10-month period were eligible. A convenience sample of patients undergoing the same types of surgery who had not predonated blood were selected from preadmission clinics. Patient charts were reviewed retrospectively to assess actual transfusion practice in all cases. RESULTS: A total of 80 patients underwent cardiac surgery (40 autologous donors, 40 nondonors) and 73 underwent orthopedic surgery (38 autologous donors, 35 nondonors). Of the autologous donors, 75 (96%) attended all scheduled donation appointments, 73 (93%) said that they were "very likely" or "likely" to predonate again, and 75 (96%) said that they would recommend autologous donation to others. There was little difference in preoperative symptoms between the autologous donors and the nondonors, although the former were more likely than the latter to report that their overall health had remained the same during the month before surgery (30 [75%] v. 21 [52%] for the cardiac surgery patients and 30 [79%] v. 18 [51%] for the orthopedic surgery patients). When the autologous donors were asked what they felt their chances would have been of receiving at least one allogeneic blood transfusion had they not predonated, the median response was 80%. When they were asked what their chances were after predonating their own blood, the median response was 0%. The autologous donors were significantly less likely to receive allogeneic blood transfusions (6 [15%] for cardiac surgery and 3 [8

  13. Imbalance in distribution of functional autologous regulatory T cells in rheumatoid arthritis

    PubMed Central

    Behrens, Frank; Himsel, Andrea; Rehart, Stefan; Stanczyk, Joanna; Beutel, Björn; Zimmermann, Stefanie Y; Koehl, Ulrike; Möller, Burkhard; Gay, Steffen; Kaltwasser, Joachim P; Pfeilschifter, Josef M; Radeke, Heinfried H

    2007-01-01

    Objectives Regulatory T cells (Tregs) exert their anti‐inflammatory activity predominantly by cell contact‐dependent mechanisms. A study was undertaken to investigate the regulatory capacity of autologous peripheral blood Tregs in contact with synovial tissue cell cultures, and to evaluate their presence in peripheral blood, synovial tissue and synovial fluid of patients with rheumatoid arthritis (RA). Methods 44 patients with RA and 5 with osteoarthritis were included in the study. The frequency of interferon (IFN)γ‐secreting cells was quantified in synovial tissue cell cultures, CD3‐depleted synovial tissue cell cultures, synovial tissue cultures co‐cultured with autologous CD4+ and with CD4+CD25+ peripheral blood T cells by ELISPOT. Total CD3+, Th1 polarised and Tregs were quantified by real‐time PCR for CD3ε, T‐bet and FoxP3 mRNA, and by immunohistochemistry for FoxP3 protein. Results RA synovial tissue cell cultures exhibited spontaneous expression of IFNγ which was abrogated by depletion of CD3+ T cells and specifically reduced by co‐culture with autologous peripheral blood Treg. The presence of Treg in RA synovitis was indicated by FoxP3 mRNA expression and confirmed by immunohistochemistry. The amount of FoxP3 transcripts, however, was lower in the synovial membrane than in peripheral blood or synovial fluid. The T‐bet/FoxP3 ratio correlated with both a higher grade of synovial tissue lymphocyte infiltration and higher disease activity. Conclusion This study has shown, for the first time in human RA, the efficacy of autologous Tregs in reducing the inflammatory activity of synovial tissue cell cultures ex vivo, while in the synovium FoxP3+ Tregs of patients with RA are reduced compared with peripheral blood and synovial fluid. This local imbalance of Th1 and Treg may be responsible for repeated rheumatic flares and thus will be of interest as a target for future treatments. PMID:17392348

  14. Dendritic cells restore CD8+ T cell reactivity to autologous HIV-1.

    PubMed

    Smith, Kellie N; Mailliard, Robbie B; Larsen, Brendan B; Wong, Kim; Gupta, Phalguni; Mullins, James I; Rinaldo, Charles R

    2014-09-01

    Recall T cell responses to HIV-1 antigens are used as a surrogate for endogenous cellular immune responses generated during infection. Current methods of identifying antigen-specific T cell reactivity in HIV-1 infection use bulk peripheral blood mononuclear cells (PBMC) yet ignore professional antigen-presenting cells (APC) that could reveal otherwise hidden responses. In the present study, peptides representing autologous variants of major histocompatibility complex (MHC) class I-restricted epitopes from HIV-1 Gag and Env were used as antigens in gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and polyfunctional cytokine assays. Here we show that dendritic cells (DC) enhanced T cell reactivity at all stages of disease progression but specifically restored T cell reactivity after combination antiretroviral therapy (cART) to early infection levels. Type 1 cytokine secretion was also enhanced by DC and was most apparent late post-cART. We additionally show that DC reveal polyfunctional T cell responses after many years of treatment, when potential immunotherapies would be implemented. These data underscore the potential efficacy of DC immunotherapy that aims to awaken a dormant, autologous, HIV-1-specific CD8+ T cell response. Assessment of endogenous HIV-1-specific T cell responses is critical for generating immunotherapies for subjects on cART. Current assays ignore the ability of dendritic cells to reveal these responses and may therefore underestimate the breadth and magnitude of T cell reactivity. As DC do not prime new responses in these assays, it can be assumed that the observed responses are not detected without appropriate stimulation. This is important because dogma states that HIV-1 mutates to evade host recognition and that CD8+ cytotoxic T lymphocyte (CTL) failure is due to the inability of T cells to recognize the autologous virus. The results presented here indicate that responses to autologous virus are generated during infection

  15. Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens

    PubMed Central

    Hessell, Ann J.; Malherbe, Delphine C.; Pissani, Franco; McBurney, Sean; Krebs, Shelly J.; Gomes, Michelle; Pandey, Shilpi; Sutton, William F.; Burwitz, Benjamin J.; Gray, Matthew; Robins, Harlan; Park, Byung S.; Sacha, Jonah B.; LaBranche, Celia C.; Fuller, Deborah H.; Montefiori, David C.; Stamatatos, Leonidas; Sather, D. Noah

    2016-01-01

    Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B–infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements. PMID:26944928

  16. Achieving Potent Autologous Neutralizing Antibody Responses against Tier 2 HIV-1 Viruses by Strategic Selection of Envelope Immunogens.

    PubMed

    Hessell, Ann J; Malherbe, Delphine C; Pissani, Franco; McBurney, Sean; Krebs, Shelly J; Gomes, Michelle; Pandey, Shilpi; Sutton, William F; Burwitz, Benjamin J; Gray, Matthew; Robins, Harlan; Park, Byung S; Sacha, Jonah B; LaBranche, Celia C; Fuller, Deborah H; Montefiori, David C; Stamatatos, Leonidas; Sather, D Noah; Haigwood, Nancy L

    2016-04-01

    Advancement in immunogen selection and vaccine design that will rapidly elicit a protective Ab response is considered critical for HIV vaccine protective efficacy. Vaccine-elicited Ab responses must therefore have the capacity to prevent infection by neutralization-resistant phenotypes of transmitted/founder (T/F) viruses that establish infection in humans. Most vaccine candidates to date have been ineffective at generating Abs that neutralize T/F or early variants. In this study, we report that coimmunizing rhesus macaques with HIV-1 gp160 DNA and gp140 trimeric protein selected from native envelope gene sequences (envs) induced neutralizing Abs against Tier 2 autologous viruses expressing cognate envelope (Env). The Env immunogens were selected from envs emerging during the earliest stages of neutralization breadth developing within the first 2 years of infection in two clade B-infected human subjects. Moreover, the IgG responses in macaques emulated the targeting to specific regions of Env known to be associated with autologous and heterologous neutralizing Abs developed within the human subjects. Furthermore, we measured increasing affinity of macaque polyclonal IgG responses over the course of the immunization regimen that correlated with Tier 1 neutralization. In addition, we report firm correlations between Tier 2 autologous neutralization and Tier 1 heterologous neutralization, as well as overall TZM-bl breadth scores. Additionally, the activation of Env-specific follicular helper CD4 T cells in lymphocytes isolated from inguinal lymph nodes of vaccinated macaques correlated with Tier 2 autologous neutralization. These results demonstrate the potential for native Env derived from subjects at the time of neutralization broadening as effective HIV vaccine elements.

  17. Clinical study of autologous cytokine-induced killer cells for the treatment of elderly patients with diffuse large B-cell lymphoma.

    PubMed

    Lu, Xue-chun; Yang, Bo; Yu, Rui-li; Chi, Xiao-hua; Tuo, Shuai; Tuo, Chao-wei; Zhu, Hong-li; Wang, Yao; Jiang, Chao-guang; Fu, Xiao-bing; Yang, Yang; Liu, Yang; Yao, Shan-qian; Dai, Han-ren; Cai, Lili; Li, Bing-jun; Han, Wei-dong

    2012-01-01

    To evaluate the effectiveness and safety of autologous cytokine-induced killer (CIK) cells in elderly patients with diffuse large B-cell lymphoma. Peripheral blood mononuclear cells (PBMC) were isolated from nine elderly patients with diffuse large B-cell lymphoma. PBMCs were augmented by priming with interferon gamma (IFN-γ) followed by IL-2 and monoclonal antibody (mAb) against CD3. Autologous CIK cells (range 5 × 10(9)-1 × 10(10)) were then infused back to individual patients; infusion was repeated every 4 weeks for 32 weeks (eight cycles). Patients were assessed for changes in lymphocyte subgroup, tumor-related biological parameters, imaging characteristics, the condition of remission, quality of life (QOL), and survival. Prior to CIK infusion, two patients were in complete remission and seven patients were in partial remission. After autologous CIK cell transfusions, the proportion of CD3+, CD3+CD8+, and CD3+CD56+ cells were significantly increased compared with baseline (P < 0.05); whereas serum levels of β2-microglobulin and LDH were significantly decreased (P < 0.05). The lymphoma symptoms were reduced and QOL was improved (P < 0.05) in all patients. All patients achieved complete remission at study endpoint. No adverse reactions were reported. Autologous CIK cell immunotherapy is safe and efficacious for the treatment of elderly patients with diffuse large B-cell lymphoma.

  18. Use of autologous growth factors in lumbar spinal fusion.

    PubMed

    Lowery, G L; Kulkarni, S; Pennisi, A E

    1999-08-01

    The results of spinal fusion, especially posteriorly above the lumbosacral junction, have been mixed. Autologous growth factor concentrate (AGF) prepared by ultraconcentration of platelets contains multiple growth factors having a chemotactic and mitogenic effect on mesenchymal stem cells and osteoblasts and may play a role in initiating bone healing. The purpose of this retrospective study is to review our results with AGF in lumbar spinal fusions. To date, AGF has been used in 39 patients having lumbar spinal fusion. The study group consisted of the first 19 consecutive cases to allow at least 6 months follow-up. The average follow-up was 13 months (range 6 to 18 months). Follow-up compliance was 91%. There were 7 men and 12 women. Average age was 52 years (range 30-72 years). Nine patients had prior back surgery. There were 8 smokers. AGF was used in posterior (n = 15) or anterior intradiscal (n = 4) fusions. AGF was used with autograft and coraline hydroxyapatite in all posterior fusions, and autograft, coral, and intradiscal spacer (carbon fiber spinal fusion cages or Synthes femoral ring) in intradiscal fusions. Posterior stabilization was used in all cases. Eight cases were single-level fusions, 6 were two-level, and 1 was a three-level fusion. Autologous iliac crest bone graft was taken in 14 cases and local autograft used in 5 cases. Posteriorly, a total of 23 levels were fused; of these, nine were at L5-S1, eight at L4-L5, five at L3-L4, and one at L2-L3. No impending pseudoarthroses were noted on plain radiographic examination at last follow-up visit. Solid fusion was confirmed in 3 patients having routine hardware removal, and in 2 patients who had surgery at an adjacent level. There was one posterior wound infection, which was managed without sequelae. When used as an adjunct to autograft, AGF offers theoretical advantages that need to be examined in controlled studies. Further study is necessary to determine whether coralline hydroxyapatite used as a

  19. [Repair of chondral defects of the knee using a combination of autologous chondrocytes and osteochondral allograft--an animal model. Part I: in vitro culture of autologous chondrocytes].

    PubMed

    Bacenková, D; Rosocha, J; Svihla, R; Vasko, G; Bodnár, J

    2001-01-01

    In the study we used in vitro cultivated autologous chondrocytes in combination with osteochondral allografts for the treatment of local defects of articular cartilage on the animal model (rabbit). Chondrocytes for in vitro cultivation were harvested by biopsy of articular cartilage of rabbit. For the monolayer cultivation we used Nutrient mix F 12 (Gibco BRL) with addition of Lascorbic acid (50 micrograms/ml, Sigma) and insulin-trasferin-selenium (A 6.26 micrograms/ml, Gibco BRL), 20% of fectal serum (Gibco BRL) and antibiotic antimycotic solution (Gibco BRL). Cultivation of chondrocytes took place at 37 degrees in the atmosphere of 5% CO2. Multiplied chondrocytes re-suspended in fibrin glue in combination with two osteochondral allografts were used for the reparation of artificial defect of the rabbit cartilage. For the analysis of collagen type II in the cultivation medium we used the principle of salting out by 30% ammonium sulphate and subsequent pepsinization in an acid environment with a repeated salting out by means of 2M of NaCl. Precipitates were dissolved in 5.0 M of acetic acid and used for SDS PAGE and immunoblotting. As a detection system we used ECL (Amersham/Pharmacia Biotech). The final average number of chondrocytes multiplied by monolayer cultivation was 1.10(5). The presence of collagen of type II has proved the preservation of the original phenotype of chondrocytes during cultivation. Bioengineering use of cell and tissue cultivation provides new options of the treatment of defect of connective tissue. Transplantation of autologous chondrocytes in combination with osteochondral allografts is on the basis of our results obtained so far a promising therapy. The aim of our work was an ex vivo expansion of autologous chondrocytes for the purpose of cell transplantation.

  20. Lymphocyte 'homing' and chronic inflammation.

    PubMed

    Sakai, Yasuhiro; Kobayashi, Motohiro

    2015-07-01

    Chronic inflammation is a response to prolonged exposure to injurious stimuli that harm and destroy tissues and promote lymphocyte infiltration into inflamed sites. Following progressive accumulation of lymphocytes, the histology of inflamed tissue begins to resemble that of peripheral lymphoid organs, which can be referred to as lymphoid neogenesis or formation of tertiary lymphoid tissues. Lymphocyte recruitment to inflamed tissues is also reminiscent of lymphocyte homing to peripheral lymphoid organs. In the latter, under physiological conditions, homing receptors expressed on lymphocytes adhere to vascular addressin expressed on high endothelial venules (HEVs), initiating a lymphocyte migration process composed of sequential adhesive interactions. Intriguingly, in chronic inflammation, HEV-like vessels are induced de novo, despite the fact that the inflamed site is not originally lymphoid tissue, and these vessels contribute to lymphocyte recruitment in a manner similar to physiological lymphocyte homing. In this review, we first describe physiological lymphocyte homing mechanisms focusing on vascular addressins. We then describe HEV-like vessel-mediated pathogenesis seen in various chronic inflammatory disorders such as Helicobacter pylori gastritis, inflammatory bowel disease (IBD), autoimmune pancreatitis and sclerosing sialadenitis, as well as chronic inflammatory cell neoplasm MALT lymphoma, with reference to our work and that of others.

  1. Lymphocytic Interstitial Pneumonia.

    PubMed

    Panchabhai, Tanmay S; Farver, Carol; Highland, Kristin B

    2016-09-01

    Lymphocytic interstitial pneumonia (LIP) is a rare lung disease on the spectrum of benign pulmonary lymphoproliferative disorders. LIP is frequently associated with connective tissue diseases or infections. Idiopathic LIP is rare; every attempt must be made to diagnose underlying conditions when LIP is diagnosed. Computed tomography of the chest in patients with LIP may reveal ground-glass opacities, centrilobular and subpleural nodules, and randomly distributed thin-walled cysts. Demonstrating polyclonality with immunohistochemistry is the key to differentiating LIP from lymphoma. The 5-year mortality remains between 33% and 50% and is likely to vary based on the underlying disease process.

  2. [Painful lymphocytic subacute thyroiditis].

    PubMed

    Cortázar, A; Ruiz de Gordejuela, J; Zabalza, I; Acinas, O; Beitia, J J

    1992-01-25

    Subacute granulomatous thyroiditis (SGT) and subacute lymphocytic thyroiditis (SLT) present a similar evolution during the first year, however, posteriorly, except on rare occasions, SGT maintains normofunction while SLT may present relapse with persistent goiter or permanent hypothyroidism requiring periodic follow up. The presence of spontaneous pain and very elevated VSG have been described accompanying SGT but not SLT histologically proven to be used for differentiating these entities. Two cases with clinical criteria and cytological diagnosis of SLT consulted for spontaneous thyroid pain are presented. VSG greater than 50 mm/1st hour was suggestive of SGT. The importance of cytology for the correct management of subacute thyroiditis is emphasized.

  3. Rapid desensitization with autologous sweat in cholinergic urticaria.

    PubMed

    Kozaru, Takeshi; Fukunaga, Atsushi; Taguchi, Kumiko; Ogura, Kanako; Nagano, Tohru; Oka, Masahiro; Horikawa, Tatsuya; Nishigori, Chikako

    2011-09-01

    The majority of patients with cholinergic urticaria presents with strong hypersensitivity to autologous sweat. Patients with severe cholinergic urticaria are frequently resistant to H(1) antagonists which are used in conventional therapies for various types of urticaria. It has been reported that desensitization using partially purified sweat antigen was effective in a patient with cholinergic urticaria. The aim of this study is to determine the usefulness of rapid desensitization with autologous sweat in severe cholinergic urticaria, because rapid desensitization has proven to be a quick and effective immunotherapy for allergies to various allergens. Six patients with severe cholinergic urticaria who are resistant to H(1) antagonists and have sweat hypersensitivity were enrolled in a rapid desensitization protocol. In all six patients, the responses for skin tests with autologous sweat were attenuated after rapid desensitization with autologous sweat. Two of the three cholinergic urticaria patients showed reduced histamine release with autologous sweat after the rapid desensitization with autologous sweat. Further, the rapid desensitization and subsequent maintenance treatment reduced the symptoms in five of the six patients. This study provides evidence that rapid desensitization with autologous sweat is beneficial for treating cholinergic urticaria patients resistant to conventional therapy who have sweat hypersensitivity.

  4. Serotype b of Aggregatibacter actinomycetemcomitans increases osteoclast and memory T-lymphocyte activation.

    PubMed

    Melgar-Rodríguez, S; Díaz-Zúñiga, J; Alvarez, C; Rojas, L; Monasterio, G; Carvajal, P; Escobar, A; Sanz, M; Vernal, R

    2016-04-01

    During periodontitis, alveolar bone resorption is associated with activation of T helper type 17 (Th17) lymphocytes and receptor activator of nuclear factor-κB ligand (RANKL) -induced osteoclasts. We previously reported that serotype b of Aggregatibacter actinomycetemcomitans has a higher capacity to trigger Th17-type differentiation and function in activated T lymphocytes and its lipopolysaccharide is a more potent immunogen compared with the other serotypes. This study aimed to investigate whether serotype b of A. actinomycetemcomitans induces higher Th17-associated RANKL production, RANKL-induced osteoclast activation, and antigen-specific memory T lymphocyte proliferation. On naive CD4(+) T lymphocytes stimulated with autologous dendritic cells primed with different A. actinomycetemcomitans serotypes, RANKL production, T-bet, GATA-3, RORC2 and Foxp3 expression, RORC2/RANKL intracellular double-expression, TRAP(+) osteoclast activation, and bone resorption were quantified. The frequency of proliferating memory T lymphocytes in response to A. actinomycetemcomitans serotypes was determined in periodontitis and healthy subjects. Naive CD4(+) T lymphocytes stimulated by serotype b-primed dendritic cells elicited higher levels of RANKL, RORC2, TRAP(+) osteoclasts, and bone resorption than the same cells stimulated with the other serotypes. RANKL positively correlated and co-expressed with RORC2. Memory T lymphocytes responding to serotype b were more frequently detected in periodontitis patients than healthy subjects. These results indicate that serotype b of A. actinomycetemcomitans is associated with higher production of RANKL and these increased levels are associated with Th17 lymphocyte induction, osteoclast activation, and bone resorption.

  5. Lenalidomide, Ibrutinib, and Rituximab in Treating Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma That Is Metastatic or Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2017-09-04

    Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  6. Human CD4low CD25high regulatory T cells indiscriminately kill autologous activated T cells

    PubMed Central

    Bryl, Ewa; Daca, Agnieszka; Jóźwik, Agnieszka; Witkowski, Jacek M

    2009-01-01

    The interest of the scientific community in regulatory CD4+ T cells has reached an enormously high level. Common agreement is that they inhibit not only the proliferation of CD4 and CD8 lymphocytes, but also the activities of natural killer cells and macrophages. However, very important issues concerning actual mechanism(s) and specificity of the action of regulatory T cells (Tregs) upon responder cells are still unsolved or vague. The best known marker for Tregs is the expression of transcription factor FoxP3, widely used for their enumeration. It is known that FoxP3 inhibits cytokine production so the most probable action of Tregs is direct. However, FoxP3 expression cannot be used for functional studies in humans. Therefore we identified human peripheral blood Tregs as a distinct, very well-defined population of peripheral blood T cells with reduced CD4 and high CD25 expression (CD4low CD25high), which fulfils the current phenotypic criteria identifying the Tregs by simultaneously expressing high amounts of FoxP3. We conclude that the definition of a CD4low CD25high phenotype is enough to unambiguously detect and study the regulatory function of these cells. On the functional level, the CD4low Tregs are able to non-specifically suppress the proliferation of autologous, previously polyclonally activated CD4+ and CD4− lymphocytes and to kill them by direct contact, probably utilizing intracellular granzyme B and perforin. PMID:19016909

  7. Human CD4low CD25high regulatory T cells indiscriminately kill autologous activated T cells.

    PubMed

    Bryl, Ewa; Daca, Agnieszka; Jóźwik, Agnieszka; Witkowski, Jacek M

    2009-09-01

    The interest of the scientific community in regulatory CD4(+) T cells has reached an enormously high level. Common agreement is that they inhibit not only the proliferation of CD4 and CD8 lymphocytes, but also the activities of natural killer cells and macrophages. However, very important issues concerning actual mechanism(s) and specificity of the action of regulatory T cells (Tregs) upon responder cells are still unsolved or vague. The best known marker for Tregs is the expression of transcription factor FoxP3, widely used for their enumeration. It is known that FoxP3 inhibits cytokine production so the most probable action of Tregs is direct. However, FoxP3 expression cannot be used for functional studies in humans. Therefore we identified human peripheral blood Tregs as a distinct, very well-defined population of peripheral blood T cells with reduced CD4 and high CD25 expression (CD4(low) CD25(high)), which fulfils the current phenotypic criteria identifying the Tregs by simultaneously expressing high amounts of FoxP3. We conclude that the definition of a CD4(low) CD25(high) phenotype is enough to unambiguously detect and study the regulatory function of these cells. On the functional level, the CD4(low) Tregs are able to non-specifically suppress the proliferation of autologous, previously polyclonally activated CD4(+) and CD4(-) lymphocytes and to kill them by direct contact, probably utilizing intracellular granzyme B and perforin.

  8. Immunotherapy with autologous dendritic cells and tumor antigens for children with refractory malignant solid tumors.

    PubMed

    Suminoe, Aiko; Matsuzaki, Akinobu; Hattori, Hiroyoshi; Koga, Yuhki; Hara, Toshiro

    2009-09-01

    Immature DCs were generated from the peripheral blood monocytes from five children with refractory solid tumors (Ewing sarcoma, synovial sarcoma, neuroblastoma) using GM-CSF and IL-4. These DCs were then pulsed with tumor-specific synthetic peptides or tumor lysates in the presence of the immunogenic protein KLH for 12 h. Pulsed DCs were administered subcutaneously every one or two weeks in an outpatient setting without any toxicity. In one patient with Ewing sarcoma, the residual tumor disappeared following autologous PBSCT and DC therapy, and a complete remission has been maintained for 77 months. In two patients with synovial sarcoma or with neuroblastoma, growth of the tumors was temporally suppressed for one and 10 months, respectively, followed by their exacerbation. A DTH response was detected against KLH in all five patients and against the tumor lysate in one patient. In the patients with a possible DC-mediated anti-tumor effect, the number of CD8(+) HLA-DR(+) lymphocytes and INF-gamma(+)CD8(+) lymphocytes increased and an elevation of the NK cell cytotoxic activity was observed during and/or after DC therapy. DC-based immunotherapy may therefore be a feasible, well-tolerated and promising approach in the treatment of children with refractory malignant tumors.

  9. Vorinostat, Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2017-02-21

    Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  10. Specific antitumour immunity of HIFU-activated cytotoxic T lymphocytes after adoptive transfusion in tumour-bearing mice.

    PubMed

    Ran, Li-Feng; Xie, Xun-Peng; Xia, Ji-Zhu; Xie, Fang-Lin; Fan, Yan-Min; Wu, Feng

    2016-01-01

    The aim of this study was to investigate the specific anti-tumour immunity of cytotoxic T lymphocytes (CTL) activated by high-intensity focused ultrasound (HIFU) after adoptive transfer in a murine tumour model. H22 tumour-bearing mice were treated by either HIFU or sham-HIFU, while naïve syngeneic mice were used as controls. They were sacrificed and the spleens were harvested 14 days after HIFU. T lymphocytes were obtained from the spleens, and then adoptively transferred into 40 mice each bearing a 3-day implanted H22 tumour. On day 14 after adoptive transfer, 10 mice were sacrificed in each group for assessment of the number of tumour-infiltrating T lymphocytes and interferon-gamma (IFN-γ) secreting cells. The remaining 30 mice were continuously observed for 60 days, and tumour growth, progression and survival were recorded. HIFU significantly increased peripheral blood CD3(+), CD4(+) levels and CD4(+)/CD8(+) ratio (P < 0.05), CTL cytotoxicity (P < 0.01) and IFN-γ and TNF-α secretion (P < 0.01) in H22 tumour-bearing mice. Adoptive transfer of HIFU-activated T lymphocytes into the autologous tumour-bearing mice induced a significant increase of tumour-infiltrating T lymphocytes and IFN-γ-secreting cells (P < 0.001). Compared to the control and sham-HIFU groups, HIFU-activated lymphocytes elicited significant inhibition of in vivo tumour growth (P < 0.01) and progression (P < 0.0001), and longer survival time in the tumour-bearing mice (P < 0.001). HIFU could enhance CTL's specific antitumour immunity. Adoptive transfer of HIFU-activated T lymphocytes could increase local antitumour immunity, and elicit stronger inhibition on tumour growth and progression, with more survival benefit in the autologous tumour-bearing mice.

  11. Use of “one-pot, mix-and-read” peptide-MHC class I tetramers and predictive algorithms to improve detection of cytotoxic T lymphocyte responses in cattle

    PubMed Central

    2014-01-01

    Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8+ cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and recombinant bovine β2-microglobulin from which p-MHC class I tetramers can be derived in ~48 h. We validated a set of p-MHC class I tetramers against a panel of CTL lines specific to seven epitopes on five different antigens of Theileria parva, a protozoan pathogen causing the lethal bovine disease East Coast fever. One of the p-MHC class I tetramers was tested in ex vivo assays and we detected T. parva specific CTL in peripheral blood of cattle at day 15-17 post-immunization with a live parasite vaccine. The algorithm NetMHCpan predicted alternative epitope sequences for some of the T. parva CTL epitopes. Using an ELISA assay to measure peptide-BoLA monomer formation and p-MHC class I tetramers of new specificity, we demonstrate that a predicted alternative epitope Tp229-37 rather than the previously reported Tp227-37 epitope is the correct Tp2 epitope presented by BoLA-6*04101. We also verified the prediction by NetMHCpan that the Tp587-95 epitope reported as BoLA-T5 restricted can also be presented by BoLA-1*02301, a molecule similar in sequence to BoLA-T5. In addition, Tp587-95 specific bovine CTL were simultaneously stained by Tp5-BoLA-1*02301 and Tp5-BoLA-T5 tetramers suggesting that one T cell receptor can bind to two different BoLA MHC class I molecules presenting the Tp587-95 epitope and that these BoLA molecules fall into a single functional supertype. PMID:24775445

  12. Induction of anti-tumour lymphocytes in cancer patients after brief exposure to supernatants from cultures of anti-CD3-stimulated allogeneic lymphocytes.

    PubMed Central

    Baxevanis, C. N.; Tsiatas, M. L.; Cacoullos, N. T.; Spanakos, G.; Liacos, C.; Missitzis, I.; Papadhimitriou, S. I.; Papamichail, M.

    1997-01-01

    The present study investigated the ability of supernatants collected from cultures of healthy donor-derived peripheral blood mononuclear cells (HD-PBMCs) stimulated with anti-CD3 monoclonal antibody (MAb) (allogeneic CD3 supernatants; ACD3S) to induce, upon brief exposure, tumour-reactive cytotoxic lymphocytes in cancer patients' PBMCs. ACD3S enhanced natural killer (NK) and lymphokine-activated killer (LAK) cell-mediated cytotoxicity. ACD3S contained increased levels of interleukins (IL) 1, 2, 6, 7 and 12, as well as of granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma-interferon (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). MAbs against these cytokines significantly reduced the ACD3S-induced cytotoxicity. ACD3S-induced cytotoxicity was not inhibited by anti-CD4, CD8 and MHC class I MAbs, but was markedly reduced in the presence of MAb against CD18. In contrast to HD-PBMC, ACD3S derived from cancer patients' lymphocytes exhibited lower levels of the above-mentioned cytokines and exerted reduced biological activity. In conclusion, ACD3S are able to activate, upon short-term incubation, tumour-reactive lymphocytes from cancer patients' PBMCs that lyse a variety of tumour targets, including autologous tumours. ACD3S contain high levels of certain cytokines that positively influence the induction of autologous tumour-reactive lymphocytes. Such supernatants can be collected easily from healthy donors and stored until use in clinical trials for adoptive cellular therapy of cancer. They may also be indicated in the construction of cytokine cocktails that have the ability to induce anti-tumour cytotoxicity. PMID:9376269

  13. Autologous Chondrocyte Implantation: Past, Present, and Future.

    PubMed

    Welch, Tyler; Mandelbaum, Bert; Tom, Minas

    2016-06-01

    Focal cartilage defects of the knee are relatively common and may increase the risk of developing osteoarthritis. Autologous chondrocyte implantation (ACI) aims to restore the integrity of isolated cartilage lesions through the induction of hyaline-like cartilage formation. Although ACI has traditionally been used as a second-line treatment, recent evidence suggests that ACI should be considered as a first-line treatment option in certain patients. Recent controlled trials also suggest that there are improved clinical outcomes among those patients who undergo ACI over the mid-term and long-term compared with those treated with microfracture or osteochondral autograft/mosaicplasty, regardless of lesion size. Recent literature also indicates that arthroscopic, second-generation and third-generation techniques are associated with better outcomes and fewer complications than first-generation ACI. In summary, ACI is an effective tool for cartilage restoration that may be more efficacious and durable than other cartilage restoration techniques for appropriate candidates.

  14. Chronic lymphocytic leukaemia

    PubMed Central

    Kipps, Thomas J.; Stevenson, Freda K.; Wu, Catherine J.; Croce, Carlo M.; Packham, Graham; Wierda, William G.; O’Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-01

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5+ B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer. PMID:28102226

  15. Chronic lymphocytic leukaemia.

    PubMed

    Kipps, Thomas J; Stevenson, Freda K; Wu, Catherine J; Croce, Carlo M; Packham, Graham; Wierda, William G; O'Brien, Susan; Gribben, John; Rai, Kanti

    2017-01-19

    Chronic lymphocytic leukaemia (CLL) is a malignancy of CD5(+) B cells that is characterized by the accumulation of small, mature-appearing lymphocytes in the blood, marrow and lymphoid tissues. Signalling via surface immunoglobulin, which constitutes the major part of the B cell receptor, and several genetic alterations play a part in CLL pathogenesis, in addition to interactions between CLL cells and other cell types, such as stromal cells, T cells and nurse-like cells in the lymph nodes. The clinical progression of CLL is heterogeneous and ranges from patients who require treatment soon after diagnosis to others who do not require therapy for many years, if at all. Several factors, including the immunoglobulin heavy-chain variable region gene (IGHV) mutational status, genomic changes, patient age and the presence of comorbidities, should be considered when defining the optimal management strategies, which include chemotherapy, chemoimmunotherapy and/or drugs targeting B cell receptor signalling or inhibitors of apoptosis, such as BCL-2. Research on the biology of CLL has profoundly enhanced our ability to identify patients who are at higher risk for disease progression and our capacity to treat patients with drugs that selectively target distinctive phenotypic or physiological features of CLL. How these and other advances have shaped our current understanding and treatment of patients with CLL is the subject of this Primer.

  16. Decreased deformability of lymphocytes in chronic lymphocytic leukemia

    NASA Astrophysics Data System (ADS)

    Zheng, Yi; Wen, Jun; Nguyen, John; Cachia, Mark A.; Wang, Chen; Sun, Yu

    2015-01-01

    This paper reports the first study of stiffness/deformability changes of lymphocytes in chronic lymphocytic leukemia (CLL) patients, demonstrating that at the single cell level, leukemic metastasis progresses are accompanied by biophysical property alterations. A microfluidic device was utilized to electrically measure cell volume and transit time of single lymphocytes from healthy and CLL patients. The results from testing thousands of cells reveal that lymphocytes from CLL patients have higher stiffness (i.e., lower deformability), as compared to lymphocytes in healthy samples, which was also confirmed by AFM indentation tests. This observation is in sharp contrast to the known knowledge on other types of metastatic cells (e.g., breast and lung cancer cells) whose stiffness becomes lower as metastasis progresses.

  17. [Morphometric analysis of lymphocyte nuclei in chronic lymphocytic leukemia].

    PubMed

    Ostapenko, V A; Kruchinskiĭ, N G; Smirnova, L A; Cherednik, A B; Nesterov, V N; Tepliakov, A I

    1994-01-01

    This work is dedicated to the study of use of quantitative analysis of cell nucleus structure for the analysis of peripheral blood lymphocytes in patients with chronic lymphocytic leukaemia. The structure of lymphocytic nuclei of healthy donors was evaluated by means of staining by toluidine blue purified cell suspensions smears. The preparations were analysed on the television measuring system "omnicon" with measurements of the following parameters: square of the nucleus, euchromatin, heterochromatin, and the ratio of heterochromatin and euchromatin squares. Actuarial analysis and nuclei classification of the previously mentioned parameters showed, that in peripheral blood of patients with chronic lymphocytic leukemia a large amount of atypical lymphocytes is present with reduced nucleus sizes. Atypical cells retain the ratio of structural components of chromatine, characteristic to normal cells, which show their low proliferative activity.

  18. Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells.

    PubMed

    Mazumder, A; Eberlein, T J; Grimm, E A; Wilson, D J; Keenan, A M; Aamodt, R; Rosenberg, S A

    1984-02-15

    In previous in vitro studies, the authors showed that phytohemagglutinin (PHA) stimulated peripheral blood lymphocytes (PBL) from cancer patients to generate cells that were lytic for fresh autologous tumor but not for lymphocytes or lymphoblasts. Thus, after IRB approval, a phase I clinical protocol was instituted in cancer patients who had failed all other therapy to determine the toxicity and effects, in vivo, of the infusion of large numbers of such PHA activated autologous PBL. Ten patients were treated on the protocol, six with sarcoma, one with melanoma, and three with colorectal cancer. Up to a total of 1.7 X 10(11) PBL were obtained from 7 to 15 successive leukaphereses, the cells from each leukapheresis being incubated in vitro in medium containing PHA and human AB serum for 2 days and then reinfused following the next leukapheresis 2 days later. Toxicity encountered included fever and chills in 10/10 patients, headaches in 5/10, nausea and vomiting in 3/10, and requirement for erythrocyte transfusion in 8/10. No evidence for autoimmune disease, abnormal serum chemical or coagulation studies, or pulmonary emboli was found. 111Indium trafficing studies showed distribution of infused cells mainly to the spleen and liver, with some accumulation in the lungs and tumor especially after repeated infusions. In 9/10 patients, activated PBL were detected in the peripheral circulation by the sixth leukapheresis. Evidence for this was found by assaying the incorporation of tritiated thymidine (3H-Tdr) into, and lysis of fresh tumor cells by, unstimulated PBL from successive leukaphereses. No tumor regression was seen in these patients with bulk disease. These studies demonstrated that large numbers of PHA-activated PBL can be safely obtained and infused into humans, achieving an increase in the number of circulating activated cells with evidence of migration of cells to tumor, lungs, liver and spleen. Further studies of the use of activated lymphocyte infusion in

  19. Mechanisms responsible for defective human T-lymphocyte sheep erythrocyte rosette function associated with hepatitis B virus infections.

    PubMed Central

    Chisari, F V; Routenberg, J A; Edgington, T S

    1976-01-01

    The expression of selected lymphocyte surface-membrane markers was evaluated in 37 patients with acute viral hepatitis B, 10 of whom were studied serially through the resolving and convalescent phases of disease. Bone marrow-derived (B) lymphocytes were identified by reference to surface immunoglobulin, whereas normal thymus-derived (T) lymphocytes were assayed by their capacity to form spontaneous nonimmune rosettes with sheep erythrocytes (E rosettes, ER). During the acute and resolving phases of viral hepatitis B, the relative and absolute number of ER-positive lymphocytes was significantly reduced, whereas the number of surface immunoglobulin-positive lymphocytes and the absolute lymphocyte count remained normal. This resulted in the appearance of a third population of cells, deficient in respect to both surface immunoglobulin and ER markers. Such cells accounted for nearly 25% of peripheral blood lymphocytes, approximately 5 x 105ml blood. Depression of the number of ER-positive lymphocytes occurred at least once during the course of disease in every patient studied serially, and was observed in 55 of 67 individual assays of the 37 cases of acute viral hepatitis B. Lymphocytes from some patients reacquired ER function when cultured in fetal calf serum but not in the presence of autologous serum. Such autologous serum was capable of suppressing ER function of lymphocytes from normal donors. The extrinsic suppression of er function by a serum factor (designated as the Rosette Inhibitory Factor), was found to be time dependent, characterized by a 4-h latent period and requiring approximately 18 h for maximum attenuation of ER function. The Serum Rosette Inhibitory Factor was: (a) heat and freeze-thaw stable, (b) nondialyzable, (c) physically separable from hepatitis B surface antigen, (d) not a lymphocytotoxic antibody, and (e) had the buoyant density of a lipoprotein. This extrinsic mechanism was observed in 41.8% of patients with reduced numbers of ER

  20. Autologous bone marrow mononuclear cells reduce therapeutic intensity for severe traumatic brain injury in children.

    PubMed

    Liao, George P; Harting, Matthew T; Hetz, Robert A; Walker, Peter A; Shah, Shinil K; Corkins, Christopher J; Hughes, Travis G; Jimenez, Fernando; Kosmach, Steven C; Day, Mary-Clare; Tsao, KuoJen; Lee, Dean A; Worth, Laura L; Baumgartner, James E; Cox, Charles S

    2015-03-01

    The devastating effect of traumatic brain injury is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure due to cerebral edema. The treatment effect of cell-based therapies in the acute post-traumatic brain injury period has not been clinically studied although preclinical data demonstrate that bone marrow-derived mononuclear cell infusion down-regulates the inflammatory response. Our study evaluates whether pediatric traumatic brain injury patients receiving IV autologous bone marrow-derived mononuclear cells within 48 hours of injury experienced a reduction in therapeutic intensity directed toward managing elevated intracranial pressure relative to matched controls. The study was a retrospective cohort design comparing pediatric patients in a phase I clinical trial treated with IV autologous bone marrow-derived mononuclear cells (n = 10) to a control group of age- and severity-matched children (n = 19). The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000 to 2008. Study patients were 5-14 years with postresuscitation Glasgow Coma Scale scores of 5-8. The treatment group received 6 million autologous bone marrow-derived mononuclear cells/kg body weight IV within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our traumatic brain injury management protocol, derived from American Association of Neurological Surgeons guidelines. The primary measure was the Pediatric Intensity Level of Therapy scale used to quantify treatment of elevated intracranial pressure. Secondary measures included the Pediatric Logistic Organ Dysfunction score and days of intracranial pressure monitoring as a surrogate for length of neurointensive care. A repeated-measure mixed model with marginal linear

  1. CD8+ T cells from vitiligo perilesional margins induce autologous melanocyte apoptosis.

    PubMed

    Wu, Jilong; Zhou, Miaoni; Wan, Yinsheng; Xu, Aie

    2013-01-01

    Cell-mediated autoimmunity has been suggested to be involved in the melanocyte apoptosis that occurs in vitiligo. We investigated the cytotoxicity to autologous melanocytes of CD8+ T cells from the perilesional margins and peripheral blood samples of vitiligo patients. CD8+ T cells isolated from skin biopsied from the edges of depigmented skin patches of vitiligo patients or from peripheral blood samples of the same donors were proliferated in culture medium. The primary cultures of CD8+ T cells and autologous melanocytes were mixed at ratios of 1:1, 1:2 or 1:5 and incubated for 3 days. The apoptosis of the melanocytes was analyzed by flow cytometry. Secreted cytokines in selected samples were measured by cytokine arrays. The results show that the CD8+ T cells were successfully isolated from the vitiligo perilesional margins. This cell population showed a significantly higher percentage of CD69 expression (56.13±3.55 versus 29.93±2.35%, p<0.01) and CD137 expression (41.74±1.06 versus 25.97±1.63%, p<0.01) compared with CD8+ T cells in peripheral blood from the same donors. The co-culturing of CD8+ T cells from lesional skin with autologous melanocytes induced apoptosis in the melanocytes (16.63±1.21, 16.71±0.63 and 18.32±1.60% for CD8+ T cells and autologous melanocytes at ratios of 1:1, 1:2 and 1:5, respectively). IL-6 levels were much higher in the co-culture (3.01-fold higher than in a melanocyte monoculture and 17.32-fold higher than in a CD8+ T-cell monoculture). The CD8+ T cells were also demonstrated to secrete more IL-13. Taken together, our data demonstrate that the infiltration of active CD8+ T cells takes place in the vitiligo perilesional margins. Those CD8+ T cells present significantly higher activation levels and higher cytotoxicity to autologous melanocytes than their counterparts from peripheral blood samples. These data suggest that CD8+ T cells are likely to be involved in the pathogenesis of vitiligo.

  2. Autologous Bone Marrow Mononuclear Cells Reduce Therapeutic Intensity for Severe Traumatic Brain Injury in Children

    PubMed Central

    Liao, George P.; Harting, Matthew T.; Hetz, Robert A.; Walker, Peter A.; DO, Shinil K. Shah; Corkins, Christopher J.; Hughes, Travis G.; Jimenez, Fernando; Kosmach, Steven C.; Day, Mary-Clare; Tsao, KuoJen; Lee, Dean A.; Worth, Laura L.; Baumgartner, James E.; Cox, Charles S.

    2014-01-01

    Objective The devastating effect of traumatic brain injury (TBI) is exacerbated by an acute secondary neuroinflammatory response, clinically manifest as elevated intracranial pressure (ICP) due to cerebral edema. The treatment effect of cell based therapies in the acute post-TBI period has not been clinically studied although preclinical data demonstrate that bone marrow derived mononuclear cell (BMMNC) infusion downregulates the inflammatory response. Our study evaluates whether pediatric TBI patients receiving intravenous, autologous BMMNCs within 48 hours of injury experienced a reduction in therapeutic intensity directed towards managing elevated ICP relative to matched controls. Design The study was a retrospective cohort design comparing pediatric patients in a Phase I clinical trial treated with intravenous autologous BMMNCs (n=10) to a control group of age and severity matched children (n=19). Setting The study setting was at Children's Memorial Hermann Hospital, an American College of Surgeons Level 1 Pediatric Trauma Center and teaching hospital for the University of Texas Health Science Center at Houston from 2000-2008. Patients Study patients were 5-14 years with post resuscitation Glasgow Coma Scale scores of 5-8. Interventions The treatment group received 6 million autologous BMMNC/kg body weight intravenously within 48 hours of injury. The control group was treated in an identical fashion, per standard of care, guided by our TBI management protocol, derived from American Association of Neurological Surgeons guidelines. Measurements The primary measure was the Pediatric Intensity Level of Therapy (PILOT) scale, used to quantify treatment of elevated ICP. Secondary measures included the Pediatric Logistic Organ Dysfunction (PELOD) score and days of ICP monitoring as a surrogate for length of neurointensive care. Main Results A repeated measure mixed model with marginal linear predictions identified a significant reduction in the PILOT score beginning

  3. Activated T lymphocytes in uveitis.

    PubMed Central

    Deschênes, J.; Char, D. H.; Kaleta, S.

    1988-01-01

    Two colour flow cytometry techniques were used to assess the activation stages of peripheral and intraocular T lymphocytes in uveitis. Increased numbers of T lymphocytes bearing the interleukin-2 (IL-2) receptors were found in intraocular fluids or peripheral blood or both of 35/51 patients with uveitis. This increased expression of IL-2 receptors on lymphocytes correlated with increased expression of other early T lymphocyte activation markers, HLA-DR and L-35. Both T helper cells (Leu-3A+) and suppressor cells (Leu 2A+) were activated in vivo. A positive correlation was seen between lymphocyte activation and clinical uveitis activity. In idiopathic uveitis activation of Leu-3A lymphocytes (helper/inducer) was significantly increased, and intraocular activation of the Leu-2A lymphocytes (cytotoxic/suppressor) was significantly decreased. These data show that some patients with idiopathic uveitis have a perturbation of T helper cells. Twenty-two of 31 patients with idiopathic uveitis, not associated with systemic disease, had increased peripheral T lymphocyte activation. This finding indicates that in some inflammations believed to be restricted to the eye an abnormal systemic immune activation exists. PMID:2964862

  4. Obinutuzumab in chronic lymphocytic leukemia.

    PubMed

    Dupuis, Jehan

    2015-09-01

    Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment.

  5. Allogeneic cellular and autologous stem cell therapy for sickle cell disease: 'whom, when and how'.

    PubMed

    Freed, J; Talano, J; Small, T; Ricci, A; Cairo, M S

    2012-12-01

    Sickle cell disease (SCD) is an autosomal recessive inherited hematological disorder characterized by chronic hemolysis and vaso-occlusion, resulting in multiorgan dysfunction and premature death. The only known curative therapy for patients with severe SCD is myeloablative conditioning and allo-SCT from HLA-matched sibling donors. In this state of the art review, we discuss current and future considerations including patient selection/eligibility, intensity of conditioning regimens, allogeneic graft sources, graft manipulation, mixed donor chimerism, organ function and stability and autologous gene correction stem cell strategies. Recent novel approaches to promote mixed donor chimerism have included the use of matched unrelated adult donors, umbilical cord blood donors, haploidentical familial donors and the utilization of nonmyeloablative, such as reduced intensity and reduced toxicity conditioning regimens. Future strategies will include gene therapy and autologous gene correction stem cell designs. Prospects are bright for novel stem and cellular approaches for patients with severe SCD, and we are currently at the end of the beginning for utilizing cellular therapeutics for the curative treatment of this chronic and debilitating condition.

  6. Scaling Aspects of Lymphocyte Trafficking

    PubMed Central

    Perelson, Alan S.; Wiegel, Frederik W.

    2010-01-01

    We consider the long lived pool of B and T cells that recirculate through blood, tissues and the lymphatic system of an animal with body mass M. We derive scaling rules (allometric relations) for: (1) the rate of production of mature lymphocytes; (2) the accumulation of lymphocytes in the tissues; (3) the flux of lymphocytes through the lymphatic system; (4) the number of lymph nodes, (5) the number of lymphocytes per clone within a lymph node, and (6) the total number of lymphocytes within a lymph node. Mass-dependent aspects of immune learning and of the immunological self are shown to be not very significant. Our treatment is somewhat heuristic and aims at a combination of immunological data with recent progress in biological scaling. PMID:19084024

  7. Lymphocyte Transformation in Chagas Disease

    PubMed Central

    Tschudi, E. Irene; Anziano, Dante F.; Dalmasso, Agustin P.

    1972-01-01

    The in vitro response of human peripheral lymphocytes to Trypanosoma (Schizotrypanum) cruzi antigens and to phytohemagglutinin was used to study the role of cellular immunity in Chagas disease (American trypanosomiasis). Solubilized T. cruzi antigens elicited 5 to 30% transformed cells in 5-day cultures of lymphocytes from adults chronically infected with T. cruzi. No major difference was noted between the response of 22 asymptomatic individuals and of 3 patients with chagasic cardiopathy. No correlation was found between degree of lymphocytic transformation and serum antibody titer. Lymphocytes from 15 normal controls yielded no significant transformation. Intradermal tests provoked a local delayed hypersensitivity reaction in infected individuals only, as evaluated clinically and histologically. The response to phytohemagglutinin of lymphocytes from chronically infected individuals was identical with that of normal controls. Images PMID:4629392

  8. Osteoarthritic articular chondrocytes stimulate autologous T cell responses in vitro.

    PubMed

    Sakata, M; Masuko-Hongo, K; Nakamura, H; Onuma, H; Tsuruha, J I; Aoki, H; Nishioka, K; Kato, T

    2003-01-01

    To clarify the presence of specific T cell immune response to autologous chondrocytes in patients with osteoarthritis (OA). Peripheral blood mononuclear cells obtained from OA or post-traumatic patients were co-cultured with irradiated autologous chondrocytes, and their proliferative response was assessed using 3H-thymidine incorporation. Expression of HLA-class II molecules was also assessed on chondrocytes by immunohistochemistry or flow cytometry. T cell responses to autologous chondrocytes in OA yielded a significantly greater mean stimulation index (6.35 +/- 1.63) compared to controls (1.21 +/- 0.09, p < 0.01). This response was partially blocked by antibodies against HLA class I, class II, CD4 or CD8. Increased expression of HLA-DP, -DQ, and -DR was observed. This study showed the autologous T cell-stimulating property of OA chondrocytes in vitro. The elucidation of the autoimmune responses may contribute to the understanding of immune-mediated mechanisms in OA.

  9. Acute mental change and hemiplegia after autologous fat injection.

    PubMed

    Kang, Jun Ho; Park, Kyung Hye; Park, Jung Soo

    2016-11-01

    Autologous fat injection is a common procedure used for skin augmentation. It is known to be safe and simple, but severe complications have been reported at times. The authors observed a patient with acute large cerebral infarction including the territories of the anterior and middle cerebral arteries and optic nerve infarction developing after autologous fat transplantation. A 32-year-old woman was referred to the emergency room of our hospital due to sudden stupor. Thirty minutes earlier, she was undergoing cosmetic autologous fat injection into the glabella area by a plastic surgeon at a private clinic. The cause was confirmed to be anterior and middle cerebral arteries infarction on brain imaging studies. When a patient presents abrupt mental change, hemiplegia, ocular pain, or blindness after autologous fat particle injection, physicians must consider cerebral infarction and combined retinal artery occlusion.

  10. Autologous anti-metatype immune response in rabbits.

    PubMed

    Voss, E W; Moore, J K; Weidner-McGufficke, K M; Denzin, L K; Bedzyk, W D; Voss, V H

    1992-02-01

    Rabbits hyperimmunized with fluorescyl-conjugated KLH exhibited bound ligand associated with a high affinity circulating IgG anti-fluorescein population. After cessation of immunogen administration the liganded complexes were eventually spontaneously cleared from the circulation. Individual rabbits synthesized autologous anti-metatype antibodies specific for ligand-antibody complexes. Autologous anti-metatype antibodies reacted optimally with autologous liganded anti-fluorescein antibodies. However, cross reactivity was noted with allogenic rabbit liganded antibodies from three affinity-purified pools. An autologous anti-metatype response, reminiscent of autoanti-idiotype responses, has important implications concerning in vivo clearance of antigen-antibody complexes and may serve as a model to study immune complex diseases.

  11. The Reed-Sternberg cell/lymphocyte rosette. I. Properties of rosettes formed between Hodgkin's cell lines and allogeneic lymphocytes.

    PubMed

    Flavell, D J; Wright, D H

    1989-02-01

    The properties of rosettes formed between the Hodgkin's cell lines, L428 and L591, and allogeneic peripheral blood mononuclear cell populations have been investigated. Immunocytochemical analysis showed that the majority of adherent cells were T-cells of both the CD4 and CD8 subsets. Only relatively few B-cells and monocytes were seen to adhere. However, when peripheral blood mononuclear cell populations were fractionated, it was found that monocytes were as good as T-cells at forming rosettes with both L428 and L591, though B-cells were shown to be poor at forming such associations. Treatment of both L428 and L591 with neuraminidase resulted in a significant reduction (P less than 0.01) in the mean number of adherent lymphocytes and in the numbers of Hodgkin's tumour cells which formed rosettes. Smaller, less significant effects were observed for Cytochalasin B and trypsin. EDTA (10(-2) M) at pH 7.2 had no significant effect on rosetting for L428 or L591. Adherence of allogeneic lymphocytes to L428 or L591 was pH dependent but did not appear to correlate with cell surface charge. Treatment of L428 cells with Fab fragments prepared from the IgG fraction of a hyperimmune rabbit anti-L428 antiserum, significantly (P less than 0.05) inhibited the adherence of allogeneic lymphocytes, but only when used at high concentration. The binding requirements of the Hodgkin's cell lines with allogeneic peripheral blood lymphocytes, as described in this study, appear to be quite different from those described for freshly isolated Hodgkin's tumour cells with autologous intratumoral lymphocytes. This suggests that the two phenomena may be unrelated. There would appear to be an absolute requirement for cell surface sialic acid for allogeneic lymphocyte attachment to the HD cell lines. This might suggest that the receptor-ligand system involved contains sialic acid as an integral part of the cell surface receptor structure involved in recognition of the appropriate ligand.

  12. Non-myeloablative autologous haematopoietic stem cell transplantation expands regulatory cells and depletes IL-17 producing mucosal-associated invariant T cells in multiple sclerosis.

    PubMed

    Abrahamsson, Sofia V; Angelini, Daniela F; Dubinsky, Amy N; Morel, Esther; Oh, Unsong; Jones, Joanne L; Carassiti, Daniele; Reynolds, Richard; Salvetti, Marco; Calabresi, Peter A; Coles, Alasdair J; Battistini, Luca; Martin, Roland; Burt, Richard K; Muraro, Paolo A

    2013-09-01

    Autologous haematopoietic stem cell transplantation has been tried as one experimental strategy for the treatment of patients with aggressive multiple sclerosis refractory to other immunotherapies. The procedure is aimed at ablating and repopulating the immune repertoire by sequentially mobilizing and harvesting haematopoietic stem cells, administering an immunosuppressive conditioning regimen, and re-infusing the autologous haematopoietic cell product. 'Non-myeloablative' conditioning regimens to achieve lymphocytic ablation without marrow suppression have been proposed to improve safety and tolerability. One trial with non-myeloablative autologous haematopoietic stem cell transplantation reported clinical improvement and inflammatory stabilization in treated patients with highly active multiple sclerosis. The aim of the present study was to understand the changes in the reconstituted immune repertoire bearing potential relevance to its mode of action. Peripheral blood was obtained from 12 patients with multiple sclerosis participating in the aforementioned trial and longitudinally followed for 2 years. We examined the phenotype and function of peripheral blood lymphocytes by cell surface or intracellular staining and multi-colour fluorescence activated cell sorting alone or in combination with proliferation assays. During immune reconstitution post-transplantation we observed significant though transient increases in the proportion of CD4+ FoxP3+ T cells and CD56(high) natural killer cell subsets, which are cell subsets associated with immunoregulatory function. CD8+ CD57+ cytotoxic T cells were persistently increased after therapy and were able to suppress CD4+ T cell proliferation with variable potency. In contrast, a CD161(high) proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161(high)CD8+ T cells were mucosal-associated invariant T cells, a novel cell population

  13. Bovine lymphocytes: recognition of cells forming spontaneous (E) rosettes.

    PubMed Central

    Higgins, D A; Stack, M J

    1977-01-01

    About 20% of thymus lymphocytes from neonatal calves formed spontaneous (E) rosettes with SRBCs in medium consisting of 50-100% foetal calf serum (FCS); other media were less satisfactory. FCS was necessary both to allow rosette formation to occur and to maintain stability of the rosettes once formed. Rosettes were stable at 0 degrees C but unstable at 18 degrees C and 37 degrees C. Dead thymus cell (sodium azide treated) did not form rosettes. Treatment of thymus cells with antiserum to bovine Ig-inhibited rosette formation, but this inhibition was considered non-specific since it also occurred with normal rabbit serum. Treatment of SRBCs with neuraminidase slightly enhanced rosette formation by thymus cells, but did not induce peripheral blood lymphocytes to form rosettes. Rosette formation did not occur under a variety of conditions with normal or neuraminidase-treated human, horse, pig, rabbit, guinea-pig, chicken or autologous RBCs. SRBC rosette forming cells were also found in lymph nodes (2-14%) and spleen (less than 5%), but rarely or never in peripheral blood and bone marrow of calves and adults. In foetuses at 80 days of gestation, 49% of thymus cells formed E rosettes. Foetal lymph node cells formed E rosettes at 160 days and spleen at 180 days. Cells with membrane-bound Ig were observed by IFT; their distribution did not coincide with the occurrence of E rosettes. E-rosette formation might be a marker for a subpopulation of bovine T cells. PMID:321167

  14. Characterization of pig lymphocyte receptors for allogeneic and non-allogeneic erythrocytes. I. Apparent common identity of both receptors.

    PubMed Central

    Salmon, H

    1982-01-01

    In the pig thymus, the proportion of allogeneic (or autologous) erythrocyte rosette forming cells (P-RFC) is always lower than that of sheep erythrocyte (non-allogeneic) rosette forming cells (S-RFC) even under saturated RBC/lymphocyte ratios and optimal dextran concentration. This difference accounted for lymphocytes rosetting with sheep erythrocytes and not with pig erythrocytes (P-S+ cells), as opposed to those lymphocytes which are able to bind both types of erythrocytes (P+S+ cells). Since formation of both sheep and pig erythrocyte rosettes is inhibited similarly by anti-T receptor serum, is inhibited reciprocally by sheep and pig erythrocyte membrane fragment and is similarly trypsin sensitive, it was concluded that the same receptor was responsible for both sheep and pig rosette formation. Furthermore it was found that P+S+ cells had a higher avidity for sheep erythrocytes (and lower for pig erythrocytes) than the other subset which did not bind pig erythrocytes. PMID:6180852

  15. Autologous fat grafting: use of closed syringe microcannula system for enhanced autologous structural grafting

    PubMed Central

    Alexander, Robert W; Harrell, David B

    2013-01-01

    Objectives Provide background for use of acquiring autologous adipose tissue as a tissue graft and source of adult progenitor cells for use in cosmetic plastic surgery. Discuss the background and mechanisms of action of closed syringe vacuum lipoaspiration, with emphasis on accessing adipose-derived mesenchymal/stromal cells and the stromal vascular fraction (SVF) for use in aesthetic, structural reconstruction and regenerative applications. Explain a proven protocol for acquiring high-quality autologous fat grafts (AFG) with use of disposable, microcannula systems. Design Explain the components and advantage of use of the patented super luer-lock and microcannulas system for use with the closed-syringe system. A sequential explanation of equipment selection for minimally traumatic lipoaspiration in small volumes is presented, including use of blunt injection cannulas to reduce risk of embolism. Results Thousands of AFG have proven safe and efficacious for lipoaspiration techniques for large and small structural fat grafting procedures. The importance and advantages of gentle harvesting of the adipose tissue complex has become very clear in the past 5 years. The closed-syringe system offers a minimally invasive, gentle system with which to mobilize subdermal fat tissues in a suspension form. Resulting total nuclear counting of undifferentiated cells of the adipose-derived -SVF suggests that the yield achieved is better than use of always-on, constant mechanical pump applied vacuum systems. Conclusion Use of a closed-syringe lipoaspiration system featuring disposable microcannulas offers a safe and effective means of harvesting small volumes of nonmanipulated adipose tissues and its accompanying progenitor cells within the SVF. Closed syringes and microcannulas are available as safe, sterile, disposable, compact systems for acquiring high-quality AFG. Presented is a detailed, step-by-step, proven protocol for performing quality autologous structural adipose

  16. Improving Therapy of Chronic Lymphocytic Leukemia (CLL) with Chimeric Antigen Receptor (CAR) T Cells

    PubMed Central

    Fraietta, Joseph A.; Schwab, Robert D.; Maus, Marcela V.

    2016-01-01

    Adoptive cell immunotherapy for the treatment of chronic lymphocytic leukemia (CLL) has heralded a new era of synthetic biology. The infusion of genetically-engineered, autologous chimeric antigen receptor (CAR) T cells directed against CD19 expressed by normal and malignant B cells represents a novel approach to cancer therapy. The results of recent clinical trials of CAR T cells in relapsed and refractory CLL have demonstrated long-term disease-free remissions, underscoring the power of harnessing and re-directing the immune system against cancer. This review will briefly summarize T cell therapies in development for CLL disease. We discuss the role of T cell function and phenotype, T cell culture optimization, CAR design, and approaches to potentiate the survival and anti-tumor effects of infused lymphocytes. Future efforts will focus on improving the efficacy of CAR T cells for the treatment of CLL and incorporating adoptive cell immunotherapy into standard medical management of CLL. PMID:27040708

  17. What Are the Key Statistics about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Leukemia (ALL) What Are the Key Statistics About Acute Lymphocytic Leukemia? The American Cancer Society’s estimates for acute lymphocytic ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  18. Treatment of Chronic Lymphocytic Leukemia by Risk Group

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Typical Treatment of Chronic Lymphocytic Leukemia Treatment options for chronic lymphocytic leukemia (CLL) vary ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  19. Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells.

    PubMed

    Akela, Ashok; Nandi, Samit Kumar; Banerjee, Dibyajyoti; Das, Partha; Roy, Subhasis; Joardar, Siddhartha Narayan; Mandal, Mohan; Das, Pradip Kumar; Pradhan, Nisith Ranjan

    2012-10-01

    A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3). Wounds were observed for 30 days for granulation tissue formation, biochemical, histomorphological and histochemical evaluation. In this study, granulation tissue appeared significantly lesser in wounds of group 3 animals followed by group 2 and 1 animals. Neovascularisation, granulation tissue formation, denser, thicker and better arranged collagen fibres, reticulin fibres and elastin fibres formation was more in group 1 as compared with other groups. It was concluded that the application of bone marrow-derived nucleated cells into the wound margins resulted in early and significantly faster rate of complete healing as compared with buffy coat of autologous blood and autologous plasma (control). This approach may be beneficial in various surface wounds that heal at a slower rate and recommended for healing of various complicated wound in future.

  20. Lymphocyte abnormalities in ankylosing spondylitis.

    PubMed Central

    Fan, P T; Clements, P J; Yu, D T; Opelz, G; Bluestone, R

    1977-01-01

    Peripheral blood T (SRBC rosette) and B (AgG- and C-receptor) lymphocyte subpopulations and responsiveness to phytohaemagglutinin (PHA) were assayed in 40 patients with ankylosing spondylitis and in 55 normal subjects. There was no significant difference in the lymphocyte concentrations or responsiveness to PHA between the two groups. However, the percentages of T lymphocytes were significantly lower in the patients irrespective of their HLA typing. This was probably due to an increase in the 'null' population since the percentages of both the AgG- and C-receptor cells were normal. PMID:303501

  1. Human gamma interferon increases the binding of T lymphocytes to endothelial cells.

    PubMed Central

    Yu, C L; Haskard, D O; Cavender, D; Johnson, A R; Ziff, M

    1985-01-01

    Binding of lymphocytes to human umbilical vein endothelial cells (EC) was quantitated by measuring adhesion of 51Cr labelled lymphocytes to endothelial cell monolayers and rosette formation between lymphocytes and EC in suspension. Mitogen stimulated human peripheral blood mononuclear cell culture supernatants and mixed lymphocyte reaction supernatants enhanced the binding of T lymphocytes to EC monolayers or suspensions preincubated with such supernatants. The active component of these supernatants appeared to be gamma interferon (IFN-gamma) since culture supernatants lost activity after heating at 56 degrees C for 60 min, exposure to pH 2.0 or treatment with anti-IFN-gamma. In addition, purified IFN-gamma increased the binding of T lymphocytes to EC (T-EC). This occurred in a concentration dependent manner when IFN-gamma was preincubated with EC but not with lymphocytes. While the optimum concentration of IFN-gamma was 250 u/ml, a significant enhancement was seen with as little as 10 u/ml. These findings suggest that IFN-gamma may play a part in the emigration of lymphocytes to perivascular chronic inflammatory sites by augmenting the adhesion of lymphocytes to the endothelium of small blood vessels. PMID:2935340

  2. Functional inactivation of lymphocytes by methylene blue with visible light.

    PubMed

    Zhang, Bo; Cheng, Zhenzhen; Mo, Qin; Wang, Li; Wang, Xun; Wu, Xiaofei; Jia, Yao; Huang, Yuwen

    2015-10-01

    Transfusion of allogeneic white blood cells (WBCs) may cause adverse reactions in immunocompromised recipients, including transfusion-associated graft-versus-host disease (TA-GVHD), which is often fatal and incurable. In this study, the in vitro effect of methylene blue with visible light (MB + L) treatment on lymphocyte proliferation and cytokine production was measured to investigate whether MB + L can be used to prevent immune reactions that result from transfused lymphocytes. WBCs and 3 μM of MB were mixed and transferred into medical PVC bags, which were then exposed to visible light. Gamma irradiation was conducted as a parallel positive control. The cells without treatment were used as untreated group. All the groups were tested for the ability of cell proliferation and cytokine production upon stimulation. After incubation with mitogen phytohemagglutinin (PHA) or plate-bound anti-CD3 plus anti-CD28, the proliferation of MB + L/gamma-irradiation treated lymphocytes was significantly inhibited (P < 0.01) as compared to the untreated ones; the proliferation inhibitive rate of the MB + L group was even higher than that of gamma-irradiated cells (73.77% ± 28.75% vs. 44.72% ± 38.20%). MB + L treated cells incubated up to 7 days with PHA also showed no significant proliferation. The levels of TNF-α, IFN-γ, IL-6, IL-8, IL-10 and IL-1β present in the supernatant of MB + L treated lymphocytes upon stimulation were significantly lower than those of untreated lymphocytes. These results demonstrated that MB + L treatment functionally and irreversibly inactivated lymphocytes by inhibiting lymphocyte proliferation and the production of cytokines. MB + L treatment might be a promising method for the prevention of adverse immune responses caused by WBCs.

  3. [Preserving autologous heart operation for dilated cardiomyopathy].

    PubMed

    Hoshino, Joji; Fukada, Yasuhisa; Hirota, Masanori; Kondo, Taichi; Isomura, Tadashi

    2013-01-01

    We report non transplant surgical procedure (preserving autologous heart operation) for the patients with dilated cardiomyopathy( DCM), clinical outcomes, and the factor of predict prognosis. Since May 2000, 258 patients received surgical procedure for 11 years. We performed mitral surgery (plasty or replacement) for the patients with more than mild mitral regurgitation (MR). We performed papirally muscule plication since 2005, and we performed 2nd chordal cutting since 2008, for the patients with MR due to mitral tethering. The surgical left ventricular reconstruction( SVR) was performed for the patients with dilated left ventricular. We use spackle tracking echocardiography to decide the type of SVR since 2008. Hospital death was 18.2%, and late cardiac death was 27.5%.Almost the cause of death was congestive heart failure and ventricular arrhythmia. Five years survival was 58%, 10 years survival was 39%. Preoperative condition, emergent operation, inotropic support, intra aortic balloon pumping(IABP),affect the prognosis. But left ventricular size did not affect it. Surgical treatment for the patient with DCM should be performed with stable preoperative condition.

  4. Autologous hematopoietic cell transplantation in multiple sclerosis.

    PubMed

    Bell, Simon M; Sharrack, Basil; Snowden, John A

    2017-01-01

    Autologous haematopoietic cell transplantation (AHCT) is an evolving treatment avenue in multiple sclerosis (MS), which may be highly effective in controlling disease activity and improving disability. However, AHCT is associated with intrinsic toxicities and risks compared with conventional therapies. With growing experience in patient selection and treatment delivery, AHCT is increasingly considered an option in patients with aggressive disease that's responding poorly to disease modifying therapy. Areas covered: This article provides an introduction to AHCT and looks at its development as a treatment for MS over the last 20 years. It also highlights potential mechanisms of action, patient selection, and future trends for this treatment approach. Expert opinion: Currently published data suggest that AHCT's use is associated with significant reduction in MS disease activity and marked improvement in disability when used in patients with highly active relapsing remitting disease. Its long term safety and efficacy have not been fully evaluated but as increasing clinical trial data are published, its use is likely to grow. Further randomised controlled studies are needed to compare AHCT with standard disease modifying therapies and to optimise transplant regimens. Mechanistic studies may provide potential markers for response and a better understanding of disease pathogenesis.

  5. Adhesive strength of autologous fibrin glue.

    PubMed

    Yoshida, H; Hirozane, K; Kamiya, A

    2000-03-01

    To establish an easy and rapid method for measuring the adhesive strength of fibrin glue and to clarify the factor(s) most affecting the strength, a study was made on the effect of the concentration of plasma components on the strength of cryoprecipitate (Cryo) prepared from a subject's own autologous plasma to be used as fibrin glue. The adhesive strength of the Cryo was measured with various supporting materials instead of animal skin using a tester of tension and compression. The results were as follows: (1) the strength of Cryo applied to ground flat glass (4 cm2) was significantly greater than that applied to clear glass, clear plastic, or smooth and flat wood chips; (2) the adhesive strength of Cryo depended on the concentration of thrombin with the optimal concentration being 50 units/ml; (3) the concentration of CaCl2 did not affect the adhesive strength of Cryo; (4) the adhesive reaction was dependent on the temperature and the adhesive strength more quickly reached a steady state at 37 degrees C than at lower temperature; (5) the adhesive strength was correlated well with the total concentration of fibrinogen and fibronectin. These results indicate that the adhesive strength of Cryo can be easily and quickly evaluated using a tester and ground glass with thrombin at 50 units/ml, and that the adhesive strength of Cryo can be predicted from the total concentration of fibrinogen and fibronectin.

  6. Autologous cord blood transplantation for metastatic neuroblastoma.

    PubMed

    Ning, Botao; Cheuk, Daniel Ka-Leung; Chiang, Alan Kwok-Shing; Lee, Pamela Pui-Wah; Ha, Shau-Yin; Chan, Godfrey Chi-Fung

    2016-03-01

    Auto-SCT is a common approach for metastatic neuroblastoma with the intention to rescue hematopoiesis after megadose chemotherapy. PBSC or BM is the usual stem cell source for auto-SCT. Auto-CBT for neuroblastoma has very rarely been performed. Currently, case reports are available for two patients only. We performed 13 auto-SCTs for high-risk neuroblastoma from 2007 to 2013, including four cases of metastatic neuroblastoma aged 11-64 months treated with auto-CBT. All four patients had partial or CR to upfront treatments before auto-CBT. Nucleated cell dose and CD34+ cell dose infused were 2.8-8.7 × 10(7) /kg and 0.36-3.9 × 10(5) /kg, respectively. Post-thawed viability was 57-76%. Neutrophil engraftment (>0.5 × 10(9) /L) occurred at 15-33 days, while platelet engraftment occurred at 31-43 days (>20 × 10(9) /L) and 33-65 days (>50 × 10(9) /L) post-transplant, respectively. There was no severe acute or chronic complication. Three patients survived for 1.9-7.7 yr without evidence of recurrence. One patient relapsed at 16 months post-transplant and died of progressive disease. Cord blood may be a feasible alternative stem cell source for auto-SCT in patients with stage 4 neuroblastoma, and outcomes may be improved compared to autologous PBSC or BM transplants.

  7. Clinical outcomes following osteochondral autologous transplantation (OATS).

    PubMed

    Lahav, Amit; Burks, Robert T; Greis, Patrick E; Chapman, Andrew W; Ford, Gregory M; Fink, Barbara P

    2006-07-01

    This study evaluated the clinical outcome in 21 patients (22 knees) undergoing osteochondral autologous transplantation (OATS) in the knee over a 5-year period. Sixteen knees in 15 patients were available for follow-up at an average of 40 months after the procedure. The clinical outcome was analyzed using the IKDC and Knee and Osteoarthritis Outcome Score (KOOS) evaluation forms, a subjective questionnaire, and a clinical examination. At final follow-up, the average KOOS result for pain was 80.6 (range: 56-94), symptoms 53.6 (range: 25-71), function of activities of daily living 93.4 (range: 79-100), function of sports and recreational activities 65.3 (range: 20-100), and quality of life 51.0 (range: 6-88). The average IKDC score was 68.2. On our subjective questionnaire, the average preoperative grade given was 3.1 (range: 1-7) with an improvement at the most recent follow-up to a grade of 8.0 (range: 5-10) (P < .00001). Thirteen (86%) patients reported that they would have the surgery again if they had to make the decision a second time. Age did not correlate with subjective results on the IKDC evaluation (P = .7048) or score difference on our questionnaire (P = .9175). This procedure provides an option for articular resurfacing of the femoral condyles for focal areas of chondral defects with promising results regarding subjective improvement.

  8. Allogeneic versus autologous blood transfusion and survival after radical prostatectomy

    PubMed Central

    Chalfin, Heather J.; Frank, Steven M.; Feng, Zhaoyong; Trock, Bruce J.; Drake, Charles G.; Partin, Alan W.; Humphreys, Elizabeth; Ness, Paul M.; Jeong, Byong C.; Lee, Seung B.; Han, Misop

    2016-01-01

    BACKGROUND Potential adverse effects of blood transfusion (BT) remain controversial, especially for clinical outcomes after curative cancer surgery. Some postulate that immune modulation after allogeneic BT predisposes to recurrence and death, but autologous superiority is not established. This study assessed whether BT is associated with long-term prostate cancer recurrence and survival a large single-institutional radical prostatectomy (RP) database. STUDY DESIGN AND METHODS Between 1994 and 2012, a total of 11,680 patients had RP with available outcome and transfusion data. A total of 7443 (64%) had complete covariate data. Clinical variables associated with biochemical recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS) were identified with Cox proportional hazards models for three groups: no BT (reference, 27.7%, n = 2061), autologous BT only (68.8%, n = 5124), and any allogeneic BT (with or without autologous, 3.5%, n = 258). RESULTS Median (range) follow-up was 6 (1–18) years. Kaplan-Meier analysis showed significantly decreased OS (but not BRFS or PCSS) in the allogeneic group versus autologous and no BT groups (p = 0.006). With univariate analysis, any allogeneic BT had a hazard ratio (HR) of 2.29 (range, 1.52–3.46; p < 0.0001) for OS, whereas autologous BT was not significant (HR, 1.04 [range, 0.82–1.32], p = 0.752). In multivariable models, neither autologous nor allogeneic BT was independently associated with BRFS, CSS, or OS, and a dose response was not observed for allogeneic units and BRFS. CONCLUSION Although allogeneic but not autologous BT was associated with decreased long-term OS, after adjustment for confounding clinical variables, BT was not independently associated with OS, BRFS, or CSS regardless of transfusion type. Notably, no association was observed between allogeneic BT and cancer recurrence. Observed differences in OS may reflect confounding. PMID:24601996

  9. Proteolysis of lymphocytic surface immunoglobulin.

    PubMed Central

    Hough, D W; McIlroy, B M; Stevenson, G T

    1977-01-01

    Limited proteolysis of lymphocytic surface immunoglobulins in guinea-pig, rabbit and man was investigated by immunofluorescence using conjugated antisera specific for immunoglobulin fragments. The cell surface IgM of guinea pig L2C leukaemic lymphocytes and rabbit blood lymphocytes was cleaved in situ at its hinge region by papain. The Fcmicron fragment remained attached to the membrane and could be stained with the appropriate anti-Fc conjugate. The surface IgD and IgM of human chronic lymphocytic leukaemia cells was cleared from the cell surface by papain, as shown by reagents directed against both Fab and Fc region determinants. This could be due either to proteolytic degradation of membrane bound Fc or to initial cleavage of Ig from the membrane at some point other than the hinge region. PMID:321347

  10. Quantifying T Lymphocyte Turnover

    PubMed Central

    De Boer, Rob J.; Perelson, Alan S.

    2013-01-01

    Peripheral T cell populations are maintained by production of naive T cells in the thymus, clonal expansion of activated cells, cellular self-renewal (or homeostatic proliferation), and density dependent cell life spans. A variety of experimental techniques have been employed to quantify the relative contributions of these processes. In modern studies lymphocytes are typically labeled with 5-bromo-2′-deoxyuridine (BrdU), deuterium, or the fluorescent dye carboxy-fluorescein diacetate succinimidyl ester (CFSE), their division history has been studied by monitoring telomere shortening and the dilution of T cell receptor excision circles (TRECs) or the dye CFSE, and clonal expansion has been documented by recording changes in the population densities of antigen specific cells. Proper interpretation of such data in terms of the underlying rates of T cell production, division, and death has proven to be notoriously difficult and involves mathematical modeling. We review the various models that have been developed for each of these techniques, discuss which models seem most appropriate for what type of data, reveal open problems that require better models, and pinpoint how the assumptions underlying a mathematical model may influence the interpretation of data. Elaborating various successful cases where modeling has delivered new insights in T cell population dynamics, this review provides quantitative estimates of several processes involved in the maintenance of naive and memory, CD4+ and CD8+ T cell pools in mice and men. PMID:23313150

  11. Intraoperative hemodilution and autologous platelet rich plasma collection: two techniques for collecting fresh autologous blood.

    PubMed

    Triulzi, D J; Ness, P M

    1995-03-01

    Intraoperative hemodilution (IH) and autologous platelet rich plasma (APRP) collection are two techniques used to obtain autologous blood in the operating room. They have been used to reduce allogeneic blood exposure in patients undergoing both cardiac and non-cardiac surgery. Both components have the advantage of providing fresh blood not subject to the storage lesion. Whole blood (IH) or platelet rich plasma is removed from the patient as anesthesia is induced and replaced with acellular fluid. The blood is transfused back after bypass or major bleeding has ceased. Although used commonly, the data supporting the use of either technique are controversial. Methodologic problems which have confounded studies evaluating their utility include: poorly defined transfusion criteria, concommitant use of other blood conservation techniques (i.e. cell salvage, pharmacologic agents, hypothermia, controlled hypotension) and changing transfusion practices with greater tolerance of normovolemic anemia. Randomized controlled studies with well defined up to date transfusion criteria are needed to identify patients likely to benefit from these techniques.

  12. Efficient and reproducible generation of tumour-infiltrating lymphocytes for renal cell carcinoma.

    PubMed

    Baldan, V; Griffiths, R; Hawkins, R E; Gilham, D E

    2015-04-28

    Tumour-infiltrating lymphocyte (TIL) therapy is showing great promise in the treatment of patients with advanced malignant melanoma. However, the translation of TIL therapy to non-melanoma tumours such as renal cell carcinoma has been less successful with a major constraint being the inability to reproducibly generate TILs from primary and metastatic tumour tissue. Primary and metastatic renal cell carcinoma biopsies were subjected to differential tumour disaggregation methods and procedures that stimulate the specific expansion of TILs tested to determine which reliably generated TIL maintained antitumour specificity. Enzymatic or combined enzymatic/mechanical disaggregation resulted in equivalent numbers of TILs being liberated from renal cell carcinoma biopsies. Following mitogenic activation of the isolated TILs with anti-CD3/anti-CD28-coated paramagnetic beads, successful TIL expansion was achieved in 90% of initiated cultures. The frequency of T-cell recognition of autologous tumours was enhanced when tumours were disaggregated using the GentleMACS enzymatic/mechanical system. TILs can be consistently produced from renal cell carcinoma biopsies maintaining autologous tumour recognition after expansion in vitro. While the method of disaggregation has little impact on the success of TIL growth, methods that preserve the cell surface architecture facilitate TIL recognition of an autologous tumour, which is important in terms of characterising the functionality of the expanded TIL population.

  13. Initiation of lymphocyte DNA synthesis.

    PubMed

    Coffman, F D; Fresa, K L; Cohen, S

    1991-01-01

    The initiation of DNA replication in T lymphocytes appears to be regulated by two distinct activities: one associated with proliferation which mediates initiation, and another associated with quiescence which blocks initiation. Activated lymphocytes and proliferating lymphoid cell lines produce an activity, termed ADR, which can initiate DNA replication in isolated, quiescent nuclei. ADR is heat-labile, has protease activity or interacts closely with a protease, and is distinct from the DNA polymerases. ADR activity is absent in quiescent lymphocytes and appears in mitogen-stimulated lymphocytes after IL-2 binding. The generation of active ADR appears to be mediated by phosphorylation of a precursor which is present in resting cells. Nuclei from mitogen-unresponsive lymphocytes fail to initiate DNA replication in response to ADR, of potential importance in the age-related decline of immunity. Quiescent lymphocytes lack ADR and synthesize an ADR-inhibitory activity. The ADR inhibitor is a heat-stable protein which suppresses the initiation of DNA synthesis, but is ineffective at suppressing elongation once DNA strand replication has begun. Nuclei from several neoplastic cell lines fail to respond to the ADR inhibitor, which may play a role in the continuous proliferation of these cells. At least one of these neoplastic cell lines produces both ADR and an inhibitory factor. These findings suggest that the regulation of proliferation is dependent on the balance between activating and inhibitory pathways.

  14. Granulocyte-macrophage colony-stimulating factor (GM-CSF)–secreting cellular immunotherapy in combination with autologous stem cell transplantation (ASCT) as postremission therapy for acute myeloid leukemia (AML)

    PubMed Central

    Borrello, Ivan M.; Stock, Wendy; Sher, Dorie; Qin, Lu; DeAngelo, Daniel J.; Alyea, Edwin P.; Stone, Richard M.; Damon, Lloyd E.; Linker, Charles A.; Maslyar, Daniel J.; Hege, Kristen M.

    2009-01-01

    Preclinical models have demonstrated the efficacy of granulocyte-macrophage colony-stimulating factor-secreting cancer immunotherapies (GVAX platform) accompanied by immunotherapy-primed lymphocytes after autologous stem cell transplantation in hematologic malignancies. We conducted a phase 2 study of this combination in adult patients with acute myeloid leukemia. Immunotherapy consisted of autologous leukemia cells admixed with granulocyte-macrophage colony-stimulating factor-secreting K562 cells. “Primed” lymphocytes were collected after a single pretransplantation dose of immunotherapy and reinfused with the stem cell graft. Fifty-four subjects were enrolled; 46 (85%) achieved a complete remission, and 28 (52%) received the pretransplantation immunotherapy. For all patients who achieved complete remission, the 3-year relapse-free survival (RFS) rate was 47.4% and overall survival was 57.4%. For the 28 immunotherapy-treated patients, the RFS and overall survival rates were 61.8% and 73.4%, respectively. Posttreatment induction of delayed-type hypersensitivity reactions to autologous leukemia cells was associated with longer 3-year RFS rate (100% vs 48%). Minimal residual disease was monitored by quantitative analysis of Wilms tumor-1 (WT1), a leukemia-associated gene. A decrease in WT1 transcripts in blood was noted in 69% of patients after the first immunotherapy dose and was also associated with longer 3-year RFS (61% vs 0%). In conclusion, immunotherapy in combination with primed lymphocytes and autologous stem cell transplantation shows encouraging signals of potential activity in acute myeloid leukemia (ClinicalTrials.gov: NCT00116467). PMID:19556425

  15. Cryopreservation of Autologous Blood (Red Blood Cells, Platelets and Plasma)

    NASA Astrophysics Data System (ADS)

    Ebine, Kunio

    Prevention of post-transfusion hepatitis is still a problem in cardiovascular surgery. We initiated the cryopreservation of autologous blood for the transfusion in elective cardiovascular surgery since 1981. This study includes 152 surgical cases in which autologous frozen, allogeneic frozen, and/or allogeneic non-frozen blood were used. In the 152 surgical cases, there were 69 cases in which autologous blood only (Group I) was used; 12 cases with autologous and allogeneic frozen blood (Group II); 46 cases with autologous and allgeneic frozen plus allogeneic non-frozen blood (Group III); and 25 cases with allogeneic frozen plus allogeneic non-frozen blood (Group IV). No hepatitis developed in Groups I (0%) and II (0%), but there was positive hepatitis in Groups III (4.3%) and IV (8.0%) . In 357 cases of those who underwent surgery with allogeneic non-frozen whole blood during the same period, the incidence rate of hepatitis was 13.7% (49/357). Patients awaiting elective surgery can store their own blood in the frozen state. Patients who undergo surgery with the cryoautotransfusion will not produce any infections or immunologic reactions as opposed to those who undergo surgery with the allogeneic non-frozen blood.

  16. Orthopaedic-induced anemia: the fallacy of autologous donation programs.

    PubMed

    Cushner, Fred D; Hawes, Thomas; Kessler, Debra; Hill, Kala; Scuderi, Giles R

    2005-02-01

    Total knee arthroplasty is associated with significant blood loss. Despite the initiation of various blood conservation modalities, allogeneic transfusion has yet to be eliminated. One hundred forty-eight patients who had unilateral primary total knee arthroplasties during a 3-year period were evaluated retrospectively for blood loss and transfusion rates. The patients were prescribed one unit of preoperative autologous donation that was to be transfused automatically on postoperative Day 1. Allogeneic transfusion was based on symptoms, and no numerical transfusion triggers were used. The preoperative autologous donation program resulted in increased preoperative anemia. Whereas only 26.2% of patients were in the high transfusion-risk group (hemoglobin >10 g/dL and < or = 13 g/dL) before surgery, 55.7% of patients were in this high-risk category after preoperative autologous donation. The patients did not recover from the autologous donations that occurred 4 weeks before surgery. A mean hemoglobin level of 14.0 g/dL was seen before donation, whereas the mean preoperative hemoglobin level decreased to 12.6 g/dL. We think that a preoperative autologous donation program leads to an increased risk of anemia before surgery.

  17. Autologous chondrocyte implantation: superior biologic properties of hyaline cartilage repairs.

    PubMed

    Henderson, Ian; Lavigne, Patrick; Valenzuela, Herminio; Oakes, Barry

    2007-02-01

    Information regarding the quality of autologous chondrocyte implantation repair is needed to determine whether the current autologous chondrocyte implantation surgical technology and the subsequent biologic repair processes are capable of reliably forming durable hyaline or hyaline-like cartilage in vivo. We report and analyze the properties and qualities of autologous chondrocyte implantation repairs. We evaluated 66 autologous chondrocyte implantation repairs in 57 patients, 55 of whom had histology, indentometry, and International Cartilage Repair Society repair scoring at reoperation for mechanical symptoms or pain. International Knee Documentation Committee scores were used to address clinical outcome. Maximum stiffness, normalized stiffness, and International Cartilage Repair Society repair scoring were higher for hyaline articular cartilage repairs compared with fibrocartilage, with no difference in clinical outcome. Reoperations revealed 32 macroscopically abnormal repairs (Group B) and 23 knees with normal-looking repairs in which symptoms leading to arthroscopy were accounted for by other joint disorders (Group A). In Group A, 65% of repairs were either hyaline or hyaline-like cartilage compared with 28% in Group B. Autologous chondrocyte repairs composed of fibrocartilage showed more morphologic abnormalities and became symptomatic earlier than hyaline or hyaline-like cartilage repairs. The hyaline articular cartilage repairs had biomechanical properties comparable to surrounding cartilage and superior to those associated with fibrocartilage repairs.

  18. Autologous hematopoietic stem cell transplantation for systemic sclerosis.

    PubMed

    Milanetti, Francesca; Bucha, Jurate; Testori, Alessandro; Burt, Richard K

    2011-03-01

    Systemic sclerosis is a rare disorder manifesting as skin and internal organ fibrosis, a diffuse vasculopathy, inflammation, and features of autoimmunity. Patients with diffuse cutaneous disease or internal organ involvement have a poor prognosis with high mortality. To date no therapy has been shown to reverse the natural course of the disease. Immune suppressive drugs are commonly utilized to treat patients, but randomized trials have generally failed to demonstrate any long-term benefit. In phase I/II trials, autologous hematopoietic stem cell transplantation (HSCT) has demonstrated impressive reversal of skin fibrosis, improved functionality and quality of life, and stabilization of internal organ function, but initial studies were complicated by significant treatment-related mortality. Treatment-related mortality was reduced by better pre-transplant evaluation to exclude patients with compromised cardiac function and by treating patients earlier in disease, allowing selected patients the option of autologous HSCT treatment. There are currently three ongoing randomized trials of autologous HSCT for systemic sclerosis: ASSIST (American Systemic Sclerosis Immune Suppression versus Transplant), SCOT (scleroderma cyclophosphamide versus Transplant), and ASTIS (Autologous Stem cell Transplantation International Scleroderma). The results from these trials should clarify the role of autologous HSCT in the currently limited therapeutic arsenal of severe systemic sclerosis.

  19. Calf Augmentation and Reshaping with Autologous Fat Grafting.

    PubMed

    Mundinger, Gerhard S; Vogel, James E

    2016-02-01

    Despite multiple advantages of fat grafting for calf augmentation and re-shaping over traditional silicone calf implants, few reports have been published. To report our technique and results with autologous fat grafting for calf augmentation and reshaping. A retrospective review of the senior author's (JEV) experience with autologous fat grafting for calf augmentation was performed. Medial and lateral calf augmentation was accomplished with injection of prepared autologous lipoaspirate intramuscularly and subcutaneously. Over a 5-year period, 13 patients underwent calf augmentation and reshaping with the described technique. Ten cases were bilateral (77%), and 3 cases (23%) were performed for congenital leg discrepancies. Mean 157 cc of prepared lipoaspirate was transferred per leg, with roughly 60% and 40% transferred into the medial and lateral calf, respectively. Four patients (31%) underwent a second round of autologous fat injection for further calf augmentation because they desired more volume. At mean 19.6 month follow-up, durable augmentation and improvement in calf contour was documented by comparison of standardized preoperative and postoperative photographs. Autologous calf fat grafting is a viable alternative to traditional implant-based calf augmentation for congenital calf discrepancies and the aesthetic pseudo-varus deformity. This technique provides results comparable to those obtainable with traditional methods. LEVEL OF EVIDENCE 4: Therapeutic. © 2015 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  20. Epstein-Barr virus-associated lymphoproliferative disorder developed following autologous peripheral blood stem cell transplantation for relapsing Hodgkin's lymphoma.

    PubMed

    Izumiya, Sakura; Ishida, Mitsuaki; Hodohara, Keiko; Yoshida, Takashi; Okabe, Hidetoshi

    2012-06-01

    Post-transplant lymphoproliferative disorders (PTLDs) are lymphoid or plasmacytic proliferations that develop as a consequence of immunosuppression in a recipient of a solid organ, bone marrow or stem cell allograft. The development of PTLDs is usually associated with Epstein-Barr virus (EBV) and the disorder is also termed EBV-associated lymphoproliferative disorder (LPD). The development of PTLD is a rare complication in autologous bone marrow/peripheral blood stem cell transplantation. In the present study, we report a case of EBV-associated LPD which developed following autologous peripheral blood stem cell transplantation for relapsing Hodgkin's lymphoma. A 51-year-old male presented with swelling of the left cervical lymph nodes. A biopsy revealed nodular sclerosis classical Hodgkin's lymphoma. Following four courses of ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) therapy, the Hodgkin's lymphoma relapsed. CHASE (cyclophosphamide, etoposide, cytarabine, dexamethasone) therapy and autologous peripheral blood stem cell transplantation were performed. In the 128 days following the transplantation, lymph node swelling was noted and a biopsy specimen demonstrated EBV-associated LPD. The serum copy number of EBV-DNA was 2.7×10(3) copies/ml. The occurrence of EBV-associated LPD may be on the rise due to the increased number of patients undergoing immunosuppression therapy. The measurement of the serum EBV-DNA copy number and the detection of EBV-infected atypical lymphocytes using in situ hybridization are significant in establishing an early accurate diagnosis and initiating the correct treatment for EBV-associated LPD in patients with immunosuppression.

  1. Autologous blood use in percutaneous nephrolithotomy.

    PubMed

    Stoller, M L; Lee, K L; Schwartz, B F; Viele, M K

    1999-09-01

    Preoperative autologous blood (AUB) donation has decreased patient exposure to allogenic blood (ALB) products and associated infectious risk. The risk of contracting hepatitis C and human immunodeficiency virus is 1 in 103,000 and 1 in 678,000, respectively, after receiving 1 U ALB. Elective surgical procedures require surgeons to offer preoperative AUB donation in California. Unused AUB is discarded. We report our use of AUB obtained for percutaneous nephrolithotomy. A retrospective study of 144 consecutive patients who underwent 193 percutaneous nephrolithotomies between January 1994 and April 1998 at one of four teaching hospitals at the University of California, San Francisco was performed. Preoperative AUB donation, transfusion rates, hemoglobin levels, blood use, and costs were analyzed. Ninety-six units of blood were collected from 63 patients (44%) and were available for 70 procedures (36%). The overall transfusion rate per procedure was 7%, with 13 patients receiving a total of 24 U, 7 AUB and 17 ALB. Eighty-nine units (92.7%) of AUB were discarded, and the transfusion rate in donors and nondonors was similar. There was no significant difference in preoperative hemoglobin or operative blood loss between donors and nondonors. The 13 transfused patients had a lower preoperative hemoglobin ( 11.5 versus 12.8 g/dL; P = 0.029) and higher operative blood loss as measured by hemoglobin level (3.2 versus 1.6 g/dL; P <0.001). Blood bank charges for ALB and AUB were $ 119/U and $244 to $498/U, respectively, depending on transportation and thawing charges. Routine preoperative blood donation adds substantial cost for minimal benefit, given the low infectious risk of ALB and the two- to fourfold higher cost of AUB. In our series, women had an increased incidence of blood transfusion compared with men. AUB donation may provide peace of mind but is rarely used and is discarded 93% of the time.

  2. Autologous Blood Transfusion in Sports: Emerging Biomarkers.

    PubMed

    Salamin, Olivier; De Angelis, Sara; Tissot, Jean-Daniel; Saugy, Martial; Leuenberger, Nicolas

    2016-07-01

    Despite being prohibited by the World Anti-Doping Agency, blood doping through erythropoietin injection or blood transfusion is frequently used by athletes to increase oxygen delivery to muscles and enhance performance. In contrast with allogeneic blood transfusion and erythropoietic stimulants, there is presently no direct method of detection for autologous blood transfusion (ABT) doping. Blood reinfusion is currently monitored with individual follow-up of hematological variables via the athlete biological passport, which requires further improvement. Microdosage is undetectable, and suspicious profiles in athletes are often attributed to exposure to altitude, heat stress, or illness. Additional indirect biomarkers may increase the sensitivity and specificity of the longitudinal approach. The emergence of "-omics" strategies provides new opportunities to discover biomarkers for the indirect detection of ABT. With the development of direct quantitative methods, transcriptomics based on microRNA or messenger RNA expression is a promising approach. Because blood donation and blood reinfusion alter iron metabolism, quantification of proteins involved in metal metabolism, such as hepcidin, may be applied in an "ironomics" strategy to improve the detection of ABT. As red blood cell (RBC) storage triggers changes in membrane proteins, proteomic methods have the potential to identify the presence of stored RBCs in blood. Alternatively, urine matrix can be used for the quantification of the plasticizer di(2-ethyhexyl)phthalate and its metabolites that originate from blood storage bags, suggesting recent blood transfusion, and have an important degree of sensitivity and specificity. This review proposes that various indirect biomarkers should be applied in combination with mathematical approaches for longitudinal monitoring aimed at improving ABT detection. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology

    PubMed Central

    Roberts, Sally; McCall, Iain W; Darby, Alan J; Menage, Janis; Evans, Helena; Harrison, Paul E; Richardson, James B

    2003-01-01

    Autologous chondrocyte implantation is being used increasingly for the treatment of cartilage defects. In spite of this, there has been a paucity of objective, standardised assessment of the outcome and quality of repair tissue formed. We have investigated patients treated with autologous chondrocyte implantation (ACI), some in conjunction with mosaicplasty, and developed objective, semiquantitative scoring schemes to monitor the repair tissue using MRI and histology. Results indicate repair tissue to be on average 2.5 mm thick. It was of varying morphology ranging from predominantly hyaline in 22% of biopsy specimens, mixed in 48%, through to predominantly fibrocartilage, in 30%, apparently improving with increasing time postgraft. Repair tissue was well integrated with the host tissue in all aspects viewed. MRI scans provide a useful assessment of properties of the whole graft area and adjacent tissue and is a noninvasive technique for long-term follow-up. It correlated with histology (P = 0.02) in patients treated with ACI alone. PMID:12716454

  4. ALS patients’ regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity

    PubMed Central

    Beers, David R.; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R.; Alsuliman, Abdullah S.; Shpall, Elizabeth J.; Rezvani, Katy

    2017-01-01

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression. PMID:28289705

  5. ALS patients' regulatory T lymphocytes are dysfunctional, and correlate with disease progression rate and severity.

    PubMed

    Beers, David R; Zhao, Weihua; Wang, Jinghong; Zhang, Xiujun; Wen, Shixiang; Neal, Dan; Thonhoff, Jason R; Alsuliman, Abdullah S; Shpall, Elizabeth J; Rezvani, Katy; Appel, Stanley H

    2017-03-09

    Neuroinflammation is a pathological hallmark of ALS in both transgenic rodent models and patients, and is characterized by proinflammatory T lymphocytes and activated macrophages/microglia. In ALS mouse models, decreased regulatory T lymphocytes (Tregs) exacerbate the neuroinflammatory process, leading to accelerated motoneuron death and shortened survival; passive transfer of Tregs suppresses the neuroinflammation and prolongs survival. Treg numbers and FOXP3 expression are also decreased in rapidly progressing ALS patients. A key question is whether the marked neuroinflammation in ALS can be attributed to the impaired suppressive function of ALS Tregs in addition to their decreased numbers. To address this question, T lymphocyte proliferation assays were performed. Compared with control Tregs, ALS Tregs were less effective in suppressing responder T lymphocyte proliferation. Although both slowly and rapidly progressing ALS patients had dysfunctional Tregs, the greater the clinically assessed disease burden or the more rapidly progressing the patient, the greater the Treg dysfunction. Epigenetically, the percentage methylation of the Treg-specific demethylated region was greater in ALS Tregs. After in vitro expansion, ALS Tregs regained suppressive abilities to the levels of control Tregs, suggesting that autologous passive transfer of expanded Tregs might offer a novel cellular therapy to slow disease progression.

  6. Sensitivity of scintigraphy with /sup 111/In-lymphocytes for detection of cardiac allograft rejection

    SciTech Connect

    Eisenberg, S.B.; Eisen, H.J.; Sobel, B.E.; Bergmann, S.R.; Bolman, R.M. 3d.

    1988-12-01

    We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively.

  7. Analysis of cerebrospinal fluid from cattle with central nervous system disorders after storage for 24 hours with autologous serum.

    PubMed

    Bellino, C; Miniscalco, B; Bertone, I; Cagnasso, A; Occhiena, E; Gianella, P; D'Angelo, A

    2015-08-13

    We compared the changes in cell morphology, total and differential cell counts between cerebrospinal fluid (CSF) samples analyzed within an hour of collection (fresh sample) and after the addition of autologous serum and storage for 24 h (stored sample) in 27 cattle with central nervous system disorders. There was a positive linear correlation between total and differential cell counts in the fresh and the stored samples. Cell morphology was preserved in all stored samples, except for increased vacuolization of mononuclear cells and cleaved nuclei of some small mononuclear cells. In the stored CSF samples, the total nucleated cell count and monocyte percentage were decreased (P = 0.01; P = 0.03), while the lymphocyte percentage was increased (P = 0.04). Mononuclear pleocytosis diagnosed in 20 fresh samples was cytologically confirmed in 12 of the 20 stored samples. In the remaining eight stored samples, the number of total nucleated cells was within the normal range. Neutrophilic pleocytosis was confirmed in all seven stored samples. The overall agreement rate between cytologic interpretation of the fresh and the stored CSF samples was 70 % (100 % for neutrophilic pleocytosis and 60 % for mononuclear pleocytosis). Adding 11 % of autologous serum to CSF samples might allow delayed analysis with a good agreement rate for CSF cytological interpretation. Caution is nonetheless warranted, as animal age, anamnesis, and neurological presentation need to be considered when interpreting stored CSF without pleocytosis.

  8. Differential human Th22-lymphocyte response triggered by Aggregatibacter actinomycetemcomitans serotypes.

    PubMed

    Díaz-Zúñiga, Jaime; Melgar-Rodríguez, Samanta; Monasterio, Gustavo; Pujol, Myriam; Rojas, Leticia; Alvarez, Carla; Carvajal, Paola; Vernal, Rolando

    2017-06-01

    In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on lipopolysaccharide (LPS) antigenicity. When T lymphocytes were stimulated with these serotypes, different patterns of T-helper (Th)1 and Th17-type of immune responses were reported. Recently, two new Th phenotypes have been described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study aimed to investigate the potential Th9 and/or Th22 lymphocyte responses when stimulated with autologous dendritic cells infected with different A. actinomycetemcomitans serotypes. Monocyte-derived dendritic cells and naïve CD4(+) T lymphocytes were obtained from healthy donors and stimulated with different serotypes of A. actinomycetemcomitans at a multiplicity of infection MOI=10(2) or their purified LPS (10-50ng/ml). The levels for the Th9 and Th22-associated cytokines, as well as the transcription factor master-switch genes implied in their differentiation Spi-B and AhR, were quantified by qPCR and ELISA. When stimulated with the serotype b of A. actinomycetemcomitans, higher levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were detected in dendritic cells, as well as higher levels of IL-22 and AhR were detected in T lymphocytes, when compared with stimulation with the other serotypes. The serotype b of A. actinomycetemcomitans has a higher capacity of trigger Th22-type of immune response in both dendritic cells and T lymphocytes. These data allow us to suggest that, when the serotype b of A. actinomycetemcomitans is a significant part of the subgingival biofilm, the Th22 polarization might be triggered within the periodontal lesion. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Effect of prolactin on carcinoembryonic antigen-specific cytotoxic T lymphocyte response induced by dendritic cells.

    PubMed

    Matera, L; Beltramo, E; Martinuzzi, E; Buttiglieri, S

    2004-08-01

    The cytokine hormone prolactin (PRL) has been shown previously to modulate native cellular responses and maturation of antigen-presenting cells. Here we have addressed its effect on the antigen-specific response of cytotoxic T lymphocytes (CTL). CTL were generated from HLA-A2 lymphocytes after three rounds of stimulation with autologous dendritic cells loaded with HLA-A2-restricted carcinoembrionic antigen (CEA) Cap-1 (YLSGANLNL) peptide. Selected cultures were expanded on cytokine-supplemented feeder-layers, enriched for CD8+ lymphocytes and analysed for PRL-receptor (PRL-R) expression and PRL responsiveness. Resting CD8+ lymphocytes were negative for PRL-R, whereas antigen-activated CD8+ lymphocytes derived from long-term cultures were highly positive. Results of a 51Cr release assay showed CTL killing of CEA-loaded, but not unloaded, T2 cell line and the CEA-positive gastric carcinoma cell line KATO, but not of the CEA-negative T leukaemia cell line Jurkat. Interferon (IFN)-gamma release, evaluated in an ELISPOT assay against CEA-loaded T2, was enhanced (P < 0.05) by concentrations of PRL (12-25 ng/ml) very close to the physiological levels (6-20 ng/ml), but was decreased (P < 0.05) by high concentrations (200 ng/ml). Pre-incubation of the stimulators with the anti-MHC class I MoAb W6.32 induced a 40-60% decrease of the PRL-boosted IFN-gamma release, thus proving the MHC restriction of the lymphocyte response. Cytotoxicity against CEA-loaded T2 and KATO cell lines was also increased by 12-25 ng (P < 0.05) and decreased (P < 0.05) by 200 ng PRL. Pre-incubation of CTL with an antibody specific for the PRL-R almost completely abrogated this effect.

  10. Effect of prolactin on carcinoembryonic antigen-specific cytotoxic T lymphocyte response induced by dendritic cells

    PubMed Central

    Matera, L; Beltramo, E; Martinuzzi, E; Buttiglieri, S

    2004-01-01

    The cytokine hormone prolactin (PRL) has been shown previously to modulate native cellular responses and maturation of antigen-presenting cells. Here we have addressed its effect on the antigen-specific response of cytotoxic T lymphocytes (CTL). CTL were generated from HLA-A2 lymphocytes after three rounds of stimulation with autologous dendritic cells loaded with HLA-A2-restricted carcinoembrionic antigen (CEA) Cap-1 (YLSGANLNL) peptide. Selected cultures were expanded on cytokine-supplemented feeder-layers, enriched for CD8+ lymphocytes and analysed for PRL-receptor (PRL-R) expression and PRL responsiveness. Resting CD8+ lymphocytes were negative for PRL-R, whereas antigen-activated CD8+ lymphocytes derived from long-term cultures were highly positive. Results of a 51Cr release assay showed CTL killing of CEA-loaded, but not unloaded, T2 cell line and the CEA-positive gastric carcinoma cell line KATO, but not of the CEA-negative T leukaemia cell line Jurkat. Interferon (IFN)-γ release, evaluated in an ELISPOT assay against CEA-loaded T2, was enhanced (P < 0·05) by concentrations of PRL (12–25 ng/ml) very close to the physiological levels (6–20 ng/ml), but was decreased (P < 0·05) by high concentrations (200 ng/ml). Pre-incubation of the stimulators with the anti-MHC class I MoAb W6·32 induced a 40–60% decrease of the PRL-boosted IFN-γ release, thus proving the MHC restriction of the lymphocyte response. Cytotoxicity against CEA-loaded T2 and KATO cell lines was also increased by 12–25 ng (P < 0·05) and decreased (P < 0·05) by 200 ng PRL. Pre-incubation of CTL with an antibody specific for the PRL-R almost completely abrogated this effect. PMID:15270849

  11. Improving diagnosis of appendicitis. Early autologous leukocyte scanning.

    PubMed

    DeLaney, A R; Raviola, C A; Weber, P N; McDonald, P T; Navarro, D A; Jasko, I

    1989-10-01

    A prospective nonrandomized study investigating the accuracy and utility of autologous leukocyte scanning in the diagnosis of apendicitis was performed. One hundred patients in whom the clinical diagnosis of appendicitis was uncertain underwent indium 111 oxyquinoline labelling of autologous leukocytes and underwent scanning 2 hours following reinjection. Of 32 patients with proved appendicitis, three scans revealed normal results (false-negative rate, 0.09). Of 68 patients without appendicitis, three scans had positive results (false-positive rate, 0.03; sensitivity, 0.91; specificity, 0.97; predictive value of positive scan, 0.94; predictive value of negative scan, 0.96; and overall accuracy, 0.95). Scan results altered clinical decisions in 19 patients. In 13 cases, the scan produced images consistent with diagnoses other than appendicitis, expediting appropriate management. Early-imaging111 In oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.

  12. Autologous hematopoietic stem cell transplantation in progressive severe multiple sclerosis.

    PubMed

    Pandit, Awadh Kishor; Prasad, Kameshwar; Seth, Tulika

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system (CNS), which is disabling and majorly involves younger population. Various available treatments in forms of immunomodulation are not very effective; however, stem cell transplantation seems to be promising in recent literature. The current case report is a novel evidence for autologous hematopoietic stem cell transplantation (HSCT) in progressive MS. A 33 year old male with secondary progressive MS (SPMS), after being failed and/or intolerance to standard approved interferon (IFN) and mitoxantrone therapy, autologous HSCT was administered. At 2years of post-stem cell transplantation follow-up, he has remained stable with some improvement in functional status (Expanded Disability Status Scale (EDSS) reduced by 1.5), with no relapse, no treatment related complications, and no fresh magnetic resonance imaging (MRI) lesions. Autologous stem cell transplantation may be beneficial in progressive forms of MS, but needs to be tested in well-designed randomized trial.

  13. Therapeutic potential of autologous stem cell transplantation for cerebral palsy.

    PubMed

    Purandare, Chaitanya; Shitole, D G; Belle, Vaijayantee; Kedari, Aarti; Bora, Neeta; Joshi, Meghnad

    2012-01-01

    Background. Cerebral palsy (CP) is a severe disabling disease with worldwide incidence being 2 to 3 per 1000 live births. CP was considered as a noncurable, nonreparative disorder, but stem cell therapy offers a potential treatment for CP. Objective. The present study evaluates the safety and efficacy of autologous bone-marrow-derived mononuclear cell (BMMNCs) transplantation in CP patient. Material and Methods. In the present study, five infusions of autologous stem cells were injected intrathecally. Changes in neurological deficits and improvements in function were assessed using Gross Motor Function Classification System (GMFCS-E&R) scale. Results. Significant motor, sensory, cognitive, and speech improvements were observed. Bowel and bladder control has been achieved. On the GMFCS-E&R level, the patient was promoted from grade III to I. Conclusion. In this study, we report that intrathecal infusion of autologous BMMNCs seems to be feasible, effective, and safe with encouraging functional outcome improvements in CP patient.

  14. [Treatment of relapsed Hodgkin lymphoma after autologous stem cell transplantation].

    PubMed

    Illés, Árpád; Simon, Zsófia; Udvardy, Miklós; Magyari, Ferenc; Jóna, Ádám; Miltényi, Zsófia

    2017-08-01

    Approximately 10-30% of Hodgkin lymphoma patients relapses or experience refractory disease after first line treatment. Nowadays, autologous stem cell transplantation can successfully salvage half of these patients, median overall survival is only 2-2.5 years. Several prognostic factors determine success of autologous stem cell transplantation. Result of transplantation can be improved considering these factors and using consolidation treatment, if necessary. Patients who relapse after autologous transplantation had worse prognosis, treatment of this patient population is unmet clinical need. Several new treatment options became available in the recent years (brentuximab vedotin and immuncheckpoint inhibitors). These new treatment options offer more chance for cure in relapsed/refractory Hodgkin patients. Outcome of allogenic stem cell transplantation can be improved by using haploidentical donors. New therapeutic options will be discussed in this review. Orv Hetil. 2017; 158(34): 1338-1345.

  15. HLA class I gene expression on human primary tumours and autologous metastases: demonstration of selective losses of HLA antigens on colorectal, gastric and laryngeal carcinomas.

    PubMed Central

    López-Nevot, M. A.; Esteban, F.; Ferrón, A.; Gutiérrez, J.; Oliva, M. R.; Romero, C.; Huelin, C.; Ruiz-Cabello, F.; Garrido, F.

    1989-01-01

    The expression of HLA class I antigens was studied in 99 primary tumour (colorectal, gastric and laryngeal carcinomas) and 57 autologous metastases using immunohistological techniques and monoclonal antibodies against class I monomorphic determinants, HLA-B isotypic determinants and HLA polymorphic determinants. Fourteen per cent of colorectal, 9.6% of gastric and 20% of laryngeal carcinomas completely lacked class I molecules. Selective losses of HLA-B antigens were also detected in 8.8, 3.4 and 5.8% of these tumours respectively. Taking into account complete and selective loss of HLA-B the average alteration in the class I molecules expression totalled 21%. The comparison of class I expression between primary tumours and autologous metastases showed differences in 24% of the patients. These differences consisted mainly in a decrease of class I expression by metastases. Nevertheless, four types of divergence were detected in laryngeal carcinomas, namely: +/-, +/+, -/+, -/-. In addition, a clear correlation between degree of differentiation and class I expression was observed in laryngeal tumours. Finally, when class I gene RFLPs were compared with DNA from 15 tumours and autologous normal mucosa or peripheral lymphocytes, no differences were detected between these samples. Images Figure 1 Figure 2 PMID:2649129

  16. Monetite granules versus particulate autologous bone in bone regeneration.

    PubMed

    Torres, Jesús; Tamimi, Iskandar; Cabrejos-Azama, Jatsue; Tresguerres, Isabel; Alkhraisat, Mohammad; López-Cabarcos, Enrique; Hernández, Gonzalo; Tamimi, Faleh

    2015-07-01

    The aim of this study was to test bone tissue response to monetite granules in comparison with intramembranous autologous bone graft in a rabbit calvaria critical size defect model. Novel monetite granules were synthesized by thermal conversion of set brushite cement. Eight female New Zealand rabbits were used for this study. Two identical 10mm diameter bicortical cranial defects were created in each animal. One of the defects was grafted with monetite granules while the contralateral was grafted with granules of intramembranous autologous bone as control. Animals were sacrificed 8 weeks after surgery and biopsies were taken for histological and histomorphometrical evaluation under light microscopy. Wilcoxon test was used for statistical analysis. The bone defects treated with either autologous bone or monetite granules were able to heal within the study period. Upon histological observation the defects treated with autologous bone granules resembled the adjacent intact calvaria, whereas the defects treated with monetite showed a high infiltration of new bone and only 13.4±8.4% of remaining granules. The percentage of bone volume in the defects of the control group (71±9%) was 16% higher than in the study group (55±10%) (p<0.05). The percentage of augmented mineralized tissue volume in the study group (68±18%) was not significantly different from the control group (p>0.05). The amount of augmented mineralized tissue in the bone defects obtained with monetite granules was not significantly different from that obtained with autologous bone. This study confirms the potential of monetite based biomaterials as an alternative to autologous bone graft. Copyright © 2015 Elsevier GmbH. All rights reserved.

  17. [Cell-based therapy options for osteochondral defects. Autologous mesenchymal stem cells compared to autologous chondrocytes].

    PubMed

    Grässel, S; Anders, S

    2012-05-01

    Cartilage defects are multifactorial and site-specific and therefore need a clear analysis of the underlying pathology as well as an individualized therapy so that cartilage repair lacks a one-for-all therapy. The results of comparative clinical studies using cultured chondrocytes in autologous chondrocyte implantation (ACI) have shown some superiority over conventional microfracturing under defined conditions, especially for medium or large defects and in long-term durability. Adult mesenchymal stem cells can be isolated from bone marrow, have the potency to proliferate in culture and are capable of differentiating into the chondrogenic pathway. They represent a promising versatile cell source for cartilage repair but the ideal conditions for cultivation and application in cartilage repair are not yet known or have not yet been characterized. Adding a scaffold offers mechanical stability and advances chondrogenic differentiation for both possible cell sources.

  18. Should Immediate Autologous Breast Reconstruction Be Considered in Women Who Require Postmastectomy Radiation Therapy? A Prospective Analysis of Outcomes.

    PubMed

    Billig, Jessica; Jagsi, Reshma; Qi, Ji; Hamill, Jennifer B; Kim, Hyungjin M; Pusic, Andrea L; Buchel, Edward; Wilkins, Edwin G; Momoh, Adeyiza O

    2017-06-01

    In women who require postmastectomy radiation therapy, immediate autologous breast reconstruction is often discouraged. The authors prospectively evaluated postoperative morbidity and satisfaction reported by women undergoing delayed or immediate autologous breast reconstruction in the setting of postmastectomy radiation therapy. Patients enrolled in the Mastectomy Reconstruction Outcomes Consortium study, who received postmastectomy radiotherapy and underwent immediate or delayed free abdominally based autologous breast reconstruction, were identified. Postoperative complications at 1 and 2 years after reconstruction were assessed. Patient-reported outcomes were evaluated using the BREAST-Q questionnaire preoperatively and at 1 and 2 years postoperatively. Bivariate analyses and mixed-effects regression models were used to compare outcomes. A total of 175 patients met the authors' inclusion criteria. Immediate reconstructions were performed in 108 patients and delayed reconstructions in 67 patients; 93.5 percent of immediate reconstructions were performed at a single center. Overall complication rates were similar based on reconstructive timing (25.9 percent immediate and 26.9 percent delayed at 1 year; p = 0.54). Patients with delayed reconstruction reported significantly lower prereconstruction scores (p < 0.0001) for Satisfaction with Breasts and Psychosocial and Sexual Well-being than did patients with immediate reconstruction. At 1 and 2 years postoperatively, both groups reported comparable levels of satisfaction in assessed BREAST-Q domains. From this prospective cohort, immediate autologous breast reconstruction in the setting of postmastectomy radiation therapy appears to be a safe option that may be considered in select patients and centers. Breast aesthetics and quality of life, evaluated from the patient's perspective, were not compromised by flap exposure to radiation therapy. Therapeutic, III.

  19. Autologous Infant and Allogeneic Adult Red Cells Demonstrate Similar Concurrent Post-Transfusion Survival in Very Low Birth Weight Neonates

    PubMed Central

    Widness, John A.; Kuruvilla, Denison J.; Mock, Donald M.; Matthews, Nell I.; Nalbant, Demet; Cress, Gretchen A.; Schmidt, Robert L.; Strauss, Ronald G.; Zimmerman, M. Bridget; Veng-Pedersen, Peter

    2015-01-01

    Objective Based on the hypothesis that neonatal autologous red blood cell (RBC) survival (RCS) is substantially shorter than adult RBC, we concurrently tracked the survival of transfused biotin-labeled autologous neonatal and allogeneic adult RBC into ventilated, very low birth weight (VLBW) infants. Study design RBC aliquots from the first clinically ordered, allogeneic adult RBC transfusion and from autologous infant blood were labeled at separate biotin densities (BioRBC) and transfused. Survival of these BioRBCs populations were concurrently followed over weeks by flow cytometric enumeration using leftover blood. Relative tracking of infant autologous and adult allogeneic BioRBC was analyzed by linear mixed modeling of batched weekly data. When possible, Kidd antigen (Jka and Jkb) mismatches between infant and donor RBCs were also used to track these two populations. Results Contrary to our hypothesis, concurrent tracking curves of RCS of neonatal and adult BioRBC in 15 study infants did not differ until week 7, after which neonatal RBC survival became shortened to 59% to 79% of adult enumeration values for uncertain reasons. Analysis of mismatched Kidd antigen RBC showed similar results, thus confirming that BioRBC tracking is not perturbed by biotin RBC labeling. Conclusions This study illustrates the utility of multi-density BioRBC labeling for concurrent measurement of RCS of multiple RBC populations in vivo. The similar RCS results observed for neonatal and adult BioRBCs transfused into VLBW infants provides strong evidence that the circulatory environment of the newborn infant—not intrinsic infant-adult RBC differences—is the primary determinant of erythrocyte survival. Trial registration Clinicaltrials.gov: NCT 00731588. PMID:26363547

  20. Autologous Infant and Allogeneic Adult Red Cells Demonstrate Similar Concurrent Post-Transfusion Survival in Very Low Birth Weight Neonates.

    PubMed

    Widness, John A; Kuruvilla, Denison J; Mock, Donald M; Matthews, Nell I; Nalbant, Demet; Cress, Gretchen A; Schmidt, Robert L; Strauss, Ronald G; Zimmerman, M Bridget; Veng-Pedersen, Peter

    2015-11-01

    Based on the hypothesis that neonatal autologous red blood cell (RBC) survival (RCS) is substantially shorter than adult RBC, we concurrently tracked the survival of transfused biotin-labeled autologous neonatal and allogeneic adult RBC into ventilated, very low birth weight infants. RBC aliquots from the first clinically ordered, allogeneic adult RBC transfusion and from autologous infant blood were labeled at separate biotin densities (biotin-labeled RBC [BioRBC]) and transfused. Survival of these BioRBCs populations were concurrently followed over weeks by flow cytometric enumeration using leftover blood. Relative tracking of infant autologous and adult allogeneic BioRBC was analyzed by linear mixed modeling of batched weekly data. When possible, Kidd antigen (Jka and Jkb) mismatches between infant and donor RBCs were also used to track these 2 populations. Contrary to our hypothesis, concurrent tracking curves of RCS of neonatal and adult BioRBC in 15 study infants did not differ until week 7, after which neonatal RCS became shortened to 59%-79% of adult enumeration values for uncertain reasons. Analysis of mismatched Kidd antigen RBC showed similar results, thus, confirming that BioRBC tracking is not perturbed by biotin RBC labeling. This study illustrates the utility of multidensity BioRBC labeling for concurrent measurement of RCS of multiple RBC populations in vivo. The similar RCS results observed for neonatal and adult BioRBCs transfused into very low birth weight infants provides strong evidence that the circulatory environment of the newborn infant, not intrinsic infant-adult RBC differences, is the primary determinant of erythrocyte survival. Clinicaltrials.gov: NCT00731588. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Preoperative autologous plateletpheresis in patients undergoing open heart surgery.

    PubMed

    Tomar, Akhlesh S; Tempe, Deepak K; Banerjee, Amit; Hegde, Radhesh; Cooper, Andrea; Khanna, S K

    2003-07-01

    Blood conservation is an important aspect of care provided to the patients undergoing cardiac operations with cardiopulmonary bypass (CPB). It is even more important in patients with anticipated prolonged CPB, redo cardiac surgery, patients having negative blood group and in patients undergoing emergency cardiac surgery. In prolonged CPB the blood is subjected to more destruction of important coagulation factors, in redo surgery the separation of adhesions leads to increased bleeding and difficulty in achieving the haemostasis and in patients with negative blood group and emergency operations, the availability of sufficient blood can be a problem. Harvesting the autologous platelet rich plasma (PRP) can be a useful method of blood conservation in these patients. The above four categories of patients were prospectively studied, using either autologous whole blood donation or autologous platelet rich plasma (PRP) harvest in the immediate pre-bypass period. Forty two patients were included in the study and randomly divided into two equal groups of 21 each, control group (Group I) in which one unit of whole blood was withdrawn, and PRP group (Group II) where autologous plateletpheresis was utilised. After reversal of heparin, autologous whole blood was transfused in the control group and autologous PRP was transfused in the PRP group. The chest tube drainage and the requirement of homologous blood and blood products were recorded. Average PRP harvest was 643.33 +/- 133.51 mL in PRP group and the mean whole blood donation was 333.75 +/- 79.58 mL in the control group. Demographic, preoperative and intra operative data showed no statistically significant differences between the two groups. The PRP group patients drained 26.44% less (p<0.001) and required 38.5% less homologous blood and blood products (p<0.05), in the postoperative period. Haemoglobin levels on day zero (day of operation) and day three were statistically not different between the two groups. We conclude

  2. Necrobiotic xanthogranuloma successfully treated with autologous stem cell transplantation.

    PubMed

    Goede, Jeroen S; Misselwitz, Benjamin; Taverna, Christian; Schanz, Urs; Dispenzieri, Angela; Hummel, Yvonne; Trüeb, Ralph M; Fehr, Jörg

    2007-04-01

    Paraproteinemia can be complicated by necrobiotic xanthogranuloma. Therapeutic options for this progressive disease are limited, and there is no agreement on a single best strategy. We report the case of a patient with a massive periorbital infiltration narrowing the palpebral fissure and blinding the patient. Conventional myeloma therapy had only limited benefit in our patient. However, he was successfully treated with high-dose chemotherapy followed by autologous stem cell transplantation, rendering the patient free of symptoms. This is the first report of autologous stem cell transplantation in a patient with necrobiotic xanthogranuloma.

  3. Splenic lymphoma with villous lymphocytes.

    PubMed

    Gupta, Ritu; Naseem, Shano; Sukumaran, Shawgi; Kashyap, Rajesh; Kaur, Sukhpreet; Paul, Lily

    2008-01-01

    Splenic lymphoma with villous lymphocytes (SLVL) is a rare disorder that comprises less than 1% of lymphoid neoplasms. It is the leukemic counterpart of splenic marginal zone lymphoma (SMZL) and is characterized by splenomegaly, often with no lymphadenopathy, moderate lymphocytosis and villous lymphocytes on peripheral blood smear. Here, we report a case of SLVL in a 56-year-old male with very high leukocyte counts, massive splenomegaly and relatively few leukemic cells with subtle villous projections on the surface. This disorder is often confused with other chronic lymphoproliferative disorders, especially chronic lymphocytic leukemia (CLL) and hairy cell leukemia and should be differentiated from them. We are reporting this case to highlight the diagnostic pitfalls associated with this disorder.

  4. Fatty acids and lymphocyte functions.

    PubMed

    Calder, P C; Yaqoob, P; Thies, F; Wallace, F A; Miles, E A

    2002-01-01

    The immune system acts to protect the host against pathogenic invaders. However, components of the immune system can become dysregulated such that their activities are directed against host tissues, so causing damage. Lymphocytes are involved in both the beneficial and detrimental effects of the immune system. Both the level of fat and the types of fatty acid present in the diet can affect lymphocyte functions. The fatty acid composition of lymphocytes, and other immune cells, is altered according to the fatty acid composition of the diet and this alters the capacity of those cells to produce eicosanoids, such as prostaglandin E2, which are involved in immunoregulation. A high fat diet can impair lymphocyte function. Cell culture and animal feeding studies indicate that oleic, linoleic, conjugated linoleic, gamma-linolenic, dihomo-gamma-linolenic, arachidonic, alpha-linolenic, eicosapentaenoic and docosahexaenoic acids can all influence lymphocyte proliferation, the production of cytokines by lymphocytes, and natural killer cell activity. High intakes of some of these fatty acids are necessary to induce these effects. Among these fatty acids the long chain n-3 fatty acids, especially eicosapentaenoic acid, appear to be the most potent when included in the human diet. Although not all studies agree, it appears that fish oil, which contains eicosapentaenoic acid, down regulates the T-helper 1-type response which is associated with chronic inflammatory disease. There is evidence for beneficial effects of fish oil in such diseases; this evidence is strongest for rheumatoid arthritis. Since n-3 fatty acids also antagonise the production of inflammatory eicosanoid mediators from arachidonic acid, there is potential for benefit in asthma and related diseases. Recent evidence indicates that fish oil may be of benefit in some asthmatics but not others.

  5. Autologous serum eye drops for dry eye

    PubMed Central

    Pan, Qing; Angelina, Adla; Zambrano, Andrea; Marrone, Michael; Stark, Walter J; Heflin, Thomas; Tang, Li; Akpek, Esen K

    2014-01-01

    Background Theoretically, autologous serum eye drops (AS) have a potential advantage over traditional therapies based on the assumption that AS serve not only as a lacrimal substitute to provide lubrication, but also contain other biochemical components mimicking natural tears more closely. The application of AS in dry eye treatment has gained popularity as a second-line therapy in the treatment of dry eye. Published studies on the subject indicate that autologous serum could be an effective treatment for dry eye. Objectives To evaluate the efficacy and safety of AS compared to artificial tears for treating dry eye. Search methods We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 3), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLD MEDLINE, (January 1950 to April 2013), EMBASE (January 1980 to April 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to April 2013), the meta Register of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We also searched the Science Citation Index Expanded database (September 2013) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 April 2013. Selection criteria We included randomized controlled trials (RCTs) in which AS was compared to artificial tears in the treatment of dry eye in adults. Data collection and analysis Two review authors independently screened all titles and abstracts and assessed full-text articles of potentially eligible trials. Two review authors extracted data and assessed the methodological quality and characteristics of the included trials.We contacted investigators for missing data

  6. Autologous serum eye drops for dry eye.

    PubMed

    Pan, Qing; Angelina, Adla; Zambrano, Andrea; Marrone, Michael; Stark, Walter J; Heflin, Thomas; Tang, Li; Akpek, Esen K

    2013-08-27

    =Theoretically, autologous serum eye drops (AS) have a potential advantage over traditional therapies based on the assumption that ASserve not only as a lacrimal substitute to provide lubrication, but also contain other biochemical components mimicking natural tears more closely. The application of AS in dry eye treatment has gained popularity as a second-line therapy in the treatment of dry eye.Published studies on the subject indicate that autologous serum could be an effective treatment for dry eye. To evaluate the efficacy and safety of AS compared to artificial tears for treating dry eye. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2013, Issue 3),Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE,(January 1950 to April 2013), EMBASE (January 1980 to April 2013), Latin American and Caribbean Literature on Health Sciences(LILACS) (January 1982 to April 2013), themetaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov(www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We also searched the Science Citation Index Expanded database (September 2013) and reference lists of included studies. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 15 April 2013. We included randomized controlled trials (RCTs) in which AS was compared to artificial tears in the treatment of dry eye in adults. Two review authors independently screened all titles and abstracts and assessed full-text articles of potentially eligible trials. Two review authors extracted data and assessed the methodological quality and characteristics of the included trials.We contacted investigators for missing data. For both primary and secondary outcomes, we reported mean differences with corresponding 95

  7. Glucose, glycolysis and lymphocyte responses.

    PubMed

    Donnelly, Raymond P; Finlay, David K

    2015-12-01

    Activated lymphocytes engage in robust growth and rapid proliferation. To achieve this, they tend to adopt a form of glucose metabolism termed aerobic glycolysis. This type of metabolism allows for the use of large amounts of glucose to generate energy, but also to support biosynthetic processes. This review article will discuss how aerobic glycolysis supports the biosynthetic demands of activated T cells, B cells and Natural Killer cells, and the emerging concept that glycolysis is integrally linked to the differentiation and function of these lymphocyte populations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Thyroid storm and lymphocytic myocarditis.

    PubMed

    Chen, Yi-Ting; Yang, Gee-Gwo; Hsu, Yung-Hsiang

    2010-01-01

    Cardiac failure is the leading cause of mortality in patients with thyroid storm. But the underlying cardiac pathology is unclear. Here, we report a 46-year-old woman who presented with hyperpyrexia and sinus tachycardia subsequent to accidental neck contusion. Her hyperthyroidism was verified by abnormal biochemical changes. Despite vigorous antithyroid treatment including a beta-blocker, glucocorticoid and potassium iodide, the patient eventually succumbed to refractory congestive heart failure in 4 days. Autopsy revealed lymphocytic myocarditis. We propose that lymphocytic myocarditis played a prominent role in her demise.

  9. Bovine WC1(+) γδ T lymphocytes modify monocyte-derived macrophage responses during early Mycobacterium avium subspecies paratuberculosis infection.

    PubMed

    Baquero, Monica M; Plattner, Brandon L

    2016-02-01

    Following Mycobacterium avium subspecies paratuberculosis (Map) infection, some calves are apparently able to successfully clear the pathogen whereas others become persistently infected; however the reasons for this remain unknown. The importance of innate immunity, and in particular the role of γδ T lymphocytes, during early anti-mycobacterial immune response is recognized but specific mechanisms remain incompletely characterized. The objective of this study was to investigate how bovine WC1(+) γδ T lymphocytes mediate macrophage function during early Map infection. To achieve this objective, Map-infected monocyte-derived macrophages (MDMs) were co-cultured either in direct contact with, or separated by a semi-permeable membrane from, autologous WC1(+) γδ T lymphocytes. Nitrites, IL-17A, IFN-γ, IL-4 and IL-10 from cell culture supernatants were measured. Expression of CD25 on WC1(+) γδ T lymphocytes, expression of MHC-I and MHC-II on MDMs and the viability of Map recovered from MDM cultures 72h after Map infection were also assessed. Map viability was significantly reduced when WC1(+) γδ T lymphocytes were co-cultured in direct contact with Map-infected MDMs. Both MDMs and WC1(+) γδ T lymphocytes generated increased concentrations of IFN-γ and IL-4 in our system, and MDM/WC1(+) γδ T lymphocyte synergism was identified for IFN-γ production. MDMs but not WC1(+) γδ T lymphocytes were a significant source of IL-17A. The presence of WC1(+) γδ T lymphocytes was associated with higher expression of MHC-I on MDMs and increased concentration of nitrites in supernatants 72h after Map infection. In conclusion, this study showed that WC1(+) γδ lymphocytes had differential effects on Map-infected macrophages in vitro.

  10. Autologous buccal mucosa graft augmentation for foreshortened vagina.

    PubMed

    Grimsby, Gwen M; Bradshaw, Karen; Baker, Linda A

    2014-05-01

    Vaginal foreshortening after pelvic surgery or radiotherapy may lead to dyspareunia and decreased quality of life. Unfortunately, little literature exists regarding treatment options for this debilitating problem. Autologous buccal mucosal grafting has been previously reported for creation of a total neovagina and the repair of postvaginoplasty vaginal stenosis. Autologous buccal mucosa offers several advantages as a replacement material for vaginal reconstruction. Vaginal and oral buccal mucosa are both hairless, moist, nonkeratinized stratified squamous epithelia. Buccal mucosa has a dense layer of elastic fibers, imparting both elasticity and strength, and acquires a robust neovascularity with excellent graft take. The graft material is readily available and donor site scars are hidden in the mouth. A 60-year-old woman had vaginal foreshortening to 4.5 cm 15 years after radical hysterectomy and brachytherapy for endometrial cancer. She was unable to have intercourse despite attempted vaginal dilation. Her foreshortened vagina was successfully augmented with autologous buccal mucosa grafting at the apex, increasing her vaginal length to 8 cm and permitting pain-free intercourse. Even in the face of an altered surgical field after radical hysterectomy and radiation, autologous buccal mucosa is an option for vaginal reconstruction for vaginal foreshortening.

  11. Autologous epidermal cell suspension: A promising treatment for chronic wounds.

    PubMed

    Zhao, Hongliang; Chen, Yan; Zhang, Cuiping; Fu, Xiaobing

    2016-02-01

    Chronic wounds have become an increasing medical and economic problem of aging societies because they are difficult to manage. Skin grafting is an important treatment method for chronic wounds, which are refractory to conservative therapy. The technique involving epidermal cell suspensions was invented to enable the possibility of treating larger wounds with only a small piece of donor skin. Both uncultured and cultured autologous epidermal cell suspensions can be prepared and survive permanently on the wound bed. A systematic search was conducted of EMBASE, Cochrane Library, PubMed and web of science by using Boolean search terms, from the establishment of the database until May 31, 2014. The bibliographies of all retrieved articles in English were searched. The search terms were: (epithelial cell suspension OR keratinocyte suspension) and chronic and wound. From the included, 6 studies are descriptive interventions and discussed the use of autologous keratinocyte suspension to treat 61 patients' chronic wound. The various methods of preparation of epidermal cell suspension are described. The advantages and shortcomings of different carriers for epidermal cell suspensions are also summarised. Both uncultured and cultured autologous epidermal cell suspensions have been used to treat chronic wounds. Although the limitations of these studies include the small number of patient populations with chronic wounds and many important problems that remain to be solved, autologous epidermal cell suspension is a promising treatment for chronic wounds. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

  12. A Role For Photodynamic Therapy In Autologous Bone Marrow Transplantation

    NASA Astrophysics Data System (ADS)

    Sieber, Fritz

    1988-02-01

    Simultaneous exposure to the amphipathic fluorescent dye merocyanine 540 (MC 540) and light of a suitable wavelength rapidly kills leukemia, lymphoma, and neuroblastoma cells but spares normal pluripotent hematopoietic stem cells. Tests in several preclinical models and early results of a phase I clinical trial suggest that MC 540-mediated photosensitization may be useful for the extracorporeal purging of autologous remission bone marrow grafts.

  13. Autologous Bone Marrow Transplantation for Poor-Prognosis Neuroblastoma

    DTIC Science & Technology

    1987-01-01

    Recent pilot studies of intensive chemotherapy and total body irradiation (TBI) followed by allogeneic bone marrow transplantation (BMT) or...autologous bone marrow transplantation (ABMT) have produced encouraging results. In this report, we update our original study in which 20 patients with

  14. Current Status of Autologous Breast Tumor Cell-based Vaccines

    PubMed Central

    Kurtz, Samantha L.; Ravindranathan, Sruthi; Zaharoff, David A.

    2015-01-01

    Summary Approximately 9 of 10 breast cancer-related deaths are attributable to metastasis. Yet, less than 4% of breast cancer patients are initially diagnosed with metastatic cancer. Therefore, the majority of breast cancer-related deaths are due to recurrence and progression of nonmetastatic disease. There is tremendous clinical opportunity for novel adjuvant strategies, such as immunotherapies, that have the potential to prevent progressive recurrences. In particular, autologous tumor cell-based vaccines can train a patient's immune system to recognize and eliminate occult disease. Autologous tumor cell-based vaccines have several advantages including safety, multivalency and patient specificity. Furthermore, because lumpectomy or mastectomy is indicated for the vast majority of breast cancer patients, resected tumors offer a readily available, patient-specific source of tumor antigen. Disadvantages of autologous tumor cell-based vaccines include poor immunogenicity and production inconsistencies. This review summarizes recent progress in the development of autologous breast tumor vaccines and offers insight for overcoming existing limitations. PMID:25308888

  15. Canine Cranial Reconstruction Using Autologous Bone Marrow Stromal Cells

    PubMed Central

    Mankani, Mahesh H.; Kuznetsov, Sergei A.; Shannon, Brian; Nalla, Ravi K.; Ritchie, Robert O.; Qin, Yixian; Robey, Pamela Gehron

    2006-01-01

    Limited-sized transplants of culture-expanded autologous or allogeneic bone marrow stromal cells (BMSCs) form cortico-cancellous bone in rodent models. Initiation of clinical studies using autologous BMSC transplantation requires effective bone formation among sizable transplants in a large animal model as well as noninvasive techniques for evaluating transplant success. Here, we obtained bone marrow from the femurs of six dogs and expanded BMSCs in tissue culture. Autologous BMSC-hydroxyapatite/tricalcium phosphate (HA/TCP) transplants were introduced into critical-sized calvarial defects and contralateral control skull defects received HA/TCP vehicle alone. At intervals ranging from 2 to 20 months, transplants were biopsied or harvested for histological and mechanical analysis. Noninvasive studies, including quantitative computed tomography scans and ultrasound, were simultaneously obtained. In all animals, BMSC-containing transplants formed significantly more bone than their control counterparts. BMSC-associated bone possessed mechanical properties similar to the adjacent normal bone, confirmed by both ultrasound and ex vivo analysis. Evaluation by quantitative computed tomography confirmed that the extent of bone formation demonstrated by histology could be discerned through noninvasive means. These results show that autologous cultured BMSC transplantation is a feasible therapy in clinical-sized bone defects and that such transplants can be assessed noninvasively, suggesting that this technique has potential for use in patients with certain bone defects. PMID:16436668

  16. Lack of autologous tissue transmission of eosinophilic plaques in cats.

    PubMed

    Moriello, K A; Kunkle, G; Miller, L M; Crowley, A

    1990-07-01

    Autologous tissue transmission of spontaneously developing feline eosinophilic plaques was attempted in 5 cats. Macerated tissue from the plaque was vigorously rubbed onto 2 scarified skin sites in each cat. The inoculated areas were observed daily for 30 days. During that time, no clinical or histologic evidence of transmission was found.

  17. How Effective is Autologous Serum Therapy in Chronic Autoimmune Urticaria

    PubMed Central

    Majid, Imran; Shah, Shazia; Hassan, Altaf; Aleem, Saima; Aziz, Khalid

    2015-01-01

    Background: Chronic autoimmune urticaria (CAU) is one of the most challenging therapeutic problems faced by a dermatologist. Recently, weekly autologous serum injections have been shown to induce a prolonged remission in this disease. Aim: To evaluate the efficacy of repeated autologous serum injections in patients with CAU. Materials and Methods: Seventy patients of CAU were prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a post-intervention follow-up of 12 weeks. Total urticaria severity score (TSS) was monitored at the baseline, at the end of treatment and lastly at the end of 12 weeks of follow up. Response to treatment was judged by the percentage reduction in baseline TSS at the end of treatment and again at the end of 12 weeks-follow-up. Results: Out of the 70 patients enrolled, 11 dropped out of the injection treatment after one or the first few doses only. Among the rest of 59 patients, only 7 patients (12%) went into a partial or complete remission and remained so over the follow-up period of 12 weeks. Forty patients (68%) did not demonstrate any significant reduction in TSS at the end of the treatment period. Rest of the 12 patients showed either a good or excellent response while on weekly injection treatment, but all of them relapsed over the follow-up period of 12 weeks. Conclusion: Autologous serum therapy does not seem to lead to any prolonged remission in patients of CAU. PMID:25657418

  18. How Effective is Autologous Serum Therapy in Chronic Autoimmune Urticaria.

    PubMed

    Majid, Imran; Shah, Shazia; Hassan, Altaf; Aleem, Saima; Aziz, Khalid

    2015-01-01

    Chronic autoimmune urticaria (CAU) is one of the most challenging therapeutic problems faced by a dermatologist. Recently, weekly autologous serum injections have been shown to induce a prolonged remission in this disease. To evaluate the efficacy of repeated autologous serum injections in patients with CAU. Seventy patients of CAU were prospectively analyzed for the efficacy of nine consecutive weekly autologous serum injections with a post-intervention follow-up of 12 weeks. Total urticaria severity score (TSS) was monitored at the baseline, at the end of treatment and lastly at the end of 12 weeks of follow up. Response to treatment was judged by the percentage reduction in baseline TSS at the end of treatment and again at the end of 12 weeks-follow-up. Out of the 70 patients enrolled, 11 dropped out of the injection treatment after one or the first few doses only. Among the rest of 59 patients, only 7 patients (12%) went into a partial or complete remission and remained so over the follow-up period of 12 weeks. Forty patients (68%) did not demonstrate any significant reduction in TSS at the end of the treatment period. Rest of the 12 patients showed either a good or excellent response while on weekly injection treatment, but all of them relapsed over the follow-up period of 12 weeks. Autologous serum therapy does not seem to lead to any prolonged remission in patients of CAU.

  19. Radionuclide labeled lymphocytes for therapeutic use

    DOEpatents

    Srivastava, Suresh C.; Fawwaz, Rashid A.; Richards, Powell

    1985-01-01

    Lymphocytes labelled with .beta.-emitting radionuclides are therapeutically useful, particularly for lymphoid ablation. They are prepared by incubation of the lymphocytes with the selected radionuclide-oxine complex.

  20. Radionuclide labeled lymphocytes for therapeutic use

    DOEpatents

    Srivastava, S.C.; Fawwaz, R.A.; Richards, P.

    1983-05-03

    Lymphocytes labelled with ..beta..-emitting radionuclides are therapeutically useful, particularly for lymphoid ablation. They are prepared by incubation of the lymphocytes with the selected radionuclide-oxine complex.

  1. Regeneration of Tissues and Organs Using Autologous Cells

    SciTech Connect

    Anthony Atala

    2010-04-28

    The Joint Commission for Health Care Organizations recently declared the shortage of transplantable organs and tissues a public health crisis. As such, there is about one death every 30 seconds due to organ failure. Complications and rejection are still significant albeit underappreciated problems. It is often overlooked that organ transplantation results in the patient being placed on an immune suppression regimen that will ultimate shorten their life span. Patients facing reconstruction often find that surgery is difficult or impossible due to the shortage of healthy autologous tissue. In many cases, autografting is a compromise between the condition and the cure that can result in substantial diminution of quality of life. The national cost of caring for persons who might benefit from engineered tissues or organs has reached $600 billion annually. Autologous tissue technologies have been developed as an alternative to transplantation or reconstructive surgery. Autologous tissues derived from the patient's own cells are capable of correcting numerous pathologies and injuries. The use of autologous cells eliminates the risks of rejection and immunological reactions, drastically reduces the time that patients must wait for lifesaving surgery, and negates the need for autologous tissue harvest, thereby eliminating the associated morbidities. In fact, the use of autologous tissues to create functional organs is one of the most important and groundbreaking steps ever taken in medicine. Although the basic premise of creating tissues in the laboratory has progressed dramatically, only a limited number of tissue developments have reached the patients to date. This is due, in part, to the several major technological challenges that require solutions. To that end, we have been in pursuit of more efficient ways to expand cells in vitro, methods to improve vascular support so that relevant volumes of engineered tissues can be grown, and constructs that can mimic the native

  2. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Types What Should You Ask Your Doctor About Acute Lymphocytic Leukemia? It is important to have frank, honest discussions ... Your Doctor About Acute Lymphocytic Leukemia? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  3. What Should You Ask Your Doctor about Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... Should You Ask Your Doctor About Chronic Lymphocytic Leukemia? As you cope with cancer and cancer treatment, ... About Chronic Lymphocytic Leukemia? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  4. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePlus

    ... Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What's New in Chronic Lymphocytic Leukemia Research and Treatment? Many ... person's outlook and whether they will need treatment. New drugs for chronic lymphocytic leukemia Dozens of new ...

  5. Variable lymphocyte receptors in hagfish

    PubMed Central

    Pancer, Zeev; Saha, Nil Ratan; Kasamatsu, Jun; Suzuki, Takashi; Amemiya, Chris T.; Kasahara, Masanori; Cooper, Max D.

    2005-01-01

    A previously uncharacterized type of variable lymphocyte receptors (VLR) was identified recently in the Sea lamprey. This jawless vertebrate generates an extensive VLR repertoire through differential insertion of neighboring diverse leucine-rich repeat (LRR) cassettes into an incomplete germ-line VLR gene. We report here VLR homologs from two additional lamprey species and the presence of two types of VLR genes in hagfish, the only other order of contemporary jawless vertebrates. As in the Sea lamprey, the incomplete hagfish germ-line VLR-A and -B genes are modified in lymphocyte-like cells to generate highly diverse repertoires of VLR-A and -B proteins via a presently undetermined mechanism. This jawless-fish mode of VLR diversification starkly contrasts with the rearrangement of Ig V(D)J gene segments used by all jawed vertebrates to produce diverse repertoires of T and B lymphocyte antigen receptors. The development of two very different strategies for receptor diversification at the dawn of vertebrate evolution ≈500 million years ago attests to the fitness value of a lymphocyte-based system of anticipatory immunity. PMID:15964979

  6. Treatment of chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  7. Rapid exacerbation of lymphocytic infundibuloneurohypophysitis

    PubMed Central

    Shibue, Kimitaka; Fujii, Toshihito; Goto, Hisanori; Yamashita, Yui; Sugimura, Yoshihisa; Tanji, Masahiro; Yasoda, Akihiro; Inagaki, Nobuya

    2017-01-01

    Abstract Rationale: Lymphocytic hypophysitis is a relatively rare autoimmune disease defined by lymphocytic infiltration to the pituitary. Its rarity and wide spectrum of clinical manifestations make clarification of the pathology difficult. Here, we describe a case we examined from the primary diagnosis to final discharge, showing the serial progression of lymphocytic infundibuloneurohypophysitis (LINH) to panhypopituitarism with extrapituitary inflammatory invasion in a short period, and responding favorably to high-dose glucocorticoid treatment. Patient concerns: Polyuria, General fatigue and Nausea/Vomiting. Diagnoses: Central diabetes insipidus (CDI), Lymphocytic infundibuloneurohypophysitis (LINH). Interventions: Desmopressin acetate, High-dose glucocorticoid (GC) treatment. Outcomes: He was prescribed desmopressin acetate and subsequently discharged. A month later, he revisited our hospital with general fatigue and nausea/vomiting. A screening test disclosed hypopituitarism with adrenal insufficiency. MRI revealed expanded contrast enhancement to the peripheral extrapituitary lesion. He received high-dose GC treatment and the affected lesion exhibited marked improvement on MRI, along with the recovery of the anterior pituitary function. Lessons: This case demonstrates the potential for classical LINH to develop into panhypopituitarsim. We consider this is the first documentation of approaching the cause of atypical LINH with progressive clinical course from the pathological viewpoint. PMID:28248860

  8. Lymphocyte receptors for pertussis toxin

    SciTech Connect

    Clark, C.G.; Armstrong, G.D. )

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  9. Use of containers with sterilizing filter in autologous serum eyedrops.

    PubMed

    López-García, José S; García-Lozano, Isabel

    2012-11-01

    To assess the effect of the use of containers with an adapted sterilizing filter on the contamination of autologous serum eyedrops. Prospective, consecutive, comparative, and randomized study. Thirty patients with Sjögren syndrome. One hundred seventy-six autologous serum containers used in home therapy were studied; 48 of them included an adapted filter (Hyabak; Thea, Clermont-Ferrand, France), and the other 128 were conventional containers. Containers equipped with a filter were tested at 7, 14, 21, and 28 days of use, whereas conventional containers were studied after 7 days of use. In addition, testing for contamination was carried out in 14 conventional containers used during in-patient therapy every week for 4 weeks. In all cases, the preparation of the autologous serum was similar. Blood agar and chocolate agar were used as regular culture media for the microbiologic studies, whereas Sabouraud agar with chloramphenicol was the medium for fungal studies. Microbiologic contamination of containers with autologous serum eyedrops. Only one of the containers with an adapted sterilizing filter (2.1%) became contaminated with Staphylococcus epidermidis after 1 month of treatment, whereas the contamination rate among conventional containers reached 28.9% after 7 days of treatment. The most frequent germs found in the samples were coagulase-negative Staphylococcus (48.6%). With regard the containers used in the in-patient setting, 2 (14.3%) became contaminated after 2 weeks, 5 (35.7%) became contaminated after 3 weeks, and 5 (50%) became contaminated after 4 weeks, leaving 7 (50%) that did not become contaminated after 1 month of treatment. Using containers with an adapted filter significantly reduces the contamination rates in autologous serum eyedrops, thus extending the use of such container by the patients for up to 4 weeks with virtually no contamination risks. Copyright © 2012 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

  10. Donor Lymphocyte Infusions Used to Treat Mixed-Chimeric and High-Risk Patient Populations in the Relapsed and Nonrelapsed Settings after Allogeneic Transplantation for Hematologic Malignancies Are Associated with High Five-Year Survival if Persistent Full Donor Chimerism Is Obtained or Maintained.

    PubMed

    Caldemeyer, Lauren E; Akard, Luke P; Edwards, John R; Tandra, Anand; Wagenknecht, Dawn R; Dugan, Michael J

    2017-07-13

    Mixed chimerism (MC), a persistent or increasing number of host cells after allogeneic hematopoietic stem cell transplantation (HSCT), is a predictor of disease relapse. Donor lymphocyte infusions (DLI) have the potential to enhance the graft-versus-malignancy (GVM) effect, reducing the risk of relapse in patients with MC. Hence, in addition to utilizing DLI in the relapsed setting, there is a motivation to pursue pre-emptive DLI for patients in complete remissions after HSCT. To assess the safety and efficacy of DLI, records of 86 patients who received DLI between 2003 and 2015 at a single institution were studied retrospectively. Patients who received DLI included 50 patients with relapsed/residual (RR) disease, 29 patients with emerging MC without detectable disease, and 7 patients in an "other" cohort who had neither RR disease nor emerging MC after HSCT. DLI were administered using a dose-escalation protocol. After DLI, 93% of MC patients converted to full donor chimerism (FDC). Nonrelapsed patients (MC and other) reported high overall survival (OS) at 1 and 5 years (83% at 1 year, 70% at 5 years for MC; 86% at 1 year, 69% at 5 years for other) and was statistically superior to 5-year OS for RR patients (nonrelapsed 69% versus RR 28%; P = .00032). Improved survival correlated with successful conversion to FDC after DLI for RR and MC cohorts: 71% 2-year OS for patients converted to FDC versus 13% for patients who failed to achieve FDC (P < .0001). DLI for nonrelapsed patients was associated with a superior 5-year progression-free survival (PFS) of 71% compared with 18% 5-year PFS in the RR group (P < .0001). Relapse/progressive disease was the most frequent cause of death (41%). Seven MC (24%), 2 other (29%), and 39 RR patients (78%) relapsed or did not respond after DLI. Overall, 6 patients (7%) died of graft-versus-host disease after DLI. Our results demonstrate a successful dose-escalation approach for nonrelapsed patients that correlated with

  11. Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes

    SciTech Connect

    Eisen, H.J.; Eisenberg, S.B.; Saffitz, J.E.; Bolman, R.M. 3d.; Sobel, B.E.; Bergmann, S.R.

    1987-04-01

    To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 (/sup 111/In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous /sup 111/In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed. In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures.

  12. Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2017-03-27

    Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma; T-Cell Large Granular Lymphocyte Leukemia

  13. Suppression of Antigen-Specific Lymphocyte Activation in Simulated Microgravity

    NASA Technical Reports Server (NTRS)

    Cooper, David; Pride, Michael W.; Brown, Eric L.; Risin, Diana; Pellis, Neal R.

    1999-01-01

    Various parameters of immune suppression are observed in astronauts during and after spaceflight, and in isolated immune cells in true and simulated microgravity. Specifically, polyclonal activation of T cells is severely suppressed in true and simulated microgravity. These recent findings with various polyclonal activators suggests a suppression of oligoclonal lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors that simulate aspects of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction (MLR), as a model for a primary immune response; a tetanus toxoid (TT) response and a B. burgdorferi (Bb) response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

  14. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  15. Serotonin Uptake Is Largely Mediated by Platelets versus Lymphocytes in Peripheral Blood Cells

    PubMed Central

    2012-01-01

    The serotonin transporter (SERT), a primary target for many antidepressants, is expressed in the brain and also in peripheral blood cells. Although platelet SERT function is well accepted, lymphocyte SERT function has not been definitively characterized. Due to their small size, platelets often are found in peripheral blood mononuclear cell preparations aimed at isolating lymphocytes, monocytes, and macrophages. The presence of different cells makes it difficult to assign SERT expression and function to specific cell types. Here, we use flow cytometry and IDT307, a monoamine transporter substrate that fluoresces after uptake into cells, to investigate SERT function in lymphocyte and platelet populations independently, as well as simultaneously without prior isolation. We find that murine lymphocytes exhibit temperature-dependent IDT307 transport but uptake is independent of SERT. Lack of measurable SERT function in lymphocytes was corroborated by chronoamperometry using serotonin as a substrate. When we examined rhesus and human mixed blood cell populations, we found that platelets, and not lymphocytes, were primary contributors to SERT function. Overall, these findings indicate that lymphocyte SERT function is minimal. Moreover, flow cytometry, in conjunction with the fluorescent transporter substrate IDT307, can be widely applied to investigate SERT in platelets from populations of clinical significance. PMID:23336055

  16. A potassium ionophore (Nigericin) inhibits stimulation of human lymphocytes by mitogens

    PubMed Central

    1978-01-01

    Nigericin, an ionophore that exchanges K+ for H+ across most biologic membranes, reversibly inhibited the proliferative response of human lymphocytes to phytohemagglutinin (PHA). Inhibition occurred at nigericin concentrations of 10(-8) M or greater, and only during the early event of mitogenesis. There was no effect if nigericin was added 24 h or later after the initiation of PHA-stimulated cultures. The effect was not the result of toxicity or impaired mitochondrial respiration. At similar concentrations, nigericin also inhibited lymphocyte responses in mixed lymphocyte cultures and to other mitogens including concanavalin A, pokeweed mitogen, and the calcium ionophore A23187. The findings support the view that one or more transmembranous events, mediated by changes in cation flux and/or membrane potential, are critical in the initial stages of lymphocyte mitogenesis. PMID:146727

  17. Tumor infiltrating lymphocyte therapy for ovarian cancer and renal cell carcinoma

    PubMed Central

    Andersen, Rikke; Donia, Marco; Westergaard, Marie Christine Wulff; Pedersen, Magnus; Hansen, Morten; Svane, Inge Marie

    2015-01-01

    Personalized cancer immunotherapy based on infusion of T cells holds the promise to specifically target a patient’s individual tumor. Accumulating evidence indicates that the T cells mediating these tumor regressions after cancer immunotherapies may primarily target patient-specific mutations expressed by the patients’ tumors and that the presence of these “neo-antigen” specific T-cells may be related to a high number of mutations in the tumor. In melanoma, treatment with autologous tumor-infiltrating lymphocytes (TILs) can mediate durable complete responses. Previous trials investigating TIL therapy in solid tumors other than melanoma have shown limited success, however none of these early trials used current preparative chemotherapy regimens, and the methods for in vitro lymphocyte expansion have changed considerably. New advances and understandings in T cell based immunotherapies have stimulated the interest in developing this approach for other indications. Here, we summarize the early clinical data in the field of adoptive cell transfer therapy (ACT) using tumor-infiltrating lymphocytes for patients with renal cell carcinoma (RCC) and ovarian cancer (OC). In addition we describe the major advances in the characterization and application of TIL therapy for patients with RCC and OC. PMID:26308285

  18. [Application of autologous fat grafting in breast reconstruction].

    PubMed

    Cai, L; Han, X F; Wang, B Q; Li, F C

    2017-09-01

    Objective: To observe the outcome of breast reconstruction with autologous fat grafting in the patients following treatment for breast cancer. Methods: The clinical data of 22 patients after breast cancer modified radical mastectomy with fat grafting for breast reconstruction from January 2012 to March 2015 at Department of Body Contouring and Liposuction Center of Plastic Surgery, Hospital of Peking Union Medical College were analyzed retrospectively. The age of 22 patients (all female) was 28 to 54 years. Fifteen patients were performed breast modified radical mastectomy 5 to 16 year ago without radiotherapy, 7 patients were performed breast modified radical mastectomy following regular radiotherapy 2 years ago. Low negative pressure liposuction technical was applied to harvest fat tissue for 400 to 800 ml which was filtrated and purified by cotton pad method in low temperature environment. Fat grafting was performed with multi-level and multi-tunnel and in multi-point injection ways. All patients were followed up by regular imaging evaluation with MRI or ultrasonography after operation every 3 months. Results: All breast reconstruction were successfully performed in 22 patients, no severe complications occurred. Among 15 patients without radiotherapy, 12 patients were performed with autologous fat grafting for breast reconstruction, 3 patients with prosthetic implantation for breast augmentation after autologous fat grafting. Among 7 patients with radiotherapy, 6 patients were performed with autologous fat grafting for breast reconstruction, 1 patient with prosthetic implantation for breast augmentation after autologous fat grafting. The volume of fat grafting was 104 to 380 ml. It took 2.5 hours to finish the operation including 1.0 to 1.5 hours for liposuction and 40 minutes for fat grafting. Next fat grafting were performed after 3 months. The fat of the breast were survived well detecting by MRI, only 1 patient had a cystic nodule which had been resected

  19. Functional invariant natural killer T-cell and CD1d axis in chronic lymphocytic leukemia: implications for immunotherapy.

    PubMed

    Weinkove, Robert; Brooks, Collin R; Carter, John M; Hermans, Ian F; Ronchese, Franca

    2013-03-01

    Invariant natural killer T cells recognize glycolipid antigens such as α-galactosylceramide presented by CD1d. In preclinical models of B-cell malignancies, α-galactosylceramide is an adjuvant to tumor vaccination, enhancing tumor-specific T-cell responses and prolonging survival. However, numerical and functional invariant natural killer T-cell defects exist in patients with some cancers. Our aim was to assess this axis in patients with chronic lymphocytic leukemia. The numbers of circulating invariant natural killer T cells and the expression of CD1d on antigen-presenting cells were evaluated in patients with chronic lymphocytic leukemia and age-matched controls. Cytokine profile and in vitro proliferative capacity were determined. Patient- and control-derived invariant natural killer T-cell lines were generated and characterized, and allogeneic and autologous responses to α-galactosylce-ramide-treated leukemia cells were assessed. Absolute numbers and phenotype of invariant natural killer T cells were normal in patients with untreated chronic lymphocytic leukemia, and cytokine profile and proliferative capacity were intact. Chemotherapy-treated patients had reduced numbers of invariant natural killer T cells and myeloid dendritic cells, but α-galactosylceramide-induced proliferation was preserved. Invariant natural killer T-cell lines from patients lysed CD1d-expressing targets. Irradiated α-galactosylceramide-treated leukemic cells elicited allogeneic and autologous invariant natural killer T-cell proliferation, and α-galactosylceramide treatment led to increased proliferation of conventional T cells in response to tumor. In conclusion, the invariant natural killer T-cell and CD1d axis is fundamentally intact in patients with early-stage chronic lymphocytic leukemia and, despite reduced circulating numbers, function is retained in fludarabine-treated patients. Immunotherapies exploiting the adjuvant effect of α-galactosylceramide may be feasible.

  20. Lymphocytic hypophysitis in a man.

    PubMed

    Guay, A T; Agnello, V; Tronic, B C; Gresham, D G; Freidberg, S R

    1987-03-01

    Fewer than 20 patients with lymphocytic adenohypophysitis have been reported, all of them women, and it usually occurs during pregnancy or the postpartum period. We report the recognition of lymphocytic adenohypophysitis in a man. The patient presented with anterior hypopituitarism and an intrasellar mass on computed tomography. Antipituitary antibodies, found in only one of the previous patients, were not present in this man, although low titer antinuclear antibodies were found. The implications of this latter finding are unclear. The patient's histocompatibility antigen (HLA) types were A2, B8, Bw58, DR1, and DR5. The degree of pituitary failure seemed out of proportion to the size of the mass seen on computed tomographic scan.

  1. Lymphocytic enteritis in a filly.

    PubMed

    Clark, E S; Morris, D D; Allen, D; Tyler, D E

    1988-11-15

    A yearling Hanoverian filly had intermittent colic for 6 weeks, chylous peritoneal effusion, and a firm mass palpable per rectum. Exploratory laparotomy revealed mesenteric lymphadenopathy, adhesion of the mesenteric root to the duodenum and jejunum, distention of the mesenteric veins and lymphatic vessels, and increased jejunal venous pressure. Lesions in the duodenum, jejunum, and colon included infiltration of lymphocytes and plasma cells in the lamina propria.

  2. Autologous blood clot embolisation in posttraumatic high-flow priapism.

    PubMed

    Akpinar, Suha; Yilmaz, Güliz

    2016-11-01

    Non-ischemic, high-flow priapism is defined as the state of painless and permanent erection of the penis which generally develops by perineal trauma. Selective transarterial embolisation is one of the treatment options. We present an 18-year-old men who had complaints of painless and permanent erection after a blunt perineal trauma. Colour Doppler ultrasound revealed a pseudoaneurysm and fistula at the left cavernosal artery. Hence autologous blood clot injection was performed to embolise the pseudoaneurysm. Due to the recanalization on the postprocedural seventh day, second embolisation was performed. One month after the second procedure, colour Doppler ultrasound revealed a 50% shrink but mild refilling in the pseudoaneurysm, whereas complete thrombus formation was observed on follow-up imaging. His priapism had fully recovered and erectile functions were totally normal at the six months and one year follow up. Autologous blood clot embolisation seems as a safe and successful treatment. © The Author(s) 2015.

  3. SECOND AUTOLOGOUS STEM CELL TRANSPLANTATION FOR RELAPSED LYMPHOMA AFTER A PRIOR AUTOLOGOUS TRANSPLANT

    PubMed Central

    Smith, Sonali M.; van Besien, Koen; Carreras, Jeanette; Bashey, Asad; Cairo, Mitchell S.; Freytes, Cesar O.; Gale, Robert Peter; Hale, Gregory A.; Hayes-Lattin, Brandon; Holmberg, Leona A.; Keating, Armand; Maziarz, Richard T.; McCarthy, Philip L.; Navarro, Willis H.; Pavlovsky, Santiago; Schouten, Harry C.; Seftel, Matthew; Wiernik, Peter H.; Vose, Julie M.; Lazarus, Hillard M.; Hari, Parameswaran

    2012-01-01

    We determined treatment-related mortality (TRM), progression free survival (PFS), and overall survival (OS) after a second autologous HCT (HCT2) for patients with lymphoma relapse after a prior HCT (HCT1). Outcomes for patients with either Hodgkin lymphoma (HL, n=21) or non-Hodgkin lymphoma (NHL, n=19) receiving HCT2 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were analyzed. The median age at HCT2 was 38 years (range, 16–61) and 22 (58%) patients had a Karnofsky performance score less than 90. HCT2 was performed >1 year after HCT1 in 82%. The probability of TRM at day 100 was 15% (95% CI, 3–22%). The 1, 3 and 5 yr probabilities of PFS were 50% (95% CI, 34–66%), 36% (95% CI, 21–52%) and 30% (95% CI, 16–46%), respectively. Corresponding probabilities of survival were 65% (95% CI, 50–79%), 36% (95% CI, 22–52%) and 30% (95% CI, 17–46%), respectively. At a median follow up of 72 months (range, 12–124 months) after HCT2, 29 patients (73%) have died, 18 (62%) secondary to relapsed lymphoma. The outcomes of patients with HL and NHL were similar. In summary, this series represents the largest reported group of patients with relapsed lymphomas undergoing SCT2 following failed SCT1, and with long-term follow-up. Our series suggests that SCT2 is feasible in patients relapsing after prior HCT1, with a lower TRM than that reported for allogeneic transplant in this setting. HCT2 should be considered for patients with relapsed HL or NHL after HCT1 without alternative allogeneic stem cell transplant options. PMID:18640574

  4. Autologous Fat Transfer in a Patient with Lupus Erythematosus Profundus

    PubMed Central

    Yoon, Jimi; Kim, Hwa Mi; Kim, Tae-Heung; Kim, Chung-Won; Sun, Young-Woo; Yoon, Tae-Jin

    2012-01-01

    Lupus erythematosus profundus, a form of chronic cutaneous lupus erythematosus, is a rare inflammatory disease involving in the lower dermis and subcutaneous tissues. It primarily affects the head, proximal upper arms, trunk, thighs, and presents as firm nodules, 1 to 3 cm in diameter. The overlying skin often becomes attached to the subcutaneous nodules and is drawn inward to produce deep, saucerized depressions. We present a rare case of lupus erythematosus profundus treated with autologous fat transfer. PMID:23139658

  5. [History of autologous blood transfusion in neurosurgical operations].

    PubMed

    Nagai, M

    1998-12-01

    The first report on predeposit autologous blood transfusion was made in 1921 by F.C. Grant, neurosurgeon in the University Hospital of Pennsylvania. The patient was a 42-year-old man with cerebellar tumor, having a rare blood type for which no donor had been listed up. 500 ml of autologous blood was obtained, kept in 0.2% sodium citrate solution in a refrigerator and retransfused following a suboccipital exploration. Clinically, no reaction was noted and there was a favorable postoperative course, and 'autotransfusion' was evaluated as a life-saving procedure. In 1925, L.E. Davis and H. Cushing reported the first case of intraoperative autotransfusion (intraoperative blood salvage). The patient was a 42-year-old man with left occipital meningioma which, due to massive bleeding, could not be removed even by two-stage operations. In a 3rd stage operation, they could remove the tumor of 120 g totally by the aid of intraoperative replacement using 600 ml autologous blood collected with a home-made suction apparatus. No adverse side-effect was noted. This procedure was performed for 23 cases and it revealed beneficial effects except in one case. In ten of the cases, the procedure was estimated as a life-saving treatment. At the present time, the appropriate use of the patients' blood for transfusion therapy is recommended due to a shortage of donors. The use of autologous blood could play a key role, not only in saving the homologous blood supply, but also in avoiding complications encountered in conventional transfusion treatments. The methods of 'Autotransfusion' originated from operations in the neurosurgical area. On that account, it is desirable that neurosurgeons should be concerned with this subject even now.

  6. Autologous Bone Graft in Foot and Ankle Surgery.

    PubMed

    Miller, Christopher P; Chiodo, Christopher P

    2016-12-01

    Bone graft is a common adjunct procedure in orthopedic surgery used for fusions, fracture repair, and the reconstruction of skeletal defects in the foot and ankle. Autologous graft, or autograft, involves the transport of bone from a donor site to another location in the same patient. It is considered by many to be the gold standard of bone grafting, as it is provides all biologic factors required for functional graft. Further, autograft is 100% histocompatible with no risk of disease transmission.

  7. [Effectiveness of topical autologous serum treatment in neurotrophic keratopathy].

    PubMed

    Guadilla, A M; Balado, P; Baeza, A; Merino, M

    2013-08-01

    To evaluate the effectiveness of 20% autologous serum as a treatment for neurotrophic keratopathy. A longitudinal, observational and descriptive study was performed on 19 patients (22 eyes) with neurotrophic keratopathy in different stages of Mackie's classification. The following variables were evaluated on the first visit, and then 4 months later: best corrected visual acuity (BCVA), subjective patient symptomatology (faces scale), Schirmer's test without anesthesia (mm), tear film break-up time (BUT) (sg) and healing of the epithelial defect (weeks). The Wilcoxon signed-rank test was used for the statistical analysis of the data. A symptomatic improvement was observed in 100% of the cases, and a 71% improvement in best corrected visual acuity (P<.05). There was also a statistically significant improvement in the Schirmer's test and BUT (P<.05). Healing of epithelial defect occurred in 71% of the cases within 6 weeks, and in 91% of the cases within 12 weeks of treatment. The remaining 9% of the cases that did not heal had a grade 3 neurotrophic keratopathy. The use of 20% autologous topical serum represents an effective treatment for grades 1 and 2 neurotrophic keratopathy, but is an insufficient treatment for a grade 3 keratopathy. In cases where there is a significant loss of tissue, the application of a higher concentration of autologous serum, or platelet-rich derivatives, or plasma rich in growth factors, may be more effective than the application of 20% autologous serum, due to their greater effect on cell proliferation. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier Espana. All rights reserved.

  8. Autologous Rib Grafts in the Management of the Crooked Nose.

    PubMed

    Porter, Paul; Kriet, J David; Humphrey, Clinton D

    2015-06-01

    Rhinoplasty is arguably one of the most challenging procedures a facial plastic surgeon performs. Numerous techniques have been developed since the inception of rhinoplasty to aid in correction of aesthetic and functional issues. Congenital, iatrogenic, and traumatic etiologies can all lead to a crooked nose. Autologous rib or costal cartilage grafting is a powerful tool that can aid the surgeon in successful correction of the crooked nose. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  9. Antibodies: Immunoconjugates and autologous cellular therapy in acute lymphoblastic leukemia.

    PubMed

    Advani, Anjali

    2015-01-01

    Using a case study of a 57-year-old man with relapsed/refractory precursor-B (pre-B) acute lymphoblastic leukemia (ALL), this review discusses treatment with immunoconjugates and autologous therapy in acute ALL. Three therapies--blinatumomab, inotuzumab, and CAR T cells--are considered here, each with advantages in specific clinical situations. These therapies represent some of the exciting advances that have been made in the treatment of ALL over the last several years.

  10. In vitro incubation of bone marrow and peripheral stem cells with vincristine and methylprednisolone: functional T-cell depletion for haploidentical and autologous transplants.

    PubMed

    Fragonas, E; Perticarari, S; Presani, G; Rabusin, M; Andolina, M; Mangiarotti, M A

    2000-11-01

    A mismatched bone marrow transplantation is feasible only if the donor's marrow lymphocytes are eliminated from the graft. This can be achieved by several methods, but all have the disadvantage of inducing a long-lasting immune deficiency while the risk of graft rejection and leukemic relapse increase. We use a sort of functional T-cell depletion by treating the cells with vincristine and methylprednisolone. This method is surely the cheapest and has allowed us to perform 60 transplants with a tolerable risk of GVHD. The treatment of the donor's lymphocytes has already been demonstrated to be able to block the mixed lymphocyte culture reaction in vitro. In this experiment Th1 and Th2 activities were almost completely blocked without reduction of lymphocyte viability and apoptosis induction.

  11. Generative surgery of cultured autologous auricular chondrocytes for nasal augmentation.

    PubMed

    Yanaga, Hiroko; Imai, Keisuke; Yanaga, Katsu

    2009-11-01

    Conventional treatment for nasal augmentation utilizes autologous grafts, allografts, or synthetic implants such as silicon implants. Silicon implants could protrude/expose or induce nasal bone resorption. Autologous grafts are usually associated with donor site morbidity and the volume of harvested tissue is limited. We had developed a new method for nasal augmentation using cultured autologous chondrocytes (CAC). The current report presents the results of a study using that method with a larger number of patients and an improved graft technique for the nasal tip. Approximately 1 cm2 of cartilage was harvested from the auricular concha and treated with collagenase, and then chondrocytes were obtained. In our multilayer culture system the chondrocytes formed immature cartilaginous tissues with a gelatinous chondroid matrix. They were injection-grafted into the subcutaneous pocket of the nasal dorsum. The chondrocytes with a gelatinous chondroid matrix change from a soft gel to hard neocartilage tissue within 2 to 3 weeks and then stabilize. The authors have used this procedure over a 6-year period on 75 cases: 58 secondary augmentation rhinoplasties following silicon implantation and 17 primary augmentation cases. The results have been satisfactory and long-lasting. Grafting of CAC is an optional method for nasal augmentation and could be used for a wide range of facial augmentation cases.

  12. AUTOLOGOUS IMMUNE COMPLEX NEPHRITIS INDUCED WITH RENAL TUBULAR ANTIGEN

    PubMed Central

    Glassock, Richard J.; Edgington, Thomas S.; Watson, J. Ian; Dixon, Frank J.

    1968-01-01

    The pathogenetic mechanism involved in a form of experimental allergic glomerulonephritis induced by immunization of rats with renal tubular antigen has been investigated. A single immunization with less than a milligram of a crude renal tubular preparation, probably containing less than 25 µg of the specific nephritogenic antigen, is effective in the induction of this form of chronic membranous glomerulonephritis. In the nephritic kidney autologous nephritogenic tubular antigen is found in the glomerular deposits along with γ-globulin and complement. When large amounts of antigen are injected during induction of the disease the exogenous immunizing antigen can also be detected in the glomerular deposits. It appears that this disease results from the formation of circulating antibodies capable of reacting with autologous renal tubular antigen(s) and the deposition of these antibodies and antigen(s) plus complement apparently as immune complexes in the glomeruli. This pathogenetic system has been termed an autologous immune complex disease and the resultant glomerulonephritis has been similarly designated. PMID:4169966

  13. Outpatient Autologous Stem Cell Transplantation for Patients With Myeloma.

    PubMed

    Paul, Thomas M; Liu, Stephen V; Chong, Elise A; Luger, Selina M; Porter, David L; Schuster, Stephen J; Tsai, Donald E; Nasta, Sunita D; Loren, Alison; Frey, Noelle; Perl, Alexander; Cohen, Adam D; Weiss, Brendan M; Stadtmauer, Edward A; Vogl, Dan T

    2015-09-01

    High-dose melphalan with autologous stem cell support improves survival for patients with myeloma. For selected patients, we have been using a protocol of short hospitalization, discharging patients to home with careful outpatient monitoring in the office, which we hypothesized would reduce complications and utilization of inpatient beds. We reviewed 301 initial autologous transplants for myeloma, categorized as brief stay (≤ 4 days, 82 patients) or prolonged stay (≥ 5 days, 219 patients). Selection for a brief stay was determined by clinical characteristics, availability of caregivers at home, distance from our medical center, and patient preference. Within the brief stay population, 67% required readmission before day + 100, but this group still had fewer cumulative hospital days (9 vs. 18, P < .0001). There were fewer documented infections among brief stay patients (22% vs. 46% P < .001) and fewer admissions to intensive care units (0% vs. 5.9%, P = .02). The groups had similar rates of bleeding (1.2% vs. 1.4% P = 1.0) and thrombosis (3.7% vs. 4.6% P = 1.0). No patients in the brief stay group died within 100 days, compared with mortality of 1.8% (P = .6) in the prolonged stay group. Carefully selected patients receiving an autologous stem cell transplant for treatment of myeloma can be managed with a brief initial hospitalization and outpatient follow-up, with low morbidity and mortality. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Clinical Allogeneic and Autologous Islet Cell Transplantation: Update

    PubMed Central

    2011-01-01

    Islet cell transplantation is categorized as a β-cell replacement therapy for diabetic patients who lack the ability to secrete insulin. Allogeneic islet cell transplantation is for the treatment of type 1 diabetes, and autologous islet cell transplantation is for the prevention of surgical diabetes after a total pancreatectomy. The issues of allogeneic islet cell transplantation include poor efficacy of islet isolation, the need for multiple donor pancreata, difficulty maintaining insulin independence and undesirable side effects of immunosuppressive drugs. Those issues have been solved step by step and allogeneic islet cell transplantation is almost ready to be the standard therapy. The donor shortage will be the next issue and marginal and/or living donor islet cell transplantation might alleviate the issue. Xeno-islet cell transplantation, β-cell regeneration from human stem cells and gene induction of the naïve pancreas represent the next generation of β-cell replacement therapy. Autologous islet cell transplantation after total pancreatectomy for the treatment of chronic pancreatitis with severe abdominal pain is the standard therapy, even though only limited centers are able to perform this treatment. Remote center autologous islet cell transplantation is an attractive option for hospitals performing total pancreatectomies without the proper islet isolation facilities. PMID:21785738

  15. Alignment of the Fibrin Network Within an Autologous Plasma Clot.

    PubMed

    Gessmann, Jan; Seybold, Dominik; Peter, Elvira; Schildhauer, Thomas Armin; Köller, Manfred

    2016-01-01

    Autologous plasma clots with longitudinally aligned fibrin fibers could serve as a scaffold for longitudinal axonal regrowth in cases of traumatic peripheral nerve injuries. Three different techniques for assembling longitudinally oriented fibrin fibers during the fibrin polymerization process were investigated as follows: fiber alignment was induced by the application of either a magnetic field or-as a novel approach-electric field or by the induction of orientated flow. Fiber alignment was characterized by scanning electron microscopy analysis followed by image processing using fast Fourier transformation (FFT). Besides FFT output images, area xmin to xmax, as well as full width at half maximum (FWHM) of the FFT graph plot peaks, was calculated to determine the relative degree of fiber alignment. In addition, fluorescently labeled human fibrinogen and mesenchymal stem cells (MSCs) were used to visualize fibrin and cell orientation in aligned and nonaligned plasma clots. Varying degrees of fiber alignment were achieved by the three different methods, with the electric field application producing the highest degree of fiber alignment. The embedded MSCs showed a longitudinal orientation in the electric field-aligned plasma clots. The key feature of this study is the ability to produce autologous plasma clots with aligned fibrin fibers using physical techniques. This orientated internal structure of an autologous biomaterial is promising for distinct therapeutic applications, such as a guiding structure for cell migration and growth dynamics.

  16. Autologous Matrix-Induced Chondrogenesis in the Knee: A Review.

    PubMed

    Lee, Yee Han Dave; Suzer, Ferzan; Thermann, Hajo

    2014-07-01

    Autologous matrix-induced chondrogenesis (AMIC) is a 1-step cartilage restoration technique that combines microfracture with the use of an exogenous scaffold. This matrix covers and mechanically stabilizes the clot. There have been an increasing number of studies performed related to the AMIC technique and an update of its use and results is warranted. Using the PubMed database, a literature search was performed using the terms "AMIC" or "Autologous Matrix Induced Chondrogenesis." A total of 19 basic science and clinical articles were identified. Ten studies that were published on the use of AMIC for knee chondral defects were identified and the results of 219 patients were analyzed. The improvements in Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee Subjective, Lysholm and Tegner scores at 2 years were comparable to the published results from autologous chondrocyte implantation (ACI) and matrix ACI techniques for cartilage repair. Our systematic review of the current state of the AMIC technique suggests that it is a promising 1-stage cartilage repair technique. The short-term clinical outcomes and magnetic resonance imaging results are comparable to other cell-based methods. Further studies with AMIC in randomized studies versus other repair techniques such as ACI are needed in the future.

  17. Procedure, applications, and outcomes of autologous fat grafting.

    PubMed

    Simonacci, Francesco; Bertozzi, Nicolò; Grieco, Michele Pio; Grignaffini, Eugenio; Raposio, Edoardo

    2017-08-01

    To systematically review the procedure, applications, and outcomes of autologous fat grafting, a promising technique with various clinical applications. Literature review of publications concerning autologous fat grafting. Since its introduction, lipofilling has become increasingly popular; however, its results are variable and unpredictable. Several modifications have been made to the procedures of fat harvesting, processing, and injecting. Surgical excision and low negative-pressure aspiration with large-bore cannulas minimize adipocyte damage during fat harvesting. The "wet" method of fat harvesting involves fluid injection at the donor site and facilitates lipoaspiration while minimizing pain and ecchymosis. For fat processing, centrifugation at a low speed is preferable to high-speed centrifugation, gravity separation or filtration. Fat injection at the recipient site should be performed using small-gauge cannulas in a fanning out pattern over multiple sessions, rather than a single session. Fat grafts exhibit not only dermal filler properties but also regenerative potential owing to the presence of stem cells in fat tissue. Thus, the clinical applications of autologous fat grafting include correction of secondary contour defects after breast reconstruction, release of painful scar contractures, and treatment of burn scars and radiodermatitis. Lipofilling is also used in aesthetic surgery, such as facial and hand rejuvenation, augmentation rhinoplasty, and breast and gluteal augmentation. The complications of lipofilling are minimal and include bruising, swelling, pain, infection, necrosis, and calcification. Lipofilling is a low-risk procedure that can be used to correct soft-tissue defects in the face, trunk, and extremities, with minimal discomfort for patients.

  18. [Therapeutic intensification and autologous stem cell transplantation in autoimmune diseases].

    PubMed

    Marjanovic, Z; Gerber, I; Toledano, C; Hen-Solal, J; Damade, R; de Saint-Cyr, I; Sarrot-Reynauld, F; Ilié, D; Daneshpouy, M; Mounier, N; Ruivard, M; Tyndall, C; Vidal, E; Quere, I; Durand, J-M; Constans, J; Farge, D

    2005-02-26

    THE PATHOPHYSIOLOGY of most autoimmune diseases is often poorly understood. EXPERIMENTAL CONSIDERATIONS and clinical experience suggest that high doses immunoablation followed by stem cell transplantation is a therapeutic option to consider for certain severe autoimmune disorders. THE CONCEPT OF RESTORING NORMAL IMMUNE REACTIVITY must in part br true since current results of 466 transplants (445 autologous, 21 allogeneic) patients suffering from various autoimmune diseases show a beneficial outcome in approximately 2/3 of the patients. TO IMPROVE THE EFFICACY AND SAFETY OF SUCH AN AGGRESSIVE PROCEDURE in patients with potentially affected vital organs by the underlying autoimmune disease, it is especially important to follow international consensus guidelines and to centrally collect clinical data for in depth analysis in the EBMT International Stem Cell Project for Autoimmune Disease in Basel, Switzerland. PHASE III STUDIES ARE RUNNING FOR SYSTEMIC SCLEROSIS (Astis, Autologous Stem cell Transplantation International Rheumatoid Arthritis Trial) started in 2003. A STUDY PROJECT IS PLANNED FOR MULTIPLE SCLEROSIS (Astims, Autologous Stem cell Transplantation International Multiple Sclerosis).

  19. Osteogenicity of autologous bone transplants in the goat.

    PubMed

    Kruyt, Moyo C; Dhert, Wouter J A; Oner, Cumhur; van Blitterswijk, Clemens A; Verbout, Abraham J; de Bruijn, Joost D

    2004-02-27

    Little is known about the specific mechanisms that make autologous graft bone (AG) superior to the current alternatives. A potential mechanism is the active bone formation by the osteoprogenitor cells within the AG. However, whether these cells survive the transplantation is questionable, especially in nonvascularized, clinically sized grafts. In the present study, we investigated the role of viability in AG implanted ectopically and orthotopically in the goat. Eight goats were operated on twice. At the first operation, pieces of vital or devitalized autologous cortical bone were implanted in the paraspinal muscles. Eight weeks later, corticocancellous plugs were taken from the femoral condyles, morselized, and reimplanted as either vital or devitalized orthotopic grafts. The goats received fluorochrome labels at 5, 7, and 9 weeks after the first operation. At 12 weeks, the goats were killed, and the samples were examined histologically. Ectopically, new bone had formed in both the vital and devitalized grafts. In the vital grafts, all three fluorochrome labels were present, indicating an early osteogenic mechanism. Within the devitalized grafts, only the 9-week label was observed. Histomorphometry indicated significantly more new bone in the vital grafts (10.3% vs. 1.7% in the devitalized grafts, P <0.01). Orthotopically, both vital and devitalized grafts showed new bone. Again, graft viability was advantageous in terms of new bone formation (14.5% vs. 9.3%, P <0.02). The cells inside the autologous bone transplants most likely survived transplantation and were capable of initiating and sustaining new bone formation.

  20. Tissue-Engineered Autologous Grafts for Facial Bone Reconstruction

    PubMed Central

    Bhumiratana, Sarindr; Bernhard, Jonathan C.; Alfi, David M.; Yeager, Keith; Eton, Ryan E.; Bova, Jonathan; Shah, Forum; Gimble, Jeffrey M.; Lopez, Mandi J.; Eisig, Sidney B.; Vunjak-Novakovic, Gordana

    2016-01-01

    Facial deformities require precise reconstruction of the appearance and function of the original tissue. The current standard of care—the use of bone harvested from another region in the body—has major limitations, including pain and comorbidities associated with surgery. We have engineered one of the most geometrically complex facial bones by using autologous stromal/stem cells, without bone morphogenic proteins, using native bovine bone matrix and a perfusion bioreactor for the growth and transport of living grafts. The ramus-condyle unit (RCU), the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatan minipigs (human-scale preclinical model). We used clinically approved decellularized bovine trabecular bone as a scaffolding material, and crafted it into an anatomically correct shape using image-guided micromilling, to fit the defect. Autologous adipose-derived stromal/stem cells were seeded into the scaffold and cultured in perfusion for 3 weeks in a specialized bioreactor to form immature bone tissue. Six months after implantation, the engineered grafts maintained their anatomical structure, integrated with native tissues, and generated greater volume of new bone and greater vascular infiltration than either non-seeded anatomical scaffolds or untreated defects. This translational study demonstrates feasibility of facial bone reconstruction using autologous, anatomically shaped, living grafts formed in vitro, and presents a platform for personalized bone tissue engineering. PMID:27306665

  1. Delayed Cranioplasty: Outcomes Using Frozen Autologous Bone Flaps

    PubMed Central

    Hng, Daniel; Bhaskar, Ivan; Khan, Mumtaz; Budgeon, Charley; Damodaran, Omprakash; Knuckey, Neville; Lee, Gabriel

    2014-01-01

    Reconstruction of skull defects following decompressive craniectomy is associated with a high rate of complications. Implantation of autologous cryopreserved bone has been associated with infection rates of up to 33%, resulting in considerable patient morbidity. Predisposing factors for infection and other complications are poorly understood. Patients undergoing cranioplasty between 1999 and 2009 were identified from a prospectively maintained database. Records and imaging were reviewed retrospectively. Demographics, the initial craniectomy and subsequent cranioplasty surgeries, complications, and outcomes were recorded. A total of 187 patients underwent delayed cranioplasty using autologous bone flaps cryopreserved at –30°C following decompressive craniectomy. Indications for craniectomy were trauma (77.0%), stroke (16.0%), subarachnoid hemorrhage (2.67%), tumor (2.14%), and infection (2.14%). There were 64 complications overall (34.2%), the most common being infection (11.2%) and bone resorption (5.35%). After multivariate analysis, intraoperative cerebrospinal fluid (CSF) leak was significantly associated with infection, whereas longer duration of surgery and unilateral site were associated with resorption. Cranioplasty using frozen autologous bone is associated with a high rate of infective complications. Intraoperative CSF leak is a potentially modifiable risk factor. Meticulous dissection during cranioplasty surgery to minimize the chance of breaching the dural or pseudodural plane may reduce the chance of bone flap. PMID:26269726

  2. Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  3. Cerebral toxoplasmosis after tandem high-dose chemotherapy and autologous hematopoietic cell transplant for neuroblastoma.

    PubMed

    Voegele, Laura; Cheerva, Alexandra C; Bertolone, Salvatore

    2013-03-01

    Toxoplasmosis is a well-recognized life-threatening complication of hematopoietic cell transplantation (HCT). This report describes a pediatric patient with stage 4 neuroblastoma who developed cerebral toxoplasmosis after tandem high-dose chemotherapy with autologous HCT. Toxoplasmosis is rare in patients undergoing autologous HCT; however, tandem autologous HCT is more immunosuppressive than a single autologous HCT. Toxoplasmosis is a potential complication in autologous as well as allogeneic transplants, and should be considered in any post-HCT patient with neurological dysfunction. Rapid diagnosis and immediate antimicrobial treatment are crucial to avoid morbidity and mortality. Evaluation of toxoplasma serology should be standard in all patients undergoing tandem autologous HCT and seropositive patients should be started on appropriate prophylactic therapy.

  4. Cost minimization analysis of preoperative erythropoietin vs autologous and allogeneic blood donation in total joint arthroplasty.

    PubMed

    Green, William Scott; Toy, Pearl; Bozic, Kevin J

    2010-01-01

    Autologous blood donation and erythropoietin (EPO) have been shown to be effective in reducing allogeneic blood transfusion, but the cost-effectiveness of these interventions remains unclear. A cost minimization analysis was performed, comparing the total costs of allogeneic blood transfusion strategy and autologous and allogeneic blood transfusion strategy for 161 primary total hip arthroplasty (THA) and 195 total knee arthroplasty (TKA) patients. An EPO cost minimization model was constructed using a previously published algorithm for blood management after total joint arthroplasty. The least costly strategy was autologous blood donation in combination with allogeneic blood for THA and TKA patients at $856 and $892 per patient, respectively. The most costly strategy was allogeneic only at $1769 and $1352 per THA and TKA patient, respectively. The EPO strategy model predicted costs similar to the autologous and allogeneic. A strategy that combines autologous blood donation with EPO for patients who cannot donate autologous blood may provide the greatest cost savings and minimize allogeneic blood transfusion.

  5. Treatment of Adult Severe Traumatic Brain Injury Using Autologous Bone Marrow Mononuclear Cells

    DTIC Science & Technology

    2014-12-01

    AD_________________ Award Number: W81XWH-11-1-0460 TITLE: TREATMENT OF ADULT SEVERE TRAUMATIC BRAIN INJURY USING AUTOLOGOUS BONE MARROW ...AUTOLOGOUS BONE MARROW MONONUCLEAR CELLS” 5a. CONTRACT NUMBER 5b. GRANT NUMBER: W81XWH-11-1-0460 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Charles S. Cox...Our primary hypothesis is that bone marrow mononuclear cell (BMMNC) autologous transplantation after TBI is safe. Our secondary hypothesis is that

  6. Bilayer Hydrogel with Autologous Stem Cells Derived from Debrided Human Burn Skin for Improved Skin Regeneration

    DTIC Science & Technology

    2013-02-01

    grafting surgeries using autologous skin. Unfortunately, large surface burn wounds lack autologous viable unin- jured tissue for grafting , making...1 Natesan et al 19 skin or tissue-engineered substitutes containing allogeneic and/or autologous cells. These tissue- engineered wound dressings...dsASC-bilayer hydrogels contribute significantly to wound healing and provide support for their use as a vascularized dermal substitute for skin

  7. Human colonic intraepithelial lymphocytes regulate the cytokines produced by lamina propria mononuclear cells

    PubMed Central

    Dehennin, J. P.; Li, Li; Sibille, C.; Geubel, A.; Vaerman, J. P.

    1997-01-01

    Using an in vitro autologous human system, the immunomodulatory function of colonic intraepithelial lymphocytes (IEL) on cytokine production by lamina propria mononuclear cells (LPMNC) has been investigated. In contrast to LPMNC, colonic IEL produced only low amounts of IL-10, interferon-γ and interleukin-2. However, co-culture experiments (IEL + LPMNC) have shown that IEL can enhance the PHA-induced synthesis of IL-2 and interferon-γ, but not IL-10 by LPMNC. Using a transwell filter culture system apparatus, this effect was shown not to require a cell-to-cell interaction. Thus, IEL in vitro may modulate the cytokine synthesis of LPMNC, through the production of soluble factors. This may prove highly relevant in the in vivo immune activation of the gastrointestinal mucosa. PMID:18472843

  8. Cytotoxic T lymphocytes against disease-associated determinant(s) in ankylosing spondylitis

    PubMed Central

    1986-01-01

    Cytotoxic T lymphocytes, induced by stimulating the PBMC of an HLA-B27+ normal individual (B27+, AS-) with the PBMC of an HLA-identical sibling suffering from ankylosing spondylitis (AS) (B27+, AS+), specifically lyse B27+, AS+ PBMC but not PBMC from HLA-27+ or B27-, AS- normal controls, or from HLA-B27- AS patients (B27-,AS+). CTL of similar specificity can also be raised by immunizing in vitro B27+,AS- cells with autologous cells modified by cross-reactive bacterial antigens. These results suggest that CTL can recognize certain bacterial antigens in association with HLA-B27 and that this interaction may lead to an inflammatory episode during the initial stages of the disease. PMID:3528379

  9. Autologous Epstein-Barr virus (EBV)-specific cytotoxic T cells for the treatment of persistent active EBV infection.

    PubMed

    Savoldo, Barbara; Huls, M Helen; Liu, Zhensheng; Okamura, Takayuki; Volk, Hans-Dieter; Reinke, Petra; Sabat, Robert; Babel, Nina; Jones, James F; Webster-Cyriaque, Jennifer; Gee, Adrian P; Brenner, Malcolm K; Heslop, Helen E; Rooney, Cliona M

    2002-12-01

    Chronic active Epstein-Barr virus (CAEBV) infection syndrome is a heterogeneous EBV-related disorder characterized by chronic fatigue, fever, lymphadenopathy, and/or hepatosplenomegaly, associated with abnormal patterns of antibody to EBV. CAEBV can range from disabling mild/moderate forms to rapidly lethal disorders. Even patients with mild/moderate disease frequently suffer adverse effects from long-term anti-inflammatory agents and have a quality of life that progressively deteriorates. It is still unknown why these individuals are unable to produce an effective immune response to control EBV, and no effective treatment is currently available. Since ex vivo-expanded EBV-specific cytotoxic T lymphocytes (EBV-CTLs) can safely restore EBV-specific cellular immune responses in immunodeficient patients, we assessed the possibility that adoptive immunotherapy might also effectively treat CAEBV infection. Following stimulation with irradiated EBV-transformed lymphoblastoid cell lines (LCLs), EBV-CTLs were successfully generated from 8 of 8 patients with the mild/moderate form of CAEBV infection. These CTLs were predominantly CD3(+) CD8(+) cells and produced specific killing of the autologous LCLs. There were 5 patients with 1- to 12-year histories of disease who were treated with 1 to 4 injections of EBV-CTLs. Following infusion, there was resolution of fatigue and malaise, disappearance of fever, and regression of lymphadenopathy and splenomegaly. The pattern and titers of anti-EBV antibodies also normalized. No toxicity was observed. There were 4 patients who did not show any relapse of disease within 6 to 36 months follow-up; one patient had recurrence of fatigue and myalgia one year after CTL infusion. We suggest that adoptive immunotherapy with autologous EBV-CTLs may represent a safe and feasible alternative treatment for patients affected with mild/moderate CAEBV infection and that this approach should be evaluated in the more severe forms of the disease.

  10. In vitro use of autologous dendritic cells improves detection of T cell responses to hepatitis B virus (HBV) antigens.

    PubMed

    Carotenuto, Patrizia; Artsen, Andrè; Niesters, Hubert G; Osterhaus, Albert D; Pontesilli, Oscar

    2009-02-01

    T lymphocyte responses to hepatitis B virus (HBV) core antigen (HBcAg) are vigorous and easily detectable in vitro during recovery from acute hepatitis B but significantly weaker in patients with chronic HBV infection. In contrast, T cell responses to hepatitis B surface antigen (HBsAg) are almost undetectable during infection and even in a substantial fraction of subjects receiving vaccination with HBsAg. The aim of this study was to investigate whether the use of dendritic cells (DCs) in an in vitro assay could increase the detection of HBV-specific T cells in these conditions. Autologous monocyte-derived DCs, compared to direct HBsAg addition to the cultures, increased the stimulation of HBs- specific T cells. These were detected in 73% of healthy subjects who had recently received hepatitis B vaccine and in 43% of patients recovering from acute hepatitis B. Likewise, proliferation in response to DC-presented HBcAg was detected in both CD4(+) and CD8(+) T cells from the majority of chronic hepatitis B patients. A longitudinal evaluation of HBc-specific T cell responses during and after a 1-year treatment with pegylated interferon (IFN)-alpha showed that HBc-specific CD4(+) T cell responses had no correlation with sustained virus suppression whereas CD8(+) T cell responses were more frequently detected in patients able to control HBV replication after therapy interruption. The use of autologous DCs as antigen-presenting cells appears applicable to clinically relevant in vitro evaluation of T cell responses, particularly in those conditions characterized by low frequency of circulating antigen-specific cells and suboptimal in vivo activation. (c) 2008 Wiley-Liss, Inc.

  11. T lymphocyte recognition of insolubilized peptide antigen.

    PubMed

    Thomas, D W; Solvay, M J

    1986-12-01

    To study the role of antigen-presenting cells (APC) in T lymphocyte responses, the stimulation requirements of a murine T cell hybridoma specific for the peptide antigen human fibrinopeptide B (hFPB)/I-Ak was examined. The fine specificity of T cell recognition of this peptide was determined by using several hFPB homologs and analogs, which indicated that the intact 14-amino acid peptide must remain intact to preserve the antigenic determinant, and that the carboxyl terminal Arg14 was important for T cell responses. Of particular interest was the finding that APC-associated hFPB failed to stimulate the T cells, and that activation was only observed with soluble peptide or by brief hFPB treatment of the T cells and APC mixed together. In addition, hFPB covalently bound to agarose beads was able to cause T cell activation, provided that I-Ak+ APC were also present in the culture. A number of control experiments were performed that showed that hFPB was not released from the bead and that the antigenic peptide involved in T cell responses remained bound to the beads. These results indicate that the form of the hFPB peptide antigen recognized by this T cell can be provided separately from APC.

  12. CCI-779 in Treating Patients With Recurrent or Refractory B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2014-05-07

    B-cell Chronic Lymphocytic Leukemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Malignant Neoplasm; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Waldenström Macroglobulinemia

  13. Opinion: Interactions of innate and adaptive lymphocytes

    PubMed Central

    Gasteiger, Georg; Rudensky, Alexander Y.

    2015-01-01

    Innate lymphocytes, including natural killer (NK) cells and the recently discovered innate lymphoid cells (ILCs) have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. Less well understood is the contribution of the adaptive immune system to the orchestration of innate lymphocyte responses. We review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which adaptive T cells function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential role of regulatory and helper T cells in these processes and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes. PMID:25132095

  14. Interactions between innate and adaptive lymphocytes.

    PubMed

    Gasteiger, Georg; Rudensky, Alexander Y

    2014-09-01

    Innate lymphocytes - including natural killer cells and the recently discovered innate lymphoid cells - have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. The contribution of the adaptive immune system to the coordination of innate lymphocyte responses is less well understood. In this Opinion article, we review our current understanding of the interactions between adaptive and innate lymphocytes, and propose a model in which T cells of the adaptive immune system function as antigen-specific sensors for the activation of innate lymphocytes to amplify and instruct local immune responses. We highlight the potential roles of regulatory and helper T cells in these processes, and discuss major questions in the emerging area of crosstalk between adaptive and innate lymphocytes.

  15. Isolation of neoantigen-specific T cells from tumor and peripheral lymphocytes

    PubMed Central

    Cohen, Cyrille J.; Gartner, Jared J.; Horovitz-Fried, Miryam; Shamalov, Katerina; Trebska-McGowan, Kasia; Bliskovsky, Valery V.; Parkhurst, Maria R.; Ankri, Chen; Prickett, Todd. D.; Crystal, Jessica S.; Li, Yong F.; El-Gamil, Mona; Rosenberg, Steven A.; Robbins, Paul F.

    2015-01-01

    Adoptively transferred tumor-infiltrating T lymphocytes (TILs) that mediate complete regression of metastatic melanoma have been shown to recognize mutated epitopes expressed by autologous tumors. Here, in an attempt to develop a strategy for facilitating the isolation, expansion, and study of mutated antigen–specific T cells, we performed whole-exome sequencing on matched tumor and normal DNA isolated from 8 patients with metastatic melanoma. Candidate mutated epitopes were identified using a peptide-MHC–binding algorithm, and these epitopes were synthesized and used to generate panels of MHC tetramers that were evaluated for binding to tumor digests and cultured TILs used for the treatment of patients. This strategy resulted in the identification of 9 mutated epitopes from 5 of the 8 patients tested. Cells reactive with 8 of the 9 epitopes could be isolated from autologous peripheral blood, where they were detected at frequencies that were estimated to range between 0.4% and 0.002%. To the best of our knowledge, this represents the first demonstration of the successful isolation of mutation-reactive T cells from patients’ peripheral blood prior to immune therapy, potentially providing the basis for designing personalized immunotherapies to treat patients with advanced cancer. PMID:26389673

  16. Suppression of antigen-specific lymphocyte activation in modeled microgravity.

    PubMed

    Cooper, D; Pride, M W; Brown, E L; Risin, D; Pellis, N R

    2001-02-01

    Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

  17. Suppression of antigen-specific lymphocyte activation in modeled microgravity

    NASA Technical Reports Server (NTRS)

    Cooper, D.; Pride, M. W.; Brown, E. L.; Risin, D.; Pellis, N. R.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

  18. Suppression of antigen-specific lymphocyte activation in modeled microgravity

    NASA Technical Reports Server (NTRS)

    Cooper, D.; Pride, M. W.; Brown, E. L.; Risin, D.; Pellis, N. R.; McIntire, L. V. (Principal Investigator)

    2001-01-01

    Various parameters of immune suppression are observed in lymphocytes from astronauts during and after a space flight. It is difficult to ascribe this suppression to microgravity effects on immune cells in crew specimens, due to the complex physiological response to space flight and the resultant effect on in vitro immune performance. Use of isolated immune cells in true and modeled microgravity in immune performance tests, suggests a direct effect of microgravity on in vitro cellular function. Specifically, polyclonal activation of T-cells is severely suppressed in true and modeled microgravity. These recent findings suggest a potential suppression of oligoclonal antigen-specific lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors as an analog of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction, as a model for a primary immune response, a tetanus toxoid response and a Borrelia burgdorferi response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

  19. Firefighter willingness to participate in a stem cell clinical trial for burns: A mixed methods study.

    PubMed

    Horch, Jenny D; Carr, Eloise C J; Harasym, Patricia; Burnett, Lindsay; Biernaskie, Jeff; Gabriel, Vincent

    2016-12-01

    Adult stem cells represent a potentially renewable and autologous source of cells to regenerate skin and improve wound healing. Firefighters are at risk of sustaining a burn and potentially benefiting from a split thickness skin graft (STSG). This mixed methods study examined firefighter willingness to participate in a future stem cell clinical trial, outcome priorities and factors associated with this decision.

  20. Assessment of genotoxicity of Lannate-90® and its plant and animal metabolites in human lymphocyte cultures.

    PubMed

    Valencia-Quintana, Rafael; Gómez-Arroyo, Sandra; Sánchez-Alarcón, Juana; Milić, Mirta; Olivares, José Luis Gómez; Waliszewski, Stefan M; Cortés-Eslava, Josefina; Villalobos-Pietrini, Rafael; Calderón-Segura, María Elena

    2016-06-01

    This study evaluated direct and metabolic genotoxic effects caused by Lannate-90®, a methomyl-based formulation (90 % active ingredient), in human lymphocyte cultures using sister chromatid exchange assay (SCE). Two processes were used for the plant promutagens evaluation: in vivo activation, applying the insecticide systemically in plants for 4 h and subsequently adding plant metabolites containing extracts to lymphocyte cultures; and in vitro activation, where the insecticide was incubated with Vicia faba S10 mix plus human lymphocyte culture. Direct treatment with the insecticide significantly increased SCE frequency in human lymphocytes (250-750 mgL-1), with cellular death observed at 1000 mgL-1 concentration. Using the extracts of Vicia faba treated with Lannate-90® to treat human lymphocytes, a dose-response relationship was observed. In lymphocyte cultures treated directly with the insecticide for 2 h, a negative response was obtained. When S10 mix was added, SCE frequency did not change significantly. Meanwhile, a mixture of S9 mammalian metabolic mix and Lannate-90® increased the SCE frequency, with an observed concentration-dependent response. Although Lannate-90® induced cellular death at the highest concentrations, it did not cause a delay in cell proliferation in any of the treatments, confirming its genotoxic action. This study is one of the first to evaluate and compare the direct effect of Lannate-90® in two bioassays, animal and vegetal, and the effect of plant and animal metabolism on its genotoxic potential.

  1. Residual tumor micro-foci and overwhelming regulatory T lymphocyte infiltration are the causes of bladder cancer recurrence

    PubMed Central

    Kalli, Francesca; Conteduca, Giuseppina; Tardito, Samuele; Curto, Monica; Grillo, Federica; Mastracci, Luca; Bernardi, Cinzia; Nasi, Giorgia; Minaglia, Francesco; Simonato, Alchiede; Carmignani, Giorgio; Ferrera, Francesca; Fenoglio, Daniela; Filaci, Gilberto

    2016-01-01

    Bladder cancer has an unexplained, high recurrence rate. Causes of recurrence might include the presence of sporadic tumor micro-foci in the residual urothelial tissue after surgery associated with an inverted ratio between intratumoral effector and regulatory T cell subsets. Hence, surgical specimens of both tumors and autologous, macroscopically/histologically free-of-tumor tissues were collected from 28 and 20 patients affected by bladder or renal cancer, respectively. The frequencies of effector (IFNγ+ and IL17+ T cells) and regulatory (CD4+CD25hiCD127lo and CD8+CD28-CD127loCD39+ Treg) T cell subpopulations among tumor infiltrating lymphocytes were analyzed by immunofluorescence, while the gene expression of MAGE-A1 and MAGE-A2 tumor-associated antigens was studied by RT-PCR. The results show that both the T cell infiltrate and the frequency of MAGE-A1/A2 gene expression were comparable in tumors and in autologous free-of-tumor tissues in bladder cancer, while the autologous free-of-tumor renal tissues showed reduced T cell infiltrate and frequency of MAGE gene expression as compared to the autologous tumors. Importantly, the intra-tumor T effector/Treg cell ratio was consistently <1 in bladder cancer patients (n. 7) who relapsed within two years, while it was always >1 in patients (n. 6) without recurrence (regardless of tumor stage) (P = 0.0006, Odds ratio = 195). These unprecedented findings clarify the pathogenic mechanism of bladder cancer recurrence and suggest that microscopically undetectable micro-foci of tumor may predispose to recurrence when associated with an inverted intratumoral T effector/Treg cell ratio. PMID:26824503

  2. Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure.

    PubMed

    Worel, Nina; Fritsch, Gerhard; Agis, Hermine; Böhm, Alexandra; Engelich, Georg; Leitner, Gerda C; Geissler, Klaus; Gleixner, Karoline; Kalhs, Peter; Buxhofer-Ausch, Veronika; Keil, Felix; Kopetzky, Gerhard; Mayr, Viktor; Rabitsch, Werner; Reisner, Regina; Rosskopf, Konrad; Ruckser, Reinhard; Zoghlami, Claudia; Zojer, Niklas; Greinix, Hildegard T

    2016-08-31

    Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10(6) CD34(+) cells/kg for a single or ≥5 × 10(6) CD34(+) cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34(+) cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34(+) cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10(6) CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19(+) and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

  3. [Adoptive transfer of T lymphocytes].

    PubMed

    Vié, H; Clémenceau, B

    2017-09-01

    Within a few years, the success of treatments based on the use of T-cells armed with a chimeric T-receptor for the CD19 molecule (CAR-T CD19) has revolutionized the perception of adoptive transfer approaches. The levels of responses observed in acute leukemias, of the order of 70-90 % are indeed unprecedented. The medical and financial enthusiasm aroused by these results has led to the current situation where more than 300 clinical trials are under way, against some thirty different antigens. This enthusiasm, well justified by the first successes, must however be tempered by the difficulties associated with the use of these cells. Indeed, the management of patients is made very complex both for medical reasons, because the toxicities associated with these treatments are important, and for technical reasons, because the preparation of T lymphocytes for therapeutic use requires dedicated structures. During this same period, knowledge of the mechanisms of regulation of T lymphocytes and the possibilities offered by synthetic biology and techniques of genome engineering have progressed considerably. Combined, they allow envisaging a true "programming" of the T lymphocytes, intended to improve the efficiency of the treatments and the safety of the patients. Medical and industrial perspectives and the role of these approaches in the arsenal of cancer therapies will depend largely on two conditions: the emergence of a robust demonstration of their effectiveness in solid tumors, and the establishment of an acceptable production and distribution model 1. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  4. Variable Lymphocyte Receptors: A Current Overview.

    PubMed

    Kasahara, Masanori

    2015-01-01

    Jawless vertebrates represented by lampreys and hagfish mount antigen-specific immune responses using variable lymphocyte receptors. These receptors generate diversity comparable to that of T-cell and B-cell receptors by assembling multiple leucine-rich repeat modules with highly variable sequences. Although it is true that jawed and jawless vertebrates have structurally unrelated antigen receptors, their adaptive immune systems have much in common. Most notable is the conservation of lymphocyte lineages. It appears that specialized lymphocyte lineages emerged in a common vertebrate ancestor and that jawed and jawless vertebrates co-opted different antigen receptors within the context of such lymphocyte lineages.

  5. Lymphocyte-platelet crosstalk in Graves' disease.

    PubMed

    Kuznik, Boris I; Vitkovsky, Yuri A; Gvozdeva, Olga V; Solpov, Alexey V; Magen, Eli

    2014-03-01

    Platelets can modulate lymphocytes' role in the pathophysiology of thyroid autoimmune diseases. The present study was performed to clarify the status of platelet-lymphocyte subpopulations aggregation in circulating blood in patients with Graves' disease (GD). One hundred and fifty patients with GD (GD group) and 45 hyperthyroid patients with toxic multinodular goiter (TMG group) were recruited in the study. Control group consisted 150 healthy subjects. Immunophenotyping of lymphocytes was performed by flow cytometry. Detection of lymphocyte-platelet aggregates (LPAs) was done using light microscope after Ficoll-gradient centrifugation. The group of GD patients exhibited reduced CD8 lymphocyte and higher CD19 cell counts compared with TMG group and healthy controls. A greater number of activated CD3, HLA-DR+ lymphocytes were observed in GD than in TMG group and control group. GD group was characterized by lower blood platelet count (232 ± 89 × 10 cells/µL) than TMG group (251 ± 97 × 10 cells/µL; P < 0.05) and control group (262 ± 95 × 10 cells/µL; P < 0.05). In GD group, more platelet-bound lymphocytes (332 ± 91 /µL) were found than that in TMG group (116 ± 67/µL, P < 0.005) and control group (104 ± 58 /µL; P < 0.001). GD is associated with higher levels of activated lymphocytes and lymphocyte-platelet aggregates.

  6. Adipose tissue lymphocytes: types and roles.

    PubMed

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  7. The cloning of T lymphocytes.

    PubMed

    Schwartz, R H

    1982-02-01

    A new era of cellular immunology is clearly at hand. It is now possible, with a little bit of effort, to isolate monoclonal populations of T cells specific for any given antigen. The implications o f this technological advance are enormous in terms of applications to basic research and clinical medicine. In this article the two basic approaches that have been used to clone T lymphocytes are outlined, the pros and cons of each technique discussed and examples are given of recent experiments which have exploited this technology to gain new insights into T-cell specificity.

  8. Effectiveness of autologous serum as an alternative to fetal bovine serum in adipose-derived stem cell engineering.

    PubMed

    Choi, Jaehoon; Chung, Jee-Hyeok; Kwon, Geun-Yong; Kim, Ki-Wan; Kim, Sukwha; Chang, Hak

    2013-09-01

    In cell culture, medium supplemented with fetal bovine serum is commonly used, and it is widely known that fetal bovine serum supplies an adequate environment for culture and differentiation of stem cells. Nevertheless, the use of xenogeneic serum can cause several problems. We compared the effects of four different concentrations of autologous serum (1, 2, 5, and 10%) on expansion and adipogenic differentiation of adipose-derived stem cells using 10% fetal bovine serum as a control. The stem cells were grafted on nude mice and the in vivo differentiation capacity was evaluated. The isolation of adipose-derived stem cells was successful irrespective of the culture medium. The proliferation potential was statistically significant at passage 2, as follows: 10% autologous serum > 10% fetal bovine serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. The differentiation capacity appeared statistically significant at passage 4, as follows: 10% fetal bovine serum > 10% autologous serum = 5% autologous serum > 2% autologous serum = 1% autologous serum. Ten percent autologous serum and 10% fetal bovine serum had greater differentiation capacity than 1 and 2% autologous serum in vivo, and no significant difference was observed between the groups at ≥ 5% concentration at 14 weeks. In conclusion, 10% autologous serum was at least as effective as 10% fetal bovine serum with respect to the number of adipose-derived stem cells at the end of both isolation and expansion, whereas 1 and 2% autologous serum was inferior.

  9. Delayed-type hypersensitivity (DTH) immune response related with EBV-DNA in nasopharyngeal carcinoma treated with autologous dendritic cell vaccination after radiotherapy.

    PubMed

    Li, Feng; Song, Dan; Lu, Yue; Zhu, Huanfeng; Chen, Zhenzhang; He, Xia

    2013-04-01

    The aim of this work was to investigate the outcome of an autologous dendritic cell (DC) vaccination in patients with stage II/III nasopharyngeal carcinomas (NPC). From 38 patients with stage II/III Epstein-Barr virus (EBV)-associated NPCs after a radiotherapy, 16 human leukocyte antigen-A2 (HLA-A2)-positive patients were enrolled and medicated with autologous DCs, which were pulsed with HLA-A2-restricted EBV-encoded latent membrane protein 2A (LMP2A) peptides. The lymphocyte subsets, serum cytokines, and EBV-DNA levels as well as the delayed-type hypersensitivity (DTH) responses were determined after vaccination combined with a radiotherapy/chemotherapy. The serum levels of interleukin-2 and interferon-γ (P<0.05) as well as the percentage of natural killer and CD4+T cells increased significantly (P<0.05) after the vaccination. Nine of 16 (56.25%) patients showed a positive skin response to the HLA-A2 restricted EBV LMP2A peptides in a DTH test. The serum EBV-DNA level decreased significantly from 1519 ± 384 to 1214 ± 211 copies/mL in the 9 DTH-positive patients (P=0.0310). No unanticipated or serious toxicity was observed and the vaccine was well tolerated. In conclusion, in NPC patients vaccinated after radiotherapy with autologous DCs, which were pulsed with EBV LMP2A peptides, Th1-specific immune responses were elicited particularly in DTH test positive individuals. The clinical results obtained are encouraging and the EBV-specific HLA-A2-restricted DC vaccination is a promising treatment for EBV-related NPCs.

  10. [Laboratory diagnosis of lymphocytic meningitis].

    PubMed

    Marí, José María Navarro; Ruiz, Mercedes Pérez; Anza, Diego Vicente

    2010-01-01

    Lymphocytic meningitis, mainly those with an acute and benign course, are caused by viruses. In our area, the most commonly involved agents are enteroviruses, herpes simplex, varicella zoster and Toscana viruses. Nucleic acids amplification techniques (NAAT) are the methods of choice to diagnose viral meningitis from cerebrospinal fluid (CSF) samples. They are more rapid and sensitive, and indeed, they are not influenced by the viability of the virus in the clinical specimen as traditional methods are. The development of commercial equipments, the degree of automation, and the use of real-time polymerase chain reaction (PCR) systems are the most important premises to choose the molecular method in each laboratory. Recently, commercial kits of real-time PCR are available for the detection of enteroviruses and herpesviruses, which are the most frequently viruses involved in meningitis. Although NAAT from the clinical sample have replaced cell culture for diagnostic purposes, the combination of both methods remain useful. When the detection of the causal agent from the CSF sample is not possible, other specimens (pharyngeal exudates, stools) or serological methods can be used. Serology is the reference method for meningitis caused by West Nile virus and lymphocytic choriomeningitis virus, which are less frequently detected in our area.

  11. Lymphocytic Oesophagitis Preliminary Ultrastructural Observations.

    PubMed

    Rubio, Carlos A; Villnow, Elisabeth; Schmidt, Peter T

    2016-05-01

    Lymphocytic oesophagitis (LyE) is a newly described entity characterized by a high number of intraepithelial lymphocytes/ high power field (≥40 CD3+IELs/HPF) in the oesophageal epithelium. The aim of the study was to investigate possible ultrastructural changes taking place in LyE at the transmission electron microscopic (TEM) level. Oesopageal biopsies from seven patients were investigated: four were consecutive patients with LyE, one with reflux oesopagitis, one with eosinophilic oesopagitis (EoE) and one with histologically normal squamous epithelium. In LyE, marked intercellular oedema (spongiosis) and a gamut of regressive changes were found in squamous cells, ranging from cytoplasmic oedema and vacuolization, to total cell disintegration. IELs also showed regressive changes ranging from ballooned, oedematous cytoplasm to signs of intracytoplasmatic disintegration. Besides hampered cell nutrition conveyed by spongiosis, putative noxious molecules contained in the intercellular spongiotic oedema might account for the dramatic TEM alterations found in LyE. The present findings provide, for the first time, "inside information" on the ultrastructural alterations taking place in LyE, both in squamous cells and in IELs. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  12. [Apoptosis in chronic lymphocytic leukemia].

    PubMed

    Giordano, M

    2000-01-01

    Chronic lymphocytic leukemia of B cells (B-CLL) is the most prevalent leukemia in the Occidental Hemisphere. It is characterized by a progressive accumulation of monoclonal CD5+ B lymphocytes, with low amounts of surface Ig. Most B-CLL cells are arrested in the G0 phase of the cell cycle; therefore their accumulation in vivo appears to result from the inhibition of apoptosis which has been attributed to over-expression of the anti-apoptotic protein Bcl-2. When cultured in vitro, spontaneous apoptosis occurs, suggesting the existence in vivo of survival-promoting factors. We here show that non-malignant leukocytes, particularly monocytes and NK cells, are able to inhibit B-CLL cells apoptosis, at least in part, through the release of soluble factors. Neutralizing antibodies directed to interferon-gamma or IL-4 only partially abolish the protecting effects of accessory cells suggesting that they are not the main cytokines involved. Increased apoptosis of B-CLL cells is not associated with modifications in the expression of Bcl-2, Fas or Fas ligand. Considering that B-CLL is associated to autoimmune phenomena and recurrent infections due to hypogammaglobulinemia, it should be interesting to correlate the activation of immune responses with disease progression.

  13. Recurrent phyllodes tumor of the breast: defining the role for skin-sparing mastectomy and autologous reconstruction.

    PubMed

    Atalla, Mohamed Anwar; Rozen, Warren Matthew; Grinsell, Damien; Hyett, Anthony; Prakash, Saurabh; Cham, Alvin

    2011-05-01

    Phyllodes tumors (PTs) are uncommon fibroepithelial tumors of the breast, noteworthy for their difficult excisions and high recurrence rates. In the setting of recurrence, there is no consensus in the literature as to the extent of excision or the impact on reconstructive options. Breast-conserving surgery and simple mastectomy have each been described with mixed reports. Despite a shift toward the selective use of skin-sparing mastectomy and nipple-areola complex-sparing mastectomy in breast carcinoma, neither the role for these techniques nor the role for breast reconstruction in recurrent PT has been described. A case report is presented demonstrating the utility of skin-sparing mastectomy and autologous breast reconstruction for locally recurrent PT of the breast, with a literature review of management options in this setting presented. The case presented highlights an appropriate setting for autologous microsurgical reconstruction of the breast in recurrent PT. The literature review highlights a lack of any published management consensus, with only the role for mastectomy suggested for recurrent high-grade or malignant lesions. A potential management algorithm is thus presented. Skin-sparing mastectomy, particularly for intermediate-grade lesions, may allow wider resections while enabling aesthetically pleasing reconstructive options without affecting recurrence rates. © Thieme Medical Publishers.

  14. Postmastectomy radiation therapy and immediate autologous breast reconstruction: integrating perspectives from surgical oncology, radiation oncology, and plastic and reconstructive surgery.

    PubMed

    Rochlin, Danielle H; Jeong, Ah-Reum; Goldberg, Leah; Harris, Timothy; Mohan, Kriti; Seal, Stella; Canner, Joe; Sacks, Justin M

    2015-03-01

    The effect of postmastectomy radiation therapy (PMRT) on immediately reconstructed abdominal wall-based tissue remains imprecisely defined. We evaluated evidence from all fields involved in care of the breast cancer patient in order to advance a unified recommendation regarding this therapeutic sequence. We performed a MEDLINE and manual reference search to identify studies of PMRT with immediate autologous breast reconstruction. Inclusion criteria required studies to describe patients, flaps, and complication rates. Analyses were based on a random effects model. Surgical and radiation oncology literature was reviewed. Eleven retrospective studies of 337 patients with an average follow-up of 18-60 months (out of 268 patients) were selected for inclusion. Overall rates of fat necrosis, revisional surgery, volume loss, and fibrosis/contracture ranged from 16.9% to 35.4%. One out of 260 patients experienced total flap loss. There was an increased probability of fat necrosis in the irradiated breast (OR = 3.13, 95% CI = 1.42-6.89, P = 0.005) among three studies with non-irradiated controls. Five studies evaluated aesthetics with variable outcomes. There is mixed evidence for the utility of PMRT with immediate autologous abdominal wall breast reconstruction. Further investigation requires prospective studies with collaboration among surgical oncologists, radiation oncologists, and plastic surgeons. © 2014 Wiley Periodicals, Inc.

  15. Human Herpesvirus-6 cytopathic inclusions: an exceptional and recognizable finding on skin biopsy during HHV6 reactivation after autologous stem-cell transplantation.

    PubMed

    Roux, Jennifer; Battistella, Maxime; Fornecker, Luc; Legoff, Jérôme; Deau, Bénédicte; Houhou, Nadira; Bouaziz, Jean-David; Thieblemont, Catherine; Janin, Anne

    2012-08-01

    Skin rash are common in immunocompromised patients, particularly after bone marrow transplantation. Human herpes virus 6 (HHV6) reactivation is often suspected, but its clinical presentation and the routine laboratory tests may be unspecific, thus leading to late diagnosis. In this case, we report specific intralymphocytic cytopathic inclusions on skin biopsy as a sign of systemic HHV6 reactivation. A 56-year-old patient presented progressive erythroderma and fever occurring after autologous hematopoietic stem-cell transplantation for mantle cell lymphoma. The skin biopsy showed a perivascular infiltrate of medium-to-large lymphocytes with irregular nuclei containing a large central basophilic inclusion surrounded by a clear halo. High levels of HHV-6 genomic in skin biopsy confirm HHV-6-induced cytopathic effect. The clinical course improved with intravenous foscavir. The specific histopathological findings encountered in this case are exceptional but recognizable, and along with HHV-6 DNA detection allow a prompt recognition of HHV6 skin rash.

  16. Interaction between human mature adipocytes and lymphocytes induces T-cell proliferation.

    PubMed

    Poloni, Antonella; Maurizi, Giulia; Ciarlantini, Marco; Medici, Martina; Mattiucci, Domenico; Mancini, Stefania; Maurizi, Angela; Falconi, Massimo; Olivieri, Attilio; Leoni, Pietro

    2015-09-01

    Adipose tissue is a critical organ that plays a major role in energy balance regulation and the immune response through intricate signals. We report on the inter-relation between mature adipocytes and lymphocytes in terms of adipocyte-derived T-cell chemo-attractants and adipocyte metabolic effects on lymphocytes. During the culture time, mature adipocytes changed their structural and functional properties into de-differentiated cells. Isolated mature adipocytes expressed significantly higher levels of CIITA, major histocompatibility complex II (human leukocyte antigen [HLA]-DR) and costimulatory signal molecule CD80 compared with adipocytes after the de-differentiation process. Moreover, human leukocyte antigen-G, which may prevent the immune responses of mesenchymal stromal cells, was expressed at lower level in mature adipocytes compared with de-differentiated adipocytes. In line with these molecular data, functional results showed different immunoregulatory properties between adipocytes before and after the de-differentiation process. Mature adipocytes stimulated the proliferation of total lymphocytes and immunoselected cell populations CD3+, CD4+ and CD8+ in a direct contact-dependent way that involved the major histocompatibility complex I and II pathways. Moreover, adipocytes secreted potential chemo-attractant factors, but data showed that adipocyte-derived culture medium was not sufficient to activate lymphocyte proliferation, suggesting that a direct contact between adipocytes and immune cells was needed. However, specific mature adipocyte cytokines enhanced lymphocyte proliferation in a mixed lymphocyte reaction. In conclusion, cross-talk occurs between adipocytes and lymphocytes within adipose tissue involving T-cell chemo-attraction by mature adipocytes. Our findings, together with current observations in the field, provide a rationale to identify adipocyte-lymphocyte cross-talk that instigates adipose inflammation. Copyright © 2015 International

  17. Enhancement of the repair of dog alveolar cleft by an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture.

    PubMed

    Yuanzheng, Chen; Yan, Gao; Ting, Li; Yanjie, Fu; Peng, Wu; Nan, Bai

    2015-05-01

    Autologous bone graft has been regarded as the criterion standard for the repair of alveolar cleft. However, the most prominent issue in alveolar cleft treatment is the high absorption rate of the bone graft. The authors' objective was to investigate the effects of an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture on the repair of dog alveolar cleft. Twenty beagle dogs with unilateral alveolar clefts created by surgery were divided randomly into four groups: group A underwent repair with an autologous iliac bone, bone marrow-derived mesenchymal stem cell, and platelet-rich fibrin mixture; group B underwent repair with autologous iliac bone and bone marrow-derived mesenchymal stem cells; group C underwent repair with autologous iliac bone and platelet-rich fibrin; and group D underwent repair with autologous iliac bone as the control. One day and 6 months after transplantation, the transplant volumes and bone mineral density were assessed by quantitative computed tomography. All of the transplants were harvested for hematoxylin and eosin staining 6 months later. Bone marrow-derived mesenchymal stem cells and platelet-rich fibrin transplants formed the greatest amounts of new bone among the four groups. The new bone formed an extensive union with the underlying maxilla in groups A, B, and C. Transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture retained the majority of their initial volume, whereas the transplants in the control group showed the highest absorption rate. Bone mineral density of transplants with the bone marrow-derived mesenchymal stem cells, platelet-rich fibrin, and their mixture 6 months later was significantly higher than in the control group (p < 0.05), and was the highest in bone marrow-derived mesenchymal stem cells and platelet-rich fibrin mixed transplants. Hematoxylin and eosin staining showed that the structure of new bones formed the best

  18. L-leucyl-l-leucine methyl ester treatment of canine marrow and peripheral blood cells: Inhibition of proliferative responses with maintenance of the capacity for autologous marrow engraftment

    SciTech Connect

    Raff, R.F.; Severns, E.; Storb, R.; Martin, P.; Graham, T.

    1988-11-01

    The success of allogeneic marrow transplantation as treatment for malignant and nonmalignant hematopoietic diseases has been restricted by the serious complications of graft-versus-host disease. Experiments in a variety of mammalian marrow transplant models have shown that removal of mature T cells from donor marrow permits engraftment without the development of GVHD. Incubation of canine marrow and peripheral blood mononuclear cells with L-leucyl-L-leucine methyl ester resulted in the inhibition of mitogen-and alloantigen induced blastogenesis, the elimination of allosensitized Cytotoxic T Lymphocyte and Natural Killer activity, and prevented the development of CTL from pCTL. The effects of these incubations were similar to those described in mice and humans. Additionally, in vitro CFU-GM growth from treated canine marrow was reduced, but could be regained when the Leu-Leu-OMe-treated marrow was cocultured with either untreated autologous peripheral blood mononuclear cells or monocyte-enriched PBMC but not with untreated monocyte-depleted PBMC. Six of seven dogs conditioned with 920 cGy total-body irradiation engrafted successfully after receiving autologous marrow that was incubated with Leu-Leu-OMe prior to infusion. These cumulative results indicate that incubation with Leu-Leu-OMe is a feasible method to deplete canine marrows of alloreactive and cytotoxic T cells prior to transplantation.

  19. Immunotherapy of HCC metastases with autologous T cell receptor redirected T cells, targeting HBsAg in a liver transplant patient.

    PubMed

    Qasim, Waseem; Brunetto, Maurizia; Gehring, Adam J; Xue, Shao-An; Schurich, Anna; Khakpoor, Atefeh; Zhan, Hong; Ciccorossi, Pietro; Gilmour, Kimberly; Cavallone, Daniela; Moriconi, Francesco; Farzhenah, Farzin; Mazzoni, Alessandro; Chan, Lucas; Morris, Emma; Thrasher, Adrian; Maini, Mala K; Bonino, Ferruccio; Stauss, Hans; Bertoletti, Antonio

    2015-02-01

    HBV-DNA integration frequently occurs in HBV-related hepatocellular carcinoma (HCC), but whether HBV antigens are expressed in HCC cells and can be targeted by immune therapeutic strategies remains controversial. Here, we first characterized HBV antigen expression in HCC metastases, occurring in a patient who had undergone liver transplantation for HBV-related HCC. We then deployed for the first time in HCC autologous T cells, genetically modified to express an HBsAg specific T cell receptor, as therapy against chemoresistant extrahepatic metastases. We confirmed that HBV antigens were expressed in HCC metastases (but not in the donor liver) and demonstrated that tumour cells were recognized in vivo by lymphocytes, engineered to express an HBV-specific T cell receptor (TCR). Gene-modified T cells survived, expanded and mediated a reduction in HBsAg levels without exacerbation of liver inflammation or other toxicity. Whilst clinical efficacy was not established in this subject with end-stage metastatic disease, we confirm the feasibility of providing autologous TCR-redirected therapy against HCC and advocate this strategy as a novel therapeutic opportunity in hepatitis B-associated malignancies. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  20. Evaluation of genotoxic potential of synthetic progestins-norethindrone and norgestrel in human lymphocytes in vitro.

    PubMed

    Ahmad, M E; Shadab, G G; Azfer, M A; Afzal, M

    2001-07-25

    The genotoxicity study of two widely used contraceptive synthetic progestins, i.e. norgestrel and norethindrone was carried out on human lymphocyte chromosomes using chromosomal aberrations (CA), sister chromatid exchanges (SCE) and cell growth kinetics as parameters. The study was carried out both in the presence as well as in the absence of metabolic activation (S(9) mix). The lymphocytes were exposed to three different concentrations of the drugs (20, 40 and 75 microg/ml for norethindrone and 10, 25 and 50 microg/ml for norgestrel) for three different durations (24, 48 and 72 h). The drug norethindrone was found to be non-genotoxic at any concentration and at any exposure duration either in the presence or in the absence of S(9) mix. But another drug norgestrel was found to affect the genetic material. It induces CA, SCE at significant level, and inhibits lymphocyte proliferation at 25 and 50 microg/ml of concentrations only. In the presence of S(9) mix the values obtained for CA, SCE and mitotic index (MI) were more significant. A time and dose relationship was also observed. It was concluded that norgestrel itself and possibly its metabolites are potent mutagens beyond a particular dose in human lymphocytes.

  1. Ultraviolet irradiation of platelet concentrate abrogates lymphocyte activation without affecting platelet function in vitro

    SciTech Connect

    Kahn, R.A.; Duffy, B.F.; Rodey, G.G.

    1985-11-01

    We studied the effect of ultraviolet (UV) radiation on platelet concentrates. Samples irradiated at 310 mm for 30 minutes at a dose of 1782 J per m2 showed no loss of platelet function in vitro as determined by adenosine diphosphate, collagen, or ristocetin-induced aggregation. Lymphocytes isolated from irradiated units were unable to act as responders or stimulators in a mixed-lymphocyte reaction. These data suggest that UV radiation of platelet concentrates may result in a cell suspension that is unable to evoke an immunological response.

  2. Long term results in refractory tennis elbow using autologous blood.

    PubMed

    Gani, Naseem Ul; Khan, Hayat Ahmad; Kamal, Younis; Farooq, Munir; Jeelani, Hina; Shah, Adil Bashir

    2014-10-27

    Tennis elbow (TE) is one of the commonest myotendinosis. Different treatment options are available and autologous blood injection has emerged as the one of the acceptable modalities of treatment. Long term studies over a larger group of patients are however lacking. The purpose of this study was to evaluate these patients on longer durations. One-hundred and twenty patients of TE, who failed to respond to conventional treatment including local steroid injections were taken up for this prospective study over the period from year 2005 to 2011 and were followed up for the minimum of 3 years (range 3-9 years). Two mL of autologous blood was taken from the ipsilateral limb and injected into the lateral epicondyle. The effectiveness of the procedure was assessed by Pain Rating Sscale and Nirschl Staging, which was monitored before the procedure, at first week, monthly for first three months, at 6 months and then 3 monthly for first year, six monthly for next 2 years and then yearly. Statistical analysis was done and a P value of <0.05 was taken as significant. The patients (76 females and 44 males) were evaluated after procedure. The mean age group was 40.67±8.21. The mean follow up was 5.7±1.72 (range 3 to 9 years). The mean pain score and Nirschl stage before the procedure was 3.3±0.9 and 6.2±0.82 respectively. At final follow up the pain score and Nirschl were 1.1±0.9 and 1.5±0.91 respectively. Autologous blood injection was found to be one of the modalities for treatment of TE. Being cheap, available and easy method of treatment, it should be considered as a treatment modality before opting for the surgery. Universal guidelines for the management of tennis elbow should be made as there is lot of controversy regarding the treatment.

  3. Preclinical safety studies on autologous cultured human skin fibroblast transplantation.

    PubMed

    Zeng, Wei; Zhang, Shuying; Liu, Dai; Chai, Mi; Wang, Jiaqi; Zhao, Yuming

    2014-01-01

    Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV™) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts.

  4. Evolutionarily stable anti-cancer therapies by autologous cell defection.

    PubMed

    Archetti, Marco

    2013-01-01

    Game theory suggests an anti-cancer treatment based on the use of modified cancer cells that disrupt cooperation within the tumor. Cancer cells are harvested from the patient, the genes for the production of essential growth factors are knocked out in vitro and the cells are then reinserted in the tumor, where they lead to its collapse. Current anti-cancer drugs and treatments based on gene therapy are prone to the evolution of resistance, because cancer is a process of clonal selection: resistant cell lines have a selective advantage and therefore increase in frequency, eventually conferring resistance to the whole tumor and leading to relapse. An effective treatment must be evolutionarily stable, that is, immune to the invasion of resistant mutant cells. This study shows how such a treatment can be achieved by autologous cell therapy using modified cancer cells, knocked out for genes coding for diffusible factors like growth factors. The evolutionary dynamics of a population of cells producing diffusible factors are analyzed using a nonlinear public goods game in a structured population in which the interaction neighborhood and the update neighborhood are decoupled. The analysis of the dynamics of the system reveals what interventions can drive the population to a stable equilibrium in which no diffusible factors are produced. A treatment based on autologous knockout cell therapy can be designed to lead to the spontaneous collapse of a tumor, without targeting directly the cancer cells, their growth factors or their receptors. Critical parameters that can make the therapy effective are identified. Concepts from evolutionary game theory and mechanism design, some of which are counterintuitive, can be adopted to optimize the treatment. Although it shares similarities with other approaches based on gene therapy and RNA interference, the method suggested here is evolutionarily stable under certain conditions. This method, named autologous cell defection, can be

  5. Autologous hematopoietic stem cell transplantation in classical Hodgkin's lymphoma

    PubMed Central

    Cortez, Afonso José Pereira; Dulley, Frederico Luiz; Saboya, Rosaura; Mendrone Júnior, Alfredo; Amigo Filho, Ulisses; Coracin, Fabio Luiz; Buccheri, Valéria; Linardi, Camila da Cruz Gouveia; Ruiz, Milton Artur; Chamone, Dalton de Alencar Fischer

    2011-01-01

    Background Hodgkin's lymphoma has high rates of cure, but in 15% to 20% of general patients and between 35% and 40% of those in advanced stages, the disease will progress or will relapse after initial treatment. For this group, hematopoietic stem cell transplantation is considered one option of salvage therapy. Objectives To evaluate a group of 106 patients with Hodgkin's lymphoma, who suffered relapse or who were refractory to treatment, submitted to autologous hematopoietic stem cell transplantation in a single transplant center. Methods A retrospective study was performed with data collected from patient charts. The analysis involved 106 classical Hodgkin's lymphoma patients who were consecutively submitted to high-dose chemotherapy followed by autologous transplants in a single institution from April 1993 to December 2006. Results The overall survival rates of this population at five and ten years were 86% and 70%, respectively. The disease-free survival was approximately 60% at five years. Four patients died of procedure-related causes but relapse of classical Hodgkin's lymphoma after transplant was the most frequent cause of death. Univariate analysis shows that sensitivity to pre-transplant treatment and hemoglobin < 10 g/dL at diagnosis had an impact on patient survival. Unlike other studies, B-type symptoms did not seem to affect overall survival. Lactic dehydrogenase and serum albumin concentrations analyzed at diagnosis did not influence patient survival either. Conclusion Autologous hematopoietic stem cell transplantation is an effective treatment strategy for early and late relapse in classical Hodgkin's lymphoma for cases that were responsive to pre-transplant chemotherapy. Refractory to treatment is a sign of worse prognosis. Additionally, a hemoglobin concentration below 10 g/dL at diagnosis of Hodgkin's lymphoma has a negative impact on the survival of patients after transplant. As far as we know this relationship has not been previously reported

  6. Evolutionarily stable anti-cancer therapies by autologous cell defection

    PubMed Central

    Archetti, Marco

    2013-01-01

    Game theory suggests an anti-cancer treatment based on the use of modified cancer cells that disrupt cooperation within the tumor. Cancer cells are harvested from the patient, the genes for the production of essential growth factors are knocked out in vitro and the cells are then reinserted in the tumor, where they lead to its collapse. Background and objectives: Current anti-cancer drugs and treatments based on gene therapy are prone to the evolution of resistance, because cancer is a process of clonal selection: resistant cell lines have a selective advantage and therefore increase in frequency, eventually conferring resistance to the whole tumor and leading to relapse. An effective treatment must be evolutionarily stable, that is, immune to the invasion of resistant mutant cells. This study shows how such a treatment can be achieved by autologous cell therapy using modified cancer cells, knocked out for genes coding for diffusible factors like growth factors. Methodology: The evolutionary dynamics of a population of cells producing diffusible factors are analyzed using a nonlinear public goods game in a structured population in which the interaction neighborhood and the update neighborhood are decoupled. The analysis of the dynamics of the system reveals what interventions can drive the population to a stable equilibrium in which no diffusible factors are produced. Results: A treatment based on autologous knockout cell therapy can be designed to lead to the spontaneous collapse of a tumor, without targeting directly the cancer cells, their growth factors or their receptors. Critical parameters that can make the therapy effective are identified. Concepts from evolutionary game theory and mechanism design, some of which are counterintuitive, can be adopted to optimize the treatment. Conclusions and implications: Although it shares similarities with other approaches based on gene therapy and RNA interference, the method suggested here is evolutionarily stable under

  7. New method to prepare autologous fibrin glue on demand.

    PubMed

    Alston, Steven M; Solen, Kenneth A; Broderick, Adam H; Sukavaneshvar, Sivaprasad; Mohammad, S Fazal

    2007-04-01

    Fibrin-based sealants are commonly employed to arrest bleeding after surgery. Usually, fibrinogen obtained from pooled human plasma is used to prepare sealants, with attendant risk of blood-borne infections. Availability of autologous fibrinogen would eliminate this risk. To prepare autologous fibrin sealant, fibrinogen was precipitated from human plasma using protamine. Under optimal conditions (10-mg/mL protamine and 22 degrees C), 96 +/- 4% of clottable fibrinogen was recovered by a simple and inexpensive technique. Nearly 50% of the plasma factor XIII was also recovered with the fibrinogen. Using bovine thrombin, the fibrinogen was clotted (1) in a specially designed mold to measure tensile strength and (2) in a lap joint between 2 aortic vessel strips to measure adhesion strength. Tensile and adhesion strengths increased with increasing fibrinogen concentration, and they were increased by the addition of calcium chloride. The addition of aprotinin and -aminocaproic acid to the fibrinogen concentrate before clotting had no effect on the mechanical properties of the clots. After adding thrombin to sealant containing 15-mg/mL fibrinogen, maximum tensile strength was achieved in 1-5 min, and maximum adhesion strength was reached in 5-15 min. For the sealant with 30-60-mg/mL fibrinogen and added calcium, the tensile strength was equivalent to that of the commercial fibrin sealant Tisseel. The adhesion strength of sealant with 30-60-mg/mL fibrinogen exceeded the adhesive strength of Tisseel under identical conditions. Autologous fibrin sealant is an attractive alternative to commercial sealants. It can be readily prepared from 5-mL plasma or more and exhibits mechanical properties equivalent to those of the leading commercial sealant.

  8. Evaluation of a laminin-alginate biomaterial, adipocytes, and adipocyte-derived stem cells interaction in animal autologous fat grafting model using 7-Tesla magnetic resonance imaging.

    PubMed

    Chen, Yo-Shen; Hsueh, Yu-Sheng; Chen, Yen-Yu; Lo, Cheng-Yu; Tai, Hao-Chih; Lin, Feng-Huei

    2017-01-01

    Biomaterials are often added to autologous fat grafts both as supporting matrices for the grafted adipocytes and as cell carrier for adipose-derived stem cells (ADSCs). This in vivo study used an autologous fat graft model to test a lamininalginate biomaterial, adipocytes, and ADSCs in immune-competent rats. We transplanted different combinations of shredded autologous adipose tissue [designated "A" for adipose tissue]), laminin-alginate beads [designated "B" for bead], and ADSCs [designated "C" for cell]) into the backs of 15 Sprague-Dawley rats. Group A received only adipocytes, Group B received only laminin-alginate beads, Group AB received adipocytes mixed with laminin-alginate beads, Group BC received laminin-alginate beads encapsulating ADSCs, and Group ABC received adipocytes and laminin-alginate beads containing ADSCs. Seven-tesla magnetic resonance imaging was used to evaluate the rats at the 1st, 6th, and 12th weeks after transplantation. At the 12th week, the rats were sacrificed and the implanted materials were retrieved for gross examination and histological evaluation. The results based on MRI, gross evaluation, and histological data all showed that implants in Group ABC had better resorption of the biomaterial, improved survival of the grafted adipocytes, and adipogenic differentiation of ADSCs. Volume retention of grafts in Group ABC (89%) was also significantly greater than those in Group A (58%) (p < 0.01). Our findings support that the combination of shredded adipose tissue with ADSCs in laminin-alginate beads provided the best overall outcome.

  9. The interaction of CD2 with its LFA-3 ligand expressed by autologous erythrocytes results in enhancement of B cell responses.

    PubMed

    Virella, G; Rugeles, M T; Hyman, B; La Via, M; Goust, J M; Frankis, M; Bierer, B E

    1988-10-15

    The addition of autologous erythrocytes to unfractionated human mononuclear cell cultures results in enhancement of B cell responses to antigens and mitogens. This costimulating effect of red cells is abrogated by their preincubation with anti-LFA-3 monoclonal antibody. Preincubation of mononuclear cells with anti-CD2 monoclonal antibodies (anti-Leu 5b, OKT11, used singly) has a down-regulating effect on B cell activation and no enhancement of B cell responses is seen when red cells are added to anti-CD2-treated cultures. These results demonstrate a functional effect on B cells of the interaction between the CD2 molecule on T lymphocytes and its natural ligand, LFA-3. The precise mechanism by which this costimulating effect on B lymphocytes takes place is unclear. The study of T cell populations and T cell activation markers shows that the addition of erythrocytes causes a small but reproducible increase in the number of cells expressing the IL-2 receptor and the addition of IL-2 enhances the response of mononuclear cells to antigenic stimulation in the presence of erythrocytes. However, the supernatants of mononuclear cell cultures stimulated with pokeweed mitogen in the presence of autologous erythrocytes show decreased levels of IL-2, compared to supernatants of cells stimulated with pokeweed mitogen alone. The same supernatants show increased levels of interferon-gamma, but the addition of this lymphokine to cultures stimulated with pokeweed mitogen has no potentiating effect. It is possible that the effect of erythrocytes is mediated by other growth and/or differentiation factors, and additional studies will be required to clarify this point.

  10. [Autologous transplantation of peripheral blood stem cells in malignant lymphomas].

    PubMed

    Sánchez Luceros, A; Koziner, B

    1995-01-01

    The administration of high dose chemotherapy and or radiotherapy with autologous hematopoietic rescue has become a treatment modality with increasing number of indications in a variety of malignant conditions. Improvements in the conditioning regimens and supportive measures used, as well as a more refined patient selection based on prognostic factors, have resulted in progressively better results. The availability of precursor cells from peripheral blood has allowed a faster restoration of hematopoiesis, decreasing the period and intensity of myelosuppression. The following revision gives an updated image of the accumulated experience with this mode of support in malignant lymphomas.

  11. Autologous Fat Transfer: An Aesthetic and Functional Refinement for Parotidectomy

    PubMed Central

    Vico, Pierre G.; Delange, Axel; De Vooght, Axel

    2014-01-01

    Parotidectomy is a surgical procedure associated to functional (Frey's syndrome) as well as aesthetic (facial asymmetry) complications that can be very disturbing for the patient. Several procedures have been described to primarily avoid or secondarily reconstruct the facial defect and treat the neurological iatrogenic syndrome. Autologous fat transfer was primarily used in 10 cases to avoid such complications. It is an easy technique widely used in cosmetic and reconstructive surgery. This technique gives very satisfying long-term results on the cosmetic as well as on the physiological point of view. PMID:25379564

  12. Autologous fat transfer: an aesthetic and functional refinement for parotidectomy.

    PubMed

    Vico, Pierre G; Delange, Axel; De Vooght, Axel

    2014-01-01

    Parotidectomy is a surgical procedure associated to functional (Frey's syndrome) as well as aesthetic (facial asymmetry) complications that can be very disturbing for the patient. Several procedures have been described to primarily avoid or secondarily reconstruct the facial defect and treat the neurological iatrogenic syndrome. Autologous fat transfer was primarily used in 10 cases to avoid such complications. It is an easy technique widely used in cosmetic and reconstructive surgery. This technique gives very satisfying long-term results on the cosmetic as well as on the physiological point of view.

  13. Intramyocardial, Autologous CD34+ Cell Therapy for Refractory Angina

    PubMed Central

    Losordo, Douglas W.; Henry, Timothy D.; Davidson, Charles; Lee, Joon Sup; Costa, Marco A.; Bass, Theodore; Mendelsohn, Farrell; Fortuin, F. David; Pepine, Carl J.; Traverse, Jay H.; Amrani, David; Ewenstein, Bruce M.; Riedel, Norbert; Story, Kenneth; Barker, Kerry; Povsic, Thomas J.; Harrington, Robert A.; Schatz, Richard A.

    2011-01-01

    Rationale A growing number of patients with coronary disease have refractory angina. Preclinical and early-phase clinical data suggest that intramyocardial injection of autologous CD34+ cells can improve myocardial perfusion and function. Objective Evaluate the safety and bioactivity of intramyocardial injections of autologous CD34+ cells in patients with refractory angina who have exhausted all other treatment options. Methods and Results In this prospective, double-blind, randomized, phase II study (ClinicalTrials.gov identifier: NCT00300053), 167 patients with refractory angina received 1 of 2 doses (1×105 or 5×105 cells/kg) of mobilized autologous CD34+ cells or an equal volume of diluent (placebo). Treatment was distributed into 10 sites of ischemic, viable myocardium with a NOGA mapping injection catheter. The primary outcome measure was weekly angina frequency 6 months after treatment. Weekly angina frequency was significantly lower in the low-dose group than in placebo-treated patients at both 6 months (6.8±1.1 versus 10.9±1.2, P=0.020) and 12 months (6.3±1.2 versus 11.0±1.2, P=0.035); measurements in the high-dose group were also lower, but not significantly. Similarly, improvement in exercise tolerance was significantly greater in low-dose patients than in placebo-treated patients (6 months: 139±151 versus 69±122 seconds, P=0.014; 12 months: 140±171 versus 58±146 seconds, P=0.017) and greater, but not significantly, in the high-dose group. During cell mobilization and collection, 4.6% of patients had cardiac enzyme elevations consistent with non-ST segment elevation myocardial infarction. Mortality at 12 months was 5.4% in the placebo-treatment group with no deaths among cell-treated patients. Conclusions Patients with refractory angina who received intramyocardial injections of autologous CD34+ cells (105 cells/kg) experienced significant improvements in angina frequency and exercise tolerance. The cell-mobilization and -collection procedures

  14. Microcephaly Caused by Lymphocytic Choriomeningitis Virus.

    PubMed

    Delaine, Maia; Weingertner, Anne-Sophie; Nougairede, Antoine; Lepiller, Quentin; Fafi-Kremer, Samira; Favre, Romain; Charrel, Rémi

    2017-09-01

    We report congenital microencephaly caused by infection with lymphocytic choriomeningitis virus in the fetus of a 29-year-old pregnant women at 23 weeks' gestation. The diagnosis was made by ultrasonography and negative results for other agents and confirmed by a positive PCR result for lymphocytic choriomeningitis virus in an amniotic fluid sample.

  15. Autologous Fat Grafting for Treating Blepharoplasty-induced Lower Eyelid Retraction

    PubMed Central

    Bernardini, Francesco P.; Fezza, John; Hartstein, Morris E.

    2016-01-01

    Summary: Autologous fat grafting for blepharoplasty-induced lower eyelid retraction offers potential for a long-term solution while avoiding the morbidity associated with posterior lamellar spacer grafts. By combining traditional methods of lifting the retracted lower eyelid with autologous fat grafting, both functional and aesthetic concerns can be successfully addressed in these patients. PMID:28293531

  16. Lymphocyte subpopulations in Sheehan's syndrome.

    PubMed

    Atmaca, Hulusi; Araslı, Mehmet; Yazıcı, Zihni Acar; Armutçu, Ferah; Tekin, Ishak Özel

    2013-06-01

    The role of autoimmunity in the development of Sheehan's syndrome is obscure. There are a limited number of studies investigating the immunological alterations accompanying Sheehan's Syndrome. Our objective was to evaluate lymphocyte subsets in these patients. We conducted a cross-sectional clinical study. Cytofluorometry was used for the immunophenotyping of peripheral blood leukocytes from patients with Sheehan's syndrome followed up in the endocrine clinic during 2005-2009. Fifteen consecutive patients (mean age 61.6 ± 11.3, range 34-75 years) and 25 healthy controls (mean age 56.7 ± 10.6, range 34-80 years) were included. There was no statistically significant difference between the groups in terms of mean age. The percentages of CD19(+), CD16(+)/56(+), CD8(+)28(-), γδTCR(+), CD8(+); the total lymphocyte counts; and the ratio of CD8(+)28(-)/CD8(+)28(+) were similar (p > 0.05) between patients and controls. Whereas the leucocyte counts (p = 0.003), the percentage of CD3 (+) DR (+) (p < 0.001), CD8(+)28(+) (p = 0.030), CD4(+)CD25(+) (p = 0.007), the ratio of CD3 (+) DR(+)/CD3 (p < 0.001) were higher; the percentage of CD3 (p = 0.020), CD4 (p < 0.001) and the ratio of CD4/CD8 (p = 0.006) were lower in patients with Sheehan's syndrome compared to healthy controls. There was a positive correlation between the duration of illness and the percentage of CD3(+)DR(+) (r = 0.53, p = 0.03) expression. Some peripheral lymphocyte cell subsets show marked variation in patients with Sheehan's syndrome in comparison to matched healthy subjects, which may have implications for altered immune regulation in these patients. High CD3 (+) DR (+) expression that correlates with the duration of illness in Sheehan's patients is suggestive of an ongoing inflammation accompanying the slow progression of pituitary dysfunction in Sheehan's syndrome. It is not clear if these cellular alterations contribute to the cause or consequence of pituitary deficiency in

  17. Posterolateral spinal fusion with nano-hydroxyapatite-collagen/PLA composite and autologous adipose-derived mesenchymal stem cells in a rabbit model.

    PubMed

    Tang, Zi-Bin; Cao, Jun-Kai; Wen, Ning; Wang, Hai-Bin; Zhang, Zhong-Wen; Liu, Zhi-Qiang; Zhou, Jin; Duan, Cui-Mi; Cui, Fu-Zhai; Wang, Chang-Yong

    2012-04-01

    Spinal fusion is routinely performed to treat low back pain caused by degeneration of intervertebral discs. An autologous bone graft derived from the iliac crest is the standard procedure used for spinal fusion. However, several shortcomings, including pseudarthrosis, pain and the need for blood transfusion are known to be associated with the procedure. Our study analysed the effectiveness of a new mineralized collagen matrix, nano-hydroxyapatite-collagen-polylactic acid (nHAC-PLA), combined with autologous adipose-derived mesenchymal stem cells (ADMSCs) as a graft material for posterolateral spinal fusion in a rabbit model. Forty rabbits were randomly divided into four groups: autologous iliac crest bone group (ACB), nHAC-PLA composite group (nHAC-PLA), autologous iliac crest bone mixed with nHAC-PLA composite group (ACB + nHAC-PLA), and nHAC-PLA composite combined with ADMSCs (ADMSCs + nHAC-PLA). The viability and the proliferation of the ADMSCs seeded on the scaffolds were evaluated by live/dead kit and MTT assay in vitro, respectively. Lumbar posterolateral fusions were assessed by manual palpation, radiographical and histological procedures, mechanical strength and scanning electronic microscopy (SEM) in 10 weeks of observation. The results showed that the rate of fusion was significantly higher in the ACB and ADMSCs + nHAC-PLA groups than that in the nHAC-PLA and ACB + nHAC-PLA groups. It was not significantly higher in the ACB group than in the ADMSCs + nHAC-PLA group. From microstructural analysis of the samples using histological staining methods, there was more new bone-like tissue formation in the ACB and ADMSCs + nHAC-PLA groups than that in the other two groups at the 10th postoperative week. Our study demonstrated the effective impact of nHAC-PLA combined with ADMSCs in rabbit posterolateral spinal fusion. Copyright © 2011 John Wiley & Sons, Ltd.

  18. Clinical application of cultured autologous human auricular chondrocytes with autologous serum for craniofacial or nasal augmentation and repair.

    PubMed

    Yanaga, Hiroko; Yanaga, Katsu; Imai, Keisuke; Koga, Mika; Soejima, Chie; Ohmori, Kitaro

    2006-05-01

    The repair of a craniofacial or nose deformity requires a large volume of reconstructive material. A conventional cartilage graft does not provide a sufficient volume of reconstructive material. Therefore, augmentation of the facial form to the defect shape is quite difficult. The authors developed a new treatment method that provides a sufficiently large volume of reconstructive material and enables an easier reconstruction of the original shape. Ages of the patients ranged between 9 and 63 years. Approximately 1 cm of auricular cartilage was collected from the auricular concha. Isolated chondrocytes were cultured with autologous serum that accelerates cell proliferation. The cells were subcultured and formed a gel-form mass. This mass, together with autologous serum, was grafted (injected) on the periosteum and into the subcutaneous pocket. The volume of grafted cultured chondrocytes ranged from 1.7 to 40 cc (1 to 5 x 10(7) cells/cc). The lesion changed from soft gel form into hard cartilage tissues within 2 to 3 weeks and stabilized. Excellent or good satisfactory results were obtained in all patients and have been maintained for periods ranging from 3 to 34 months. No patient experienced absorption of cultured chondrocytes. Biopsy of the newly formed tissues showed that it was an elastic cartilage derived from the original tissue. A small number of chondrocytes obtained from a 1-cm auricular cartilage are successfully cultured into a large number of cells in a gel form. Those autologous auricular chondrocytes in a gel form allow for the repair of complicated shapes of the defect area. This technique is applicable to various treatments for craniofacial or nose deformity.

  19. Combining Microfractures, Autologous Bone Graft, and Autologous Matrix-Induced Chondrogenesis for the Treatment of Juvenile Osteochondral Talar Lesions.

    PubMed

    D'Ambrosi, Riccardo; Maccario, Camilla; Ursino, Chiara; Serra, Nicola; Usuelli, Federico Giuseppe

    2017-05-01

    The purpose of this study was to evaluate the clinical and radiologic outcomes of patients younger than 20 years, treated with the arthroscopic-talus autologous matrix-induced chondrogenesis (AT-AMIC) technique and autologous bone graft for osteochondral lesion of the talus (OLT). Eleven patients under 20 years (range 13.3-20.0) underwent the AT-AMIC procedure and autologous bone graft for OLTs. Patients were evaluated preoperatively (T0) and at 6 (T1), 12 (T2), and 24 (T3) months postoperatively, using the American Orthopaedic Foot & Ankle Society Ankle and Hindfoot (AOFAS) score, the visual analog scale and the SF-12 respectively in its Mental and Physical Component Scores. Radiologic assessment included computed tomographic (CT) scan, magnetic resonance imaging (MRI) and intraoperative measurement of the lesion. A multivariate statistical analysis was performed. Mean lesion size measured during surgery was 1.1 cm(3) ± 0.5 cm(3). We found a significant difference in clinical and radiologic parameters with analysis of variance for repeated measures ( P < .001). All clinical scores significantly improved ( P < .05) from T0 to T3. Lesion area significantly reduced from 119.1 ± 29.1 mm(2) preoperatively to 77.9 ± 15.8 mm(2) ( P < .05) at final follow-up as assessed by CT, and from 132.2 ± 31.3 mm(2) to 85.3 ± 14.5 mm(2) ( P < .05) as assessed by MRI. Moreover, we noted an important correlation between intraoperative size of the lesion and body mass index (BMI) ( P = .011). The technique can be considered safe and effective with early good results in young patients. Moreover, we demonstrated a significant correlation between BMI and lesion size and a significant impact of OLTs on quality of life. Level IV, retrospective case series.

  20. Novel treatments for chronic lymphocytic leukemia and moving forward.

    PubMed

    Brown, Jennifer R; Porter, David L; O'Brien, Susan M

    2014-01-01

    The last several years have seen an explosion of novel therapies for chronic lymphocytic leukemia (CLL). These include the antibody obintutuzumab (GA-101), as well as small-molecule inhibitors of key pathways involved in the pathogenesis of CLL, specifically the B-cell receptor (BCR) pathway (especially Bruton's tyrosine kinase [BTK] and P13K), and the antiapoptotic pathway (especially BCL-2). We will consider each in turn, focusing on the molecules most advanced in clinical development. There has also been extensive development in rewiring the patient's own immune system to treat CLL. This has been done through modifying autologous T cells to express a chimeric antigen receptor (CAR). Thus far all CAR-T preparations have targeted the CD19 antigen. This is a good rational for B-cell malignancies as CD19 expression is limited to B-cell malignancies and normal B cells. The in vivo amplification of the transduced T cells relies on signaling and co-signaling domains and provides significant killing of CLL cells. As exciting as these novel agents and approaches are, they obviously beg the question, will chemotherapy as a treatment for CLL soon be obsolete? Although chemotherapy is associated with known short-term toxicities, it has the advantage of being completed in a short period of time and being relatively inexpensive in comparison to novel therapies. In addition, long-term follow-up of results with chemoimmunotherapy have now identified a group of patients whose remissions are maintained for more than 10 years. An important question that will arise going forward is how to incorporate novel agents without eliminating the long term benefits possible with chemoimmunotherapy in a subset of patients with CLL.

  1. Lenalidomide and Chronic Lymphocytic Leukemia

    PubMed Central

    González-Rodríguez, Ana Pilar; Payer, Angel R.; Acebes-Huerta, Andrea; Huergo-Zapico, Leticia; Villa-Alvarez, Monica; Gonzalez-García, Esther; Gonzalez, Segundo

    2013-01-01

    Lenalidomide is an oral immunomodulatory drug used in multiple myeloma and myelodysplastic syndrome and most recently it has shown to be effective in the treatment of various lymphoproliferative disorders such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma. The mechanism of action of lenalidomide varies depending on the pathology, and in the case of CLL, it appears to primarily act by restoring the damaged mechanisms of tumour immunosurveillance. This review discusses the potential mechanism of action and efficacy of lenalidomide, alone or in combination, in treatment of CLL and its toxic effects such as tumor lysis syndrome (TLS) and tumor flare reaction (TFR), that make its management different from other hematologic malignancies. PMID:24163824

  2. Management of chronic lymphocytic leukemia.

    PubMed

    Stilgenbauer, Stephan; Furman, Richard R; Zent, Clive S

    2015-01-01

    Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) is usually diagnosed in asymptomatic patients with early-stage disease. The standard management approach is careful observation, irrespective of risk factors unless patients meet the International Workshop on CLL (IWCLL) criteria for "active disease," which requires treatment. The initial standard therapy for most patients combines an anti-CD20 antibody (such as rituximab, ofatumumab, or obinutuzumab) with chemotherapy (fludarabine/cyclophosphamide [FC], bendamustine, or chlorambucil) depending on multiple factors including the physical fitness of the patient. However, patients with very high-risk CLL because of a 17p13 deletion (17p-) with or without mutation of TP53 (17p-/TP53mut) have poor responses to chemoimmunotherapy and require alternative treatment regimens containing B-cell receptor (BCR) signaling pathway inhibitors. The BCR signaling pathway inhibitors (ibrutinib targeting Bruton's tyrosine kinase [BTK] and idelalisib targeting phosphatidyl-inositol 3-kinase delta [PI3K-delta], respectively) are currently approved for the treatment of relapsed/refractory CLL and all patients with 17p- (ibrutinib), and in combination with rituximab for relapsed/refractory patients (idelalisib). These agents offer great efficacy, even in chemotherapy refractory CLL, with increased tolerability, safety, and survival. Ongoing studies aim to determine the best therapy combinations with the goal of achieving long-term disease control and the possibility of developing a curative regimen for some patients. CLL is associated with a wide range of infectious, autoimmune, and malignant complications. These complications result in considerable morbidity and mortality that can be minimized by early detection and aggressive management. This active monitoring requires ongoing patient education, provider vigilance, and a team approach to patient care.

  3. Autologous Blood Injection Works for Recalcitrant Lateral Epicondylitis

    PubMed Central

    Bostan, Bora; Balta, Orhan; Aşçı, Murat; Aytekin, Kürşad; Eser, Enes

    2016-01-01

    Background: Recalcitrant lateral epicondylitis may be a disabling condition. Treatment of this condition is still controversial. Aims: In the present prospective study, we evaluated the long-term results of autologous blood injection for the treatment of recalcitrant lateral epicondylitis. Study Design: Prospective clinical study. Methods: A total of 42 elbows of 40 consecutive patients (28 female, 12 male) were enrolled in this prospective study. Seven patients left the study (3 patients moved to another city, 1 patient died in the second week due to a heart condition, 1 patient quit the study because of the resolution of pain in the fourth week and 2 patients did not agree to the second injection). Thirteen patients were lost to third year follow-up. Therefore, a total of 21 elbows of 20 patients with 3 years of follow-up were included in this study. The mean age of the patients was 47.25 years (range, 20–68 years). Results: Visual analogue scale (VAS), Nirschl score and grip strength were significantly improved after injections when compared to before treatment. The best improvement in terms of grip strength, Nirschl score and VAS score was detected at the one year follow-up. The improvement in Nirschl and VAS score sustained until the third year. Conclusion: We suggest that autologous blood injection for the treatment of recalcitrant lateral epicondylitis is an effective, safe and successful procedure in the long-term. PMID:27403393

  4. AUTOLOGOUS CHONDROCYTE TRANSPLANTATION-SERIES OF 3 CASES

    PubMed Central

    Gobbi, Riccardo Gomes; Demange, Marco Kawamura; Barreto, Ronald Bispo; Pécora, José Ricardo; Rezende, Múrcia Uchõa de; Filho, Tarcisio E.P Barros; Lombello, Christiane Bertachini

    2015-01-01

    Hyaline cartilage covers joint surfaces and plays an important role in reducing friction and mechanical loading on synovial joints such as the knee. This tissue is not supplied with blood vessels, nerves or lymphatic circulation, which may be one of the reasons why joint cartilage has such poor capacity for healing. Chondral lesions that reach the subchondral bone (osteochondral lesions) do not heal and may progress to arthrosis with the passage of time. In young patients, treatment of chondral defects of the knee is still a challenge, especially in lesions larger than 4 cm. One option for treating these patients is autologous chondrocyte transplantation/implantation. Because this treatment does not violate the subchondral bone and repairs the defect with tissue similar to hyaline cartilage, it has the theoretical advantage of being more biological, and mechanically superior, compared with other techniques. In this paper, we describe our experience with autologous chondrocyte transplantation/implantation at the Institute of Orthopedics and Traumatology, Hospital das Clínicas, University of Sâo Paulo, through a report on three cases. PMID:27022579

  5. Tissue engineering on matrix: future of autologous tissue replacement.

    PubMed

    Weber, Benedikt; Emmert, Maximilian Y; Schoenauer, Roman; Brokopp, Chad; Baumgartner, Laura; Hoerstrup, Simon P

    2011-05-01

    Tissue engineering aims at the creation of living neo-tissues identical or close to their native human counterparts. As basis of this approach, temporary biodegradable supporter matrices are fabricated in the shape of a desired construct, which promote tissue strength and provide functionality until sufficient neo-tissue is formed. Besides fully synthetic polymer-based scaffolds, decellularized biological tissue of xenogenic or homogenic origin can be used. In a second step, these scaffolds are seeded with autologous cells attaching to the scaffold microstructure. In order to promote neo-tissue formation and maturation, the seeded scaffolds are exposed to different forms of stimulation. In cardiovascular tissue engineering, this "conditioning" can be achieved via culture media and biomimetic in vitro exposure, e.g., using flow bioreactors. This aims at adequate cellular differentiation, proliferation, and extracellular matrix production to form a living tissue called the construct. These living autologous constructs, such as heart valves or vascular grafts, are created in vitro, comprising a viable interstitium with repair and remodeling capabilities already prior to implantation. In situ further in vivo remodeling is intended to recapitulate physiological vascular architecture and function. The remodeling mechanisms were shown to be dominated by monocytic infiltration and chemotactic host-cell attraction leading into a multifaceted inflammatory process and neo-tissue formation. Key molecules of these processes can be integrated into the scaffold matrix to direct cell and tissue fate in vivo.

  6. Autologous hematopoietic stem cells for refractory Crohn's disease.

    PubMed

    DiNicola, C A; Zand, A; Hommes, D W

    2017-05-01

    Autologous hematopoietic stem cells are gaining ground as an effective and safe treatment for treating severe refractory Crohn's disease (CD). Autologous hematopoietic stem cell therapy (AHSCT) induces resetting of the immune system by de novo regeneration of T-cell repertoire and repopulation of epithelial cells by bone-marrow derived cells to help patients achieve clinical and endoscopic remission. Areas covered: Herein, the authors discuss the use of AHSCT in treating patients with CD. Improvements in disease activity have been seen in patients with severe autoimmune disease and patients with severe CD who underwent AHSCT for a concomitant malignant hematological disease. Clinical and endoscopic remission has been achieved in patients treated with AHSCT for CD. The only randomized trial published to date, the ASTIC Trial, did not support further use of AHSCT to treat CD. Yet, critics of this trial have deemed AHSCT as a promising treatment for severe refractory CD. Expert opinion: Even with the promising evidence presented for HSCT for refractory CD, protocols need to be refined through the collaboration of GI and hemato-oncology professionals. The goal is to incorporate safe AHSCT and restore tolerance by delivering an effective immune 'cease fire' as a treatment option for severe refractory CD.

  7. Autologous stem cell transplant with gene therapy for Friedreich ataxia.

    PubMed

    Tajiri, Naoki; Staples, Meaghan; Kaneko, Yuji; Kim, Seung U; Zesiewicz, Theresa A; Borlongan, Cesar V

    2014-09-01

    We advance the overarching hypothesis that stem cell therapy is a potent treatment for Friedreich's ataxia (FRDA). Here, we discuss the feasibility of autologous transplantation in FRDA, highlighting the need for the successful isolation of the FRDA patient's bone marrow-derived mesenchymal stem cells, followed by characterization that these cells maintain the GAA repeat expansion and the reduced FXN mRNA expression, both hallmark features of FRDA. Next, we discuss the need for assessment of the proliferative capability and pluripotency of FRDA patient's bone marrow-derived mesenchymal stem cells. In particular, we view the need for characterizing the in vitro differentiation of bone marrow-derived mesenchymal stem cells into the two cell types primarily affected in FRDA, peripheral neurons and cardiomyocytes. Finally, we discuss the need to test the application of bone marrow-derived mesenchymal stem cells as potent autologous donor cells for FRDA. The demonstration of the functional correction of the mutated gene in these cells will be a critical endpoint of determining the potential of stem cell therapy in FRDA. We envision a gene-based cell transplant strategy as a likely therapeutic approach for FRDA, involving stable insertion of functional human bacterial artificial chromosomes or BACs containing the intact FXN gene into stem cells, thereafter leading to the expression of frataxin protein in differentiated neurons/cardiomyocytes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Alteration of Skin Properties with Autologous Dermal Fibroblasts

    PubMed Central

    Thangapazham, Rajesh L.; Darling, Thomas N.; Meyerle, Jon

    2014-01-01

    Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices. PMID:24828202

  9. A quicker preparation method for autologous fibrin glue.

    PubMed

    Yoshida, H; Kamiya, A

    1998-12-01

    To establish a quicker preparation procedure for cryoprecipitate (Cryo) from a patient's autologous plasma, to be used as fibrin glue, we examined the effects of various conditions on the concentrations and yields of coagulation factors in Cryo. Human plasma from healthy volunteers was divided and treated under various freezing, shaking and defrosting conditions. The concentrations of fibrinogen, plasminogen, fibronectin, and factor XIII in Cryo were then measured. Results were as follows: (1) concentrations and yields of plasma components in Cryo obtained from plasma stored at -20 degrees C were significantly higher than those in Cryo from plasma stored at -80 degrees C; (2) shaking at 70 cycles/min during the freezing process had a favorable effect on the concentrations and yields of coagulation factors in the Cryo; (3) a shaking thaw process in a cold water bath was a rapid method for obtaining adequate yields of coagulation factors; (4) shaking in the defrosting process did not affect the yields of coagulation factors. These results indicated that Cryo containing high concentrations of coagulation factors could be prepared easily and rapidly from a patient's autologous plasma (within 4-5 h).

  10. Diaphragmatic reconstruction with autologous tendon engineered from mesenchymal amniocytes.

    PubMed

    Fuchs, Julie R; Kaviani, Amir; Oh, Jung-Tak; LaVan, David; Udagawa, Taturo; Jennings, Russell W; Wilson, Jay M; Fauza, Dario O

    2004-06-01

    This study examined the effects of amniocyte-based engineered tendons on partial diaphragmatic replacement. Ovine mesenchymal amniocytes were labeled with green fluorescent protein (GFP), expanded, and seeded into a collagen hydrogel. Composite grafts (20 to 25 cm2) based on acellular dermis (group I), or acellular small intestinal submucosa (group II) received either a cell-seeded or an acellular hydrogel within their layers. Newborn lambs (n = 20) underwent partial diaphragmatic replacement with either an acellular or a cellular autologous construct from either group. At 3 to 12 months' postoperatively, implants were subjected to multiple analyses. Diaphragmatic hernia recurrence was significantly higher in animals with acellular grafts (5 of 5) then in animals with cellular ones (1 of 4) in group I (P <.05) but not in group II (3 of 6 and 4 of 5, respectively). Cellular grafts had higher modular (5.27 +/- 1.98 v. 1.27 +/- 0.38 MPa) and ultimate (1.94 +/- 0.70 v. 0.29 +/- 0.05 MPa) tensile strength than acellular implants in group I (P <.05), but not in group II. Quantitative analyses showed no differences in extracellular matrix components between cellular and acellular implants in either group. All cellular implants showed GFP-positive cells. Diaphragmatic repair with an autologous tendon engineered from mesenchymal amniocytes leads to improved mechanical and functional outcomes when compared with an equivalent acellular bioprosthetic repair, depending on scaffold composition. The amniotic fluid may be a preferred cell source for engineered diaphragmatic reconstruction.

  11. Augmentation-mastopexy using an autologous parenchymal sling.

    PubMed

    Steinbacher, Derek M; Singh, Navin; Katz, Ryan; Khalifeh, Marwan

    2010-10-01

    Mastopexy-augmentation is an important treatment to address breast deflation. Combining these two procedures is technique-sensitive, with a reported high revision rate and propensity for complications. We describe an approach to achieve aesthetic breast correction in an effective, reproducible, and safe manner while minimizing untoward sequela. A vertical mastopexy, using a superior dermoglandular pedicle, is coupled with a subpectoral breast implant with the support of a longitudinal autologous sling of breast fascia, termed autologous sling augmentation-mastopexy. Twenty consecutive patients, aged 25-49 years, were treated by this technique, with a follow-up period of at least 1 year. Aesthetic improvement of breast shape, projection, and nipple position were achieved in all patients. No major complications, including infection, necrosis, or implant exposure, occurred. Minor wound-healing deficits at the inferior aspect of the vertical resection occurred in three patients. One patient required implant exchange early postoperatively because of saline leakage. No revisions were necessary to adjust breast symmetry or nipple position. We describe a mastopexy-augmentation technique, based on patient selection, mastopexy resection pattern, and implant size and position, to improve breast aesthetics safely and reproducibly while minimizing complications and the need for near-term revision.

  12. Research using autologous cord blood - time for a policy change.

    PubMed

    Han, Michael X; Craig, Maria E

    2013-08-19

    • Type 1 diabetes results from the loss of normal immunological self-tolerance, which may be attributable to the failure of Foxp3+ regulatory T cells (Tregs). Umbilical cord blood is rich in Tregs and therefore has the potential to prevent or delay the onset of type 1 diabetes. A pilot trial is currently underway in Australia to examine whether infusion of autologous cord blood can prevent type 1 diabetes in high-risk children with serum antibodies to multiple β-cell antigens. • A number of other potential therapeutic indications for autologous cord blood have been proposed, including cerebral palsy and hypoxic-ischaemic encephalopathy. • Recruitment to clinical trials using cord blood is influenced by divergent public and private cord blood banking policy in Australia. The burgeoning consumer demand for storage of cord blood highlights the need for regulatory bodies to develop and adapt policies to facilitate research that may extend the use of cord blood beyond currently recognised indications. • Consumers, researchers and policymakers must also recognise specific ethical issues associated with collection and storage of cord blood, including storage in public and private banks, informed consent, ownership, access and the principle of beneficence.

  13. From fresh heterologous oocyte donation to autologous oocyte banking

    PubMed Central

    Stoop, D.

    2012-01-01

    Introduction: Today, oocyte donation has become well established, giving rise to thousands of children born worldwide annually. The introduction of oocyte cryopreservation through vitrification allows the introduction of egg banking, improving the efficiency and comfort of oocyte donation. Moreover, the vitrification technique can now enable autologous donation of oocytes to prevent future infertility. Methods: We evaluated fresh heterologous oocyte donation in terms of obstetrical and perinatal outcome as well as of the reproductive outcome of past donors. We then evaluated the efficiency of a closed vitrification device and its clinical applications within ART. Thirdly, we evaluated the opinion of women with regard to preventive egg freezing and the efficiency of a human oocyte in relation to age. Results: Oocyte donation is associated with an increased risk of first trimester bleeding and pregnancy induced hypertension. Donating oocytes does not seem to increase the likelihood for a later need of fertility treatment. The chance of an oocyte to result in live birth (utilization rate) in women <37 years old remains constant with a mean of 4.47%. A significant proportion of young women would consider safeguarding their reproductive potential through egg freezing or are at least open to the idea. Discussion and Conclusion: The introduction of efficient oocyte cryopreservation has revolutionized oocyte donation through the establishment of eggbank donation. The technique also enables women to perform autologous donation after preventive oocyte storage in order to circumvent their biological clock. PMID:24753920

  14. OSTEOCHONDRAL AUTOLOGOUS TRANSPLANTATION FOR TREATING CHONDRAL LESIONS IN THE PATELLA

    PubMed Central

    Cohen, Moises; Amaro, Joicemar Tarouco; Fernandes, Ricardo de Souza Campos; Arliani, Gustavo Gonçalves; Astur, Diego da Costa; Kaleka, Camila Cohen; Skaf, Abdalla

    2015-01-01

    Objective: The primary aim of this study was to assess the clinical and functional evolution of patients with total-thickness symptomatic cartilaginous injury of the patellar joint surface, treated by means of osteochondral autologous transplantation. Methods: This prospective study was conducted from June 2008 to March 2011 and involved 17 patients. The specific questionnaires of Lysholm, Kujala and Fulkerson were completed preoperatively and one year postoperatively in order to assess the affected knee, and SF-36 was used to assess these patients’ general quality of life. The nonparametric paired Wilcoxon test was used for statistical analysis on the pre and postoperative questionnaires. The data were analyzed using the SPSS for Windows software, version 16.0, and a significance level of 5% was used. Results: The Lysholm preoperative and postoperative average scores were 54.59 and 75.76 points (p < 0.05). The Fulkerson pre and postoperative average scores were 52.53 and 78.41 points (p < 0.05). Conclusions: We believe that autologous osteochondral transplantation is a good treatment method for total-thickness symptomatic chondral lesions of the joint surface of the patella. PMID:27042645

  15. Alteration of skin properties with autologous dermal fibroblasts.

    PubMed

    Thangapazham, Rajesh L; Darling, Thomas N; Meyerle, Jon

    2014-05-13

    Dermal fibroblasts are mesenchymal cells found between the skin epidermis and subcutaneous tissue. They are primarily responsible for synthesizing collagen and glycosaminoglycans; components of extracellular matrix supporting the structural integrity of the skin. Dermal fibroblasts play a pivotal role in cutaneous wound healing and skin repair. Preclinical studies suggest wider applications of dermal fibroblasts ranging from skin based indications to non-skin tissue regeneration in tendon repair. One clinical application for autologous dermal fibroblasts has been approved by the Food and Drug Administration (FDA) while others are in preclinical development or various stages of regulatory approval. In this context, we outline the role of fibroblasts in wound healing and discuss recent advances and the current development pipeline for cellular therapies using autologous dermal fibroblasts. The microanatomic and phenotypic differences of fibroblasts occupying particular locations within the skin are reviewed, emphasizing the therapeutic relevance of attributes exhibited by subpopulations of fibroblasts. Special focus is provided to fibroblast characteristics that define regional differences in skin, including the thick and hairless skin of the palms and soles as compared to hair-bearing skin. This regional specificity and functional identity of fibroblasts provides another platform for developing regional skin applications such as the induction of hair follicles in bald scalp or alteration of the phenotype of stump skin in amputees to better support their prosthetic devices.

  16. Autologous blood preparations rich in platelets, fibrin and growth factors

    PubMed Central

    FIORAVANTI, C.; FRUSTACI, I.; ARMELLIN, E.; CONDÒ, R.; ARCURI, C.; CERRONI, L.

    2015-01-01

    SUMMARY Objectives Bone regeneration is often needed prior to dental implant treatment due to the lack of adequate quantity and quality after infectious diseases. The greatest regenerative power was obtained with autologous tissue, primarily the bone alive, taken from the same site or adjacent sites, up to the use centrifugation of blood with the selection of the parts with the greatest potential regenerative. In fact, various techniques and technologies were chronologically successive to cope with an ever better preparation of these concentrates of blood. Our aim is to review these advances and discuss the ways in which platelet concentrates may provide such unexpected beneficial therapeutic effects. Methods The research has been carried out in the MEDLINE and Cochrane Central Register of Controlled Trials database by choosing keywords as “platelet rich plasma”, “platelet rich fibrin”, “platelet growth factors”, and “bone regeneration” and “dentistry”. Results Autologous platelet rich plasma is a safe and low cost procedure to deliver growth factors for bone and soft tissue healing. Conclusion The great heterogeneity of clinical outcomes can be explained by the different PRP products with qualitative and quantitative difference among substance. PMID:28042422

  17. Mixed Dementia

    MedlinePlus

    ... community Use our Virtual Library Treatment and outcomes back to top Because most people with mixed dementia are diagnosed with a single type of dementia, physicians often base their prescribing decisions on the type of dementia ...

  18. In vitro studies of poison oak immunity. I. In vitro reaction of human lymphocytes to urushiol.

    PubMed Central

    Byers, V S; Epstein, W L; Castagnoli, N; Baer, H

    1979-01-01

    Poison oak, ivy, and sumac dermatitis is a T-cell-mediated reaction against urushiol, the oil found in the leaf of the plants. This hapten is extremely lipophilic and concentrates in cell membranes. A blastogenesis assay employing peripheral blood lymphocytes obtained from humans sensitized to urushiol is described. The reactivity appears 1--3 wk after exposure and persists from 6 wk to 2 mon. The dose-response range is narrow, with inhibition occurring at higher antigen concentrations. Urushiol introduced into the in vitro culture on autologous lymphocytes, erythrocytes and heterologous erythrocytes produces equal results as measured by the optimal urushiol dose, the intensity of reaction, and the frequency of positive reactors. This suggests that the urushiol is passed from introducer to some other presenter cell. Although the blastogenically reactive cell is a T cell, there is also a requirement for an accessory cell, found in the non-T-cell population, for reactivity. Evidence is presented that this cell is a macrophage. PMID:315414

  19. Pertussis toxin activates adult and neonatal naive human CD4+ T lymphocytes.

    PubMed

    Tonon, Sandrine; Badran, Bassam; Benghiat, Fleur Samantha; Goriely, Stanislas; Flamand, Véronique; Willard-Gallo, Karen; Willems, Fabienne; Goldman, Michel; De Wit, Dominique

    2006-07-01

    Pertussis toxin (PTX) is known to be mitogenic for T lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA(+)CD4(+) T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-alpha and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box p3 (Foxp3) protein accumulation in naive CD4(+) T cells. Addition of autologous dendritic cells was found to be required for the production of high levels of IFN-gamma by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-kappaB and NFAT transcription factors. Overall, responses of neonatal CD4(+) T cells to PTX were similar to those of adult CD45RA(+)CD4(+) naive T cells except for their blunted CD40 ligand up-regulation. We suggest that the adjuvant properties of PTX during primary cell-mediated immune responses involve a direct action on naive T lymphocytes in addition to activation of antigen-presenting cells.

  20. Effects of tartrazine on proliferation and genetic damage in human lymphocytes.

    PubMed

    Atlı Şekeroğlu, Zülal; Güneş, Büşra; Kontaş Yedier, Seval; Şekeroğlu, Vedat; Aydın, Birsen

    2017-06-01

    The color additive, tartrazine (TRZ), is widely used in food products, drugs and cosmetics. Genotoxicity of TRZ and its metabolites has not been investigated in detail in the presence and absence of a metabolic activator (S9 mix) in human. Therefore, the aim of this study is to investigate the cytotoxic and genotoxic effects of TRZ and its metabolites on cultured human lymphocytes by using chromosome aberration (CA) and micronucleus (MN) tests. Cultures were treated with 625, 1250 and 2500 μg/ml of TRZ in the presence and absence of S9 mix. TRZ showed cytotoxic activity at the highest concentration due to significant decrease in mitotic index (MI) in the absence of S9 mix when compared with solvent control. TRZ and metabolites significantly increased the CAs and aberrant cells in the presence and absence of S9 mix at the higher concentrations. Increased MN values in cultures with and without S9 mix were found to significantly at the highest concentration when tested. Our results indicated that while both TRZ and its metabolites have genotoxic potential on human lymphocyte cultures with and without S9 mix, TRZ can induce cytotoxicity at the highest concentration in culture without S9 mix under the experimental conditions.

  1. Degeneration and atrophy of the thymus of lethally irradiated dogs, rescued by transfusion of cryopreserved autologous blood leukocytes

    SciTech Connect

    Calvo, W.; Fliedner, T.M.; Herbst, E.W.; Huegl, E.B.; Boedey, B.

    1987-12-01

    Dogs exposed to a fatal radiation dose of 12 Gy were rescued by transfusion of autologous blood leukocytes. A severe acute and long-lasting damage to the thymus was observed. The acute damage, as observed on the tenth day, consisted of a marked reduction in the number of lymphocytes, degeneration of Hassall's bodies, and hemorrhage. Long-term effects, observed several months after irradiation, were partial to total atrophy of the thymus. Regeneration, when it occurred, was limited to a few small isolated areas in which lymphopoiesis was supported by epithelial reticular cells. In contrast, the lymph nodes of all dogs had abundant cortical lymphopoiesis. The abundant hemopoiesis present in the marrow from the tenth day after irradiation until the end of the observation period should have provided sufficient circulating precursor cells to seed the thymus and regenerate the organ to the same extent as that observed in the other blood-forming organs. The impairment of lymphopoietic regeneration in the thymus seems to be due, therefore, to damage caused by irradiation on the specific stroma of the organ, which is not able to support such activity.

  2. Autologous Pure Platelet-Rich Plasma Dermal Injections for Facial Skin Rejuvenation: Clinical, Instrumental, and Flow Cytometry Assessment.

    PubMed

    Cameli, Norma; Mariano, Maria; Cordone, Iole; Abril, Elva; Masi, Serena; Foddai, Maria Laura

    2017-06-01

    Platelet-rich plasma (PRP) is an emerging treatment in dermatology recently proposed for skin rejuvenation. To evaluate the efficacy and safety of autologous pure PRP dermal injections on facial skin rejuvenation, investigating the cellularity of PRP samples. Twelve patients underwent 3 sessions of PRP injection at 1-month intervals. The clinical and instrumental outcomes were evaluated before (T0) and 1 month (T1) after the end of treatment by means of transepidermal water loss, corneometry, Cutometer, Visioscan, and Visioface. A flow cytometry characterization on PRP and peripheral blood (PB) samples was performed. Clinical and patient evaluation showed improvement of skin texture. Skin gross elasticity, skin smoothness parameters, skin barrier function, and capacitance were significantly improved. No difference between PRP and PB lymphocyte immunological asset was observed. A leukocyte population (mainly CD3) and neutrophils depletion were documented in all the PRP samples. This instrumental study demonstrated that PRP poor in leukocytes can provide objective improvements in skin biostimulation. Flow cytometry showed no variability among the PRP samples using a reproducible separation system and a low content in proinflammatory cells. Although a pilot study, it may be helpful for future investigations on PRP cellularity.

  3. In vitro adherence of lymphocytes to dermal endothelium under shear stress: implications in pathobiology and steroid therapy of acute cutaneous GVHD.

    PubMed

    Sackstein, Robert; Messina, Jane L; Elfenbein, Gerald J

    2003-01-15

    The extravasation of leukocytes at sites of inflammation critically depends on initial shear-resistant adhesive interactions between leukocytes in blood flow and target tissue endothelium. Dermal lymphocytic infiltrates are a hallmark feature of acute cutaneous graft-versus-host disease (acGVHD) following allogeneic hematopoietic stem cell (allo-HSC) transplantation. These infiltrates occur commonly during periods of profound lymphopenia, suggesting that the dermal endothelial adhesive mechanism(s) promoting lymphocyte emigration in acGVHD are highly efficient. To examine this issue, we performed Stamper-Woodruff assays on frozen sections of biopsy specimens of cutaneous lesions occurring within 100 days of HSC transplantation in 22 autologous hematopoietic stem cell transplant (auto-HSCT) and 25 allo-HSCT recipients. By using this shear-based assay, we observed lymphocyte adherence to papillary dermal vascular structures in all punch biopsy specimens of allo-HSCT recipients who had clinicohistologic evidence of acGVHD and who were not receiving steroids, whereas no lymphocyte adherence was observed within skin specimens from allo-HSCT recipients who did not develop acGVHD. Within the group of auto-HSCT recipients, 2 of 22 skin biopsies demonstrated lymphocyte binding to dermal vessels. Among allo-HSCT patients receiving steroid therapy for acGVHD, lymphocyte binding to dermal endothelium was abrogated prior to resolution of rash in those who responded, yet binding was persistent in skin from one patient whose rash did not respond to steroid therapy. Collectively, these data indicate that the papillary endothelium of skin in acGVHD displays heightened capacity to support lymphocyte adhesion under shear stress conditions and suggest that down-modulation of this endothelial adhesive capability may be one mechanism by which steroids abrogate acGVHD reactions.

  4. [Evolution and phylogeny of B lymphocytes].

    PubMed

    Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2016-01-01

    B lymphocytes are one of the most important cell types involved in the immune response of mammals. The origin and evolution of this cellular type is unknown, but the B lymphocyte bona fide appeared first in fish. In this review we analize the principal components of the immune response of invertebrates, their phylogenetic distribution and the permancence of some properties that allowed the emergence of the B lymphocyte. We started from the idea that many of the components that characterize the B lymphocyte are found distributed among the invertebrates, however, it is in the B lymphocyte, where all these components that give this type of cell its identity, converged. The actual knowledge we have in regards of the lymphocytes comes, in the most part, from physiological studies in mammals, being the mice the more representative. The origin of the B lymphocyte, its alternative mechanisms for generating receptor diversity, its immune effector response, and the generation of memory, require an evolutionary and multidisiplinary approach for its study.

  5. [Therapeutic efficacy of dendritic cells pulsed by autologous tumor cell lysate in combination with CIK cells on advanced renal cell carcinoma].

    PubMed

    Wang, Hui; Feng, Fang; Zhu, Mingao; Wang, Roushu; Wang, Xiaoping; Wu, Ying; Zhuang, Zhixiang

    2015-01-01

    To investigate the clinical efficacy of dendritic cells (DCs) sensitization by autologous tumor cell lysate in combination with cytokine-induced killer (CIK) cells on patients with advanced renal cell carcinoma and detect their immune functions and adverse effects. The study analyzed retrospectively 82 patients with advanced renal cell carcinoma admitted in our department from January 2011 to December 2013. Peripheral blood mononuclear cells (PBMCs) were isolated from the above patients. Adherent cells were cultured to produce DCs. The DCs were pulsed with autologous tumor cell lysate (Ag) to produce Ag-DC. T lymphocytes were cultured to prepare CIK. The Ag-DC was co-cultured with CIK to produce Ag-DC-CIK vaccine, and then the phenotypes of the DCs and the secretion of IL-12 were evaluated. CIK cell proliferation was determined, too. The 41 patients received the immunotherapy of Ag-DC-CIK, and the other 41 patients received CIK cell therapy alone. After 2 cycles of treatment, the changes of T cell subtypes and cytokines released in the peripheral blood were evaluated. The therapeutic outcomes were evaluated with the help of imageology. The adverse effects were also observed. Compared with the DCs alone, DCs pulsed with autologous tumor cell lysates expressed significantly surface molecules CD11c, CD83, CD86 and HLA-DR, and the release of IL-12 significantly increased. CIK cell proliferation was significantly enhanced after co-cultured with the Ag-DC. Meanwhile, the percentages of CD3⁺CD8⁺ cells and CD3⁺CD56⁺ cells went up significantly compared with the controls. Clinical responses of the Ag-DC-CIK treatment group were much better than those of the control group. No severe adverse effects were seen in the two groups. DCs derived from PBMCs of advanced renal cell carcinoma patients harboring the autologous tumor cell antigens can differentiate into mature DCs, which facilitate the proliferation of CIK cells. Ag-DC-CIK vaccine improves the immune status of

  6. ACTION OF SERUM ON LYMPHOCYTES IN VITRO

    PubMed Central

    Carrel, Alexis; Ebeling, Albert H.

    1923-01-01

    It may be concluded that, under the conditions of the experiments: 1. Lymphocytes and large mononuclear cells can live and increase greatly in numbers in blood serum, while fibroblasts are not capable of doing so. 2. While living in serum, lymphocytes and large mononuclear cells manufacture and secrete substances which may be used as food material by the fibroblasts. 3. It is probable that lymphocytes and large mononuclear cells synthetize from the nitrogenous compounds contained in serum the substances which fibroblasts and epithelial cells require for their multiplication. PMID:19868806

  7. Chylothorax Associated with Chronic Lymphocytic Leukemia

    PubMed Central

    Kohmoto, Osamu; Kawabe, Kazumi; Ono, Hideya; Yanagimoto, Ryuta; Arimoto, Junji; Hatada, Atsutoshi; Suruda, Tadatoshi; Minakata, Yoshiaki

    2016-01-01

    An 80-year-old man who had suffered from chronic lymphocytic leukemia (CLL) and achieved complete remission was admitted to our hospital due to right pleural effusion. Thoracentesis revealed that the effusion was chyle. Lymphoscintigraphy showed an obstruction of the thoracic duct below the sternum. CD45-gated flow cytometry of the pleural effusion showed elevated numbers of CD5- and CD23-positive lymphocytes and a high serum level of soluble interleukin-2 receptor. These results suggested that the chylothorax was caused by the obstruction of the thoracic duct by the sludging of either abnormal lymphocytes of CLL or transformed malignant lymphoma cells. PMID:27980266

  8. The dependence of autologous chondrocyte transplantation on varying cellular passage, yield and culture duration.

    PubMed

    Salzmann, Gian M; Sauerschnig, Martin; Berninger, Markus T; Kaltenhauser, Theresa; Schönfelder, Martin; Vogt, Stephan; Wexel, Gabriele; Tischer, Thomas; Sudkamp, Norbert; Niemeyer, Philipp; Imhoff, Andreas B; Schöttle, Philip B

    2011-09-01

    Matrix-assisted chondrocyte transplantation (m-ACI) still lacks any standardization in its execution in terms of cell passage (P), cell yield (C) and in vitro membrane-holding time (T). It was the goal of this study to analyze the effect of shifting cell culture parameters (P, C, T) on the in vitro as well as in vivo effort of a regulated animal m-ACI. Autologous rabbit knee articular chondrocytes were seeded within bilayer collagen I/III 3-D matrices in variation of P, C and T. Each time, 2 PCT-identical by 2 PCT-identical cell-matrix-constructs (CMC)/animal were created. Simultaneously 2 (PCT-distinct) were re-implanted (CMC-e) autologous into artificial trochlear pristine chondral defects in vivo to remain for 12 weeks while the remaining 2 were harvested (CMC-i) for immediate in vitro analysis at the time of transplantation of their identical twins. mRNA of both, CMC-e regenerates and CMC-i membranes, was analyzed for Collagen-1,-2,-10, COMP, Aggrecan, Sox9 expression by use of a mixed linear model, multiple regression analysis. Generally, CMC-i values were higher than CMC-e values for differentiation targets; the opposite was true for dedifferentiation targets. Regarding individual gene expression, in vivo regenerate cell-matrix properties were significantly dependent on initial cell-matrix in vitro values as a sign of linearity. The parameter membrane-holding time (T) had strongest effects on the resulting mRNA expression with slightly less impact of the parameter passage (P), whereas cell yield (C) had clearly less effects. Noting differences between in vitro and in vivo data, in general, optimal expression patterns concerning chondrogenic differentiation were achieved by few passages, medium cellular yield, short membrane-holding time. Clinical m-ACI may benefit from optimal orchestration of the cell culture parameters passage, yield and time. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. [A micro-method for PHA-induced stimulation of human lymphocytes. I. Communication: Technical considerations (author's transl)].

    PubMed

    Pees, H; Pappas, A

    1975-10-01

    A microculture system is described for PHA-induced stimulation of human peripheral lymphocytes. Following purification on Ficoll-Isopaque cells are incubated in microplates (Falcon 3040) for 66 hours in 5% CO2 using PHA-P (Difco) as a stimulant. DNA-synthesis is measured by labelling with 3H-thymidine (spec. act. 400 mCi/mmole) 16 hours prior to the end of the test. Using a multiple automatic sample harvester rapid evaluation is possible. Several variables were analyzed and optimal conditions defined for PHA- and cell-concentration, time dependence, thymidine dosage and buffer capacity of the medium. High variability and otherwise unexplained loss of lymphocyte stimulation in a population of "normal donors" are often due to acute viral infections, especially during the incubation period. On the other hand, source and concentration of serum are of equal importance since sera of healthy individuals differ greatly in their capacity to support PHA-induced stimulation of normal allogeneic lymphocytes. Using pooled or autologous serum we found the reproducibility of the technique to be good. Provided optimal conditions are employed the microtest system described herein should be ideal for in-vitro-analysis of inhibitory or stimulating factors in cancer patients' sera.

  10. Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

    PubMed Central

    Batiuk, T D; Kung, L; Halloran, P F

    1997-01-01

    Cyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-gamma and IL-2 mRNA accumulation, and IFN-gamma production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed. PMID:9312192

  11. Human B lymphocytes show greater susceptibility to H2O2 toxicity than T lymphocytes.

    PubMed

    Farber, C M; Liebes, L F; Kanganis, D N; Silber, R

    1984-05-01

    Lymphocytes from patients with chronic lymphocytic leukemia (CLL) and from normal subjects were incubated with a glucose-glucose oxidase hydrogen peroxide (H2O2) generating system to study the effect of oxidant stress on these cells. Within 4 hr, 90% of normal but only 21% of CLL lymphocytes remained viable. When normal and CLL preparations enriched in B or T cells were exposed to H2O2, B lymphocytes from both groups were highly susceptible to oxidative damage while T lymphocytes were relatively resistant. The H2O2 scavenger catalase prevented the cytotoxicity. The present work identifies the human B lymphocyte as a cell that should be a suitable target for selective killing by H2O2-generating systems.

  12. Long Term Results in Refractory Tennis Elbow Using Autologous Blood

    PubMed Central

    Gani, Naseem ul; Khan, Hayat Ahmad; Kamal, Younis; Farooq, Munir; Jeelani, Hina; Shah, Adil Bashir

    2014-01-01

    Tennis elbow (TE) is one of the commonest myotendinosis. Different treatment options are available and autologous blood injection has emerged as the one of the acceptable modalities of treatment. Long term studies over a larger group of patients are however lacking. The purpose of this study was to evaluate these patients on longer durations. One-hundred and twenty patients of TE, who failed to respond to conventional treatment including local steroid injections were taken up for this prospective study over the period from year 2005 to 2011 and were followed up for the minimum of 3 years (range 3-9 years). Two mL of autologous blood was taken from the ipsilateral limb and injected into the lateral epicondyle. The effectiveness of the procedure was assessed by Pain Rating Sscale and Nirschl Staging, which was monitored before the procedure, at first week, monthly for first three months, at 6 months and then 3 monthly for first year, six monthly for next 2 years and then yearly. Statistical analysis was done and a P value of <0.05 was taken as significant. The patients (76 females and 44 males) were evaluated after procedure. The mean age group was 40.67±8.21. The mean follow up was 5.7±1.72 (range 3 to 9 years). The mean pain score and Nirschl stage before the procedure was 3.3±0.9 and 6.2±0.82 respectively. At final follow up the pain score and Nirschl were 1.1±0.9 and 1.5±0.91 respectively. Au