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Sample records for autologous mixed lymphocyte

  1. Ro/SSA inhibits the autologous mixed lymphocyte reaction.

    PubMed Central

    Karsh, J; Harley, J B; Goldstein, R; Lazarovits, A I

    1993-01-01

    To test the hypothesis that the Ro/SSA autoantigen can be recognized as antigenic by the human immune system, lymphocytes obtained from normal volunteers were used in in vitro assays evaluating the ability of Ro/SSA (mol. wt 60 kD) to induce B and/or T cell responses. Bovine Ro/SSA strongly inhibited the autologous mixed lymphocyte reaction in a dose-dependent manner without similar effects on concurrently performed allogeneic mixed lymphocyte reactions or T cell proliferation induced by phytohaemagglutinin. Using three colour FACS analysis, Ro/SSA was found to decrease the percentage of CD4+CD45+RA+ T cells in the proliferative, S+(G2+M), phase of the cell cycle. Associated with the decrease in the percentage of suppressor-inducer cells, was the finding that Ro/SSA was able to augment RF production in pokeweed mitogen stimulated cultures of peripheral blood lymphocytes. PMID:7678209

  2. 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

  3. Staphylococcal protein A primed leukocytes enhance the autologous mixed lymphocyte reaction

    SciTech Connect

    Berk, G.I.; Lederman, M.M.; Liebman, M.L.; Ellner, J.J.

    1986-04-01

    Human peripheral blood mononuclear cells (PBMC) were preincubated for 3 days in medium alone or with various mitogens then washed and irradiated. The preincubated cells then were cultured with autologous T-cells in an autologous mixed lymphocyte reaction (AMLR). Staphylococcal protein A (SPA) pretreatment of PBMC enhanced autologous T-lymphocyte proliferation from 1375 +/- 321 cpm (mean +/- SEM untreated PBMC) to 42,467 +/- 7985 cpm (SPA primed PBMC) (p less than 0.01). The ability of SPA treated PBMC to enhance the AMLR was not simply a reflection of their proliferation in preculture, as PBMC precultured with phytohemagglutinin and concanavalin A showed greater proliferation than SPA-treated PBMC yet only minimally enhanced the AMLR. Kinetic studies and pre-exposure of PBMC to graded doses of gamma radiation showed that SPA augmentation of the AMLR was mediated by 2 components which differed in kinetics and radiosensitivity. Although incubation of PBMC with SPA did not increase the percentage of cells with detectable surface Ia antigen, SPA did increase the density of Ia in the preincubated cells. Cell separation studies revealed that SPA enhancement of the AMLR was not mediated by T-cells, but was mediated by a non-adherent non-E-rosetting fraction of cells. SPA enhancement of the AMLR was associated with an increased Ia density in the stimulator population but not with an increase in Ia positive cells and was mediated by proliferation-dependent and proliferation-independent mechanisms.

  4. Characterization of a cellular inhibitory activity affecting the human autologous mixed lymphocyte reaction

    SciTech Connect

    Haynes, M.K.

    1987-01-01

    The human autologous mixed lymphocyte reaction, peripheral blood T cells are stimulated to proliferate when co-cultured with irradiated, autologous, non-T cells was studied. ({sup 3}H)-thymidine uptake was maximal on day 7 and observable on day 9. Non-adherent and adherent fractions of non-T population and lectin-activated T cell blasts contributed. Unseparated non-T stimulator cells were used. Autologous T cells, when added as irradiated third party cells, reduced AMLR proliferative responses. Depletion of Fc IgG receptor-bearing cells (T{gamma}) from T cell population by (a) IgG-sensitized ox erythrocyte rosetting (EA-rosettes) or (b) adsorption of the T{gamma} cells onto a Sepharose 6MB {approximately} BSA/anti-BSA immune complex column resulted in enhanced AMLR proliferation not attributed solely to an increase in CD8+ AMLR responder cell phenotype. Isolated T{gamma} populations exhibited a reversed helper/suppressor phenotype containing HLA DR+ and CD8+ cells. Dual labeling studies demonstrated 7-24% of CD8+ cells expressed DR antigens. After separation, AMLR proliferative capacity was localized in T-depleted population.

  5. Generation of chronic myelogenous leukemia-specific T cells in cytokine-modified autologous mixed lymphocyte/tumor cell cultures.

    PubMed

    Müller, L; Provenzani, C; Pawelec, G

    2001-01-01

    Chronic myelogenous leukemia (CML) may be amenable to cell-based adoptive immunotherapy, as suggested by the graft-versus-leukemia effect of bone marrow transplantation and the therapeutic benefit of donor leukocyte infusions. Specific adoptive immunotherapy without bone marrow transplantation might be more effective and less cost-intensive. Professional antigen-presenting cells, the dendritic cells, from patients with CML are derived from the malignant clone and may stimulate antileukemia T-cell responses. Autologous T cells may also be able to recognize tumor antigens on CML cells directly. Here, the authors show that CD4 and CD8 T-cell responses to autologous CML cells can be generated in vitro rapidly and effectively by performing modified autologous mixed lymphocyte/tumor cell cultures (MLTC) in serum-free medium in the presence of cytokines known to support dendritic cell differentiation. MLTC-sensitized T cells secreted large amounts of the type 1 cytokine interferon-gamma, as well as interleukin (IL)-2. However, they also secreted a variety of other cytokines, including the type 2-subtype cytokine IL-13 but not the classic type 2 cytokines IL-4, IL-5, and IL-10. Monoclonal populations of CML-specific CD4 cells could be derived from these lines in limited numbers but showed markedly enhanced reactivity. This suggests that CML-specific T cells are relatively rare in these autologous MTLC-derived sensitized populations, but that their isolation and propagation would yield much more potent antitumor effector cells for use in adoptive immunotherapy without the need for bone marrow transplantation. PMID:11759071

  6. Natural killer cell activity and autologous mixed lymphocyte response of splenic, mesenteric lymph node, and colonic lymphocytes during DMH-induced colon carcinogenesis in the rat.

    PubMed

    Locniskar, M; Nauss, K M; Newberne, P M

    1987-07-01

    Two in vitro models of immune surveillance were used to examine the immune status of the gut-associated lymphoid tissue, mesenteric lymph nodes, and spleen during the early stages of 1,2-dimethylhydrazine (DMN)-induced colon tumorigenesis. DMH- and vehicle-treated Fischer rats were sacrificed at one of three time points: one week, two months, or five months after cessation of treatment. Colonic, lymph node, and splenic natural killer cell cytolytic activity toward YAC-1 tumor targets and T-cell response to autologous Ia-induced blastogenesis were measured at each time point. We found little change in natural killer cell activity or T-cell proliferation induced by autologous Ia gene products at these time periods. PMID:2954798

  7. Ability of bovine mammary macrophages to enhance proliferation of autologous blood and mammary secretion lymphocytes.

    PubMed

    Concha, C; Holmberg, O

    1990-02-01

    Cells were obtained by centrifuging the mammary secretion of healthy udders of 19 cows during the dry-period and during mid-lactation. The suspended cells were incubated in plastic wells. Those adhered cells classified as mammary macrophages were incubated with pokeweed mitogen (PWM). Autologous peripheral blood lymphocytes were added to wells containing untreated macrophage cultures or cultures pretreated with PWM. In seven cows autologous dry-period mammary lymphocytes were added instead of blood lymphocytes. The macrophages + lymphocyte cultures were subjected to the lymphocyte stimulation test (LST). For comparison, peripheral blood lymphocytes and dry-period secretion lymphocytes were also subjected to the LST in the presence of PWM. In all cases, mitogenic responses were higher in pretreated macrophage cultures than in background control cultures. The stimulation indices (SI) showed that PWM-pretreated dry-period mammary macrophages enhanced the proliferation of autologous peripheral blood lymphocytes to a greater extent than did blood lymphocytes plus PWM (49 +/- 10 v. 30 +/- 6; P less than or equal to 0.05). Mammary macrophages taken from the same cows but during midlactation also clearly induced proliferation of autologous peripheral blood lymphocytes but to a lesser extent than dry-period macrophages (16 +/- 2 v. 49 +/- 10; 16 +/- 2 v. 30 +/- 6; P less than or equal to 0.01 and P less than or equal to 0.05). The PWM pretreatment of mammary macrophages increased the proliferation of autologous dry-period mammary lymphocytes by at least a factor of three (28 +/- 8 v. 8 +/- 2 P less than or equal to 0.05). The present results indicate that bovine mammary macrophages pretreated with PWM enhance proliferation as well as modulation of mammary and peripheral blood lymphocytes. The modulation of lymphocyte stimulation as demonstrated here in vitro, has great significance regarding aspects of local immunostimulation related to modern treatment of mastitis. PMID

  8. 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

  9. 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

  10. Nonspecific suppressor T cells cause decreased mixed lymphocyte culture reactivity in bone marrow transplant patients

    SciTech Connect

    Harada, M.; Ueda, M.; Nakao, S.; Kondo, K.; Odaka, K.; Shiobara, S.; Matsue, K.; Mori, T.; Matsuda, T.

    1986-07-15

    Decreased reactivity in mixed lymphocyte culture (MLC) was observed in patients within 1 yr after allogeneic and autologous bone marrow transplantation. Suppressor activity of peripheral blood mononuclear cells (PBMC) from transplant patients was studied by adding these cells as modulator cells to a bidirectional MLC with cells from normal individuals. PBMC from transplant patients markedly suppressed MLC reactivity in a dose-dependent manner. Suppressor activity was present in cells forming rosettes with sheep erythrocytes. Treatment of modulator cells with monoclonal antibodies against T cell differentiation antigens (OKT8, OKIa1) and complement completely abolished suppression of MLC. Suppressor activity was unaffected by 30 Gy irradiation. Suppressor activity declined gradually after transplantation and was inversely correlated with MLC reactivity of each patient at a significant level (p less than 0.01). These observations suggest that OKT8+ Ia+ radioresistant suppressor T cells play a role in the development of decreased MLC reactivity observed during the early post-transplant period.

  11. 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

  12. A phase I clinical trial utilizing autologous tumor-infiltrating lymphocytes in patients with primary hepatocellular carcinoma

    PubMed Central

    Weng, De-Sheng; Zhou, Zhong-Guo; Pan, Ke; Pan, Qiu-Zhong; Wang, Qi-Jing; Liu, Qing; He, Jia; Zhao, Jing-Jing; Li, Jiang; Chen, Min-Shan; Chang, Alfred E.; Li, Qiao; Xia, Jian-Chuan

    2015-01-01

    This report describes an ongoing Phase I clinical trial testing the safety of adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) in patients with primary hepatocellular carcinoma (HCC). Fifteen HCC patients were treated with their activated and expanded TILs following tumor resection. From a total of 17 patients with HCC, TIL were successfully expanded from 15 patients (88%), whereas two patients showed minimal or no expansion of TIL. Transient increase in the frequency of T cells was observed after adoptive transfer who was found only associated with grade I flu-like symptoms and malaise. After a median follow-up of 14 months, 15 patients (100%) were alive; and 12 patients (80%) showed no evidence of disease, 3 patients (patient 1,11,12) had tumor recurrence. The time to the diagnosis of tumor recurrence following therapy ranged from 105 to 261 days. These results indicate that immunotherapy with activated and expanded autologous TIL could be successfully performed with low toxicity, thus would serve as a novel treatment modality for patients with HCC. PMID:26515587

  13. 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

  14. Higher infused lymphocyte dose predicts higher lymphocyte recovery, which in turn, predicts superior overall survival following autologous hematopoietic stem cell transplantation for multiple myeloma.

    PubMed

    Hiwase, Devendra K; Hiwase, Smita; Bailey, Michael; Bollard, Geraldine; Schwarer, Anthony P

    2008-01-01

    Autologous stem cell transplantation (ASCT) is the standard of care for patients with multiple myeloma (MM) younger than 70 years. However, despite this aggressive therapy most patients will still die of progressive disease. Recent reports have suggested that lymphocyte recovery is an important predictor of relapse or progressive disease in a number of hematologic malignancies including MM. We have conducted retrospective analysis of factors that could predict overall (OS) and progression free survival (PFS) in patients with MM who had ASCT. One hundred nineteen patients with multiple myeloma underwent ASCT. The median OS and PFS were 64 and 32 months, respectively. Univariate and multivariate analysis using Cox proportional hazards regression model showed that absolute lymphocyte count on day 30 following ASCT (ALC-30), international staging system (ISS) stage at diagnosis, and age at diagnosis significantly influenced OS and PFS following ASCT. OS (96 versus 48 months, P = .04) and PFS (43 versus 29 months, P = .03) following ASCT were higher in patients with ALC-30 >or=1.0 x 10(9)/L compared to patients ALC-30 <1.0 x 10(9)/L. Higher ALC-60, ALC-100, ALC-180, and ALC-365 did not predict superior OS and PFS. Patients with early-stage disease had significantly higher OS (ISS stages I, II, and III: 96, 53, and 29 months, respectively; P = .0023) and PFS (ISS stages I, II, and III: 55.5, 31, and 12 months, respectively; P = .027) compared to patients with advanced-stage disease at diagnosis. On univariate analysis, the type of initial chemotherapy (melphalan, VAD, PCAB), lymphocyte count on day of leukapheresis, and the lymphocyte dose infused (LY-DO) significantly influenced lymphocyte recovery following ASCT. Patients who received higher lymphocyte dose (LY-DO) >or=0.2 x 10(9)/kg had higher median ALC-15 (0.25 versus 0.19 x 10(9)/L; P = .3), ALC-30 (1.20 versus 0.99 x 10(9)/L; P = .08), ALC-60 (1.90 versus 1.01 x 10(9)/L; P = .013), ALC-100 (1.58 versus 1.03 x 10

  15. Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer.

    PubMed

    Bernhard, Helga; Neudorfer, Julia; Gebhard, Kerstin; Conrad, Heinke; Hermann, Christine; Nährig, Jörg; Fend, Falko; Weber, Wolfgang; Busch, Dirk H; Peschel, Christian

    2008-02-01

    The human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immunotherapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines. We describe the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2-overexpressing breast cancer. The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood. The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases. The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy. This study suggests the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and proposes the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors. PMID:17646988

  16. 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.

  17. [Immunotherapy of autologous focus of infiltrating lymphocytes in resection of pulmonary tuberculosis].

    PubMed

    Zhestkov, K G; Zemskov, V M; Batyrov, F A

    2001-01-01

    The development of immunotherapy modalities using active immunologically "trained" cells obtained just from a focus of tuberculous inflammation is a promising direction of the prevention and treatment of recurrent tuberculosis. Thirty patients were examined. A procedure was developed for autoimmunotherapy. The study showed it possible to obtain living, sterile, tuberculous inflammation focus-trophic lymphocytes in the amount sufficient for an immunotherapeutical effect. Autoimmunotherapy was found to reduce the number of postoperative recurrences (6% in the experimental group versus 20% in the control one), promoted prompter recovery of tuberculous bronchitis, earlier normalization of the parameters of systemic and antituberculous immunity after surgery. Densitometric analysis of X-ray films revealed a significant focal consolidation (by 1.37 times) after using focus-infiltrating lymphocytes. Autoimmunotherapy using focus-infiltrating lymphocytes makes it possible to improve the outcomes of surgical treatment of patients with pulmonary tuberculosis by reducing the risk of postoperative recurrent tuberculosis, to apply resection interventions in disseminated and bilateral pulmonary tuberculosis more extensively, to use saving resections aimed at removing the basic focus of a tuberculous lesion if there are disseminated focal seedings, and to promote the solution of a problem of the surgical management of patients with drug-resistant mycobacteria. PMID:11858084

  18. Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients

    PubMed Central

    2012-01-01

    Background Adoptive cell therapy may be based on isolation of tumor-specific T cells, e.g. autologous tumor infiltrating lymphocytes (TIL), in vitro activation and expansion and the reinfusion of these cells into patients upon chemotherapy induced lymphodepletion. Together with high-dose interleukin (IL)-2 this treatment has been given to patients with advanced malignant melanoma and impressive response rates but also significant IL-2 associated toxicity have been observed. Here we present data from a feasibility study at a Danish Translational Research Center using TIL adoptive transfer in combination with low-dose subcutaneous IL-2 injections. Methods This is a pilot trial (ClinicalTrials.gov identifier: NCT00937625) including patients with metastatic melanoma, PS ≤1, age <70, measurable and progressive disease and no involvement of the central nervous system. Six patients were treated with lymphodepleting chemotherapy, TIL infusion, and 14 days of subcutaneous low-dose IL-2 injections, 2 MIU/day. Results Low-dose IL-2 considerably decreased the treatment related toxicity with no grade 3–4 IL-2 related adverse events. Objective clinical responses were seen in 2 of 6 treated patients with ongoing complete responses (30+ and 10+ months), 2 patients had stable disease (4 and 5 months) and 2 patients progressed shortly after treatment. Tumor-reactivity of the infused cells and peripheral lymphocytes before and after therapy were analyzed. Absolute number of tumor specific T cells in the infusion product tended to correlate with clinical response and also, an induction of peripheral tumor reactive T cells was observed for 1 patient in complete remission. Conclusion Complete and durable responses were induced after treatment with adoptive cell therapy in combination with low-dose IL-2 which significantly decreased toxicity of this therapy. PMID:22909342

  19. The role of HLA-DR antigens in PPD-stimulated lymphocyte-monocyte interactions.

    PubMed

    Haar, D; Heron, I

    1982-11-01

    Autologous monocytes are required for an optimal lymphocyte proliferative response to purified protein derivate of tuberculin (PPD) in vitro and for a mixed lymphocyte culture induced by alloantigens. In the proliferative response to PPD we found that autologous monocytes could be replaced with HLA-DR-compatible monocytes and partly with HLA-DR semi-identical. In spite of a statistically significant difference between autologous and HLA-DR disparate monocytes in their cooperative capacity with PPD-stimulated lymphocytes, replacement in nearly one third of the cases was possible. These findings were supported by more detailed studies in which increasing numbers of allogenic and autologous monocytes were added to the isolated lymphocytes in the presence of PPD. It is concluded that the serologically defined HLA-DR antigens alone give insufficient information of the restriction elements controlling the PPD-stimulated lymphocyte-monocyte interactions. PMID:6184773

  20. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  2. Human dendritic cells process and present Listeria antigens for in vitro priming of autologous CD4+ T lymphocytes.

    PubMed

    Eppler, Elisabeth; Walch, Michael; Latinovic-Golic, Sonja; Dumrese, Claudia; Filgueira, Luis; Groscurth, Peter

    2005-02-01

    The role of human dendritic cells (DC) in the immune response toward intracellularly growing Listeria was analyzed under in vitro conditions using several morphological and functional methods. DC incubated with Listeria innocua and L. monocytogenes, respectively, readily phagocytosed the bacteria. Listeria did not impair viability and immunogenic potential of human DC. Listerial antigens were found to be processed within the lysosomal compartment of DC and colocalized with major histocompatibility complex (MHC) class II molecules, as shown by fluorescence and transmission electron microscopy. DC challenged with apathogenic L. innocua were highly effective in priming autologous naive T cells (mainly CD4+) in vitro. The T cells strongly proliferated in the presence of DC incubated with L. innocua, which could be significantly inhibited by anti-MHC II mAb. L. innocua-primed T cells were also successfully stimulated by DC harboring the pathogenic L. monocytogenes, either the wild-type strain EGD or the p60 reduced mutant strain RIII. From our results, we conclude that human DC infected with nonpathogenic intracellular bacteria are able to efficiently prime naive T cells, which are then suitable for recognition of antigens derived from related virulent bacterial species. This in vitro human model provides an interesting tool for basic research in infectious immunology and possibly for a new immunotherapy. PMID:15812647

  3. Poor Mixed Lymphocyte Reaction Stimulatory Capacity of Leukemic B Cells of Chronic Lymphocytic Leukemia Patients Despite the Presence of Ia Antigens

    PubMed Central

    Halper, James P.; Fu, Shu Man; Gottlieb, Alice B.; Winchester, Robert J.; Kunkel, Henry G.

    1979-01-01

    The human Ia-like antigens, selectively expressed on B lymphocytes, are now recognized to be closely associated with, or identical to, the gene products of the major histocompatibility complex responsible for stimulation in the mixed lymphocyte reaction. The leukemic B lymphocytes of patients with chronic lymphocytic leukemia express these antigens very well. In the present study they were readily detected by several techniques utilizing both allo- and heteroantisera. However, the leukemic B cells from most patients were found to be extremely poor stimulating cells in the mixed lymphocyte reaction. This was particularly apparent when comparisons were made on a B-cell basis with isolated normal B lymphocytes. Leukemic cell death, abnormal kinetics of leukemic cell-mediated stimulation, and serum or cellular suppressor factors do not appear to explain these findings. Studies comparing cells from a leukemic patient with those of her HLA identical sibling and results of mixed lymphocyte reactions between normal and leukemic subjects discordant for D-region-associated Ia antigens ruled out genetic explanations for the differences observed. Experiments with normal peripheral blood mononuclear cells depleted of T cells and monocytes exclude the quantitative deficiency of monocytes which is found in the peripheral blood of most leukemic patients as an explanation. The present results with chronic lymphocytic leukemia cells indicate that the mere expression of the Ia-like antigens by cell populations does not render them effective stimulators. The accumulated evidence obtained indicate that abnormalities, particularly of membrane function and metabolism, known to occur in chronic lymphocytic leukemia lymphocytes may be involved in the poor stimulatory capacity of the leukemic B cells. PMID:159311

  4. High-dose chemotherapy and autologous stem cell transplantation for relapsed or refractory nodular lymphocyte predominant Hodgkin lymphoma.

    PubMed

    Akhtar, S; Elhassan, T A M; Edesa, W; Rauf, M S; Zahir, M N; Maghfoor, I

    2016-01-01

    Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma. We report our results of relapsed/refractory NLPHL patients who received high-dose chemotherapy and autogenic stem cell transplantation (HDC auto-SCT). Seventeen NLPHL patients received HDC auto-SCT (1996–2014): male 14 and female 3, with median age at diagnosis of 22 years, at HDC auto-SCT 28 years (15–58 years). At the time of relapse/progression, 13 (76 %) had NLPHL and 4 (24 %) had transformed diffuse large B cell lymphoma. The reason for HDC auto-SCT was refractory NLPHL in 12 patients and relapsed in 5 patients. Salvage chemotherapy was etoposide, methylprednisolone, cisplatinum, and Ara-C (ESHAP); eight patients also received rituximab with ESHAP. HDC was carmustine, etoposide, cytarabine, and melphalan (BEAM). Post-auto-SCT, complete remission was achieved in 14 (82 %), partial remission in 1 (6 %), and progressive disease in 2 (12 %) patients. The median follow-up is 63 months from auto-SCT (6–124 months). Of the nine patients who received only ESHAP, four had post-auto-SCT events versus no event in all eight patients who received rituximab+ESHAP. Kaplan–Meier estimates of 5-year event-free survival for the whole group is 76 %: rituximab+salvage (100 %) versus salvage alone (56 %), P=0.041. Overall survival is 94 %: 100 versus 89 %, respectively, P=not significant (NS). Even in refractory NLPHL patients, long-term disease-free survival is possible after HDC auto-SCT. Post-auto-SCT relapse or progression can still be managed with chemo/chemo+immunotherapy/ radiation. These encouraging results of rituximab in salvage setting should be explored further in a clinical trial setting for this patient population. PMID:26467917

  5. 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. PMID:26644451

  6. 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.

  7. Improved relapse-free survival after autologous stem cell transplantation does not translate into better quality of life in chronic lymphocytic leukemia: lessons from the randomized European Society for Blood and Marrow Transplantation-Intergroup study.

    PubMed

    de Wreede, Liesbeth C; Watson, Maggie; van Os, Marleen; Milligan, Donald; van Gelder, Michel; Michallet, Mauricette; Dreger, Peter; Dearden, Claire E; Homewood, Janis; Dupuis, Jehan; Leporrier, Michel; Karas, Michal; Corront, Bernadette; Baerlocher, Gabriela M; Herr, Wolfgang; Choquet, Sylvain; Niederwieser, Dietger W; Sutton, Laurent; Kröger, Nicolaus; de Witte, Theo M; Schetelig On Behalf Of The Chronic Malignancies Working Party Of The Ebmt And The Uk Medical Research Council, Johannes

    2014-02-01

    In chronic lymphocytic leukemia (CLL) medical progress is driven by clinical studies with relapse-free survival (RFS) as the primary endpoint. The randomized EBMT-Intergroup trial compared high-dose therapy and autologous stem cell transplantation (ASCT) to observation and demonstrated a substantial improvement of RFS without showing improved overall survival for the transplant arm. Here we report quality of life (QoL) information of the first 3 years following randomization from that study. The main objective was to assess the impact of treatment on QoL over time. Two secondary analyses were performed to further investigate the impact of ASCT and relapse on QoL. In the primary analysis, we demonstrate an adverse impact of ASCT on QoL which was largest at 4 months and continued throughout the first year after randomization. Further, we demonstrated a sustained adverse impact of relapse on QoL which worsened over time. Despite better disease control by ASCT the side effects thus turned the net effect towards inferior QoL in the first year and comparable QoL in the following 2 years after randomization. This study emphasizes the importance of information concerning QoL impacts when patients are counseled about treatments aimed at improving RFS in the absence of a survival benefit. PMID:24123244

  8. 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.

  9. 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

    2016-06-17

    B-Cell Prolymphocytic Leukemia; 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-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  10. 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

  11. The biological effect of three thymosin fraction 5 polypeptides in the murine mixed lymphocyte reaction.

    PubMed Central

    Baxevanis, C N; Perez, S; Kokkinopoulos, D; Papamichail, M

    1985-01-01

    The biological effects of three thymosin fraction 5 polypeptides, designated as beta 10, beta 4, and alpha 1 were tested in the MLR of mouse splenocytes, lymph node cells and thymocytes against syngeneic or allogeneic stimulators. It was found that all three polypeptides, after in vivo and in vitro treatment of the responder cell population, could enhance the allogeneic MLR. These polypeptides were also able to induce significant syngeneic MLR in systems where responder cells were used against irradiated syngeneic splenocytes. In addition, while beta 4 was shown to have a weak stimulatory effect on allogeneic MLR utilizing thymocytes as the responder cell type, alpha 1 could strongly induce such responses when syngeneic splenocytes were included into the culture system. Preincubation of purified mature T cells or thymocytes with alpha 1 has shown these cells to be the target of this polypeptide action. Thus, it appears that thymosin fraction 5 polypeptides not only initiate differentiation processes of immature T cells, but also exert their effects on mature T lymphocytes. PMID:3156810

  12. Interleukin 1 beta synergises with interleukin 2 in the outgrowth of autologous tumour-reactive CD8+ effectors.

    PubMed Central

    Baxevanis, C. N.; Dedoussis, G. V.; Gritzapis, A. D.; Stathopoulos, G. P.; Papamichail, M.

    1994-01-01

    Using peritoneal fluid or pleural effusion obtained from 20 patients with lung, ovarian or metastatic breast cancer, we separated tumour cells from malignant effusion-associated mononuclear cells (MEMNCs) using discontinuous Ficoll-Hypaque density gradients. CD3+ T lymphocytes represented the main population of MEMNCs. The mean +/- s.d. CD4/CD8 ratio of MEMNC suspensions was 1.18 +/- 0.40. MEMNCs proliferated and expanded in vitro with human interleukin 2 (IL-2) either as CD3+ CD8+ cells or as CD3+ CD4+ cells or as mixed populations of CD8+ and CD4+ cells. Preferential cytolytic activity against autologous tumour cells was demonstrated in IL-2-activated MEMNC cultures with excess CD3+ CD8+ cells. In contrast, effectors derived from IL-2-activated cultures with excess CD3+ CD4+ cells lysed both autologous and allogeneic tumour target cells. The addition on day 0 of interleukin 1 beta (IL-1 beta) to MEMNCs cultured in the presence of IL-2 was effective in promoting the growth of CD3+ CD8+ cells and augmenting the cytotoxicity against autologous tumour. Simultaneously, the production of gamma-interferon (IFN-gamma) was increased in these cultures. This is the first report suggesting that IL-1 beta synergises with IL-2 to induce autologous tumour-specific CD8+ cytotoxic T lymphocytes (CTLs) within the MEMNC population. Selective enrichment in T-cell subsets by IL-1 beta may be useful in cellular adoptive immunotherapy using cells isolated from malignant effusions. PMID:7917907

  13. Comparison of immune status and 1,2-dimethylhydrazine induced tumorigenesis in brown--Norway and Fischer rats. Emphasis on splenic and colonic lymphocyte function.

    PubMed

    Locniskar, M; Nauss, K M; Kauffman, P; Newberne, P M

    1985-01-01

    Sym 1,2-dimethylhydrazine (DMH)-induced colon tumorigenesis was studied in immunologically different strains of rat: the Brown--Norway which is known to be immunologically a low-responder and the Fischer a high-responder. Brown--Norway rats received a total dose of 75, 150 or 225 mg DMH/kg or vehicle and Fischer rats received 150 mg DMH/kg or vehicle over a 3-week period. Rats were killed 5 months after the final treatment. Lymphocytes were isolated from the spleen and colon from rats treated with 150 mg DMH/kg or vehicle. Natural killer (NK) cell activity and the autologous mixed lymphocyte response (AMLR) as well as colon tumor incidence were compared between the two strains. Splenic and colonic intraperithelial lymphocytes (IEL) from the Brown--Norway strain demonstrated low NK activity and reduced splenic T lymphocyte proliferation in response to autologous non-T lymphocytes. As well, colonic lamina propria lymphocyte (LPL) proliferation was low and Brown--Norway rats had a low incidence of DMH-induced colon neoplasms (7%). In comparison, the Fischer rats had more effective splenic and IEL NK killing, enhanced splenic AMLR, enhanced LPL proliferation and a higher incidence of colon tumors (20%). PMID:3871659

  14. Chronic phase CML patients possess T cells capable of recognising autologous tumour cells.

    PubMed

    Müller, Ludmila; Pawelec, Graham

    2002-05-01

    Much circumstantial evidence points to the immunogenicity of chronic myloid leukemia (CML) cells, most impressively the well-established T cell-dependent GvL effect seen in bone marrow transplantation. However, only a small number of shared antigens expressed by CML cells have been identified as potential targets for T cell-mediated immune responses which might be exploited for immunotherapy. It may be that unique antigens expressed by individual tumours are more potent rejection antigens if the patient's own T cells could be encouraged to react against them. Work is reviewed here which documents that in vitro mixed cultures between autologous T cells and dendritic cells of chronic-phase CML patients can give rise to sensitised T cells capable of recognising the patient's tumour cells. Additionally, mixed autologous tumour cell/lymphocyte cultures, modified by the addition of cytokine cocktails, may also result in the generation of similarly sensitised T cells. These results could be exploited for adoptive immunotherapy, and possibly, after identification of the antigens recognised, also for active immunotherapy, i.e. including therapeutic vaccination. PMID:12148904

  15. 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

  16. Autologous Microvascular Breast Reconstruction

    PubMed Central

    Ramakrishnan, Venkat

    2013-01-01

    Autologous microvascular breast reconstruction is widely accepted as a key component of breast cancer treatment. There are two basic donor sites; the anterior abdominal wall and the thigh/buttock region. Each of these regions provides for a number of flaps that are successfully utilised in breast reconstruction. Refinement of surgical technique and the drive towards minimising donor site morbidity whilst maximising flap vascularity in breast reconstruction has seen an evolution towards perforator based flap reconstructions, however myocutaneous flaps are still commonly practiced. We review herein the current methods of autologous microvascular breast reconstruction. PMID:23362474

  17. 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

  18. 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. PMID:24750320

  19. Autologous, hapten-modified vaccine as a treatment for human cancers.

    PubMed

    Berd, D; Kairys, J; Dunton, C; Mastrangelo, M J; Sato, T; Maguire, H C

    1998-12-01

    We have devised a novel approach to active immunotherapy based on modification of autologous cancer cells with the hapten, dinitrophenyl (DNP). The treatment program consists of multiple intradermal injections of DNP-modified autologous tumor cells mixed with BCG. Administration of DNP-vaccine to patients with metastatic melanoma induces a unique reaction- the development of inflammation in metastatic masses. Histologically, this consists of infiltration of T lymphocytes, most of which are CD8+. These T cells usually produce interferon-gamma in situ. Moreover, they represent expansion of T-cell clones with novel T-cell receptor (TCR) structures. Occasionally, administration of DNP-vaccine results in regression of measurable metastases. The most common site of regression has been small lung metastases. Administration of DNP-vaccine to patients in the postsurgical adjuvant setting produces a more striking clinical effect. Of 62 patients with clinically evident stage III melanoma who had undergone lymphadenectomy, the 5-year relapse-free survival rate was 45% and the overall survival rate was 58%. These results appear to be better than those obtained with high-dose interferon, although a randomized phase III trial is required to prove that point. A recent phase I study suggests that this therapeutic approach is also applicable to stage III ovarian cancer. There appear to be no insurmountable impediments to applying this approach to much larger numbers of patients or to developing it as a standard cancer treatment. PMID:9865679

  20. Nodular sclerosing, mixed cellularity and lymphocyte-depleted variants of Hodgkin's disease are probable dendritic cell malignancies.

    PubMed Central

    Kennedy, I C; Hart, D N; Colls, B M; Nimmo, J C; Willis, D A; Angus, H B

    1989-01-01

    The normal counterpart of the Reed-Sternberg cell and its mononuclear variant, collectively referred to as Hodgkin's cells (HC), remains controversial. The possibility that HC are malignant dendritic cells was tested by using a panel of 38 monoclonal antibodies to phenotype the cells from 16 cases of Hodgkin's disease (HD), excluding lymphocyte-predominant HD, and the Hodgkin's cell line L428. The results were then compared with the known phenotype of human dendritic cells. HC stained strongly for HLA Class I and Class II antigens. The leucocyte common antigen was weakly expressed in most cases. Expression of T and B cell markers was unusual, with the exception of the CD40 antigen which was found on a majority of HC. HC commonly expressed the CD11a, CR4 (CD11c), CD15, CD18 and a number of activation antigens but did not stain with a variety of macrophage-specific antibodies. The antigenic phenotype of L428 and the HC of case material were similar. This immunocytological analysis failed to support a lymphocyte or macrophage origin for HC. Instead the antigenic phenotype of the Reed-Sternberg cell and its mononuclear variant more closely resembles that of dendritic cells than of any other haemopoietic cell normally resident in lymph nodes. PMID:2787713

  1. Effects of 8-aminoguanosine and 2'-deoxyguanosine on the human mixed lymphocyte reaction (MLR). I. Description of the inhibition

    SciTech Connect

    Scott, M.E.; Gilbertsen, R.B.

    1986-03-05

    Patients deficient in purine nucleoside phosphorylase (PNP) generally have a pronounced deficiency in T cell function with no deleterious effect on B cell function. It has been demonstrated that high concentrations of 8-amino-guanosine (8-AG), an inhibitor of PNP, in combination with the PNP substrate 2'-deoxyguanosine (dGuo) can inhibit mitogen and antigen responsiveness of human lymphocytes in culture. The studies described here evaluated the effects of 8-AG and dGuo on the human MLR. Normal human lymphocytes were isolated from venous blood using Ficoll-Hypaque gradients. Stimulator cells, pretreated with mitomycin C (50 ..mu..g/ml), were added with an equal number of responder cells (2 x 10/sup 5/) to the wells of flat-bottomed microtiter plates. Cell proliferation was quantitated by the uptake of /sup 3/H-thymidine (TdR) during the final 4 hrs of six-day cultures. dGuo at 10-50 ..mu..M had no effect or stimulated proliferation, while dGuo at > 75 ..mu..M was markedly inhibitory. 8-AG alone at 100 ..mu..M had essentially no effect on TdR uptake. 8-AG (10-100 ..mu..M) plus dGuo (50 ..mu..M) produced a concentration-dependent inhibition of the MLR resulting in 8-AG IC/sub 50/s generally < 60 ..mu..M. Coaddition of 50 ..mu..M 2'-deoxycytidine, hypoxanthine or adenine partially prevented inhibition of the MLR.

  2. Inhibition of protein phosphorylation by synthetic peptides from the Fc region of human IgG during the mixed lymphocyte response

    SciTech Connect

    McClurg, M.R.; Hahn, G.S.; Plummer, J.M.

    1986-03-01

    Certain synthetic peptides derived from the Fc region of human IgG suppressed protein, RNA, and DNA synthesis during mixed lymphocyte reactions. Responder mononuclear cells were incubated with medium or agents that alter phosphorylation of cellular proteins before immunomodulatory Fc peptides and stimulator cells were added. Incubating cells with trifluoperazine which inhibits calcium binding to calmodulin and inhibits protein kinase C (PKC) increased inhibition of the MLR induced by Fc peptides. Conversely, incubating cells with dubutyryl cyclic AMP (DBcAMP), calmodulin, 1,2-diolein, or phorbol myristate acetate (PMA) abolished inhibition of the MLR induced by Fc peptides. Inhibition of the MLR by Fc ..gamma.. peptides was not affected when DBcAMP or PMA was added after peptide addition. The PKC activity of cell homogenates was decreased by 69% when Fc..gamma.. peptides were present during the MLR. The in vitro phosphorylation of histone Hl by partially purified PKC from lymphocytes was inhibited 74% in the presence of Fc..gamma.. peptides. These results indicate that suppression of the MLR induced by Fc..gamma.. peptides is dependent on inhibition of protein phosphorylation by kinases including protein kinase C. The inhibition of phosphorylation may be related to the ability of Fc..gamma.. peptides to reverse animal models of autoimmune disease.

  3. Outcomes of donor lymphocyte infusion for treatment of mixed donor chimerism after a reduced-intensity preparative regimen for pediatric patients with nonmalignant diseases.

    PubMed

    Haines, Hilary L; Bleesing, Jack J; Davies, Stella M; Hornung, Lindsey; Jordan, Michael B; Marsh, Rebecca A; Filipovich, Alexandra H

    2015-02-01

    Mixed donor chimerism is increasingly common in the pediatric hematopoietic stem cell transplantation (HSCT) setting because of the increased use of reduced-intensity preparative regimens for nonmalignant diseases. Donor lymphocyte infusion (DLI) is potentially useful in the treatment of mixed donor chimerism, but little are data available on the use of DLI in this setting. We conducted a retrospective review of 27 pediatric patients who received DLI for mixed donor chimerism between January 2006 and December 2010 after receiving a preparative regimen of alemtuzumab, fludarabine, and melphalan. Twenty-one patients (78%) were alive at a median of 35 months post-transplant. Seven patients (26%) sustained full donor chimerism after DLI only at a median of 35 months post-HSCT. Nine patients (33%) continued with mixed donor chimerism (median, 38% [range, 18% to 70%]) at a median of 37 months after DLI only. Five patients underwent unconditioned stem cell boosts or second conditioned transplants after no improvement in donor chimerism was seen following DLI. Donor source appeared to contribute to outcomes after DLI; patients with mismatched unrelated donors had earlier first decline in chimerism and timing of first DLI, a higher response rate to DLI, and an increased rate of graft-versus-host disease (GVHD). There was no response to DLI in patients with matched sibling donors. Ten patients, all with improvement in chimerism after DLI, developed acute GVHD after DLI, with 3 having grade III GVHD. Three patients developed chronic GVHD after DLI. These data illustrate the potential efficacy of DLI in the treatment of mixed donor chimerism after a reduced-intensity preparative regimen. PMID:25464116

  4. 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

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

    PubMed

    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

  6. Autologous gastrointestinal reconstruction.

    PubMed

    Bianchi, A

    1995-02-01

    The patient with short bowel syndrome is essentially unable to absorb sufficient nutrients. This is caused by either short mucosal contact time, insufficient mucosal surface area (enterocyte mass), or a combination of the two. Management consists primarily in sustaining health and growth by intravenous nutrition and in enhancing the natural intestinal adaptation response. Surgery in the form of autologous gastrointestinal reconstruction (AGIR) is designed to redistribute the patient's own residual absorptive bowel to enhance adaptation and, possibly, to increase the absorptive mucosal surface by neomucosal growth. The alternative and ultimate fallback procedure in the management of intestinal failure is bowel transplantation, with its associated serious immunosuppression-related complications. Imaginative AGIR techniques provide new hope for the future. PMID:7728509

  7. Autologous blood storage in obstetrics.

    PubMed

    Herbert, W N; Owen, H G; Collins, M L

    1988-08-01

    Autologous transfusion, storage of one's own blood for subsequent infusion if needed, is safe and effective in a variety of scheduled operative procedures. Obstetric involvement in such programs is very limited, however. Thirty pregnant women with placenta previa or other potential complications underwent 55 phlebotomies in an autologous transfusion program. Phlebotomies were performed at an average gestational age of 32.4 weeks (range 13-40). Changes in mean diastolic blood pressure and pulse were minimal. Electronic fetal monitoring tracings were normal during the 34 procedures in which it was used. The frequency of mild donor reactions (4%) was consistent with that in nonpregnant donors. After entry into this program, 15 patients received a total of 29 U of packed red blood cells (23 autologous; six homologous). Homologous transfusion was avoided in 86.7% of patients receiving blood. Selected pregnant women can participate safely in autologous blood collection programs, minimizing the need, and therefore the risks, of homologous transfusion. PMID:3292974

  8. Antigen Presenting Cells and Stromal Cells Trigger Human Natural Killer Lymphocytes to Autoreactivity: Evidence for the Involvement of Natural Cytotoxicity Receptors (NCR) and NKG2D

    PubMed Central

    Poggi, Alessandro; Zocchi, Maria Raffaella

    2006-01-01

    Human natural killer (NK) lymphocytes should not damage autologous cells due to the engagement of inhibitory receptor superfamily (IRS) members by HLA-I. Nevertheless, NK cells kill self cells expressing low levels or lacking HLA-I, as it may occur during viral infections (missing-self hypothesis). Herein, we show that human NK cells can be activated upon binding with self antigen presenting cells or stromal cells despite the expression of HLA-I. Indeed, NK cells can kill and produce pro-inflammatory and regulating cytokines as IFN-γ, TNF-α and IL10 during interaction with autologous dendritic cells or bone marrow stromal cells or skin fibroblasts. The killing of antigen presenting and stromal cells is dependent on LFA1/ICAM1 interaction. Further, the natural cytotoxicity receptors (NCR) NKp30 and NKp46 are responsible for the delivery of lethal hit to DC, whereas NKG2D activating receptor, the ligand of the MHC-related molecule MIC-A and the UL16 binding protein, is involved in stromal cell killing. These findings indicate that different activating receptors are involved in cell to self cell interaction. Finally, NK cells can revert the veto effect of stromal cells on mixed lymphocyte reaction further supporting the idea that NK cells may alter the interaction between T lymphocytes and microenvironment leading to autoreactivity. PMID:17162374

  9. Autologous gluteal lipograft.

    PubMed

    Nicareta, Beatriz; Pereira, Luiz Haroldo; Sterodimas, Aris; Illouz, Yves Gérard

    2011-04-01

    In the past 25 years, several different techniques of lipoinjection have been developed. The authors performed a prospective study to evaluate the patient satisfaction and the rate of complications after an autologous gluteal lipograft among 351 patients during January 2002 and January 2008. All the patients included in the study requested gluteal augmentation and were candidates for the procedure. Overall satisfaction with body appearance after gluteal fat augmentation was rated on a scale of 1 (poor), 2 (fair), 3 (good), 4 (very good), and 5 (excellent). The evaluation was made at follow-up times of 12 and 24 months. The total amount of clean adipose tissue transplanted to the buttocks varied from 100 to 900 ml. In nine cases, liponecrosis was treated by aspiration with a large-bore needle connected to a 20-ml syringe, performed as an outpatient procedure. Infection of the grafted area also occurred for four patients and was treated by incision drainage and use of antibiotics. Of the 21 patients who expressed the desire of further gluteal augmentation, 16 had one more session of gluteal fat grafting. The remaining five patients did not have enough donor area and instead received gluteal silicone implants. At 12 months, 70% reported that their appearance after gluteal fat augmentation was "very good" to "excellent," and 23% responded that their appearance was "good." Only 7% of the patients thought their appearance was less than good. At 24 months, 66% reported that their appearance after gluteal fat augmentation was "very good" (36%) to "excellent" (30%), and 27% responded that their appearance was "good." However, 7% of the patients continued to think that their appearance was less than good. At this writing, the average follow-up time for this group of patients has been 4.9 years. The key to successful gluteal fat grafting is familiarity with the technique, knowledge of the gluteal topography, and understanding of the patient's goals. With experience, the

  10. Immunological characterization of a γδ T-cell stimulatory ligand on autologous monocytes

    PubMed Central

    Sathiyaseelan, Thillainayagam; Naiman, Brian; Welte, Stefan; Machugh, Niall; Black, Samuel J; Baldwin, Cynthia L

    2002-01-01

    Bovine γδ T cells are stimulated to proliferate by autologous monocytes. This is referred to as the autologous mixed leucocyte reaction (AMLR). It has been shown previously that the stimulatory component is constitutively expressed on the monocyte plasma membrane and is a protein or has a protein moiety. Here we showed that γδ T-cell responses to the monocytes requires interaction with the T-cell receptor because Fab1 fragments of a monoclonal antibody (mAb) that reacts with the δ chain of the T-cell receptor blocked proliferation in the AMLR. Monocyte molecules involved in stimulation were also characterized further by biochemical and immunological methods. A mAb, named M5, was generated by immunizing mice with bovine monocytes and shown to block the ability of monocytes to stimulate in the AMLR. Treatment of monocytes or monocyte membranes with high salt, chelating agents or phospholipase C did not affect their ability to stimulate γδ T-cell proliferation or reactivity with mAb M5 indicating the ability of monocytes to stimulate does not involve peripheral membrane components or a glycosyl-phosphatidylinsositol (GPI)-anchored components. Hence it was concluded that the stimulation occurred as a result of intergral membrane proteins including that recognized by mAb M5. The ligand for mAb M5 was on all bovine monocytes and to a lower level on granulocytes but not on lymphocytes. MAb M5 also reacted with sheep monocytes but not with human monocytes or murine macrophages, in agreement with a previous reports that sheep monocytes but not human or mouse mononuclear phagocytes have the capacity to stimulate bovine γδ T cells in in vitro cultures. The level of expression of the M5 ligand was not altered by γ-irradiation or culture of monocytes with lipopolysaccharide but it was decreased following culture with interferon-γ-containing cell culture supernatants. PMID:11872093

  11. Autologous chondrocytes. Autologous chondrocyte implantation: more data needed.

    PubMed

    2011-05-01

    There is no standard surgical treatment for young adults with persistent, incapacitating symptoms of knee cartilage damage. ChondroCelect is the first cell therapy product to be authorised in the European Union. It contains a dense suspension of chondrocytes cultured from a biopsy of the patient's knee cartilage for 4 weeks before being reimplanted. Clinical evaluation of Chondro-Celect only includes one trial, versus subchondral microfracture, in 118 patients. After 3 years of follow-up, there was no difference in the symptom score between the groups. Histological outcome was better after autologous chondrocyte implantation, but methodological problems make it difficult to interpret the observed difference. Long-term functional outcomes remain to be determined. More joint complications occurred after autologous chondrocyte implantation than after subchondral bone microfracture: more frequently symptomatic cartilage hypertrophy (27% versus 13%, possibly related to the implantation technique), joint swelling (22% versus 6.6%), joint effusion (24% versus 9.8%), and joint crepitations (18% versus 6.6%). Autologous chondrocyte implantation was sometimes associated with flu-like syndrome (in 7.8% of patients), which did not occur with the microfracture technique. Autologous chondrocyte implantation is more complex than microfracture. During routine use, there is a risk that one patient will inadvertently receive chondrocytes collected from another patient, leading to a risk of rejection. In practice, this autologous chondrocyte product should only be used by highly specialised teams, and its assessment must continue. PMID:21648176

  12. 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

  13. B lymphocyte function in patients with rheumatoid arthritis: impact of regulatory T lymphocytes and macrophages--modulation by antirheumatic drugs.

    PubMed

    Petersen, J

    1988-04-01

    The present work analyses B lymphocyte functions in vitro in patients with rheumatoid arthritis (RA). The impact of gold salts and penicillamine on human B lymphocyte function in vitro is discussed. Synovial fluid monocytes/macrophages increased both the polyclonally induced and the antigen-induced blood lymphocyte proliferation and increased the numbers of immunoglobulin-secreting blood B lymphocytes generated by pokeweed mitogen (PWM), a T cell-dependent polyclonal activator. The lymphostimulatory factor(s) interleukin-1, which can be produced by monocytes/macrophages, was found in most cell-free synovial fluid specimens, but only in a few paired serum samples. Thus, in vivo activated synovial monocytes/macrophages may modulate lymphocyte functions. Compared to blood, synovial fluid T lymphocytes comprised fewer T4+ (helper/inducer) cells and more T8+ (suppressor/cytotoxic) cells. Synovial fluid lymphocytes proliferated poorly when stimulated polyclonally. However, the proliferative responses to microbial antigens as well as the lectin-induced lymphokine production equaled those of blood lymphocytes. In about half of RA patients, T4+ cells from synovial fluid increased the PWM-induced immunoglobulin secretion by autologous blood B lymphocytes to higher levels as compared to similar experiments with blood T4+ cells. Synovial fluid T8+ cells suppressed PWM-induced immunoglobulin production of autologous mononuclear cells to the same degree as seen with blood T8+ cells. A large proportion of synovial fluid T subsets expressed Ia antigens, probably due to in vivo activation. Thus, synovial T helper/inducer and T suppressor/cytotoxic cells may modulate the functional activities of synovial B lymphocytes. Among mononuclear cells isolated from synovial fluid and synovial tissue, considerable numbers of B lymphocytes spontaneously secreting IgG were found; fewer B cells secreted IgM and IgA. Rheumatoid factor activity was noted in about 7% of the IgG-producing cells

  14. Rebooting autoimmunity with autologous HSCT.

    PubMed

    Snowden, John A

    2016-01-01

    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. PMID:26744435

  15. Modulation of human lymphocyte mitogen responsiveness and interleukin-2 production by polymorphonuclear leukocytes.

    PubMed

    Lyte, M

    1990-06-01

    The response of human peripheral blood lymphocytes to the mitogenic lectins phytohemagglutinin (PHA) and pokeweed mitogen (PWM) was examined in the presence of autologous polymorphonuclear leukocytes (PMN). Experiments were performed at sub-optimal and optimal mitogen concentrations employing lymphocyte: PMN ratios over a three log cell concentration range. Increases of up to 25,000-fold in mitogen stimulated lymphocyte proliferation as determined by 3H-thymidine incorporation were observed in PMN supplemented lymphocyte cultures as compared to lymphocytes cultured in the absence of PMN or with irradiated lymphocytes serving as filler cells. Similar results were obtained for PHA stimulated IL-2 production. The degree of enhancement of lymphocyte reactivity by PMN was also shown to be dependent on the source of serum supplementation (autologous versus xenogeneic). These results indicate that cell ratio is a critical factor in examining lymphocyte-PMN interactions as well as serum supplementation used. Early reports which have indicated a suppressive or no effect of PMN on lymphocyte reactivity based on a single lymphocyte: PMN cell ratio may need to be re-evaluated. PMID:1967045

  16. Tolerance and efficacy of autologous or donor-derived T cells expressing CD19 chimeric antigen receptors in adult B-ALL with extramedullary leukemia

    PubMed Central

    Dai, Hanren; Zhang, Wenying; Li, Xiaolei; Han, Qingwang; Guo, Yelei; Zhang, Yajing; Wang, Yao; Wang, Chunmeng; Shi, Fengxia; Zhang, Yan; Chen, Meixia; Feng, Kaichao; Wang, Quanshun; Zhu, Hongli; Fu, Xiaobing; Li, Suxia; Han, Weidong

    2015-01-01

    The engineering of T lymphocytes to express chimeric antigen receptors (CARs) aims to establish T cell-mediated tumor immunity rapidly. In this study, we conducted a pilot clinical trial of autologous or donor- derived T cells genetically modified to express a CAR targeting the B-cell antigen CD19 harboring 4-1BB and the CD3ζ moiety. All enrolled patients had relapsed or chemotherapy-refractory B-cell lineage acute lymphocytic leukemia (B-ALL). Of the nine patients, six had definite extramedullary involvement, and the rate of overall survival at 18 weeks was 56%. One of the two patients who received conditioning chemotherapy achieved a three-month durable complete response with partial regression of extramedullary lesions. Four of seven patients who did not receive conditioning chemotherapy achieved dramatic regression or a mixed response in the haematopoietic system and extramedullary tissues for two to nine months. Grade 2–3 graft-versus-host disease (GVHD) was observed in two patients who received substantial donor-derived anti-CD19 CART (chimeric antigen receptor-modified T) cells 3–4 weeks after cell infusions. These results show for the first time that donor-derived anti-CD19 CART cells can cause GVHD and regression of extramedullary B-ALL. This study is registered at www.clinicaltrials.gov as NCT01864889. PMID:26451310

  17. Growth of tumor-infiltrating lymphocytes from human solid cancers: summary of a 5-year experience.

    PubMed

    Yannelli, J R; Hyatt, C; McConnell, S; Hines, K; Jacknin, L; Parker, L; Sanders, M; Rosenberg, S A

    1996-02-01

    Between 1989 and 1993, 255 tumor biopsies representing 4 tumor histologies (melanoma, breast cancer, colon cancer and renal cell cancer) were received by the Surgery Branch of the National Cancer Institute. Tumor-infiltrating lymphocytes (TIL) were grown from single-cell suspensions of tumor biopsies over the course of 30-45 days. The TIL were grown in medium containing IL-2. To obtain numbers suitable for therapy (>10(11)), TIL were expanded using a large-scale system of cell culture and harvesting. While the largest number of biopsies was obtained from melanoma patients, TIL were successfully grown from 160 of 255 tumor biopsies representing all 4 histologies. Under the culture conditions employed, several characteristics of TIL expansion were observed. The cell surface phenotype of TIL which grew out from the tumor biopsies was generally a mix of CD3+/CD4+ or CD3+/CD8+ lymphocytes. Only TIL from melanoma biopsies were found to be consistently cytolytic and, in many cases, lysed autologous tumor cells preferentially. Interestingly, TIL derived from extra-nodal sites of metastatic melanoma biopsies (subcutaneous, lung, bowel; 36 of 67, 54%) were more likely to have these cytolytic characteristics than TIL derived from tumor-involved lymph node biopsies (7 of 39, 18%). The present study summarizes 5 years of laboratory effort and validates the technologies developed for the large-scale growth and harvesting of TIL. In addition, it summarizes the laboratory effort supporting previously published clinical reports on TIL from our group. PMID:8621219

  18. [Autologous Fat Grafting in Scar Revision].

    PubMed

    Yu, Pan-xi; Cai, Jing-long

    2016-04-01

    Regenerative medicine is an emerging discipline. Adipose tissue is a rich source of fat cells and mesenchymal stem cells, and autologous fat grafting has increasingly been applied in plastic surgeries and dermatological treatments. This paper reviews the latest advances in autologous fat grafting in scar revision. PMID:27181904

  19. Bronchoalveolar lavage cell--lymphocyte interactions in normal nonsmokers and smokers. Analysis with a novel system.

    PubMed

    deShazo, R D; Banks, D E; Diem, J E; Nordberg, J A; Baser, Y; Bevier, D; Salvaggio, J E

    1983-05-01

    We investigated the ability of smoker and nonsmoker pulmonary alveolar macrophages (AM) to facilitate lymphocyte proliferative responses in a novel system allowing separation of lymphocyte and AM effects. Bronchoalveolar lavage cells (BLC) were obtained from 7 nonsmokers and 5 older smokers and cultured with purified peripheral blood lymphocytes (PL) and the mitogen phytohemagglutinin. Increasing amounts of BLC were added such that BLC/PL ratios were 1:100, 1:10, 1:2, 1:1 of either autologous or homologous PL. Lymphocyte proliferation was dose-related, increasing with 1:100 and 1:10 BLC/PL ratios, and decreasing to or below initial responses with 1:2 or 1:1 ratios. Depletion of T-lymphocytes from BLC demonstrated that these effects were mediated by AM. Phytohemagglutinin (PHA) dose-response curves of nonsmokers obtained using autologous or homologous PL were not different. When BLC from smokers were cultured with autologous PL, lymphocyte proliferative responses were less than those of similar cultures from nonsmokers. However, when similar smoker BLC were cultured with homologous PL from nonsmokers, proliferative responses were not different from those of nonsmokers. Peak proliferative responses of peripheral blood mononuclear cells were not different from maximal proliferative responses of PL-BLC cultures at any PHA dose. These data show that human AM provide dose-related help and suppression of mitogen-induced lymphocyte proliferation similar to that reported with peripheral blood macrophages. Smoker AM facilitated mitogen-driven proliferation of homologous PL in a normal fashion, demonstrating the utility of this culture system in distinguishing lymphocyte effects present in autologous cultures. PMID:6601923

  20. 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

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

    PubMed

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

    2016-01-01

    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

  2. Sepsis after autologous fat grafting.

    PubMed

    Talbot, Simon G; Parrett, Brian M; Yaremchuk, Michael J

    2010-10-01

    Autologous fat grafting is an increasingly popular technique, with numerous examples of excellent results. Adherence to key principles, including sterile technique and low-volume injection throughout layers of tissue, appears to be critical to obtaining good results. Reports of adverse outcomes are infrequent, but several case reports document both infectious and aesthetic complications. This case report represents an extreme complication, including abscess formation, life-threatening sepsis, and residual deformity. It serves as yet another reminder that early adoption of surgical procedures by those without a sound understanding of the underlying principles and techniques can have disastrous consequences. Furthermore, physicians operating on any patient must understand the potential for complications and be able to manage these appropriately when they occur. PMID:20885205

  3. Verification system for postoperative autologous blood retransfusion.

    PubMed

    Yoshikawa, Takeki; Kimura, Eizen; Kobayashi, Shinji; Ishihara, Ken

    2013-01-01

    Medical staff members should match blood products with patients using a barcode authentication system for blood transfusion to prevent medical accidents. However, our hospital only verifies the blood products of the Japanese Red Cross Society and the preserved autologous blood, not the autologous blood salvaged during the operation or from the oxygenator. In this study, we developed the barcode medication administration system and mobile device for verification. This system will prevent blood transfusion errors in the ward setting. PMID:23920751

  4. [Autologous transfusion in obstetrics and fetal safety].

    PubMed

    Rech, F; Patella, A; Cecchi, A; Ippolito, M; Indraccolo, S R

    1994-06-01

    It is common knowledge that for modern medicine transfusion therapy represents a precious resource and an often mandatory option. It is equally known that autohemotransfusion (or autologous transfusion) provides further advantages: certainty of blood availability when necessary, absence of transfusion reactions, elimination of the risk of infections that is still associated with the traditional homologous transfusions. In its most widespread application, autotransfusion provides for the donation of one or more units of autologous blood, mostly before elective surgery. Even in obstetrics the practice of autologous blood donation with the aim of autotransfusion is finding increasing employment. However, there are still controversial aspects and the need is pointed out for more authoritative verifications as refers to the alleged innocuity to the fetus of acute maternal blood loss. The present study was performed to contribute personal experience to a better definition of the possible interactions between autologous blood donation during pregnancy and unborn child welfare. To this end, 80 term pregnant women underwent fetal heart rate electronic monitoring before, during and after the donation of one unit of autologous blood. Both during and after the phlebotomy there were no cardiotocographic signs of fetal hypo-oxygenation. Even the non stress tests performed at a distance of 24 hours and those that were periodically repeated afterwards were normal, confirming the safety of autologous predonation during pregnancy. However, the authors think that in obstetrics it is still premature to consider the experimental phase of autotransfusion as definitively exhausted. PMID:7936387

  5. Different stimulating capacity of B and T lymphocytes in primary and secondary allogeneic reactions: cellular detection of HLA-D products on T lymphocytes.

    PubMed

    Wollman, E E; Cohen, D; Fradelizi, D; Sasportes, M; Dausset, J

    1980-11-01

    The present study was undertaken to define the best way to produce and to test primed lymphocyte typing (PLT) cells using B- and T-enriched lymphocyte suspensions. Intrafamilial PLT cells were produced with primed unseparated and T purified lymphocytes against haplo-identical donors' T and B cells. These PLT cells were then restimulated with a panel of related or unrelated individuals' T and B cells and with allogeneic in vitro activated T cells. The best discrimination was obtained when PLT reagents, regardless of the production method, were restimulated by a B-enriched population of peripheral lymphocytes. Furthermore, the results have shown that enriched primed or unprimed T cell suspensions stimulated by enriched T lymphocytes did not give any proliferation. Experiments performed to explain the results led us to distinguish 2 different phenomena: in primary cultures, the addition of monocytes autologous to the responder cell restored the proliferation of enriched T cells stimulated by T lymphocytes. In secondary cultures, the addition of monocytes autologous to the PLT cell did not restore the proliferation of PLT lymphocytes stimulated by enriched T cells. This was shown to be due to the lack of Dr antigen on the stimulating cell: if allogeneically activated T cells were used as stimulating lymphocytes, a DR-specific proliferative response appeared. This correlates with serologic findings were DR determinants are found on activated T cells and not on unprimed T lymphocytes. However, this difference might be only quantitative, since peripheral lymphocytes could be primed by T cells and be DR specifically restimulated. PMID:6968771

  6. 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.

  7. Recurrent abortions and lymphocyte transfusions.

    PubMed

    Bjercke, S

    1994-05-01

    Normal pregnancies depend on successful implantation of the placenta in the uterus. The trophoblast which forms the ultimate interface between the fetal and maternal tissue seems to lack the foreign (allo) antigens (namely HLA/TLX) required to induce immunological rejection reactions in the mother. It was previously believed that the trophoblast expressed paternal allo antigens and that successful pregnancies were dependent on so called 'kind' (non-cytotoxic or non-complement binding) blocking antibodies in order to protect the fetal unit from maternal cytotoxic T-cells and -antibodies. Blocking antibodies attached to paternal antigens on the trophoblast were assumed to prevent maternal cytotoxic T cell and cytotoxic antibodies from recognising the trophoblast as foreign tissue. On this assumption it was reasoned that transfusions of paternal HLA-expressing lymphocytes would increase maternal antipaternal HLA (TLX) blocking antibodies and thus be beneficial to women who experienced multiple miscarriages. There is, however, no scientific evidence for a specific immune response after lymphocyte transfusions that fulfil this function. Immunological tests, as for example mixed lymphocyte culture (MLC), on peripheral blood lymphocytes do not seem to reflect the local immune state in the uterus, either in the pregnant or the non-pregnant state. Since the trophoblast forms the ultimate interface between fetal and maternal tissue, its structure, secretions, and interaction with the decidua must be of definite importance for implantation of the blastocyst and growth of the embryo. PMID:8009967

  8. Chronic lymphocytic leukemia (CLL)

    MedlinePlus

    CLL; Leukemia - chronic lymphocytic (CLL) ... Byrd JC, Flynn JM. Chronic lymphocytic leukemia. In: Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE, eds. Abeloff's Clinical Oncology. 5th ed. Philadelphia, PA: Elsevier ...

  9. Acute Lymphocytic Leukemia

    MedlinePlus

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  10. [Current Cancer Immunotherapy Using Activated Lymphocytes - Do Lymphocytes Actually Recognize Cancer Cells ?].

    PubMed

    Yamaguchi, Yoshiyuki; Katata, Yousuke; Okawaki, Makoto; Yamamura, Masahiro; Sawaki, Akira

    2015-09-01

    Molecular cloning of interleukin-2(IL-2)has enabled adoptive cell therapy(ACT)to be established by using autologous activated lymphocytes. The low of regenerative medicine will promote the active development of ACT for public use, and ACTs that utilize tumor-infiltrating lymphocytes(TIL), in vitro tumor-sensitized lymphocytes, natural killer T cells, and gammadelta T cells are being evaluated as advanced medical treatments in Japan. In addition, chimeric antigen receptor genemodified T(CAR-T)cells and T cell receptor gene-modified T(TCR-T)cells are available for investigational clinical use. CART and TCR-T cells have been associated with serious adverse events as well as drastic clinical efficacies, indicating the importance of choosing the antigens to be targeted. Presently, it is accurate to state that lymphocytes do recognize cancer cells. Clinical ACT research focusing on TIL and mutated cancer antigens will be initiated for the development of personalized immunotherapy for cancer in the future. PMID:26469157

  11. 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.

  12. Postoperative Autologous Reinfusion in Total Knee Replacement

    PubMed Central

    Crescibene, A.; Martire, F.; Gigliotti, P.; Rende, A.; Candela, M.

    2015-01-01

    Surgeries for total knee replacement (TKR) are increasing and in this context there is a need to develop new protocols for management and use of blood transfusion therapy. Autologous blood reduces the need for allogeneic blood transfusion and the aim of the present study was to verify the safety and the clinical efficacy. An observational retrospective study has been conducted on 124 patients, undergoing cemented total knee prosthesis replacement. Observed population was stratified into two groups: the first group received reinfusion of autologous blood collected in the postoperative surgery and the second group did not receive autologous blood reinfusion. Analysis of data shows that patients undergoing autologous blood reinfusion received less homologous blood bags (10.6% versus 30%; p = 0.08) and reduced days of hospitalization (7.88 ± 0.7 days versus 8.96 ± 2.47 days for the control group; p = 0.03). Microbiological tests were negative in all postoperatively salvaged and reinfused units. Our results emphasize the effectiveness of this procedure and have the characteristics of simplicity, low cost (€97.53 versus €103.79; p < 0.01), and easy reproducibility. Use of autologous drainage system postoperatively is a procedure that allows reducing transfusion of homologous blood bags in patients undergoing TKR. PMID:26442168

  13. 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.

  14. 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

  15. 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

  16. 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. PMID:18075192

  17. 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.

  18. [Studies of immunological status, following autologous bone marrow transplantation in man (author's transl)].

    PubMed

    Gorin, N C; Muller, J Y; Salmon, C; Fine, J M; Rouger, P; Fortier, B; Petit, J C; Girard, O; Leblanc, G; David, R; Stachowiak, J; Parlier, Y; Najman, A; Duhamel, G

    1980-05-10

    Following transplant, circulating immunoglobulin levels fell moderately and remained depressed less than 2 months for IgG, and for variable and longer periods of time for IgM and IgA. Repeated quantitative determinations of antibodies against multiple antigens did not show any decrease in the pretransplant levels. Indeed some patients developed herpes and cytomegalovirus infections to which they responded by a sharp increase in antibody titers. In 2 cases, a primary immunization was demonstrated (against CMV and BK virus) with increasing levels of IgM and IgG antibodies. Lymphocyte counts in peripheral blood returned to 500 mm# between day 10 and 29 (median day 18) and to pretransplant values within 6 weeks. Non specific stimulation of lymphocytes by mitogens in the immediate post-transplant period showed a decreased response to PHA and Con A, whereas the responses to pokeweek mitogens and alloantigens were only slightly diminished. The degree of the responses was related to the dose of cryopreserved marrow infused. We conclude that:--although the minimum dose for autologous bone marrow transplantation in man is around 0,5 10(8) nucleated bone marrow cells/Kg, much higher doses should be used to ensure faster and better restoration of immune reactivity.--The similarity of the immunological dysfunction following autologous and allogeneous bone marrow transplantation suggest that, in the immediate post-transplant period, the role of GVHD in cellular immunity depression may be minimal. PMID:7008023

  19. Sweet Syndrome After Autologous Stem Cell Transplant.

    PubMed

    Alkan, Ali; İdemen, Celal; Okçu Heper, Aylin; Utkan, Güngör

    2016-02-01

    Sweet syndrome (acute febrile neutrophilic dermatosis) is a rare clinical entity characterized by skin lesions, neutrophilia, fever, and neutrophilic infiltration of the dermis. It may be a consequence of malignant disease, comorbidities, or drugs. We present a case of acute febrile neutrophilic dermatosis in a patient after autologous stem cell transplant. PMID:25748978

  20. 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

  1. 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. PMID:26779485

  2. 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

  3. 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

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

    ClinicalTrials.gov

    2016-06-10

    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

  5. 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

  6. 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.

  7. Autologous Fat Grafting Improves Facial Nerve Function

    PubMed Central

    Klinger, Marco; Lisa, Andrea; Caviggioli, Fabio; Maione, Luca; Murolo, Matteo; Vinci, Valeriano; Klinger, Francesco Maria

    2015-01-01

    We describe the case of a 45-year-old male patient who presented a retractile and painful scar in the nasolabial fold due to trauma which determined partial motor impairment of the mouth movements. We subsequently treated him with autologous fat grafting according to Coleman's technique. Clinical assessments were performed at 5 and 14 days and 1, 3, and 6 months after surgical procedure and we observed a progressive release of scar retraction together with an important improvement of pain symptoms. A second procedure was performed 6 months after the previous one. We observed total restoration of mimic movements within one-year follow-up. The case described confirms autologous fat grafting regenerative effect on scar tissue enlightening a possible therapeutic effect on peripheral nerve activity, hypothesizing that its entrapment into scar tissue can determine a partial loss of function. PMID:26167327

  8. Achieving ideal breast aesthetics with autologous reconstruction

    PubMed Central

    2015-01-01

    Achieving ideal breast aesthetic has become a top priority for women considering breast reconstruction following mastectomy. The use of autologous tissue is generally regarded as providing the most natural results because donor tissues quality and consistency is similar to that of the native breast. There are several donor sites that are particularly useful for autologous reconstruction that include the abdomen, gluteal region, posterior thorax, and the thigh. Traditional and microsurgical techniques can be used. Shaping is a critical component and involves a basic understanding of the footprint, conus, and skin envelope. This manuscript will review many aspects of breast shaping in-order to achieve aesthetically pleasing results in a predictable manner. PMID:26005645

  9. [Nutritional pathway for autologous stem cell transplantation].

    PubMed

    Aoyama, Takashi; Imataki, Osamu; Inoue, Naomi; Katsumata, Mina; Katsuta, Tomoko; Kataoka, Tomomi; Yoshida, Takashi; Mochizuki, Takahiro; Motokawa, Satoshi; Tamai, Yotaro; Hagiwara, Shotaro; Kawakami, Kimihiro

    2007-08-01

    We developed a nutritional pathway for autologous stem cell transplantation (SCT) to be applied in our transplantation unit. We performed autologous SCT for 37 patients with malignant lymphoma and multiple myeloma during from April 2003 to July 2005. For 10 of them who underwent SCT since 2005,we intervened with nutritional support using our original nutritional pathway,to monitor the clinical course of SCT from the aspect of dietetics with a dietician making assessments of the individual nutrition status. From comparing the 2 groups with (n=27) or without (n=10) the nutritional pathway, oral intake at day 14 was significantly increased from 1,038 kcal to 1,440 kcal,and at discharge developed from 1,167 kcal to 1,446 kcal without statistical significance. Patients whose body weight decreased more than 5% were reduced from 52%(14/27) to 10%(1/10),and 3 days reduction of the CVC insertion period was observed after the intervention. Although the long-term clinical outcome was not fully evaluated, the efficacy of nutritional pathway for autologous SCT was suggested. PMID:17687206

  10. Canine PHA-stimulated adherent cell enhance interferon-gamma production and proliferation of autologous peripheral blood mononuclear cells.

    PubMed

    Ide, Kaori; Momoi, Yasuyuki; Iwasaki, Toshiroh

    2005-03-01

    Dendritic cells are specialized antigen-presenting cells with immuno-modulating functions that are attractive for clinical applications for cancer immunotherapy. This study examined immunostimulatory functions of phytohemagglutinin (PHA)-stimulated adherent cells (PHA-Ad cells) from peripheral blood mononuclear cells (PBMCs) in dogs. PHA-Ad cells enhanced interferon-gamma from autologous PBMC in vitro. PHA-Ad cells also stimulated antigen-independent proliferation of peripheral blood lymphocytes. These results suggest that PHA-Ad cells from PBMC possess a stimulatory function to evoke anti-tumour immunity and that they demonstrate potential for therapeutic applications in dogs. PMID:19379211

  11. 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. PMID:24131074

  12. 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.

  13. Human thymocytes bind to autologous and allogeneic thymic epithelial cells in vitro.

    PubMed Central

    Singer, K H; Wolf, L S; Lobach, D F; Denning, S M; Tuck, D T; Robertson, A L; Haynes, B F

    1986-01-01

    The thymus plays a critical role in the generation of immunocompetent T lymphocytes. In the thymus, lymphocytes are in close contact with epithelial cells, and this contact is necessary for T-cell maturation. Using cultured human thymic epithelial (TE) cells, we have found that human thymocytes bind to human TE cells in vitro. Thymocytes bound to both allogeneic and autologous TE cells and to the epidermoid carcinoma cell line A431 but did not bind to epidermal keratinocytes or to thymic fibroblasts. Thymocyte binding to TE cells was trypsin- and cytochalasin B-sensitive. Indirect immunofluorescence assays showed that both mature (T6-, T3+) and immature (T6+, T3-) thymocytes bound TE cells. In our system, TE-thymocyte binding was not inhibited by antibodies to class I or class II major histocompatibility antigens. In vitro binding of thymocytes to TE cells may represent a correlate of in vivo TE-thymocyte interactions and provides a model system for the study of human intrathymic T-lymphocyte maturation and activation. Images PMID:3092215

  14. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    PubMed Central

    Potdar, PD; Subedi, RP

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia. PMID:24693170

  15. Challenge assay in vitro using lymphocyte blastogenesis for the contact hypersensitivity assay.

    PubMed

    Kashima, R; Okada, J; Ikeda, Y; Yoshizuka, N

    1993-10-01

    To confirm positivity in routine guinea pig studies, contact allergenicity was investigated by a challenge assay in vitro using a co-culture of autologous lymphocytes passed through a nylon-wool column and antigen-presenting cells (APCs) modified with or without antigen. Proliferation of the lymphocytes primed with ovalbumin and/or 2,4-dinitrochlorobenzene was antigen specific and dependent on the presence of APCs (peripheral blood monocytes, splenic macrophages and macrophages induced by liquid paraffin). For another nine haptens, primed lymphocytes proliferated significantly more than control lymphocytes; the stimulation index (SI; ratio between [3H]methylthymidine ([3H]TdR) incorporation of lymphocytes with antigen-modified APCs and [3H]TdR incorporation of lymphocytes with APCs not modified by antigen) was 1.6-4.8 in sensitized animals whereas it was about 1.0 in control animals. Sodium dodecyl sulfate did not cause lymphocyte proliferation. The SI value in vitro was correlated with both the positive rate in vivo (r = 0.736) and the mean response score in vivo (r = 0.645). Thus, it was possible to confirm that positivity in routine experiments was a true sign of allergy. A combination of this assay and short-term animal studies would provide an efficient assessment of the allergic potential of chemicals. PMID:8225135

  16. 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.

  17. 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.

  18. Increased lung epithelial permeability in HIV-infected patients with isolated cytotoxic T-lymphocytic alveolitis

    SciTech Connect

    Meignan, M.; Guillon, J.M.; Denis, M.; Joly, P.; Rosso, J.; Carette, M.F.; Baud, L.; Parquin, F.; Plata, F.; Debre, P. )

    1990-05-01

    HIV-related lymphocytic alveolitis is common in HIV-seropositive patients without lung infection or tumor. In some of them a fraction of alveolar lymphocytes are HIV-specific cytotoxic T-lymphocytes (CTL) bearing the CD8 and D44 cell surface markers and capable of killing HIV-infected alveolar macrophages. In order to evaluate the in vivo effect of these CTL on lung function, we measured the pulmonary clearance of aerosolized 99mTc-diethylene triamine penta-acetate (DTPA-CI) on 24 occasions in 22 patients with lymphocytic alveolitis. DTPA-CI has been selected as a highly sensitive test to detect injury of the lung epithelium. In 13 of the patients, we found a high DTPA-CI of 4.56 +/- 2.54%.min-1 (mean +/- SD), suggesting an increase of the epithelial permeability. The lymphocytic alveolitis was then characterized by a high cellularity, a high proportion of lymphocytes (59 +/- 18%), mainly composed of CD8+D44+ T-lymphocytes (149 +/- 109 cells/mm3), which spontaneously exhibited a cytolytic activity against the autologous alveolar macrophages in a standard 51Cr release assay. In the remaining 11 patients, DTPA-CI was normal (less than 1.78%.min-1), lymphocytic alveolitis being characterized by a low number or an absence of CD8+D44+ alveolar lymphocytes (9 +/- 13 cells/mm3) with no significant cytolytic activity. In the whole group, a significant correlation (r = 0.74, p = 0.0004) was found between the DTPA-CI and the number of CD8+D44+ lymphocytes and their cytotoxic activity against alveolar macrophages. Altogether, these results suggest that an injury of the lung epithelium could result from a HIV-specific CTL-induced immunologic conflict.

  19. Cytotoxic human lymphocytes: from in vitro testing (1970s) to immunotherapy (1990s).

    PubMed

    Sinkovics, J; Horvath, J

    1993-01-01

    The senior author was the recipient of a contract (1-CP3-3292) from the National Cancer Institute, USA (NCI) in the early 1970s. The aim of NCI's targeted research program was the establishment of a tumour-specific human lymphocyte-mediated cytotoxicity assay. Neither lymphocyte growth factors nor monoclonal antibodies for lymphocyte typing were available. Tumour-specific populations of lymphocytes could not be maintained but their presence in ficoll-hypaque preparations of blood buffy coats or in primary cultures of tumours was clearly recognized. Another indiscriminately cytotoxic population of lymphocytes had usually overridden the tumour-specific population. In contradistinction to the ruling doctrine of the era, indiscriminately cytotoxic lymphocytes were readily found in the blood of tumour-bearing patients and healthy individuals (the senior author's lymphocytes were shown to practice indiscriminate cytotoxicity in 1971, an observation first interpreted as "immune surveillance at work" in an individual daily exposed to patients with metastatic cancers). Instead of converting the subject matter of the contract from a tumour-specific to a non-specific cytotoxicity assay, the NCI prematurely "phased it out" (but continued the project as intramural research). Nevertheless, many functions of cytotoxic lymphocytes that had become by now well established were foreshadowed during the early 1970s with the limited support of that NCI contract and funds from other sources. Here we recount those early observations; present the outlines of adoptive immunotherapy with various autologous lymphocyte populations and in a separate report in this volume give a technical description how these lymphocyte populations are prepared in the laboratory for therapeutic reinfusions into the patient. PMID:8191863

  20. Autologous stem cell transplantation for adult acute leukemia in 2015: time to rethink? Present status and future prospects.

    PubMed

    Gorin, N-C; Giebel, S; Labopin, M; Savani, B N; Mohty, M; Nagler, A

    2015-12-01

    The use of autologous stem cell transplantation (ASCT) as consolidation therapy for adult patients with acute leukemia has declined over time. However, multiple randomized studies in the past have reported lower relapse rates after autologous transplantation compared with chemotherapy and lower non-relapse mortality rates compared with allogeneic transplantation. In addition, quality of life of long-term survivors is better after autologous transplantation than after allogeneic transplantation. Further, recent developments may improve outcomes of autograft recipients. These include the use of IV busulfan and the busulfan+melphalan combination, better detection of minimal residual disease (MRD) with molecular biology techniques, the introduction of targeted therapies and post-transplant maintenance therapy. Therefore, ASCT may nowadays be reconsidered for consolidation in the following patients if and when they reach a MRD-negative status: good- and at least intermediate-1 risk acute myelocytic leukemia in first CR, acute promyelocytic leukemia in second CR, Ph-positive acute lymphocytic leukemia. Conversely, patients with MRD-positive status or high-risk leukemia should not be considered for consolidation with ASCT. PMID:26281031

  1. Autologous Graft-versus-Tumor Effect: Reality or Fiction?

    PubMed Central

    2016-01-01

    In contrast to allogeneic hematopoietic stem cell transplantation, the current dogma is not an evidence of graft-versus-tumor effect in autologous hematopoietic stem cell transplantation; thus, it is assumed that autologous hematopoietic stem cell transplantation only relies on the high-dose chemotherapy to improve clinical outcomes. However, recent studies argue in favor of the existence of an autologous graft-versus-tumor without the detrimental complications of graft-versus-host disease due to the nonspecific immune response from the infused donor alloreactive immune effector cells in allogeneic hematopoietic stem cell transplantation. Herein, this paper reviews the clinical evidence of an autologous graft-versus-tumor effect based on the autograft collected and infused host immune effector cells and host immunity recovery after autologous hematopoietic stem cell transplantation affecting clinical outcomes in cancer patients.

  2. Chronic lymphocytic leukaemia.

    PubMed

    Scarfò, Lydia; Ferreri, Andrés J M; Ghia, Paolo

    2016-08-01

    Chronic lymphocytic leukaemia (CLL) is the most common leukaemia among the adults in the Western World. CLL (and the corresponding nodal entity small lymphocytic lymphoma, SLL) is classified as a lymphoproliferative disorder characterised by the relentless accumulation of mature B-lymphocytes showing a peculiar immunophenotype in the peripheral blood, bone marrow, lymph nodes and spleen. CLL clinical course is very heterogeneous: the majority of patients follow an indolent clinical course with no or delayed treatment need and with a prolonged survival, while others experience aggressive disease requiring early treatment followed by frequent relapses. In the last decade, the improved understanding of CLL pathogenesis shed light on premalignant conditions (i.e., monoclonal B-cell lymphocytosis, MBL), defined new prognostic and predictive markers, improving patient stratification, but also broadened the therapeutic armamentarium with novel agents, targeting fundamental signaling pathways. PMID:27370174

  3. 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

  4. Breast Augmentation With Autologous Fat Injection

    PubMed Central

    Li, Fa-Cheng; Chen, Bing; Cheng, Lin

    2014-01-01

    Introduction Autologous fat transplantation has attracted great interest in breast augmentation for cosmetic purpose. In the present study, we reported our experience in fat grafting in breast in 105 cases, and some detailed procedure concerning efficacy and safety of grafting was evaluated. Methods Fat was harvested using 20-mL syringe attached to a 3-hole blunt cannula in a diameter not beyond 3 mm. After washing with cool normal saline to remove blood, the fat was managed with open method using cotton towel as a platform for concentration fat tissue and separating them from fluids, oil, and debris. A 14-gauge, 1-hole blunt cannula was used to place the fat through 3-mm incision on inframammary fold. The fat was infiltrated into the breast from deep to superficial subcutaneous plane. Results Between July 2002 and August 2010, 105 patients have undergone this procedure. The age distribution of the patients ranged from 18 to 45 years, with a mean of 31.3 years. Grafted fat volume has ranged from 120 to 250 mL (average, 205 mL) per breast per session. All women had a significant improvement in their breast size and shape postoperatively, and the breasts were soft and natural in appearance. Conclusions Liposuction and autologous fat transplantation is a suitable approach for augmentation mammaplasty. PMID:25003461

  5. Autologous stem cells for personalised medicine.

    PubMed

    Prasongchean, Weerapong; Ferretti, Patrizia

    2012-09-15

    Increasing understanding of stem cell biology, the ability to reprogramme differentiated cells to a pluripotent state and evidence of multipotency in certain adult somatic stem cells has opened the door to exciting therapeutic advances as well as a great deal of regulatory and ethical issues. Benefits will come from the possibility of modelling human diseases and develop individualised therapies, and from their use in transplantation and bioengineering. The use of autologous stem cells is highly desirable, as it avoids the problem of tissue rejection, and also reduces ethical and regulatory issues. Identification of the most appropriate cell sources for different potential applications, development of appropriate clinical grade methodologies and large scale well controlled clinical trials will be essential to assess safety and value of cell based therapies, which have been generating much hope, but are by and large not yet close to becoming standard clinical practice. We briefly discuss stem cells in the context of tissue repair and regenerative medicine, with a focus on individualised clinical approaches, and give examples of sources of autologous cells with potential for clinical intervention. PMID:22561284

  6. The lymph node in chronic lymphocytic leukemia.

    PubMed

    Dick, F R; Maca, R D

    1978-01-01

    Lymph nodes were examined from 41 cases of typical chronic lymphocytic leukemia (CLL). Degree of immaturity was graded as absent to minimal (Grade I), moderate (Grade II) and marked (Grade III). A moderate degree of immaturity was found in the lymph node in 14 of 41 cases even though the cells seen on the initial bone marrow and peripheral blood smears obtained from these patients were essentially all mature. The morphology of these nodes could be confused with poorly differentiated lymphocytic or mixed lymphocytic-histiocytic lymphoma in terms of the degree of immaturity present. A marked degree of immaturity present. A marked degree of immaturity was found in 5 cases; the morphology of these cases resembled histiocytic lymphoma. In the remaining 22 cases immaturity was essentially absent. The morphology of these cases was similar to that of diffuse well differentiated lymphocytic lymphoma. Our studies suggest that a moderate degree of immaturity in the lymph node of patients with CLL does not indicate that these patients will have a marked shortening of their survival. PMID:580071

  7. 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. PMID:6972906

  8. 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

  9. 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.

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

    PubMed

    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

  11. 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

  12. 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

  13. 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

  14. 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. PMID:26944928

  15. 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

  16. 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

  17. An analysis of a preoperative pediatric autologous blood donation program

    PubMed Central

    Letts, Merv; Perng, Richard; Luke, Brian; Jarvis, James; Lawton, Louis; Hoey, Steve

    2000-01-01

    Objective To determine the efficacy of a pediatric autologous blood donation program. Design A retrospective study of patient charts and blood-bank records. Setting The Children’s Hospital of Eastern Ontario, Ottawa, a tertiary care, pediatric centre. Patients One hundred and seventy-three children who received blood transfusions for a total of 182 procedures between June 1987 and June 1997. Interventions Autologous and homologous blood transfusion required for major surgical intervention, primarily spinal fusion. Main outcome measures Surgeons’ accuracy in predicting the number of autologous blood units required for a given procedure, compliance rate (children’s ability to donate the requested volume of blood), utilization rate of autologous units and rate of allogeneic transfusion. Results The surgeons’ accuracy in predicting the number of autologous units required for a given procedure was 53.8%. The compliance rate of children to donate the requested amount of blood was 80.3%. In children below the standard age and weight criteria for blood donation the compliance rate was 75.5%. The utilization rate of autologous units obtained was 84.4% and the incidence of allogeneic transfusion was 26.6%. Conclusions There was a high rate of compliance and utilization of predonated autologous blood in the children in the study. Preoperative blood donation programs are safe and effective in children, even in those below the standard age and weight criteria of 10 years and 40 kg. PMID:10812347

  18. Role of autologous bladder-neck slings: a urogynecology perspective.

    PubMed

    Zoorob, Dani; Karram, Mickey

    2012-08-01

    The concept of the autologous pubovaginal sling involves supporting the proximal urethra and bladder neck with a piece of graft material, achieving continence either by providing a direct compressive force on the urethra/bladder outlet or by reestablishing a reinforcing platform or hammock against which the urethra is compressed during transmission of increased abdominal pressure. Pubovaginal slings using a biological sling material (whether autologous, allograft, or xenograft) can be used successfully to manage primary or recurrent stress incontinence. This article addresses the indications for the use of an autologous bladder-neck sling, describes the surgical techniques, and discusses outcomes and technical considerations. PMID:22877713

  19. Indium-111 autologous leukocyte imaging in pancreatitis

    SciTech Connect

    Anderson, J.R.; Spence, R.A.; Laird, J.D.; Ferguson, W.R.; Kennedy, T.L.

    1986-03-01

    Thirty-nine patients with acute pancreatitis have been assessed using a prognostic factor grading system, abdominal ultrasound, and autologous leukocyte imaging. Both prognostic factor grading and leukocyte imaging can accurately assess the severity of the disease early in its course. All patients with a negative indium-labeled leukocyte image recovered without sequelae, whereas five of the 12 patients with a positive image developed complications, including two deaths. Abdominal ultrasound is of no value in assessing severity, but is a useful method of detecting those patients with gallstone-associated disease. In patients with suspected abscess formation following acute pancreatitis, indium leukocyte imaging does not differentiate between fat necrosis and abscess formation. In this situation, computerized tomography should be carried out before laparotomy is undertaken.

  20. Characterization of Ex Vivo Expanded Tumor Infiltrating Lymphocytes from Patients with Malignant Melanoma for Clinical Application

    PubMed Central

    Junker, Niels; thor Straten, Per; Andersen, Mads Hald; Svane, Inge Marie

    2011-01-01

    Clinical trials of adoptive transfer of autologous tumor infiltrating lymphocytes (TILs) to patients with advanced malignant melanoma have shown remarkable results with objective clinical responses in 50% of the treated patients. In order to initiate a clinical trial in melanoma, we have established a method for expanding TILs to clinical relevant quantities in two steps with in 8 weeks. Further characterization of expanded TILs revealed an oligoclonal composition of T-cells with an effector memory like phenotype. When autologous tumor was available, TILs showed specific activity in all patients tested. TIL cultures contained specificity towards tumor cells as well as peptides derived from tumor-associated antigens (TAAs) during expansion procedures. PMID:21773037

  1. Pre-radiation lymphocyte harvesting and post-radiation reinfusion in patients with newly diagnosed high grade gliomas

    PubMed Central

    Ye, Xiaobu; Gladstone, Douglas E.; Ambady, Prakash; Nirschl, Thomas R.; Borrello, Ivan; Golightly, Marc; King, Karen E.; Holdhoff, Matthias; Karp, Judith; Drake, Charles G.; Grossman, Stuart A.

    2015-01-01

    Radiation (RT), temozolomide (TMZ), and dexamethasone in newly diagnosed high grade gliomas (HGG) produces severe treatment-related lymphopenia (TRL) that is associated with early cancer-related deaths. This TRL may result from inadvertent radiation to circulating lymphocytes. This study reinfused lymphocytes, harvested before chemo-radiation, and assessed safety, feasibility, and trends in lymphocyte counts. Patients with newly diagnosed HGG and total lymphocyte counts (TLC) ≥ 1000 cells/mm3 underwent apheresis. Cryopreserved autologous lymphocytes were reinfused once radiation was completed. Safety, feasibility, and trends in TLC, T cell subsets and cytokines were studied. Serial TLC were also compared with an unreinfused matched control group. Ten patients were harvested (median values: age 56 years, dexamethasone 3 mg/day, TLC/CD4 1980/772 cells/mm3). After 6 weeks of RT/TMZ, TLC fell 69 % (p < 0.0001) with similar reductions in CD4, CD8 and NK cells but not Tregs. Eight patients received lymphocyte reinfusions (median = 7.0 × 107 lymphocytes/kg) without adverse events. A post-reinfusion TLC rise of ≥300 cells/mm3 was noted in 3/8 patients at 4 weeks and 7/8 at 14 weeks which was similar to 23 matched controls. The reduced CD4/CD8 ratio was not restored by lymphocyte reinfusion. Severe lymphopenia was not accompanied by elevated serum interleukin-7 (IL-7) levels. This study confirms that severe TRL is common in HGG and is not associated with high plasma IL-7 levels. Although lymphocyte harvesting/rein-fusion is feasible and safe, serial lymphocyte counts are similar to unreinfused matched controls. Studies administering higher lymphocyte doses and/or IL-7 should be considered to restore severe treatment-related lymphopenia in HGG. PMID:26070554

  2. Autologous and allogeneic serum eye drops. The Dutch perspective.

    PubMed

    van der Meer, Pieter F; Seghatchian, Jerard; de Korte, Dirk

    2015-08-01

    If regular artificial tears are ineffective for treatment of ocular surface disorders (including extreme dry eye syndrome), serum eye drops (SEDs) may provide a way to relieve the symptoms. However, not all patients are eligible to donate blood to produce autologous SEDs. Therefore, the use of allogeneic SEDs (obtained from voluntary blood donors) should be explored as an alternative for autologous SEDs. The Dutch blood bank organization is currently looking into the possibilities to provide allogeneic SEDs, as (GMP) regulations become stricter, making it for hospitals more difficult to provide autologous SEDs. To demonstrate effectiveness of both autologous and allogeneic SEDs, a clinical trial is planned. The current status of SEDs in The Netherlands is described. This paper is based on summary of the presentation given at the DGTI meeting in Dresden. PMID:26138910

  3. 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

  4. Human gamma interferon production by cytotoxic T lymphocytes sensitized during hepatitis A virus infection

    SciTech Connect

    Maier, K.; Gabriel, P.; Koscielniak, E.; Stierhof, Y.D.; Wiedmann, K.H.; Flehmig, B.; Vallbracht, A.

    1988-10-01

    The production of interferon (IFN) during a chromium-51 release assay with hepatitis A virus (HAV)-infected fibroblasts and autologous peripheral blood lymphocytes from patients with acute HAV infection was studied to determine whether IFN plays a role in immunopathogenesis of hepatitis A infection in humans. Skin fibroblasts of eight patients after acute HAV infection and from two control persons without history of current of past HAV infection were infected with HAV. Peripheral blood lymphocytes were collected at different times after the onset of icterus and tested in a chromium-51 release assay against autologous HAV-infected skin fibroblasts for their cytolytic and IFN-producing activity. The IFN produced during the assay was characterized and found to have the properties of human gamma IFN. Cytotoxicity and gamma IFN release were virus specific. The cell types responsible for both functions were characterized and found to be in the HLA-dependent T8/sup +/ lymphocyte subset. Considering that gamma IFN has an antiviral effect on persistent HAV infection in vitro and that it probably accounts for stimulation of HLA class I antigen expression on hepatocytes, these experimental results presented here demonstrate that human gamma IFN produced by HAV-specific T cells may participate in pathogenesis of hepatitis A infection in humans.

  5. Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-16

    B-cell Chronic Lymphocytic 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

  6. Benign monoclonal expansion of CD8+ lymphocytes in HIV infection

    PubMed Central

    Smith, P.; Cavenagh, J.; Milne, T.; Howe, D.; Wilkes, S.; Sinnott, P.; Forster, G.; Helbert, M.

    2000-01-01

    Background—A transient expansion of the CD8+ T cell pool normally occurs in the early phase of HIV infection. Persistent expansion of this pool is observed in two related settings: diffuse infiltrative lymphocytosis syndrome (DILS) and HIV associated CD8+ lymphocytosis syndrome. Aim—To investigate a group of HIV infected patients with CD8+ lymphocytosis syndrome with particular emphasis on whether monoclonality was present. Methods—A group of 18 patients with HIV-1 infection and persistent circulating CD8+ lymphocytosis was compared with 21 HIV positive controls. Serum samples were tested for antinuclear antibodies, antibodies to extractable nuclear antigens, immunoglobulin levels, paraproteins, human T lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus, and cytomegalovirus serology. Lymphocyte phenotyping and HLA-DR typing was performed, and T cell receptor (TCR) gene rearrangement studies used to identify monoclonal populations of T cells. CD4+ and CD8+ subsets of peripheral blood lymphocytes were purified to determine whether CD8+ populations inhibited HIV replication in autologous CD4+ cells. Results—A subgroup of patients with HIV-1 infection was found to have expanded populations of CD8+ T cell large granular lymphocytes persisting for 6 to 30 months. The consensus immunophenotype was CD4- CD8+ DRhigh CD11a+ CD11c+ CD16- CD28± CD56- CD57+, consistent with typical T cell large granular lymphocytes expressing cellular activation markers. Despite the finding of monoclonal TCR gene usage in five of 18 patients, there is evidence that the CD8+ expansions are reactive populations capable of mediating non-cytotoxic inhibition of HIV replication. Conclusions—A subgroup of HIV positive patients has CD8+ lymphocytosis, but despite the frequent occurrence of monoclonal TCR gene usage there is evidence that this represents an immune response to viral infection rather than a malignant disorder. Key Words: HIV infection • CD8+ lymphocytosis • clonality

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

    ClinicalTrials.gov

    2016-02-16

    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

  8. 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

  9. 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

  10. 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

  11. Effects of cycloheximide on B-chronic lymphocytic leukaemic and normal lymphocytes in vitro: induction of apoptosis.

    PubMed Central

    Collins, R. J.; Harmon, B. V.; Souvlis, T.; Pope, J. H.; Kerr, J. F.

    1991-01-01

    A number of reports indicate that protein synthesis is a requirement for the occurrence of apoptosis. In this study, the effect of the protein synthesis inhibitor cycloheximide (CHM) on spontaneous apoptosis of B-chronic lymphocytic leukaemia (B-CLL) cells, previously shown to occur when they are cultured in RPMI-1640 medium with autologous or heterologous serum, was examined. No definite inhibition of apoptosis was observed. Indeed, CHM-treatment augmented apoptosis in the B-CLL cultures and also induced apoptosis of cultured normal peripheral blood lymphocytes. Augmentation was dose-dependent for B-CLL cells over the concentration range 10(-6) M (0.28 micrograms ml-1) to 10(-2) M (2800 micrograms ml-1), resulting in 9% to 98% apoptosis respectively by 24 h of culture (r = 0.619, P = 0.0008). Normal lymphocytes were affected by CHM over the range 10(-4) M to 10(-2) M, resulting in 7% to 74% apoptosis respectively (r = 0.794, P = 0.0001). Inhibition of protein synthesis in these cells by CHM was virtually complete at a concentration of 10(-3) M. The findings are in accord with some recent reports indicating that suppression of protein synthesis by CHM does not inhibit apoptosis in all circumstances. They also illustrate the marked susceptibility of B-CLL cells, compared with normal lymphocytes, to the induction of apoptosis by this drug. The manner in which CHM triggers apoptosis of some cell types is at present uncertain. Images Figure 1 Figure 4 PMID:1911193

  12. Prolactin as a modulator of lymphocyte responsiveness provides a possible mechanism of action for cyclosporine.

    PubMed Central

    Hiestand, P C; Mekler, P; Nordmann, R; Grieder, A; Permmongkol, C

    1986-01-01

    Lymphocyte responsiveness in rats was found to depend on serum prolactin levels. Blocking pituitary prolactin release with bromocriptine severely reduces lymphocyte reactivity in vitro (mixed lymphocyte reaction) as well as in vivo (graft-versus-host reaction). In addition, evidence for a prolactin/growth hormone-related mRNA species produced in mitogen- and antigen-stimulated lymphocytes has been obtained. Prolactin was shown to compete in a dose-dependent fashion with the immunosuppressant cyclosporine (cyclosporin A) for a common binding site on the surface of T lymphocytes. Further, stimulation of prolactin secretion reversed the immunosuppression induced by cyclosporine. We conclude that prolactin is involved in the maintenance of T-cell immunocompetence and that the immunosuppressive effects of cyclosporine may be mediated by the displacement of prolactin from binding sites on lymphocytes. Images PMID:2939454

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

    ClinicalTrials.gov

    2016-05-04

    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

  14. Influence of macrophages on HSV-1 induced IL 2 production by human lymphocytes

    SciTech Connect

    Clouse, K.A.; Orosz, C.G.; Sheridan, J.F.

    1986-03-05

    Previous work has demonstrated that human peripheral blood mononuclear cells (PBMC) from HSV-1 seropositive individuals produce interleukin 2 (IL 2) following stimulation in vitro with uv-inactivated herpes simplex virus type 1 (HSV antigen). This study investigated the accessory macrophage (MO) and monokine requirements for IL 2 production by enriched T lymphocytes from HSV-1 seropositive individuals. Following removal of accessory MO populations, enriched T lymphocytes did not secrete IL 2 in response to HSV antigen. However, IL 2 production was restored by the addition of autologous, ..gamma..-irradiated (5000R) MO. HSV antigen-pulsed MO also induced IL 2 production by enriched T lymphocytes. Furthermore, when HSV-pulsed macrophages were treated with paraformaldehyde they no longer caused T lymphocytes to produce IL 2 unless exogenous monokines were provided. Neither exogenous monokines nor purified human IL 1 could support HSV antigen induced IL 2 production in the absence of MO. These studies demonstrated that MO are required for HSV-induced IL 2 production by T lymphocytes from HSV-1 seropositive individuals. Furthermore, these MO appear to provide two functions required for IL 2 production: viral antigen display and monokine production.

  15. Immunization with stallion lymphocytes for treatment of recurrent spontaneous abortion in thoroughbred mares.

    PubMed

    Mathias, S; Allen, W R

    2000-01-01

    The incidence of recurrent spontaneous abortion within the human population in the Western world is low (2-5%) but significant, and a proportion of these pregnancy losses are thought to have an underlying immunological cause. Immunization of women who have a history of recurrent spontaneous abortion with lymphocytes isolated from their husband or a third party donor is one of several forms of immunotherapy used to treat the problem. Early pregnancy loss in Thoroughbred mares is also significant and, as in women, a small number of mares undergo repeated pregnancy losses. Two trials have been performed in which Thoroughbred mares suffering from recurrent spontaneous abortion before day 150 of gestation were immunized with lymphocytes isolated from the mating stallion or from an unrelated stallion. The first trial, which was conducted without control mares, resulted in a very high live birth rate (97%) for the mares (n=24) treated. Therefore, a second controlled double-blinded trial was established in which randomly selected mares (n=17) were treated with stallion (heterologous) lymphocytes and control mares (n=13) were injected with their own (autologous) lymphocytes. The live birth rates after these treatments were 88 and 77%, respectively. Thus, immunization with stallion lymphocytes had no effect on the incidence of abortion in mares suffering from recurrent spontaneous abortion. PMID:20681180

  16. 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. PMID:10726885

  17. 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. PMID:27514593

  18. 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.

  19. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... key statistics about acute lymphocytic leukemia? What is acute lymphocytic leukemia? Cancer starts when cells in the body begin ... leukemias). The rest of this document focuses on acute lymphocytic leukemia (ALL) in adults. For information on ALL in ...

  20. Second autologous stem cell transplant for multiply relapsed Hodgkin's disease.

    PubMed

    Lin, T S; Avalos, B R; Penza, S L; Marcucci, G; Elder, P J; Copelan, E A

    2002-05-01

    Therapeutic options for patients with Hodgkin's disease who relapse after high-dose chemotherapy with autologous stem cell support are limited. Salvage chemotherapy is not curative, and allogeneic stem cell transplantation in this setting is associated with mortality rates of 40-65%. We report our institution's experience with second autologous transplants in this patient population. Five patients (median age 36) with relapsed Hodgkin's disease underwent a second autologous stem cell transplant at a median of 66 months after first transplant. Four patients received CBV, and one patient received BuCy as conditioning. Neutrophil and platelet engraftment occurred by days +10 and +16, respectively. All patients achieved a complete response, and no relapses have occurred after a median follow-up of 42 months. All four patients who received CBV developed interstitial pneumonitis, and two patients died of pulmonary complications 37 and 48 months following second transplant. Three patients remain alive and disease-free 41, 42 and 155 months after second transplant. These data indicate that second autologous transplantation should be considered for selected patients who relapse after a prolonged response to first autologous transplant. However, BCNU pneumonitis is the major toxicity in patients who have undergone previous mantle radiation and received busulfan with first transplant. PMID:12040474

  1. 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.

  2. Chimeric autologous/allogeneic constructs for skin regeneration.

    PubMed

    Rasmussen, Cathy Ann; Tam, Joshua; Steiglitz, Barry M; Bauer, Rebecca L; Peters, Noel R; Wang, Ying; Anderson, R Rox; Allen-Hoffmann, B Lynn

    2014-08-01

    The ideal treatment for severe cutaneous injuries would eliminate the need for autografts and promote fully functional, aesthetically pleasing autologous skin regeneration. NIKS progenitor cell-based skin tissues have been developed to promote healing by providing barrier function and delivering wound healing factors. Independently, a device has recently been created to "copy" skin by harvesting full-thickness microscopic tissue columns (MTCs) in lieu of autografts traditionally harvested as sheets. We evaluated the feasibility of combining these two technologies by embedding MTCs in NIKS-based skin tissues to generate chimeric autologous/allogeneic constructs. Chimeric constructs have the potential to provide immediate wound coverage, eliminate painful donor site wounds, and promote restoration of a pigmented skin tissue possessing hair follicles, sweat glands, and sebaceous glands. After MTC insertion, chimeric constructs and controls were reintroduced into air-interface culture and maintained in vitro for several weeks. Tissue viability, proliferative capacity, and morphology were evaluated after long-term culture. Our results confirmed successful MTC insertion and integration, and demonstrated the feasibility of generating chimeric autologous/allogeneic constructs that preserved the viability, proliferative capacity, and structure of autologous pigmented skin. These feasibility studies established the proof-of-principle necessary to further develop chimeric autologous/allogeneic constructs for the treatment of complex skin defects. PMID:25102552

  3. Optimum conditions for the chicken lymphocyte transformation test.

    PubMed

    Barta, O; Barta, V; Pierson, F W

    1992-01-01

    Optimum conditions for chicken (Gallus gallus) lymphocyte transformation tests were determined. Thrice-washed chicken buffy-coat cells obtained after slow centrifugation (40 x g for 10 minutes) responded substantially better to mitogenic stimulation than lymphocytes isolated on separation media containing Ficoll. Maximum responses were obtained with 2 x 10(7) lymphoid cells/ml. Responses to the mitogens were greatest when fetal bovine serum was used at a 5% concentration or pooled chicken serum and autologous plasma were used at a 1.25% concentration. Optimum mitogen concentrations varied with individual birds, timing of the culture, temperature of incubation, and serum concentration in the cultures. When 1.25% chicken serum was used in the cultures, responses were usually greatest with final concentrations of 30-50 micrograms/ml of concanavalin A (Con A) and 30-50 micrograms/ml of phytohemagglutinin-P (PHA-P). The optimum concentration of pokeweed mitogen (PWM) varied from 1 to 40 micrograms/ml among the birds and was practically impossible to establish in general. The incubation in humidified air with 5% CO2 was significantly better at 40 C than at 37 C. The total culture time of 40 hours including pulsing with 3H-thymidine during the final 16 hours of incubation was the best for Con A- and PHA-P-stimulated cells, whereas a longer incubation of 64 hours gave the highest results with PWM stimulations. PMID:1485878

  4. Optimum conditions for the turkey lymphocyte transformation test.

    PubMed

    Barta, O; Barta, V; Domermuth, C H; Pierson, F W

    1992-01-01

    Optimum conditions for turkey lymphocyte transformation tests were determined. Thrice-washed turkey buffy-coat cells obtained after slow centrifugation (40 x g, 10 minutes) responded well to mitogenic stimulation. Turkey lymphocytes isolated on Ficoll-containing separation media largely lost their ability to respond to mitogens. Maximum responses were obtained with 2 x 10(7) lymphoid cells/ml. Responses to the mitogens were greatest when bovine fetal serum was used at a 2.5% concentration or pooled turkey serum and autologous plasma were used at a 1.25% concentration. Higher concentrations of turkey serum or plasma decreased the responses when sub-optimum doses of concanavalin-A (Con A) or phytohemagglutinin-P (PHA-P) were used. Serum-free cultures gave higher stimulation indices than cultures with serum only when sub-optimum doses of Con A or PHA-P were used. Optimum mitogen concentrations varied with individual birds, timing of the culture, temperature of incubation, and serum concentration in the cultures. Responses were usually greatest with final concentrations of 5 micrograms Con A/ml, 10 micrograms PHA-P/ml, and 20 micrograms pokeweed mitogen (PWM)/ml and when the cultures were incubated in 96-well microplates at 40 C in humidified air with 5% CO2 for 40-42 hours with pulsing with 3H-thymidine during the final 16 hours of incubation. PMID:1627110

  5. Stem cell transplantation for indolent lymphoma and chronic lymphocytic leukemia

    PubMed Central

    Gribben, John G; Hosing, Chitra; Maloney, David G.

    2012-01-01

    The indolent lymphomas, including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) remain incurable with standard therapy. Autologous hematopoietic stem cell transplantation (HSCT[JHA1]) is feasible and has low treatment related mortality in follicular lymphoma, but there are questions relating to optimal timing of the procedure, conditioning regimen and late effects. Myeloablative allogeneic HSCT is associated with high treatment related morbidity and mortality, few late relapses, but is applicable to only a small number of patients. The major focus of HSCT in these lymphomas has been with reduced intensity conditioning (RIC) allogeneic HSCT, which is applicable to the age distribution of these diseases and which exploit the graft versus lymphoma effect in these diseases. Steps to further decrease the morbidity and mortality of the RIC HSCT and in particular to reduce the incidence of chronic extensive graft versus host disease while maintaining tumor control remain the major focus. Many potential treatments are available for indolent lymphomas and CLL, and appropriate patient selection and the timing of HSCT remain controversial. The use of HSCT must always be weighed against the risk of the underlying disease, particularly in a setting where improvements in treatment are leading to improved outcome. PMID:21195313

  6. 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. PMID:27260108

  7. Autologous splenic transplantation for splenic trauma.

    PubMed Central

    Pisters, P W; Pachter, H L

    1994-01-01

    OBJECTIVE: The authors reviewed the experimental evidence, surgical technique, complications, and results of clinical trials evaluating the role of autologous splenic transplantation for splenic trauma. SUMMARY BACKGROUND DATA: Splenorrhaphy and nonoperative management of splenic injuries have now become routine aspects in the management of splenic trauma. Unfortunately, not all splenic injuries are readily amenable to conventional spleen-conserving approaches. Heterotopic splenic autotransplantation has been advocated for patients with severe grade IV and V injuries that would otherwise mandate splenectomy. For this subset of patients, splenic salvage by autotransplantation would theoretically preserve the critical role the spleen plays in the host's defense against infection. METHODS: The relevant literature relating to experimental or clinical aspects of splenic autotransplantation was identified and reviewed. Data are presented on the experimental evaluation of autogenous splenic transplantation, methods and complications of autotransplantation, choice of anatomic site and autograft size, and results of clinical trials in humans. RESULTS: The most commonly used technique of autotransplantation in humans involves implanting tissue homogenates or sections of splenic parenchyma into pouches created in the gastrocolic omentum. Most authors have observed evidence of splenic function with normalization of postsplenectomy thrombocytosis, immunoglobulin M levels, and peripheral blood smears. Some degree of immune function of transplanted grafts has been demonstrated with in vivo assays, but the full extent of immunoprotection provided by human splenic autotransplants is currently unknown. CONCLUSIONS: Multiple human and animal studies have established that splenic autotransplantation is a relatively safe and easily performed procedure that results in the return of some hematologic and immunologic parameters to baseline levels. Some aspects of reticuloendothelial

  8. Neospora caninum-infected cattle develop parasite-specific CD4+ cytotoxic T lymphocytes.

    PubMed

    Staska, Lauren M; McGuire, Travis C; Davies, Christopher J; Lewin, Harris A; Baszler, Timothy V

    2003-06-01

    Cattle infected with Neospora caninum readily experience transplacental parasite transmission, presumably after maternal parasitemia, leading to abortion or birth of congenitally infected calves. Cytotoxic T lymphocytes (CTL) are important mediators of protective immunity against Toxoplasma gondii, an intracellular apicomplexan protozoan closely related to N. caninum. In this study, N. caninum-specific CTL expanded from peripheral blood mononuclear cells of two major histocompatibility complex-mismatched, experimentally infected cattle were identified by using a (51)Cr release cytotoxicity assay. Enrichment and blocking of CD4(+)- and CD8(+)-T-lymphocyte effector subsets indicated that CD4(+) CTL killed N. caninum-infected, autologous target cells and that killing was mediated through a perforin/granzyme pathway. Detection and characterization of CTL responses to N. caninum in the natural, outbred, bovine host will facilitate identification of immunogens and design of immunization strategies to induce parasite-specific CTL against transplacental N. caninum transmission in cattle. PMID:12761108

  9. Cytotoxic T-lymphocyte activity specific for hemagglutinin (H) protein of canine distemper virus in dogs.

    PubMed

    Hirama, Kyoko; Togashi, Ken-ichi; Wakasa, Chiaki; Yoneda, Misako; Nishi, Toshiya; Endo, Yasuyuki; Miura, Ryuichi; Tsukiyama-Kohara, Kyoko; Kai, Chieko

    2003-01-01

    Cytotoxic T-lymphocyte (CTL) responses to hemagglutinin (H) protein of canine distemper virus (CDV) were evaluated in dogs using the replication-deficient adenovirus protein expression system. Skin fibroblasts were isolated from two dogs and were infected with recombinant adenovirus bearing the CDV-H gene (Ade-CDVH). CTL assay was performed using fibroblasts expressing CDV-H protein as target cells and peripheral blood lymphocytes (PBL) collected from the same dogs one week after immunization of CDV as effector cells. Specific cytotoxic activity was observed against autologous but not heterologous fibroblasts expressing CDV-H protein. These results indicate that the CTL epitope(s) were localized in the H protein. PMID:12576714

  10. Improving therapy of chronic lymphocytic leukemia with chimeric antigen receptor T cells.

    PubMed

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

    2016-04-01

    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 redirecting 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

  11. Neospora caninum-Infected Cattle Develop Parasite-Specific CD4+ Cytotoxic T Lymphocytes

    PubMed Central

    Staska, Lauren M.; McGuire, Travis C.; Davies, Christopher J.; Lewin, Harris A.; Baszler, Timothy V.

    2003-01-01

    Cattle infected with Neospora caninum readily experience transplacental parasite transmission, presumably after maternal parasitemia, leading to abortion or birth of congenitally infected calves. Cytotoxic T lymphocytes (CTL) are important mediators of protective immunity against Toxoplasma gondii, an intracellular apicomplexan protozoan closely related to N. caninum. In this study, N. caninum-specific CTL expanded from peripheral blood mononuclear cells of two major histocompatibility complex-mismatched, experimentally infected cattle were identified by using a 51Cr release cytotoxicity assay. Enrichment and blocking of CD4+- and CD8+-T-lymphocyte effector subsets indicated that CD4+ CTL killed N. caninum-infected, autologous target cells and that killing was mediated through a perforin/granzyme pathway. Detection and characterization of CTL responses to N. caninum in the natural, outbred, bovine host will facilitate identification of immunogens and design of immunization strategies to induce parasite-specific CTL against transplacental N. caninum transmission in cattle. PMID:12761108

  12. Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    PubMed Central

    Premkumar, Sumana; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Senthilkumar, Rajappa; Srinivasan, Thangavelu; Reena, Helen C.; Preethy, Senthilkumar; Abraham, Samuel J. K.

    2013-01-01

    Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life. PMID:23653878

  13. 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

  14. Autologous blood donation in support of cardiac surgery: a preliminary report on a hospital-based autologous donor programme.

    PubMed

    Pinkerton, P H

    1994-11-01

    The purpose of this study was to assess the success or otherwise of the introduction of an autologous blood programme in support of cardiac surgery in reducing patient exposure to allogeneic blood products and to assess the guideline of two units as the collection schedule for such patients. Sixty-six patients were enrolled in the programme provided they met defined clinical conditions and donated one, two or three units of blood at seven-day intervals, using isovolaemic conditions. One minor vasovagal adverse reaction was recorded. Of the 66 patients, 51 (77%) avoided allogeneic red cells and 42 (64%) received no allogeneic product. If each patient deposited two units, 51 (77%) would have required no allogeneic red cells; if three units were deposited, 57 (86%) patients would have required no allogeneic red cells, but 60 units would be surplus to requirements. Comparison of 52 patients for coronary artery bypass grafting who were autologous donors, with 130 patients undergoing the procedure before the availability of autologous blood, supports the suggestions that there is increased readiness to initiate transfusion of autologous blood and that exposure to allogeneic red cells is reduced. However, exposure to allogeneic products of all kinds is not reduced. It is concluded that the collection of two units of autologous blood is appropriate for most eligible patients and that this reduces exposure to allogeneic red cells.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7828248

  15. Autologous blood injection for the treatment of recurrent mandibular dislocation.

    PubMed

    Coser, R; da Silveira, H; Medeiros, P; Ritto, F G

    2015-08-01

    The purpose of the present study was to evaluate the effectiveness of autologous blood injection in the treatment of recurrent temporomandibular joint dislocation. Eleven patients diagnosed with recurrent dislocation of the joint that could not be self-reduced, received bilateral injections of autologous blood in the superior joint compartment and pericapsular region. During a follow-up period ranging from 24 to 35 months (average 29.6 months), eight patients (72.7%) did not show new episodes of dislocation. The most advocated treatment for recurrent dislocation is eminectomy, which involves a skin incision, with the risk of damaging the facial nerve, requires general anaesthesia, and presents an average success rate of 85% according to the literature. Autologous blood injection is a simple, rapid, minimally invasive, and cost-effective technique, with a low possibility of complications, and is a feasible alternative treatment before surgical intervention. PMID:26022511

  16. Improving diagnosis of appendicitis. Early autologous leukocyte scanning

    SciTech Connect

    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 appendicitis 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-imaging In 111 oxyquinoline autologous leukocyte scanning is a practical and highly accurate adjunct for diagnosing appendicitis.

  17. Therapeutic Potential of Autologous Stem Cell Transplantation for Cerebral Palsy

    PubMed Central

    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. PMID:23259143

  18. Techniques of autologous pericardial leaflet replacement for aortic valve reconstruction.

    PubMed

    Rankin, J Scott; Nöbauer, Christian; Crooke, Philip S; Schreiber, Christian; Lange, Rüdiger; Mazzitelli, Domenico

    2014-08-01

    Glutaraldehyde-fixed autologous pericardium rarely calcifies or retracts, and it is a useful substitute for cardiac valve leaflets. Current understanding of aortic valve geometry provides good models for aortic leaflet design, and pericardial leaflet construction is illustrated in this article for bicuspid and tri-leaflet valves. Outcomes have been characterized by low valve-related complication rates, and results of recent series are encouraging. Perhaps sufficient data are available to consider autologous pericardial leaflet replacement in highly selected younger patients with irreparable leaflets and contraindications to warfarin. PMID:25087813

  19. A review of the application of autologous blood transfusion.

    PubMed

    Zhou, J

    2016-01-01

    Autologous blood transfusion (ABT) has been gradually attracting more attention due to the increasingly prominent problem of blood transfusion safety and blood shortage in recent years. With the rapid development of blood conservation techniques, blood component separation technology, blood transfusion medicine and a constant increase in clinical needs, ABT technology has been expanded and innovated to a large degree. In this study, the development of preoperative autologous blood donation (PABD), acute normovolemic hemodilution (ANH), intraoperative and postoperative autotransfusion, and other new technologies and theories are reviewed and existing questions are analyzed. Challenges and applications are also discussed in order to provide reference for peers. PMID:27533770

  20. Autologous hematopoietic stem cell transplantation for mediastinal extramedullary plasmocytoma.

    PubMed

    Abdelkefi, Abderrahmene; Ben Othman, Tarek; Torjman, Lamia; Ladeb, Saloua; Ben Ghorbel, Imed; Lakhal, Amed; Ben Amor, Ramzi; Miled, Mohamed; Kchir, Mohamed-Nidhameddine; Ben Abdeladhim, Abdeladhim

    2003-07-01

    Extramedullary plasmocytoma (EMP) is a rare cell neoplasm most frequently localised in the upper respiratory tract. We report the case of a 43 year-old-man, with an unusual presentation of EMP developing in the mediastinum, two years after a diagnosis of solitary plasmocytoma of the bone which was successfully treated by local irradiation. In this aggressive presentation, we decided to perform an autologous hematopoietic stem cell transplantation. Two months after transplantation, CT scan showed disappearance of the mediastinal mass and immunofixation of the serum was normal. Selected cases of diffuse EMP, could benefit from intensive treatment followed by autologous hematopoietic stem cell transplantation. PMID:14534964

  1. A review of the application of autologous blood transfusion

    PubMed Central

    Zhou, J.

    2016-01-01

    Autologous blood transfusion (ABT) has been gradually attracting more attention due to the increasingly prominent problem of blood transfusion safety and blood shortage in recent years. With the rapid development of blood conservation techniques, blood component separation technology, blood transfusion medicine and a constant increase in clinical needs, ABT technology has been expanded and innovated to a large degree. In this study, the development of preoperative autologous blood donation (PABD), acute normovolemic hemodilution (ANH), intraoperative and postoperative autotransfusion, and other new technologies and theories are reviewed and existing questions are analyzed. Challenges and applications are also discussed in order to provide reference for peers. PMID:27533770

  2. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC).

    PubMed

    Huh, Sung Woo; Shetty, Asode Ananthram; Ahmed, Saif; Lee, Dong Hwan; Kim, Seok Jung

    2016-01-01

    Degenerative and traumatic articular cartilage defects are common, difficult to treat, and progressive lesions that cause significant morbidity in the general population. There have been multiple approaches to treat such lesions, including arthroscopic debridement, microfracture, multiple drilling, osteochondral transplantation and autologous chondrocyte implantation (ACI) that are currently being used in clinical practice. Autologous bone-marrow mesenchymal cell induced chondrogenesis (MCIC) is a single-staged arthroscopic procedure. This method combines a modified microfracture technique with the application of a bone marrow aspirate concentrate (BMAC), hyaluronic acid and fibrin gel to treat articular cartilage defects. We reviewed the current literatures and surgical techniques for mesenchymal cell induced chondrogenesis. PMID:27489409

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

    PubMed Central

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

    2015-01-01

    Background: 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. Methods: 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. Results: 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. Conclusion: 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. PMID:25867267

  4. 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. PMID:26295729

  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. 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. Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models

    PubMed Central

    Florek, Mareike; Sega, Emanuela I.; Leveson-Gower, Dennis B.; Baker, Jeanette; Müller, Antonia M. S.; Schneidawind, Dominik; Meyer, Everett

    2014-01-01

    Acute graft-versus-host disease (GVHD) is induced by alloreactivity of donor T cells toward host antigens presented on antigen-presenting cells (APCs). Apoptotic cells are capable of inducing tolerance by altering APC maturation. Apoptosis can be induced by extracorporeal photopheresis (ECP). We demonstrate that the use of ECP as a prophylaxis prior to conditioning significantly improves survival (P < .0001) after bone marrow transplantation (BMT) by inhibiting the initiation phase of acute GVHD in a murine BMT model. ECP-treated autologous splenocytes resulted in immune tolerance in the host, including reduced dendritic cell activation with decreased nuclear factor-κB engagement, increased regulatory T-cell (Treg) numbers with enhanced expression of cytolytic T lymphocyte-associated antigen 4, potentiating their suppressive function. The protective effect required host production of interleukin-10 and host Tregs. Conventional T cells that entered this tolerant environment experienced reduced proliferation, as well as a reduction of tissue homing and expression of activation markers. The induction of this tolerant state by ECP was obviated by cotreatment with lipopolysaccharide, suggesting that the inflammatory state of the recipient prior to treatment would play a role in potential clinical translation. The use of prophylactic ECP may provide an alternative and safe method for immunosuppression in the bone marrow transplant setting. PMID:25030062

  8. Autologous apoptotic cells preceding transplantation enhance survival in lethal murine graft-versus-host models.

    PubMed

    Florek, Mareike; Sega, Emanuela I; Leveson-Gower, Dennis B; Baker, Jeanette; Müller, Antonia M S; Schneidawind, Dominik; Meyer, Everett; Negrin, Robert S

    2014-09-11

    Acute graft-versus-host disease (GVHD) is induced by alloreactivity of donor T cells toward host antigens presented on antigen-presenting cells (APCs). Apoptotic cells are capable of inducing tolerance by altering APC maturation. Apoptosis can be induced by extracorporeal photopheresis (ECP). We demonstrate that the use of ECP as a prophylaxis prior to conditioning significantly improves survival (P < .0001) after bone marrow transplantation (BMT) by inhibiting the initiation phase of acute GVHD in a murine BMT model. ECP-treated autologous splenocytes resulted in immune tolerance in the host, including reduced dendritic cell activation with decreased nuclear factor-κB engagement, increased regulatory T-cell (Treg) numbers with enhanced expression of cytolytic T lymphocyte-associated antigen 4, potentiating their suppressive function. The protective effect required host production of interleukin-10 and host Tregs. Conventional T cells that entered this tolerant environment experienced reduced proliferation, as well as a reduction of tissue homing and expression of activation markers. The induction of this tolerant state by ECP was obviated by cotreatment with lipopolysaccharide, suggesting that the inflammatory state of the recipient prior to treatment would play a role in potential clinical translation. The use of prophylactic ECP may provide an alternative and safe method for immunosuppression in the bone marrow transplant setting. PMID:25030062

  9. What Is Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... blood, and lymphoid tissue 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 ...

  10. 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

  11. Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction.

    PubMed

    Martins, Deborah B; Farias-Eisner, Gina; Mandelbaum, Rachel S; Hoang, Han; Bradley, James P; Lee, Justine C

    2016-05-01

    Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction. PMID:27579233

  12. Potential of autologous NK cell therapy to eradicate leukemia

    PubMed Central

    Abdel-Azim, Hisham; Heisterkamp, Nora

    2015-01-01

    B-precursor acute lymphoblastic leukemia (BP-ALL) patients are immunocompromised. We recently reported that functional natural killer (NK) cells can be grown from patient bone marrow and blood samples at diagnosis. Surprisingly, such NK cells exhibit cytotoxicity against autologous BP-ALL cells. Here, we outline unanswered questions, challenges and possible applications associated with these findings. PMID:25949882

  13. Intraoperative Indocyanine Green Laser Angiography in Pediatric Autologous Ear Reconstruction

    PubMed Central

    Martins, Deborah B.; Farias-Eisner, Gina; Mandelbaum, Rachel S.; Hoang, Han; Bradley, James P.

    2016-01-01

    Summary: Skin flap vascularity is a critical determinant of aesthetic results in autologous ear reconstruction. In this study, we investigate the use of intraoperative laser-assisted indocyanine green angiography (ICGA) as an adjunctive measure of skin flap vascularity in pediatric autologous ear reconstruction. Twenty-one consecutive pediatric patients undergoing first-stage autologous total ear reconstruction were retrospectively evaluated. The first 10 patients were treated traditionally (non-ICGA), and the latter 11 patients were evaluated with ICGA intraoperatively after implantation of the cartilage construct and administration of suction. Relative and absolute perfusion units in the form of contour maps were generated. Statistical analyses were performed using independent sample Student t test. Statistically significant differences in exposure and infection were not found between the 2 groups. However, decreased numbers of surgical revisions were required in cases with ICGA versus without ICGA (P = 0.03), suggesting that greater certainty in skin flap perfusion correlated with a reduction in revision surgeries. In cases of exposure, we found an average lowest absolute perfusion unit of 14.3, whereas cases without exposure had an average of 26.1 (P = 0.02), thereby defining objective parameters for utilizing ICGA data in tailoring surgical decision making for this special population of patients. Defined quantitative parameters for utilizing ICGA in evaluating skin flap vascularity may be a useful adjunctive technique in pediatric autologous ear reconstruction. PMID:27579233

  14. [Chronic lymphocytic leukemia].

    PubMed

    Aoki, Sadao

    2016-03-01

    Currently, several novel drugs are available for chronic lymphocytic leukemia (CLL) in Western countries. Of these drugs, those that inhibit the B-cell receptor (BCR) signaling pathway are the most promising. Ibrutinib inhibits BTK in the BCR pathway and can be administered orally. The results of several clinical trials suggest that ibrutinib is highly effective against relapsed/resistant (RR) and treatment-naïve CLL. Furthermore, ibrutinib shows equivalent efficacy on CLL with the 17p deletion. Idelalisib, which also blocks the BCR pathway, inhibits PIK3delta and induces CLL cell death. Clinical trials have shown outstanding efficacy of idelalisib against RR-CLL, especially when administered with antiCD20 antibodies. This drug is also effective against CLL with the 17p deletion. ABT-199 is another novel drug; it inhibits BCL2 signaling, not the BCR pathway, and can be administered orally. The efficacy of ABT-199 against RR-CLL has been demonstrated in a number of clinical trials. These drugs have only mild toxicity and can be used for patients in poor general condition. Unfortunately, none of these drugs have yet been approved in Japan. Rapid resolution of the 'drug lag' problem is necessary. PMID:27076234

  15. [Large granular lymphocyte leukemia].

    PubMed

    Lazaro, Estibaliz; Caubet, Olivier; Menard, Fanny; Pellegrin, Jean-Luc; Viallard, Jean-François

    2007-11-01

    Large granular lymphocyte (LGL) leukemia is a clonal proliferation of cytotoxic cells, either CD3(+) (T-cell) or CD3(-) (natural killer, or NK). Both subtypes can manifest as indolent or aggressive disorders. T-LGL leukemia is associated with cytopenias and autoimmune diseases and most often has an indolent course and good prognosis. Rheumatoid arthritis and Felty syndrome are frequent. NK-LGL leukemias can be more aggressive. LGL expansion is currently hypothesized to be a virus (Ebstein Barr or human T-cell leukemia viruses) antigen-driven T-cell response that involves disruption of apoptosis. The diagnosis of T-LGL is suggested by flow cytometry and confirmed by T-cell receptor gene rearrangement studies. Clonality is difficult to determine in NK-LGL but use of monoclonal antibodies specific for killer cell immunoglobulin-like receptor (KIR) has improved this process. Treatment is required when T-LGL leukemia is associated with recurrent infections secondary to chronic neutropenia. Long-lasting remission can be obtained with immunosuppressive treatments such as methotrexate, cyclophosphamide, and cyclosporine A. NK-LGL leukemias may be more aggressive and refractory to conventional therapy. PMID:17596907

  16. 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

  17. 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

  18. Allogeneic cell-mediated immunotherapy for breast cancer after autologous stem cell transplantation: a clinical pilot study.

    PubMed

    Or, R; Ackerstein, A; Nagler, A; Kapelushnik, J; Naparstek, E; Samuel, S; Amar, A; Bruatbar, C; Slavin, S

    1998-03-01

    Allogeneic cell therapy (allo-CT) is emerging as an effective treatment for patients relapsing after allogeneic bone marrow transplantation (BMT), indicating that tumor cells resisting chemoradiotherapy may still respond to immunocompetent allogeneic lymphocytes. We investigated possible graft-versus-tumor (GVT) effects in six patients with metastatic breast cancer that would be comparable to the graft-versus-leukemia (GVL) phenomenon occurring after allogeneic BMT in hematologic malignancies. The patients were cytoreduced with high-dose chemotherapy and autologous stem cell transplantation (ASCT), and were treated ambulatory with allo-CT consisting of adoptive transfer of HLA-matched donor peripheral blood lymphocytes (PBL) activated in vivo with human recombinant interleukin-2 (rIL-2). If no graft-versus-host disease (GVHD) developed, allo-CT was augmented with infusion of donor PBL, preactivated in vitro with rIL-2. Treatment was well tolerated, with low therapy-related toxicity in all patients. Two patients developed signs and symptoms compatible with GVHD grade I-II, one of whom shows no evidence of disease at more than 34 months out. In the remaining patients, progression-free survival following allo-CT ranged between 7 and 13 months. Allogeneic cell-mediated, cytokine-activated immunotherapy might be utilized for induction of GVT in metastatic breast cancer. A search for techniques to boost chimerism without severe GVHD is indicated. PMID:9557210

  19. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor.

    PubMed Central

    Kawakami, Y; Eliyahu, S; Delgado, C H; Robbins, P F; Rivoltini, L; Topalian, S L; Miki, T; Rosenberg, S A

    1994-01-01

    By cDNA expression cloning we have isolated a gene encoding a shared human melanoma antigen recognized by HLA-A2 restricted autologous and allogenic tumor-infiltrating lymphocytes (TILs) from patients with metastatic melanoma. By using both transient and stable expression systems, transfection of this gene into non-antigen-expressing HLA-A2+ cell lines resulted in recognition by the antigen-specific TILs. The sequence of this cDNA revealed a previously undescribed putative transmembrane protein whose expression was restricted to melanoma and melanocyte cell lines and human retina but no other fresh or cultured normal tissues tested or other tumor histologies. Thus, we have identified a gene encoding a melanocyte lineage-specific protein (MART-1; melanoma antigen recognized by T cells 1) that is a widely shared melanoma antigen recognized by the T lymphocytes of patients with established malignancy. Identification of this gene opens possibilities for the development of immunotherapies for patients with melanoma. PMID:8170938

  20. In vitro characteristics on human lymphocyte functions of a new immunomodulatory agent, a cyclic peptide, cyclomunine.

    PubMed Central

    Niaudet, P; Beaurain, G; Leibowitch, J; Bach, J F

    1980-01-01

    Cyclomunine, a cyclic peptide extracted from Fusarium equisiti, inhibits responses of human lymphocytes to mitogens, soluble antigens and allogeneic cells and the proliferation of lymphoblastoid cell lines. Cyclomunine has little effect on small lymphocytes but acts rather on lymphoblasts. It has no effect on fibroblasts and myeloid cells. Cyclomunine partially inhibits the generation of suppressor cells induced by Con A and the generation of cytotoxic T cells in a mixed lymphocyte culture and totally inhibits the in vitro synthesis of Ig by PBL. Cyclomunine merits consideration as a new in vitro anti-lymphoblastic agent. PMID:6451339

  1. [Effect of synthetic beta-carotene on the formation of cytolytic T-lymphocytes].

    PubMed

    Efimov, S A; Vakulova, L A; Rytenko, A N; Samokhvalov, G I; Sergeev, I M

    1984-06-01

    The effect of intraperitoneal injection of beta-carotene in different doses on the formation of cytolytic T lymphocytes (CTL) in a one-way mixed lymphocyte culture (MLC) of allogeneic mice was studied. The maximal cytotoxic activity of lymphocytes was attained in the MLC with splenocytes of mice which received 10 mg/kg beta-carotene 6 days before experimentation. The correlation was studied between the beta-carotene ability to stimulate CTL formation and antineoplastic activity. It was discovered that injection of beta-carotene in doses and times provoking maximal CTL induction had no effect on the animals' lifespan and the size of transplanted sarcoma 180. PMID:6234949

  2. Tandem autologous versus autologous/allogeneic transplantation for multiple myeloma: propensity score analysis.

    PubMed

    Kawamura, Koji; Ikeda, Takashi; Hagiwara, Shotaro; Mori, Takehiko; Shinagawa, Atsushi; Nishiwaki, Kaichi; Ohashi, Kazuteru; Kubonishi, Shiro; Fukuda, Takahiro; Ito, Toshiro; Tomita, Naoto; Ichinohe, Tatsuo; Kato, Koji; Morishima, Yasuo; Atsuta, Yoshiko; Sunami, Kazutaka; Kanda, Yoshinobu

    2016-09-01

    Autologous hematopoietic stem cell transplantation (auto-HCT) is considered a standard therapy for transplant-eligible patients with multiple myeloma, while allogeneic HCT (allo-HCT) is controversial. We retrospectively analyzed 765 patients with myeloma who underwent tandem transplantation between 1998 and 2012 using Japanese registry data. We evaluated the clinical outcomes of tandem auto-HCT (n = 676) and auto/allo-HCT (n = 89). To adjust for a selection bias, we compared overall survival (OS) between the two groups by a propensity score analysis. The probability of OS at six years was 58.5% for the tandem auto-HCT group and 54.4% for the tandem auto/allo-HCT group (p = 0.47). In a matched-pair analysis based on the propensity score, the difference in survival between the two groups was not statistically significant, although the survival curve appeared to reach a plateau beyond five years in the auto/allo group. Further strategies to reduce treatment-related mortality and enhance a graft-versus-myeloma effect are necessary to improve OS. PMID:26961137

  3. Prognosis of chronic lymphocytic leukemia from infrared spectra of lymphocytes

    NASA Astrophysics Data System (ADS)

    Schultz, Christian P.; Liu, Kan-Zhi; Johnston, James B.; Mantsch, Henry H.

    1997-06-01

    Peripheral mononuclear cells obtained from blood of normal individuals and from patients with chronic lymphocytic leukemia (CLL) were investigated by infrared spectroscopy and multivariate statistical analysis. Not only are the spectra of CLL cells different from those of normal cells, but hierarchical clustering also separated the CLL cells into a number of subclusters, based on their different DNA content, a fact which may provide a useful diagnostic tool for staging (progression of the disease) and multiple clone detection. Moreover, there is evidence for a correlation between the increased amount of DNA in the CLL cells and the in-vivo doubling time of the lymphocytes in a given patient.

  4. Lymphocytic hypophysitis in the elderly.

    PubMed

    Sellayah, Renishka; Gonzales, Michael; Fourlanos, Spiros; King, James

    2015-11-01

    We report a 73-year-old woman with lymphocytic hypophysitis who presented with atypical clinical features and what appeared to be pituitary apoplexy on radiological analysis. Lymphocytic hypophysitis is a rare cause of pituitary dysfunction, and is thought to be an autoimmune disorder. It typically affects young peri-partum women, with clinical features that are related to pituitary hypofunction, and an uncertain natural history. It is difficult to radiologically differentiate lymphocytic hypophysitis from pituitary macroadenoma, therefore, the gold standard of diagnosis remains histological. It is rarely reported in the elderly (> 70 years old), however, given its unpredictable clinical course it remains an important differential diagnosis in patients of this age group who present with features suggestive of pituitary dysfunction. PMID:26094558

  5. Management of chronic lymphocytic leukemia

    PubMed Central

    Ghia, Paolo; Hallek, Michael

    2014-01-01

    In the last decade, the management of chronic lymphocytic leukemia has undergone profound changes that have been driven by an improved understanding of the biology of the disease and the approval of several new drugs. Moreover, many novel drugs are currently under evaluation for rapid approval or have been approved by regulatory agencies, further broadening the available therapeutic armamentarium for patients with chronic lymphocytic leukemia. The use of novel biological and genetic parameters combined with a careful clinical evaluation allows us to dissect some of the heterogeneity of the disease and to distinguish patients with a very mild onset and course, who often will not need any treatment, from those with an intermediate prognosis and a third group with a very aggressive course (high-risk leukemia). On this background, it becomes increasingly challenging to select the right treatment strategy. In this paper, we describe our own approach to the management of different patients with chronic lymphocytic leukemia. PMID:24881042

  6. Approach to Chronic Lymphocytic Meningitis.

    PubMed

    Khadilkar, Satish V; Nadkarni, Nilesh

    2015-09-01

    Chronic meningitis is a common clinical problem. Early diagnosis and appropriate therapy is important in improving the overall outcome and to prevent long-lasting sequels. As many etiological agents lead to the development of chronic lymphocytic meningitis, it is important to develop a systematic approach to the diagnosis; taking clues from history, examination and laboratory tests, to make an accurate diagnosis and institute appropriate therapy. This review focuses on the diagnostic approach towards the commonly encountered situation of chronic lymphocytic meningitis. Chronic meningitis is defined as meningeal inflammation that persists for more than 4 weeks. Chronic meningitis accounts for less than 10% of all the cases of meningitis.1 Causes of chronic lymphocytic meningitis are mainly divided into infectious and non-infectious listed in Table 1.2 Due to advancement in investigations, diseases causing chronic meningitis may be diagnosed earlier than 4 weeks and hence the definition should be considered as a rough guideline. PMID:27608867

  7. Preparative electrophoresis of living lymphocytes

    NASA Technical Reports Server (NTRS)

    Vanoss, C. J.; Bigazzi, P. E.; Gillman, C. F.; Allen, R. E.

    1974-01-01

    Vertical liquid columns containing low molecular weight dextran density gradients can be used for preparative lymphocyte electrophoresis on earth, in simulation of 0 gravity conditions. Another method that has been tested at 1 G, is the electrophoresis of lymphocytes in a upward direction in vertical columns. By both methods up to 10 to the 7th power lymphocytes can be separated at one time in a 30 cm glass column of 8 mm inside diameter, at 12 v/cm, in 2 hours. Due to convection and sedimentation problems, the separation at 1 G is less than ideal, but it is expected that at 0 gravity electrophoresis will prove to be a uniquely powerful cell separation tool. The technical feasibility of electrophoresing inert particles at 0 G has been proven earlier, during the flight of Apollo 16.

  8. Allogeneic and autologous bone marrow transplantation for acute nonlymphocytic leukemia.

    PubMed

    Hurd, D D

    1987-12-01

    Current results show that 50% of young patients with ANLL who undergo allogeneic BMT experience prolonged DFS and may be cured. Encouraging results with high-dose chemo/radiotherapy and autologous BMT are likewise being reported. In addition, some studies using intensive postremission treatment without BMT have shown results comparable to many transplant series. As better ways of preventing GVHD are found, the morbidity and mortality of allogeneic BMT should be reduced and the benefits of transplantation for curing patients with ANLL should be increased. However, the applicability of allogeneic BMT will remain limited due to the availability of compatible donors whether related or unrelated. Further studies are needed in the use of postremission intensive therapy with and without autologous bone marrow support. However, results to date should engender the same degree of enthusiastic optimism that followed the early reports of improved outcome with allogeneic BMT when applied to first remission patients. PMID:3321445

  9. Correction of deep gluteal depression by autologous fat grafting.

    PubMed

    Lewis, C M

    1992-01-01

    In the past, the traditional method of contouring the iliac crest and lateral femoral areas has been liposuction or the surgical removal of the bulges. Unfortunately, this method fails to correct the deep gluteal depression juxtaposed at these two sites. Since we use autologous fat grafts to correct contouring deficiencies elsewhere, it seems logical to investigate whether this technique is applicable to correcting this deformity. We have performed autologous fat grafting to the gluteal depression on 12 patients who underwent lipoplasty of the iliac crest and lateral femoral sites. The longest followup was one year. We have found that this method corrects the deep gluteal depression and yields an improved aesthetic contour. This article describes the technique, addresses the problems encountered, and shows postoperative results. PMID:1626462

  10. Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma without Cryopreservation

    PubMed Central

    Al-Anazi, Khalid Ahmed

    2012-01-01

    High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation is considered the standard of care for multiple myeloma patients who are eligible for transplantation. The process of autografting comprises the following steps: control of the primary disease by using a certain induction therapeutic protocol, mobilization of stem cells, collection of mobilized stem cells by apheresis, cryopreservation of the apheresis product, administration of high-dose pretransplant conditioning therapy, and finally infusion of the cryopreserved stem cells after thawing. However, in cancer centers that treat patients with multiple myeloma and have transplantation capabilities but lack or are in the process of acquiring cryopreservation facilities, alternatively noncryopreserved autologous stem cell therapy has been performed with remarkable success as the pretransplant conditioning therapy is usually brief. PMID:22693672

  11. Computer-assisted selection of donor sites for autologous grafts

    NASA Astrophysics Data System (ADS)

    Krol, Zdzislaw; Zeilhofer, Hans-Florian U.; Sader, Robert; Hoffmann, Karl-Heinz; Gerhardt, Paul; Horch, Hans-Henning

    1997-05-01

    A new method is proposed for a precise planning of autologous bone grafts in cranio- and maxillofacial surgery. In patients with defects of the facial skeleton, autologous bone transplants can be harvested from various donor sites in the body. The preselection of a donor site depends i.a. on the morphological fit of the available bone mass and the shape of the part that is to be transplanted. A thorough planning and simulation of the surgical intervention based on 3D CT studies leads to a geometrical description and the volumetric characterization of the bone part to be resected and transplanted. Both, an optimal fit and a minimal lesion of the donor site are guidelines in this process. We use surface similarity and voxel similarity measures in order to select the optimal donor region for an individually designed transplant.

  12. 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

  13. Incomplete defect filling after third generation autologous chondrocyte implantation

    PubMed Central

    Pietschmann, Matthias F.; Ficklscherer, Andreas; Gülecyüz, Mehmet F.; Hammerschmid, Florian; Müller, Peter E.

    2016-01-01

    Introduction Third generation autologous chondrocyte implantation (ACI) is a suitable method for the treatment of cartilage defects in the knee joint. However, knowledge about the development of graft thickness and the clinical relevance of incomplete defect filling in the postoperative course is low. This prospective study analyses the graft integration into the surrounding cartilage, with special consideration of the graft thickness. Material and methods A total of 71 consecutive patients with 79 cartilage defects were treated with third generation autologous chondrocyte implantation (NOVOCART 3D) in the knee. Follow-up magnetic resonance imaging (MRI) was performed at 0.25, 0.5, 1 and 2 years. Graft thickness was measured compared to the surrounding healthy cartilage. The International Knee Documentation Committee (IKDC) scoring system and the visual analogue scale (VAS) were used for clinical evaluation. Cartilage defect filling was classified as the percentage of the surrounding cartilage. Results The average graft thickness showed a significant increase between 3 and 6 months after autologous chondrocyte implantation. Incomplete defect filling occurred in 44 (55.7%) cases. Of these, 33 cases showed incomplete defect filling grade I (> 75%), 10 cases were grade II (> 50%) and one case grade III (> 25%). Incomplete defect filling grade IV (< 25%) was not observed. Incomplete defect filling occurred significantly more often in women (p = 0.021), without worse clinical results. Conclusions Graft thickness after third generation autologous chondrocyte implantation shows increasing graft thickness over the period of 2 years postoperatively. A high rate of incomplete defect filling in the surrounding cartilage was observed, without worse clinical results. PMID:27478460

  14. 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. PMID:26126219

  15. 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

  16. Delayed Cranioplasty: Outcomes Using Frozen Autologous Bone Flaps.

    PubMed

    Hng, Daniel; Bhaskar, Ivan; Khan, Mumtaz; Budgeon, Charley; Damodaran, Omprakash; Knuckey, Neville; Lee, Gabriel

    2015-09-01

    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

  17. Anatomic and physiological fundamentals for autologous breast reconstruction

    PubMed Central

    Mohan, Anita T.

    2015-01-01

    The success of autologous tissue transfer is reliant on adequate blood supply and as we endeavour to tailor our reconstructive options through our flap choices and design. Autologous breast reconstruction has made substantial progress over the years and the evolution of refinements over the last 30 years has allowed flaps to be based on specific perforators. The ultimate goal of breast reconstruction following mastectomy is to match optimal tissue replacement with minimal donor-site expenditure. In parallel surgeons will seek ways to ensure safe flap design and harvest while maintaining predictability and reliable tissue perfusion. Better understanding of the vascular anatomy and physiology of the cutaneous circulation of soft tissues, and that of patterns of blood flow from individual perforator has provided insight to advance perforator flap harvest and modifications in flap design. The aim of this article is to review the principles of blood supply and flap design exemplified through common flaps used in autologous breast reconstructive surgery, to better understand approaches for safe flap harvest and transfer of well perfused tissue. PMID:26005644

  18. Autologous Matrix-Induced Chondrogenesis in the Knee

    PubMed Central

    Suzer, Ferzan; Thermann, Hajo

    2014-01-01

    Objective: 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. Design and methods: 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. Results: 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. Conclusions: 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. PMID:26069694

  19. Tissue-engineered autologous grafts for facial bone reconstruction.

    PubMed

    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

    2016-06-15

    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, native bovine bone matrix, and a perfusion bioreactor for the growth and transport of living grafts, without bone morphogenetic proteins. The ramus-condyle unit, the most eminent load-bearing bone in the skull, was reconstructed using an image-guided personalized approach in skeletally mature Yucatán 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 nonseeded 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

  20. How Is Acute Lymphocytic Leukemia Classified?

    MedlinePlus

    ... How is acute lymphocytic leukemia treated? How is acute lymphocytic leukemia classified? Most types of cancers are assigned numbered ... ALL are now named as follows: B-cell ALL Early pre-B ALL (also called pro-B ...

  1. Targeted Therapy for Acute Lymphocytic Leukemia

    MedlinePlus

    ... Monoclonal antibodies to treat acute lymphocytic leukemia Targeted therapy for acute lymphocytic leukemia In recent years, new ... These drugs are often referred to as targeted therapy. Some of these drugs can be useful in ...

  2. 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.

  3. 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.

  4. Leukemia -- Chronic T-Cell Lymphocytic

    MedlinePlus

    ... Chronic T-Cell Lymphocytic: Overview Print to PDF Leukemia - Chronic T-Cell Lymphocytic: Overview Approved by the ... Platelets that help the blood to clot About leukemia Types of leukemia are named after the specific ...

  5. 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.

  6. Fingolimod reduces cerebral lymphocyte infiltration in experimental models of rodent intracerebral hemorrhage

    PubMed Central

    Rolland, William B.; Lekic, Tim; Krafft, Paul R.; Hasegawa, Yu; Altay, Orhan; Hartman, Richard; Ostrowski, Robert; Manaenko, Anatol; Tang, Jiping; Zhang, John H.

    2013-01-01

    T-lymphocytes promote cerebral inflammation, thus aggravating neuronal injury after stroke. Fingolimod, a sphingosine 1-phosphate receptor analog, prevents the egress of lymphocytes from primary and secondary lymphoid organs. Based on these findings, we hypothesized fingolimod treatment would reduce the number of T-lymphocytes migrating into the brain, thereby ameliorating cerebral inflammation following experimental intracerebral hemorrhage (ICH). We investigated the effects of fingolimod in two well-established murine models of ICH, implementing intrastriatal infusions of either bacterial collagenase (cICH) or autologous blood (bICH). Furthermore, we tested the long term neurological improvements by Fingolimod in a collagenase-induced rat model of ICH. Fingolimod, in contrast to vehicle administration alone, improved neurological functions and reduced brain edema at 24 and 72 hours following experimental ICH in CD-1 mice (n=103; p<0.05). Significantly fewer lymphocytes were found in blood and brain samples of treated animals when compared to the vehicle group (p<0.05). Moreover, fingolimod treatment significantly reduced the expression of intercellular adhesion molecule-1 (ICAM-1), interferon-γ (INF-γ), and interleukin-17 (IL-17) in the mouse brain at 72 hours post-cICH (p<0.05 compared to vehicle). Long-term neurocognitive performance and histopathological analysis were evaluated in Sprague-Dawley rats between 8 and 10 weeks post-cICH (n=28). Treated rats showed reduced spatial and motor learning deficits, along with significantly reduced brain atrophy and neuronal cell loss within the basal ganglia (p<0.05 compared to vehicle). We conclude that fingolimod treatment ameliorated cerebral inflammation, at least to some extent, by reducing the availability and subsequent brain infiltration of T-lymphocytes, which improved the short and long-term sequelae after experimental ICH in rodents. PMID:23261767

  7. Killing of Brucella antigen-sensitized macrophages by T lymphocytes in bovine brucellosis.

    PubMed

    Wyckoff, John H; Potts, Richard D

    2007-12-15

    The present study was an investigation into the role of T lymphocytes in the killing of antigen-sensitized macrophages (M Phi) in bovine brucellosis. Following confirmation of bovine T lymphocyte cell lines derived from Brucella abortus Strain 19 vaccinated steers as antigen-specific in proliferation studies using various antigens, we adapted an apoptosis assay for evaluation of cytotoxicity by these bovine T cells against autologous monocyte-derived macrophages (MDM Phi) as target cells. Various B. abortus antigen preparations were tested including whole gamma-irradiated B. abortus bacteria (gamma BA), a soluble cytosolic protein fraction and a membrane-associated protein fraction. Both polyclonal and cloned T lymphocyte cell lines exhibited cytotoxicity against MDM Phi targets in an antigen-specific fashion. Polyclonal and cloned T lymphocyte cell lines demonstrated cytotoxic responses to varying degrees against B. abortus antigens regardless of whether the antigen used was whole nonviable bacteria, a soluble protein extract or a membrane-associated fraction of extracted bacteria. To further develop correlation of these responses to an in vivo host defense mechanism, cytotoxicity was evaluated using target cells that had been infected with live B. abortus S19 or B. abortus Strain 2308. Cytotoxic responses were also demonstrated consistently against infected targets with either strain of B. abortus although in most cases, cytotoxicity was higher against target cells sensitized with gamma BA compared to those infected with live bacteria. Cloned T lymphocyte cell lines were all CD4+, CD8(-) cells indicating that the observed cytotoxic responses were most likely due to an inflammatory Th1 response and may represent an important host defense mechanism induced by vaccination with live attenuated strains of B. abortus in cattle. PMID:17904229

  8. Fingolimod reduces cerebral lymphocyte infiltration in experimental models of rodent intracerebral hemorrhage.

    PubMed

    Rolland, William B; Lekic, Tim; Krafft, Paul R; Hasegawa, Yu; Altay, Orhan; Hartman, Richard; Ostrowski, Robert; Manaenko, Anatol; Tang, Jiping; Zhang, John H

    2013-03-01

    T-lymphocytes promote cerebral inflammation, thus aggravating neuronal injury after stroke. Fingolimod, a sphingosine 1-phosphate receptor analog, prevents the egress of lymphocytes from primary and secondary lymphoid organs. Based on these findings, we hypothesized fingolimod treatment would reduce the number of T-lymphocytes migrating into the brain, thereby ameliorating cerebral inflammation following experimental intracerebral hemorrhage (ICH). We investigated the effects of fingolimod in two well-established murine models of ICH, implementing intrastriatal infusions of either bacterial collagenase (cICH) or autologous blood (bICH). Furthermore, we tested the long term neurological improvements by Fingolimod in a collagenase-induced rat model of ICH. Fingolimod, in contrast to vehicle administration alone, improved neurological functions and reduced brain edema at 24 and 72 h following experimental ICH in CD-1 mice (n=103; p<0.05). Significantly fewer lymphocytes were found in blood and brain samples of treated animals when compared to the vehicle group (p<0.05). Moreover, fingolimod treatment significantly reduced the expression of intercellular adhesion molecule-1 (ICAM-1), interferon-γ (INF-γ), and interleukin-17 (IL-17) in the mouse brain at 72 h post-cICH (p<0.05 compared to vehicle). Long-term neurocognitive performance and histopathological analysis were evaluated in Sprague-Dawley rats between 8 and 10 weeks post-cICH (n=28). Treated rats showed reduced spatial and motor learning deficits, along with significantly reduced brain atrophy and neuronal cell loss within the basal ganglia (p<0.05 compared to vehicle). We conclude that fingolimod treatment ameliorated cerebral inflammation, at least to some extent, by reducing the availability and subsequent brain infiltration of T-lymphocytes, which improved the short and long-term sequelae after experimental ICH in rodents. PMID:23261767

  9. In vivo protection of activated Tyr22-dihydrofolate reductase gene-modified canine T lymphocytes from methotrexate

    PubMed Central

    Gori, Jennifer L.; Beard, Brian C.; Williams, Nathaniel P.; Ironside, Christina; Swanson, Debra; McIvor, R. Scott; Kiem, HP

    2013-01-01

    Background Nonmyeloablative allogeneic hematopoietic stem cell (HSC) transplantation can cure malignant and nonmalignant diseases affecting the hematopoietic system, such as severe combined immunodeficiencies, aplastic anemia and hemoglobinopathies. Although nonmyeloablative is favored over myeloablative transplantation for many patients, graft rejection remains problematic. One strategy to decrease rejection is to protect donor activated T cells in the graft from methotrexate (MTX) by genetically modifying the cells to express MTX-resistant dihydrofolate reductase (Tyr22-DHFR), leaving the immunosuppressive effects of MTX to act solely on activated host T lymphocytes, shifting the balance to favor allogeneic engraftment. Methods To evaluate MTX resistance of Tyr22-DHFR+ T lymphocytes in vivo, we transplanted dogs with autologous CD34+ cells modified with YFP and DHFR-GFP lentivirus vectors. Dogs were then treated with a standard MTX regimen (days 1, 3, 6, and 11) following immune activation with a foreign antigen as a surrogate assay to mimic early transplantation. Results DHFR-GFP+ gene marking was maintained in CD3+CD25+ and CD4+ T lymphocytes after MTX treatment while the level of T lymphocytes that expressed only a fluorescent reporter (YFP+) decreased. These data show that Tyr22-DHFR expression protects T lymphocytes from MTX toxicity in dogs, highlighting a clinically relevant application for preserving donor T lymphocytes during post transplantation immunosuppression. Conclusions These findings have implications for clinical translation of MTX-resistant T cells to facilitate engraftment of allogeneic cells following nonmyeloablative conditioning and minimize the risk of rejection. In summary, Tyr22-DHFR expression in T lymphocytes provides chemoprotection from MTX-mediated elimination in the context of immune activation in vivo. PMID:23666780

  10. Regional transfusion centre preoperative autologous blood donation programme: the first two years.

    PubMed Central

    Howard, M. R.; Chapman, C. E.; Dunstan, J. A.; Mitchell, C.; Lloyd, H. L.

    1992-01-01

    OBJECTIVE--To assess the efficacy of a regional autologous blood donation programme. DESIGN--Clinical and laboratory data were collected and stored prospectively. Transfusion data were collected retrospectively from hospital blood bank records. SETTING--Northern Region Blood Transfusion Service and 14 hospitals within the Northern Regional Health Authority. SUBJECTS--505 patients referred for autologous blood donation before elective surgery. MAIN OUTCOME MEASURES--Patient eligibility, adverse events from donation, autologous blood units provided, and autologous and allogeneic blood units transfused within 10 days of operation. RESULTS--Of 505 patients referred, 354 donated at least one unit. 78 of 151 referred patients who did not donate were excluded at the autologous clinic, mostly because of anaemia or ischaemic heart disease. In 73 cases the patient, general practitioner, or hospital consultant decided against donation. 363 autologous procedures were undertaken. In 213 (59%) cases all requested units were provided. The most common reasons for incomplete provision were late referral or anaemia. Adverse events accompanied 24 of 928 donations (2.6%). Transfusion data were obtained for 357 of the 363 procedures. 281 donors were transfused; autologous blood only was given to 225, autologous and allogeneic blood was given to 52, and allogeneic blood only was given to four. 648 of 902 (72%) units of autologous blood were transfused. Complete provision of requested autologous units was followed by allogeneic transfusion in 12 of 208 procedures (5.8%). Incomplete provision was followed by allogeneic transfusion in 44 of 149 procedures (30%). CONCLUSIONS--This study shows the feasibility of a regional autologous transfusion programme. Autologous donors only infrequently received allogeneic transfusion. Patients should be appropriately selected and referred early. PMID:1493393

  11. 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.

  12. The course of lymphocytic hypophysitis.

    PubMed

    Bitton, R N; Slavin, M; Decker, R E; Zito, J; Schneider, B S

    1991-07-01

    A 27-year-old woman presented to our institution in her seventh month of pregnancy with complaints of headache and visual field disturbance. Workup revealed bitemporal hemianopia, a markedly enlarged pituitary gland on computed tomography scan, and biochemical evidence of partial hypopituitarism. At surgery, a biopsy specimen of the pituitary gland was taken revealing lymphocytic hypophysitis. The patient was treated with steroids and replacement doses of thyroid hormone. Visual fields improved postoperatively. A repeat computed tomography scan obtained 2 months after an uneventful pregnancy showed that her pituitary had regained normal size and contour. Over the next 9 months she had gradual recovery of all pituitary function. This case allowed us to follow and document the course of lymphocytic hypophysitis from its presentation as a macroadenoma with partial hypopituitarism to full recovery of both size and hormonal function of the pituitary. Lymphocytic hypophysitis should be considered in the differential diagnosis of a pituitary mass or pituitary dysfunction presenting in pregnancy. In patients with suspected lymphocytic hypophysitis and a pituitary mass, a trial of steroids may be therapeutic. PMID:2053072

  13. [Ultrastructure of blood lymphocytes in dairy cows with chronic lymphocytic leukemia].

    PubMed

    Cerný, L; Hajdu, I

    1982-03-01

    The morphology of blood lymphocytes was studied ultrastructurally in cows with chronical lymphocytic leucosis (CLL) and in healthy controls. A significantly higher occurrence of the so-called nuclear pockets in the leucaemic lymphocytes was found (13.8% v. 0.83% in healthy animals). The surfaces of lymphocytes were stained with ruthenium red; this showed the possibility of differentiating two distinct populations of lymphocytes in peripheral blood. In this way, a prevalence of B-lymphocytes, constituting 89.7% of all lymphocytes, was demonstrated in animals suffering from CLL. PMID:6179285

  14. Aiolos and Lymphocyte Mimicry in Lung Cancer

    PubMed Central

    Terada, Lance S; Liu, Zhe

    2014-01-01

    Aggressive carcinomas tend to adopt behaviors normally restricted to lymphocytes, including anchorage-independent mobilization, response to chemokines, and modulation of local inflammatory conditions. In a recent study we identified the lymphocyte-restricted chromatin regulator Aiolos as an epigenetic driver of lymphocyte mimicry in lung cancer that links immune cell development to metastatic behavior. PMID:27308319

  15. 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

    2016-03-28

    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

  16. Human cytotoxic T lymphocytes against the Plasmodium falciparum circumsporozoite protein.

    PubMed Central

    Malik, A; Egan, J E; Houghten, R A; Sadoff, J C; Hoffman, S L

    1991-01-01

    Cytotoxic T lymphocytes (CTL) against the circumsporozoite (CS) protein of malaria sporozoites protect against malaria in rodents. Although there is interest in developing human vaccines that induce CTL against the Plasmodium falciparum CS protein, humans have never been shown to produce CTL against any Plasmodium species protein or other parasite protein. We report that when peripheral blood mononuclear cells (PBMC) from three of four volunteers immunized with irradiated P. falciparum sporozoites were stimulated in vitro with a recombinant vaccinia virus expressing the P. falciparum CS protein or a peptide including only amino acids 368-390 of the P. falciparum CS protein [CS-(368-390)], the PBMC lysed autologous Epstein-Barr virus-transformed B cells transfected with the P. falciparum CS protein gene or incubated with CS-(368-390) tricosapeptide. Activity was antigen specific, genetically restricted, and dependent on CD8+ T cells. In one volunteer, seven peptides reflecting amino acids 311-400 were tested, and, as in B10.BR mice, CTL activity was only associated with the CS-(368-390) peptide. Development of an assay for studying human CTL against the CS and other malaria proteins and a method for constructing target cells by direct gene transfection provide a foundation for studying the role of CTL in protection against malaria. PMID:1707538

  17. Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials.

    PubMed

    Topalian, S L; Muul, L M; Solomon, D; Rosenberg, S A

    1987-08-24

    The potential utility of tumor-infiltrating lymphocytes (TIL) in the adoptive immunotherapy of human tumors has been suggested by murine experiments showing these cells to be 50-100 times more powerful than LAK cells in treating advanced metastatic disease. A method for the large-scale expansion of human TIL for the use of these cells in clinical trials is described in this report. TIL were successfully expanded on an experimental scale from 24 of 25 consecutive human tumors, including six melanomas, ten sarcomas, and eight adenocarcinomas. Tumors were digested enzymatically to yield single cell suspensions which were cultured in RPMI 1640 medium with 10% human serum and 1000 U/ml recombinant interleukin-2. Lymphocytes constituted from 3% to 74% of single cell tumor suspensions, and expanded from 2.9-fold to 9.1 X 10(8)-fold over a culture period ranging from 14 to 100 days. Nine of 24 TIL cultures lysed fresh autologous tumor targets in 4 h chromium release assays. Cell surface phenotyping identified cultured TIL as activated cytotoxic/suppressor T cells. Subsequently, large-scale expansion of TIL was successful in generating more than 10(10) lymphocytes in five of eight consecutive cases. Clinical trials employing the adoptive transfer of expanded TIL to patients with metastatic disease have begun. PMID:3305708

  18. In vitro modeling of the interaction between human epithelial cells and lymphocytes upon influenza infection.

    PubMed

    Ilyushina, Natalia A; Wright, Peter F

    2016-09-01

    Influenza viruses are a continuous threat to humans because of their ability to cross species barriers and adapt to new hosts. Data from murine studies, along with limited human data, suggest that CD8(+) cytotoxic T lymphocytes (CTL) that recognize conserved epitopes of structural influenza proteins are the main mediators of influenza virus clearance. Additionally, the fact that many CTLs recognize epitopes shared between different influenza strains offers the potential for broad cross-strain immunity. However, the mechanisms of cellular immunity against influenza viruses are poorly defined in humans, where the CTL response has been hard to measure and interpret. We developed a novel CTL assay that utilizes fully differentiated nasal human epithelial cells taken from volunteers as permissive targets for autologous peripheral blood-derived influenza virus-specific cytotoxic T lymphocytes. This in vitro system of human lymphocyte-epithelial cell co-cultures can be considered as the closest approximation to events in vivo and can be employed for studying the interactions between the pathogen and human host. Modeling of the natural interaction process between the primary cell type that supports the productive replication of influenza and immune cells may allow us to put in perspective CTLs as a correlate of immunity to influenza in humans. PMID:27102577

  19. Potentiation of a tumor cell susceptibility to autologous CTL killing by restoration of wild-type p53 function.

    PubMed

    Thiery, Jérôme; Dorothée, Guillaume; Haddada, Hedi; Echchakir, Hamid; Richon, Catherine; Stancou, Rodica; Vergnon, Isabelle; Benard, Jean; Mami-Chouaib, Fathia; Chouaib, Salem

    2003-06-15

    Inactivation of p53 has been implicated in many types of tumors particularly in non-small cell lung carcinoma, one of the most common cancers in which p53 mutation has been frequently identified. The aim of this study was to investigate the influence of p53 status on the regulation of tumor susceptibility to specific CTL-mediated cell death. For this purpose, we used a cytotoxic T lymphocyte clone, Heu127, able to lyse the human autologous lung carcinoma cell line, IGR-Heu, in a HLA-A2-restricted manner. Direct genomic DNA sequencing revealed that IGR-Heu expresses a mutated p53 at codon 132 of the exon 5 which results in the loss of p53 capacity to induce the expression of the p53-regulated gene product p21(waf/CIP1). Initial experiments demonstrated that IGR-Heu was resistant to Fas, TNF, and TRAIL apoptotic pathways. This correlated with the lack of p55 TNFRI, Fas, DR4, and DR5 expression. The effect of wild-type (wt) p53 restoration on the sensitization of IGR-Heu to autologous CTL clone lysis was investigated following infection of the tumor cell line with a recombinant adenovirus encoding the wt p53 (Adwtp53). We demonstrate that the restoration of wt p53 expression and function resulted in a significant potentiation of target cell susceptibility to CTL-mediated lysis. The wt p53-induced optimization of tumor cell killing by specific CTL involves at least in part Fas-mediated pathway via induction of CD95 expression by tumor cells but does not appear to interfere with granzyme B cytotoxic pathway. PMID:12794118

  20. 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

  1. Ibrutinib or Idelalisib in Treating Patients With Persistent or Relapsed Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Non-Hodgkin Lymphoma After Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-04-08

    Chronic Lymphocytic Leukemia; Non-Hodgkin Lymphoma; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Small Lymphocytic Lymphoma

  2. Induction of 6-thioguanine-resistant lymphocytes in Fischer 344 rats following in vivo exposure to N-ethyl-N-nitrosourea and cyclophosphamide

    SciTech Connect

    Aidoo, A.; Lyn-Cook, L.E.; Mittelstaedt, R.A.; Heflich, R.H.; Casciano, D.A. )

    1991-01-01

    The authors have developed a limiting dilution clonal assay for determining the frequency of 6-thioguanine-resistant (TG{sup r}) lymphocytes produced in rats by in vivo exposure to genotoxic agents. Lymphocyte cloning efficiencies (CEs) were highest in plates containing both irradiated TK6 cells and irradiated autologous feeder cells. To measure the effects of chemical mutagens on the frequency of TG{sup r} lymphocytes, rats were given a single i.p. injection of N-ethyl-N-nitrosourea (ENU), a direct-acting alkylating agent, cyclophosphamide (CP), an indirect acting alkylating agent. Lymphocytes were isolated, primed, and cloned at 4 weeks after CP treatment and at 1,2,4 and 6 weeks after ENU treatment. CE in these cultures ranged from 12% to 27%. Cultures were also established for measuring CE in the presence of 6-thioguanine (TG). The dose-dependent responses obtained with both ENU and CP treatments suggest that rat lymphocytes are sensitive to direct- and indirect-acting alkylating agents administered in vivo and that the rat lymphocyte assay is a useful complement to the in vivo/in vitro mouse assay for determining the mutagenicity of environmental toxicants.

  3. TGFβ Signaling Intersects with CD103 Integrin Signaling to Promote T-Lymphocyte Accumulation and Antitumor Activity in the Lung Tumor Microenvironment.

    PubMed

    Boutet, Marie; Gauthier, Ludiane; Leclerc, Marine; Gros, Gwendoline; de Montpreville, Vincent; Théret, Nathalie; Donnadieu, Emmanuel; Mami-Chouaib, Fathia

    2016-04-01

    Homing of CD8(+) T lymphocytes to the tumor microenvironment is an important step for mounting a robust antitumor immune response. TGFβ is responsible for CD103 (αEβ7) integrin induction in activated intraepithelial CD8(+) T lymphocytes. However, the interplay between TGFβ and CD103 and their contribution to T-cell infiltration and antitumor activity remain unknown. Here, we used viable human lung tumor slices and autologous tumor antigen-specific T-lymphocyte clones to provide evidence that CD103 is directly involved in T-lymphocyte recruitment within epithelial tumor islets and intratumoral early T-cell signaling. Moreover, TGFβ enhanced CD103-dependent T-cell adhesion and signaling, whereas it inhibited leukocyte function-associated antigen (LFA)-1 (αLβ2) integrin expression and LFA-1-mediated T-lymphocyte functions. Mechanistic investigations revealed that TGFβ bound to its receptors (TGFBR), which promoted the recruitment and phosphorylation of integrin-linked kinase (ILK) by TGFBR1. We further show that ILK interacted with the CD103 intracellular domain, resulting in protein kinase B (PKB)/AKT activation, thereby initiating integrin inside-out signaling. Collectively, our findings suggest that the abundance of TGFβ in the tumor microenvironment may in fact engage with integrin signaling pathways to promote T-lymphocyte antitumor functions, with potential implications for T-cell-based immunotherapies for cancer. Cancer Res; 76(7); 1757-69. ©2016 AACR. PMID:26921343

  4. Prospective Randomized Controlled Trial to Analyze the Effects of Intermittent Pneumatic Compression on Edema Following Autologous Femoropopliteal Bypass Surgery

    PubMed Central

    te Slaa, Alexander; Dolmans, Dennis E. J. G. J.; Ho, Gwan H.; Mulder, Paul G. H.; van der Waal, Jan C. H.; de Groot, Hans G. W.

    2010-01-01

    Background Patients who undergo autologous femoropopliteal bypass surgery develop postoperative edema in the revascularized leg. The effects of intermittent pneumatic compression (IPC) to treat and to prevent postreconstructive edema were examined in this study. Methods In a prospective randomized trial, patients were assigned to one of two groups. All patients suffered from peripheral arterial disease, and all were subjected to autologous femoropopliteal bypass reconstruction. Patients in group 1 used a compression stocking (CS) above the knee exerting 18 mmHg (class I) on the leg postoperatively for 1 week (day and night). Patients in group 2 used IPC on the foot postoperatively at night for 1 week. The lower leg circumference was measured preoperatively and at five postoperative time points. A multivariate analysis was done using a mixed model analysis of variance. Results A total of 57 patients were analyzed (CS 28; IPC 29). Indications for operation were severe claudication (CS 13; IPC 13), rest pain (10/5), or tissue loss (7/11). Revascularization was performed with either a supragenicular (CS 13; IPC10) or an infragenicular (CS 15; IPC 19) autologous bypass. Leg circumference increased on day 1 (CS/IPC): 0.4%/2.7%, day 4 (2.1%/6.1%), day 7 (2.5%/7.9%), day 14 (4.7%/7.3%), and day 90 (1.0%/3.3%) from baseline (preoperative situation). On days 1, 4, and 7 there was a significant difference in leg circumference between the two treatment groups. Conclusions Edema following femoropopliteal bypass surgery occurs in all patients. For the prevention and treatment of that edema the use of a class I CS proved superior to treatment with IPC. The use of CS remains the recommended practice following femoropopliteal bypass surgery. PMID:21104251

  5. 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

  6. 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.

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

    PubMed Central

    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.

    2013-01-01

    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 CD56high 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 CD161high proinflammatory CD8+ T cell subset was depleted at all time-points post-transplantation. Phenotypic characterization revealed that the CD161highCD8+ T cells were mucosal-associated invariant T cells, a novel cell population originating

  8. Identification of Vaccine Candidate Peptides in the NcSRS2 Surface Protein of Neospora caninum by Using CD4+ Cytotoxic T Lymphocytes and Gamma Interferon-Secreting T Lymphocytes of Infected Holstein Cattle

    PubMed Central

    Staska, Lauren M.; Davies, Christopher J.; Brown, Wendy C.; McGuire, Travis C.; Suarez, Carlos E.; Park, Joo Youn; Mathison, Bruce A.; Abbott, Jeffrey R.; Baszler, Timothy V.

    2005-01-01

    Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4+ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4+- and CD8+-T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-γ) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Four experimentally infected cattle with six different major histocompatibility complex (MHC) class II haplotypes were the source of immune cells used to identify NcSRS2 peptides presented by Holstein MHC haplotypes. NcSRS2 peptides were mapped by using IFN-γ secretion by rNcSRS2-stimulated, short-term T-lymphocyte cell lines, IFN-γ enzyme-linked immunospot (ELISPOT) assay with peripheral blood mononuclear cells, and 51Cr release cytotoxicity assay of rNcSRS2-stimulated effector cells. Four N. caninum-infected Holstein cattle developed NcSRS2 peptide-specific T lymphocytes detected ex vivo in peripheral blood by IFN-γ ELISPOT and in vitro by measuring T-lymphocyte IFN-γ production and cytotoxicity. An immunodominant region of NcSRS2 spanning amino acids 133 to 155 was recognized by CD4+ T lymphocytes from the four cattle. These findings support investigation of subunit N. caninum vaccines incorporating NcSRS2 gene sequences or peptides for induction of NcSRS2 peptide-specific CTL and IFN-γ-secreting T lymphocytes in cattle with varied MHC genotypes. PMID:15731029

  9. Purine nucleoside modulation of functions of human lymphocytes.

    PubMed

    Priebe, T; Platsoucas, C D; Seki, H; Fox, F E; Nelson, J A

    1990-09-01

    The accumulation of endogenous substrates in patients with adenosine deaminase deficiency or purine nucleoside phosphorylase deficiency is believed to be responsible for the immunodeficiency observed in these patients. To identify the lymphocyte populations that are most susceptible to these substrates, we investigated the effect of their nucleoside analogs on a number of T and B cell functions of human lymphocytes. We found that tubercidin (Tub), 2-chloro 2'deoxyadenosine (2CldA), 2-fluoro adenine arabinoside-5'phosphate (FaraAMP), and 9-beta-D-arabinosyl guanine (AraGua) inhibited the proliferative responses of human peripheral blood mononuclear cells (PBMC) to polyclonal activators (PHA, OKT3 mab) or to allogeneic PBMC in mixed lymphocyte cultures (MLC). Addition of recombinant IL-2 from the beginning of the culture did not alter the inhibition by Tub of the proliferative responses of PBMC. These purine nucleoside analogs also inhibited the proliferative responses of purified human peripheral blood CD4+ and CD8+ T cells to PHA and of purified B cells to SAC. The concentrations of these nucleosides required to achieve a given degree of inhibition of proliferative responses of T lymphocyte subpopulations or B cells was similar, suggesting that these analogs do not exhibit any selectivity for these purified lymphocyte populations. Tub and FaraAMP, respectively, inhibited and enhanced, at the effector phase, both NK cytotoxicity and specific T cell-mediated cytotoxicity. In contrast to these findings, LAK cytotoxicity at the effector phase was not significantly inhibited by Tub, and was not enhanced by FaraAMP. Both analogs inhibited rIL-2-induced proliferative responses of PBMC, but did not affect the generation of LAK cytotoxicity (induction phase) against the K562 targets when added at the beginning of the culture. This suggests that DNA synthesis is not required for LAK cell induction. Both Tub and FaraAMP inhibited immunoglobulin production (IgG and IgM) by

  10. Carotid Repair Using Autologous Adipose-Derived Endothelial Cells

    PubMed Central

    Froehlich, Harald; Gulati, Rajiv; Boilson, Barry; Witt, Tyra; Harbuzariu, Adriana; Kleppe, Laurel; Dietz, Allan B.; Lerman, Amir; Simari, Robert D.

    2009-01-01

    Background and Purpose Adipose tissue is an abundant source of endothelial cells as well as stem and progenitor cells which can develop an endothelial phenotype. It has been demonstrated that these cells have distinct angiogenic properties in vitro and in vivo. However, whether these cells have the capacity to directly improve large vessel form and function following vascular injury remains unknown. To define whether delivery of adipose-derived endothelial cells (ADECs) would improve healing of injured carotid arteries, a rabbit model of acute arterial injury was employed. Methods Autologous rabbit ADECS were generated utilizing defined culture conditions. To test the ability of ADECs to enhance carotid artery repair, cells were delivered intra-arterially following acute balloon injury. Additional delivery studies were performed following functional selection of cells prior to delivery. Results Following rabbit omental fat harvest and digestion, a proliferative, homogenous, and distinctly endothelial population of ADECs was identified. Direct delivery of autologous ADECs resulted in marked re-endothelialization 48 hours following acute vascular injury as compared to saline controls (82.2 ±26.9% vs 4.2±3.0% p<0.001). Delivery of ADECs that were selected for their ability to take up acetylated LDL significantly improved vasoreactivity and decreased intimal formation following vascular injury. Conclusions Taken together, these data suggest that ADECs represent an autologous source of proliferative endothelial cells which demonstrate the capacity to rapidly improve re-endothelialization, improve vascular reactivity, and decrease intimal formation in a carotid artery injury model. PMID:19286583

  11. Immunological aspects of allogeneic and autologous mesenchymal stem cell therapies.

    PubMed

    Hoogduijn, M J; Roemeling-van Rhijn, M; Korevaar, S S; Engela, A U; Weimar, W; Baan, C C

    2011-12-01

    Mesenchymal stem cells (MSCs) have potential for therapeutic application as an immunomodulatory and regenerative agent. The immunogenicity and survival of MSCs after infusion are, however, not clear and evidence suggests that allogeneic but also autologous MSCs disappear rapidly after infusion. This may be associated with the susceptibility of MSCs to lysis by natural killer (NK) cells, possibly a result of culture-induced stress. In the present study we examined whether NK cell-mediated lysis of MSCs could be inhibited by immunosuppressive drugs. Human MSCs were isolated from adipose tissue and expanded in culture. Peripheral blood mononuclear cells were activated with interleukin (IL)-2 (200 U/ml) and IL-15 (10 ng/ml) for 7 days. CD3(-)CD16(+)CD56(+) NK cells were then isolated by fluorescence-activated cell sorting and added to europium-labeled MSCs for 4 hr in the presence or absence of immunosuppressive drugs. Lysis of MSCs was determined by spectrophotometric measurement of europium release. Nonactivated NK cells were not capable of lysing MSCs. Cytokine-activated NK cells showed upregulated levels of granzyme B and perforin and efficiently lysed allogeneic and autologous MSCs. Addition of tacrolimus, rapamycin or sotrastaurin to the lysis assay did not inhibit MSC killing. Furthermore, preincubation of activated NK cells with the immunosuppressive drugs for 24 hr before exposure to MSCs had no effect on MSC lysis. Last, addition of the immunosuppressants before and during the activation of NK cells, reduced NK cell numbers but did not affect their capacity to lyse MSCs. We conclude that the immunosuppressive drugs tacrolimus, rapamycin, and sotrastaurin are not capable of inhibiting the lysis of allogeneic and autologous MSCs by activated NK cells. Other approaches to controlling lysis of MSCs should be investigated, as controlling lysis may determine the efficacy of MSC therapy. PMID:21732766

  12. 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. PMID:23211390

  13. 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.

  14. Ocular toxicity following high dose chemotherapy and autologous transplant.

    PubMed

    Rubin, P; Hulette, C; Khawly, J A; Elkordy, M; Hussein, A; Vredenburgh, J J; Jaffe, G J; Peters, W P

    1996-07-01

    A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful. PMID:8832031

  15. Autologous Fat Grafting: The Science Behind the Surgery.

    PubMed

    Zielins, Elizabeth R; Brett, Elizabeth A; Longaker, Michael T; Wan, Derrick C

    2016-04-01

    An invaluable part of the plastic surgeon's technical arsenal for soft tissue contouring, fat grafting continues to be plagued by unpredictable outcomes, resulting in either reoperation and/or patient dissatisfaction. Thus, extensive research has been conducted into the effects of adipose tissue procurement, processing, and placement on fat graft quality at both the cellular level and in terms of overall volume retention. Herein, we present an overview of the vast body of literature in these areas, with additional discussion of cell-assisted lipotransfer as a therapy to improve volume retention, and on the controversial use of autologous fat in the setting of prior irradiation. PMID:26961989

  16. Achieving ideal donor site aesthetics with autologous breast reconstruction

    PubMed Central

    2015-01-01

    The appearance of the donor site following breast reconstruction with abdominal flaps has become an important topic for study. Given the variety of flaps that are derived from the abdomen, decisions are often based on how much muscle and fascia will be harvested. Comparisons between muscle sparing and non-muscle sparing techniques have been performed with outcomes related to function and contour. Closure techniques will vary and include primary fascial closure, mesh reinforcement and additional fascial plication all of which can produce natural and sometimes improved abdominal contours. Proper patient selection however is important. This manuscript will describe various techniques in order to achieve ideal abdominal contour following autologous reconstruction. PMID:26005646

  17. 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

  18. 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

  19. Persistent seropositivity for yellow fever in a previously vaccinated autologous hematopoietic stem cell transplantation recipient.

    PubMed

    Hayakawa, Kayoko; Takasaki, Tomohiko; Tsunemine, Hiroko; Kanagawa, Shuzo; Kutsuna, Satoshi; Takeshita, Nozomi; Mawatari, Momoko; Fujiya, Yoshihiro; Yamamoto, Kei; Ohmagari, Norio; Kato, Yasuyuki

    2015-08-01

    The duration of a protective level of yellow fever antibodies after autologous hematopoietic stem cell transplantation in a previously vaccinated person is unclear. The case of a patient who had previously been vaccinated for yellow fever and who remained seropositive for 22 months after autologous peripheral blood stem cell transplantation for malignant lymphoma is described herein. PMID:26068870

  20. Effective Cytotoxic T Lymphocyte Targeting of Persistent HIV-1 during Antiretroviral Therapy Requires Priming of Naive CD8+ T Cells

    PubMed Central

    Smith, Kellie N.; Mailliard, Robbie B.; Piazza, Paolo A.; Fischer, Will; Korber, Bette T.; Fecek, Ronald J.; Ratner, Deena; Gupta, Phalguni; Mullins, James I.

    2016-01-01

    ABSTRACT Curing HIV-1 infection will require elimination of persistent cellular reservoirs that harbor latent virus in the face of combination antiretroviral therapy (cART). Proposed immunotherapeutic strategies to cure HIV-1 infection include enhancing lysis of these infected cells by cytotoxic T lymphocytes (CTL). A major challenge in this strategy is overcoming viral immune escape variants that have evaded host immune control. Here we report that naive CD8+ T cells from chronic HIV-1-infected participants on long-term cART can be primed by dendritic cells (DC). These DC must be mature, produce high levels of interleukin 12p70 (IL-12p70), be responsive to CD40 ligand (CD40L), and be loaded with inactivated, autologous HIV-1. These DC-primed CD8+ T cell responders produced high levels of gamma interferon (IFN-γ) in response to a broad range of both conserved and variable regions of Gag and effectively killed CD4+ T cell targets that were either infected with the autologous latent reservoir-associated virus or loaded with autologous Gag peptides. In contrast, HIV-1-specific memory CD8+ T cells stimulated with autologous HIV-1-loaded DC produced IFN-γ in response to a narrow range of conserved and variable Gag peptides compared to the primed T cells and most notably, displayed significantly lower cytolytic function. Our findings highlight the need to selectively induce new HIV-1-specific CTL from naive precursors while avoiding activation of existing, dysfunctional memory T cells in potential curative immunotherapeutic strategies for HIV-1 infection. PMID:27247230

  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. 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. 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. PMID:2460248

  4. Human CD4+ effector T lymphocytes generated upon TCR engagement with self-peptides respond defectively to IL-7 in their transition to memory cells

    PubMed Central

    González-Pérez, Gabriela; Segovia, Norma C; Rivas-Carvalho, Amaranta; Reyes, Diana P; Torres-Aguilar, Honorio; Aguilar-Ruiz, Sergio R; Irles, Claudine; Soldevila, Gloria; Sánchez-Torres, Carmen

    2013-01-01

    The peripheral repertoire of CD4+ T lymphocytes contains autoreactive cells that remain tolerant through several mechanisms. However, nonspecific CD4+ T cells can be activated in physiological conditions as in the course of an ongoing immune response, and their outcome is not yet fully understood. Here, we investigate the fate of human naive CD4+ lymphocytes activated by dendritic cells (DCs) presenting endogenous self-peptides in comparison with lymphocytes involved in alloresponses. We generated memory cells (Tmem) from primary effectors activated with mature autologous DCs plus interleukin (IL)-2 (Tmauto), simulating the circumstances of an active immune response, or allogeneic DCs (Tmallo). Tmem were generated from effector cells that were rested in the absence of antigenic stimuli, with or without IL-7. Tmem were less activated than effectors (demonstrated by CD25 downregulation) particularly with IL-7, suggesting that this cytokine may favour the transition to quiescence. Tmauto and Tmallo showed an effector memory phenotype, and responded similarly to polyclonal and antigen-specific stimuli. Biochemically, IL-7-treated Tmallo were closely related to conventional memory lymphocytes based on Erk-1/2 activation, whereas Tmauto were more similar to effectors. Autologous effectors exhibited lower responses to IL-7 than allogeneic cells, which were reflected in their reduced proliferation and higher cell death. This was not related to IL-7 receptor expression but rather to signalling deficiencies, according to STAT5 activation These results suggest that ineffective responses to IL-7 could impair the transition to memory cells of naive CD4+ T lymphocytes recognizing self-peptides in the setting of strong costimulation. PMID:23454917

  5. 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

  6. Management of Contaminated Autologous Grafts in Plastic Surgery

    PubMed Central

    Centeno, Robert F; Desai, Ankit R; Watson, Marla E

    2008-01-01

    Background: Contamination of autologous grafts unfortunately occurs in plastic surgery, but the literature provides no guidance for management of such incidents. Methods: American Society of Aesthetic Plastic Surgery members were asked to complete an online survey that asked about the number and causes of graft contaminations experienced, how surgeons dealt with the problem, the clinical outcomes, and patient disclosure. Results: Nineteen hundred surgeons were asked to participate in the survey, and 223 responded. Of these, 70% had experienced at least 1 graft contamination incident, with 26% experiencing 4 or more. The most frequently reported reason for graft contamination was a graft falling on the floor (reported by 75%). Nearly two thirds of the contaminated grafts related to craniofacial procedures. Ninety-four percent of grafts were managed with decontamination and completion of the operation. The most common method of decontamination was washing with povidone-iodine, but this practice is contrary to recommendations in the literature. Only 3 surgeons (1.9%) said a clinical infection developed following decontaminated graft use. Patients were not informed in 60% of graft contamination incidents. The survey results and review of the literature led to development of algorithms for the management of inadvertent graft contamination and patient disclosure. Conclusions: Although autologous grafts do become contaminated in plastic surgery, the overwhelming majority can be safely decontaminated and produce minimal or no clinical sequelae. The algorithms presented are intended to serve as guides for prevention of contamination events or for their management should they occur. PMID:18496583

  7. 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

  8. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    PubMed Central

    Fernandes, Sandra; Brooks, Robert; Gumbleton, Matthew; Park, Mi-Young; Russo, Christopher M.; Howard, Kyle T.; Chisholm, John D.; Kerr, William G.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs) and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi) mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT. PMID:26052545

  9. 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

  10. 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

  11. MR imaging of osteochondral grafts and autologous chondrocyte implantation

    PubMed Central

    Millington, S. A.; Szomolanyi, P.; Marlovits, S.

    2006-01-01

    Surgical articular cartilage repair therapies for cartilage defects such as osteochondral autograft transfer, autologous chondrocyte implantation (ACI) or matrix associated autologous chondrocyte transplantation (MACT) are becoming more common. MRI has become the method of choice for non-invasive follow-up of patients after cartilage repair surgery. It should be performed with cartilage sensitive sequences, including fat-suppressed proton density-weighted T2 fast spin-echo (PD/T2-FSE) and three-dimensional gradient-echo (3D GRE) sequences, which provide good signal-to-noise and contrast-to-noise ratios. A thorough magnetic resonance (MR)-based assessment of cartilage repair tissue includes evaluations of defect filling, the surface and structure of repair tissue, the signal intensity of repair tissue and the subchondral bone status. Furthermore, in osteochondral autografts surface congruity, osseous incorporation and the donor site should be assessed. High spatial resolution is mandatory and can be achieved either by using a surface coil with a 1.5-T scanner or with a knee coil at 3 T; it is particularly important for assessing graft morphology and integration. Moreover, MR imaging facilitates assessment of complications including periosteal hypertrophy, delamination, adhesions, surface incongruence and reactive changes such as effusions and synovitis. Ongoing developments include isotropic 3D sequences, for improved morphological analysis, and in vivo biochemical imaging such as dGEMRIC, T2 mapping and diffusion-weighted imaging, which make functional analysis of cartilage possible. PMID:16802126

  12. 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

  13. Ibrutinib and Rituximab Compared With Fludarabine Phosphate, Cyclophosphamide, and Rituximab in Treating Patients With Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2016-09-13

    Anemia; Fever, Sweat, and Hot Flashes; 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; Weight Change

  14. 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

  15. Functional characteristics of intraepithelial lymphocytes from mouse small intestine. II. In vivo and in vitro responses of intraepithelial lymphocytes to mitogenic and allogeneic stimuli.

    PubMed Central

    Mowat, A M; MacKenzie, S; Baca, M E; Felstein, M V; Parrott, D M

    1986-01-01

    Although isolated intraepithelial lymphocytes (IEL) have been shown to have specific and non-specific cytolytic functions, their ability to proliferate in response to T-cell mitogens or alloantigens is controversial. Here we show that IEL from mouse small intestine do not respond to mitogens such as concanavalin A and phytohaemagglutinin A or in mixed lymphocyte reactions unless an accessory spleen cell is also present. Adherent spleen cells possess the most potent helper function, but a dividing accessory cell may also be required. Supernatants from stimulated lymphocytes also assist IEL to proliferate in vitro, particularly in the presence of adherent accessory cells. IEL could not mediate lethal graft-versus-host disease in irradiated hosts, but could produce popliteal lymph node hypertrophy or splenomegaly in unirradiated hosts. Thus, IEL have the potential for proliferative activities characteristic of T cells, but they require accessory cells and/or factors such as interleukin-2 for their function in vitro and in vivo. PMID:2942464

  16. Stimulation of human tonsillar lymphocytes in vitro

    PubMed Central

    Oettgen, H. F.; Silber, R.; Miescher, P. A.; Hirschhorn, K.

    1966-01-01

    We have studied the in vitro behaviour of cultured human tonsillar lymphocytes. In comparison with peripheral blood lymphocytes these cells show a higher degree of formation of large cells and mitoses in control cultures without any additive. They behave in a manner similar to peripheral blood lymphocytes when cultured with phytohaemagglutinin (PHA), streptolysin S (SLS) and specific antigens. The only exception is a lack of response to streptolysin O (SLO). PMID:5916348

  17. Increased transendothelial migration of scleroderma lymphocytes

    PubMed Central

    Stummvoll, G; Aringer, M; Grisar, J; Steiner, C; Smolen, J; Knobler, R; Graninger, W

    2004-01-01

    Background: CD4+ T lymphocytes play an important part in the pathogenesis of scleroderma (systemic sclerosis, SSc) and predominate in perivascular SSc skin lesions. Both soluble and membrane bound adhesion molecules are overexpressed in SSc, possibly influencing lymphocyte/endothelial cell (EC) contact. Objective: To assess the transendothelial migration capacity of peripheral lymphocytes in vitro. Patients and methods: Collagen was covered with human umbilical vein endothelial cells (HUVEC), and peripheral blood mononuclear cells (PBMC) of patients and matched healthy controls (HC) were added in parallel experiments. Before and after fractionated harvest of non-adherent, bound, and migrated lymphocytes, the CD4/CD8 ratio and the lymphocytic expression of activation markers and adhesion molecules were analysed by fluorocytometry. Results: 13 (SD 12)% of the SSc PBMC migrated compared with only 5 (5)% HC PBMC (p<0.0002); this increase was primarily due to the migration of CD3+ T lymphocytes and mainly to a larger proportion of CD4+ cells within this CD3+ fraction (71 (SD 14)% for SSc v 56 (14)% for HC, p<0.03), leading to an increased CD4/CD8 ratio among migrated SSc lymphocytes in comparison with controls (3.3 (1.5) v 1.62 (0.93), p<0.006). Among migrated SSc CD4+ T lymphocytes, the frequency of HLA-DR+ cells was increased; migrated lymphocytes highly expressed the adhesion molecules CD11a, CD49d, CD29, and CD44. Conclusion: Transendothelial migration of CD4+ T lymphocytes is enhanced in SSc, and migrating cells exhibit an activated phenotype. The data suggest that activated CD3+CD4+ lymphocytes as found in SSc peripheral blood are prone to transvascular migration, thus contributing to the formation of typical perivascular lymphocytic infiltrates. PMID:15082489

  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. No effect of autologous growth factors (AGF) around ungrafted loaded implants in dogs.

    PubMed

    Jensen, Thomas Bo; Bechtold, J E; Chen, X; Vestermark, M; Søballe, K

    2010-08-01

    Autologous growth factors (AGF) is a growth-factor-rich concentrate of platelets, white blood cells and fibrinogen. Application of AGF was presumed to improve implant fixation and gap healing of non-grafted, loaded implants. We inserted one loaded titanium implant intra-articularly in each medial femoral condyle of eight dogs. Each implant was surrounded by a 0.75 mm gap. One implant in each dog was coated with AGF prior to implantation whereas the contralateral implant served as a control. AGF was prepared by isolating the buffy-coat from blood and further concentrated using an Interpore Cross UltraConcentrator. Platelet counts were increased from a median baseline of 168x10(3)/microl to 1003x10(3)/microl in AGF. However, AGF had no significant effect on implant fixation or bone formation. Even though AGF increased ultimate shear strength and energy absorption by approximately 50%, these differences had a p-value less than 0.05. The sample size in this study was small and any negative conclusions should be taken with caution due to low statistical power. We have previously demonstrated that AGF significantly improves fixation and incorporation of grafted implants. AGF might require mixing with an osteoconductive grafting material in order to provide a scaffold on which to foster bone growth and to keep the growth factors on location for a prolonged period. PMID:19856178

  20. No effect of autologous growth factors (AGF) around ungrafted loaded implants in dogs

    PubMed Central

    Bechtold, J. E.; Chen, X.; Vestermark, M.; Søballe, K.

    2009-01-01

    Autologous growth factors (AGF) is a growth-factor-rich concentrate of platelets, white blood cells and fibrinogen. Application of AGF was presumed to improve implant fixation and gap healing of non-grafted, loaded implants. We inserted one loaded titanium implant intra-articularly in each medial femoral condyle of eight dogs. Each implant was surrounded by a 0.75 mm gap. One implant in each dog was coated with AGF prior to implantation whereas the contralateral implant served as a control. AGF was prepared by isolating the buffy-coat from blood and further concentrated using an Interpore Cross UltraConcentrator. Platelet counts were increased from a median baseline of 168×103/μl to 1003×103/μl in AGF. However, AGF had no significant effect on implant fixation or bone formation. Even though AGF increased ultimate shear strength and energy absorption by approximately 50%, these differences had a p-value less than 0.05. The sample size in this study was small and any negative conclusions should be taken with caution due to low statistical power. We have previously demonstrated that AGF significantly improves fixation and incorporation of grafted implants. AGF might require mixing with an osteoconductive grafting material in order to provide a scaffold on which to foster bone growth and to keep the growth factors on location for a prolonged period. PMID:19856178

  1. 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. PMID:27331299

  2. Early immune recovery after autologous transplantation in non-Hodgkin lymphoma patients: predictive factors and clinical significance.

    PubMed

    Valtola, Jaakko; Varmavuo, Ville; Ropponen, Antti; Selander, Tuomas; Kuittinen, Outi; Kuitunen, Hanne; Keskinen, Leena; Vasala, Kaija; Nousiainen, Tapio; Mäntymaa, Pentti; Pelkonen, Jukka; Jantunen, Esa

    2016-09-01

    Limited data is available about the factors affecting early immune recovery or its clinical significance after autologous stem cell transplantation (auto-SCT). We prospectively analyzed factors affecting early immune recovery and outcome among 72 non-Hodgkin lymphoma (NHL) patients. Absolute lymphocyte count 15 d after auto-SCT (ALC-15) ≥ 0.5 × 10(9)/L was associated with the use of plerixafor (p = 0.004), the number of CD34(+) cells (p = 0.015), and CD34(+) CD38(-) cells (p = 0.005) in the grafts. ALC-15 ≥ 0.5 × 10(9)/L was associated with improved overall survival (p = 0.021). In patients with aggressive histology, ALC-15 ≥ 0.5 × 10(9)/L was beneficial in regard to both progression-free survival (p = 0.015) and overall survival (p = 0.002). Early immune recovery seems to be important in transplanted patients with NHL and, therefore, an easy and affordable method for disease-related risk analysis. Patients with aggressive histology and slow immune recovery may need additional post-transplant treatment. PMID:26763346

  3. Successful treatment with autologous peripheral blood stem cell transplantation for acquired immunodeficiency syndrome (AIDS)-related malignant lymphoma.

    PubMed

    NAGAI, Yuya; MORI, Minako; INOUE, Daichi; KIMURA, Takaharu; SHIMOJI, Sonoko; TOGAMI, Katsuhiro; TABATA, Sumie; MATSUSHITA, Akiko; NAGAI, Kenichi; Imai, Yukihiro; Takafuta, Toshiro; Takahashi, Takayuki

    2009-11-01

    A 62-year-old man was diagnosed with human immunodeficiency virus (HIV) infection while suffering from recurrent herpes zoster infection. Laboratory examination revealed CD4(+) lymphocyte count 16 cells/mul and HIV loading 150,000 copies/ml at presentation. In addition, he had multiple lymph node swelling. Histologic diagnosis of a biopsied lymph node was diffuse, large, B cell-type malignant lymphoma. The karyotype of the lymphoma cells was t(8;14)(q24;q32), which was confirmed by G-banding and fluorescent in situ hybridization. Positron emission tomography (PET)-combined CT scanning revealed systemic extranodal tumors involving the gastrointestinal tract, pancreas, and bone marrow. The clinical stage of the lymphoma was IVB and the international prognosis index was categorized as high. Complete remission (CR) of the lymphoma was obtained after 2 courses of CHOP (cyclophosphamide, adriamycin, vincristine, prednisolone) chemotherapy and 4 subsequent courses of rituximab-combined CHOP (R-CHOP). Highly active antiretroviral therapy (HAART) was started at the initiation of CHOP. Because of the poor prognosis of AIDS-related lymphoma, he received autologous peripheral blood stem cell transplantation with the MEAM protocol (ranimustine, etoposide, cytarabine, melphalan) as a conditioning procedure without a severe infectious episode. He remains in CR 24 months after the transplantation. PMID:20009441

  4. 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.

  5. Lymphocytic panniculitis: an algorithmic approach to lymphocytes in subcutaneous tissue.

    PubMed

    Shiau, Carolyn J; Abi Daoud, Marie S; Wong, Se Mang; Crawford, Richard I

    2015-12-01

    The diagnosis of panniculitis is a relatively rare occurrence for many practising pathologists. The smaller subset of lymphocyte-predominant panniculitis is further complicated by the diagnostic consideration of T cell lymphoma involving the subcutaneous tissue, mimicking inflammatory causes of panniculitis. Accurate classification of the panniculitis is crucial to direct clinical management as treatment options may vary from non-medical therapy to immunosuppressive agents to aggressive chemotherapy. Many diseases show significant overlap in clinical and histological features, making the process of determining a specific diagnosis very challenging. However, with an adequate biopsy including skin and deep subcutaneous tissue, a collaborative effort between clinician and pathologist can often lead to a specific diagnosis. This review provides an algorithmic approach to the diagnosis of lymphocyte-predominant panniculitis, including entities of septal-predominant pattern panniculitis (erythema nodosum, deep necrobiosis lipoidica, morphea profunda and sclerosing panniculitis) and lobular-predominant pattern panniculitis (lupus erythematous panniculitis/lupus profundus, subcutaneous panniculitis-like T cell lymphoma, cutaneous γ-δ T cell lymphoma, Borrelia infection and cold panniculitis). PMID:26602413

  6. Lymphocytic thrombophilic arteritis: an enigma.

    PubMed

    Kalegowda, Inchara Yeliur; Tirumalae, Rajalakshmi; Murthy, K Srinivasa; Rout, Pritilata

    2014-09-01

    A 55-year-old woman presented with a 5-year history of livedo racemosa on her limbs. Histology showed vasculitis of medium-sized arteries with a circumferential, hyalinised, intraluminal fibrin ring. Her laboratory investigations did not indicate any underlying systemic disease. The findings were consistent with lymphocytic thrombophilic arteritis (LTA), alias macular arteritis, which is a recently described entity. The importance of LTA lies in the fact that it is a close clinical and microscopic mimic of polyarteritis nodosa (PAN). LTA is believed to be a distinct entity by some and as a form of PAN by others. We have discussed this case in our report. PMID:25284860

  7. Lymphocytic Thrombophilic Arteritis: An Enigma

    PubMed Central

    Kalegowda, Inchara Yeliur; Tirumalae, Rajalakshmi; Murthy, K Srinivasa; Rout, Pritilata

    2014-01-01

    A 55-year-old woman presented with a 5-year history of livedo racemosa on her limbs. Histology showed vasculitis of medium-sized arteries with a circumferential, hyalinised, intraluminal fibrin ring. Her laboratory investigations did not indicate any underlying systemic disease. The findings were consistent with lymphocytic thrombophilic arteritis (LTA), alias macular arteritis, which is a recently described entity. The importance of LTA lies in the fact that it is a close clinical and microscopic mimic of polyarteritis nodosa (PAN). LTA is believed to be a distinct entity by some and as a form of PAN by others. We have discussed this case in our report. PMID:25284860

  8. Locomotor responses of human CD45 lymphocyte subsets: preferential locomotion of CD45RO+ lymphocytes in response to attractants and mitogens.

    PubMed Central

    Newman, I; Wilkinson, P C

    1993-01-01

    The CD45RO+ population of lymphocytes from human blood contains a higher proportion of locomotor cells than the CD45RA+ population. Direct from blood there were few locomotor lymphocytes (< 15%), but, among these, a higher proportion of CD45RO+ than of CD45RA+ cells responded to the chemotactic stimuli, foetal calf serum (FCS) and interleukin-2 (IL-2) in polarization assays. Likewise, after overnight culture, a higher proportion of CD45RO+ cells responded to IL-8. Culture for 24-72 hr in activators such as anti-CD3, purified protein derivative (PPD), phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) or in an allogeneic mixed leucocyte reaction (AMLR) increased the proportion of locomotor lymphocytes to 20-60%, and the CD45RO+ subset showed proportionately more polarized cells than the CD45RA+ subset after culture with all the above activators. Preferential migration of CD45RO+ cells into collagen gels was also seen after culture in antigenic stimuli (PPD or AMLR) but not with polyclonal activators (alpha CD3 or Con A). Double labelling showed that, within the CD4+ and CD8+ subsets, antigen-stimulated CD45RO+ T cells invaded collagen gels in higher proportions than CD45RA+ T cells. Clustering of lymphocytes with accessory cells is an essential prerequisite for locomotion and, after culture in alpha CD3, CD45RO+ lymphocytes were found preferentially in clusters with monocytes. In all of the above populations, CD45RO+ lymphocytes were larger in size. These findings suggest that, not only selective adhesion to vascular endothelium as reported earlier, but also selective locomotion recruits CD45RO+ lymphocytes into sites of inflammation. PMID:8436407

  9. The Efficacy and Safety of Autologous Transfusion in Unilateral Total Knee Arthroplasty

    PubMed Central

    Yoo, Moon-Jib; Ryu, Jee-Won; Kim, Jeong-Sang

    2015-01-01

    Purpose Although allogeneic blood transfusion is the most common method of transfusion in total knee arthroplasty (TKA), there are reports showing significant decrease in the amount of allogeneic transfusion and incidence of side effects after combined use of autologous transfusion. The purpose of this study is to investigate the efficacy of using an autologous transfusion device in TKA. Materials and Methods Patients who underwent TKA at our institution from January 2003 to January 2014 were divided into two groups: group A (n=127) who received allogeneic transfusion only in TKA and group B (n=118) who received autologous transfusion via an autologous transfusion device and allogeneic transfusion. In both groups, the patients were transfused when the hemoglobin level was below 9 g/dL. In group B, blood collected by the autologous transfusion device was transfused only once after surgery. The total blood loss volume, total transfusion volume, and the presence of side effects were assessed based on medical records. Results Group A received 294.6 mL more allogeneic transfusion than group B (p<0.001). There were no significant differences with regard to the development of side effects between groups. Conclusions Application of an autologous transfusion device during TKA can be effective in reducing the allogeneic transfusion volume. Moreover, allogeneic transfusion was not necessary after autologous transfusion in some patients. PMID:26389070

  10. Effect of hyperbaric oxygen therapy combined with autologous platelet concentrate applied in rabbit fibula fraction healing

    PubMed Central

    Neves, Paulo César Fagundes; de Campos Vieira Abib, Simone; Neves, Rogério Fagundes; Pircchio, Oronzo; Saad, Karen Ruggeri; Saad, Paulo Fernandes; Simões, Ricardo Santos; Moreira, Marcia Bento; de Souza Laurino, Cristiano Frota

    2013-01-01

    OBJECTIVES: The purpose is to study the effects of hyperbaric oxygen therapy and autologous platelet concentrates in healing the fibula bone of rabbits after induced fractures. METHODS: A total of 128 male New Zealand albino rabbits, between 6–8 months old, were subjected to a total osteotomy of the proximal portion of the right fibula. After surgery, the animals were divided into four groups (n = 32 each): control group, in which animals were subjected to osteotomy; autologous platelet concentrate group, in which animals were subjected to osteotomy and autologous platelet concentrate applied at the fracture site; hyperbaric oxygen group, in which animals were subjected to osteotomy and 9 consecutive daily hyperbaric oxygen therapy sessions; and autologous platelet concentrate and hyperbaric oxygen group, in which animals were subjected to osteotomy, autologous platelet concentrate applied at the fracture site, and 9 consecutive daily hyperbaric oxygen therapy sessions. Each group was divided into 4 subgroups according to a pre-determined euthanasia time points: 2, 4, 6, and 8 weeks postoperative. After euthanasia at a specific time point, the fibula containing the osseous callus was prepared histologically and stained with hematoxylin and eosin or picrosirius red. RESULTS: Autologous platelet concentrates and hyperbaric oxygen therapy, applied together or separately, increased the rate of bone healing compared with the control group. CONCLUSION: Hyperbaric oxygen therapy and autologous platelet concentrate combined increased the rate of bone healing in this experimental model. PMID:24141841

  11. Co-transplantation of autologous MSCs delays islet allograft rejection and generates a local immunoprivileged site

    PubMed Central

    Ben Nasr, Moufida; Vergani, Andrea; Avruch, James; Liu, Liye; Kefaloyianni, Eirini; D’Addio, Francesca; Tezza, Sara; Corradi, Domenico; Bassi, Roberto; Valderrama-Vasquez, Alessandro; Usuelli, Vera; Kim, James; Azzi, Jamil; Essawy, Basset El; Markmann, James; Abdi, Reza

    2016-01-01

    Aims Mesenchymal stem cells (MSCs) are multipotent cells with immunomodulatory properties. We tested the ability of MSCs to delay islet allograft rejection. Methods Mesenchymal stem cells were generated in vitro from C57BL/6 and BALB/c mice bone marrow, and their immunomodulatory properties were tested in vitro. We then tested the effect of a local or systemic administration of heterologous and autologous MSCs on graft survival in a fully allogeneic model of islet transplantation (BALB/c islets into C57BL/6 mice). Results In vitro, autologous, but not heterologous, MSCs abrogated immune cell proliferation in response to alloantigens and skewed the immune response toward a Th2 profile. A single dose of autologous MSCs co-transplanted under the kidney capsule with allogeneic islets delayed islet rejection, reduced graft infiltration, and induced long-term graft function in 30 % of recipients. Based on ex vivo analysis of recipient splenocytes, the use of autologous MSCs did not appear to have any systemic effect on the immune response toward graft alloantigens. The systemic injection of autologous MSCs or the local injection of heterologous MSCs failed to delay islet graft rejection. Conclusion Autologous, but not heterologous, MSCs showed multiple immunoregulatory properties in vitro and delayed allograft rejection in vivo when co-transplanted with islets; however, they failed to prevent rejection when injected systemically. Autologous MSCs thus appear to produce a local immunoprivileged site, which promotes graft survival. PMID:25808641

  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. 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. PMID:25568727

  13. 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. PMID:25568727

  14. Lymphocyte apoptosis in murine Pneumocystis pneumonia

    PubMed Central

    Shi, Xin; LeCapitaine, Nicole J; Rudner, Xiaowen L; Ruan, Sanbao; Shellito, Judd E

    2009-01-01

    Background Apoptosis of lymphocytes is important in the termination of an immune response to infection but has also been shown to have detrimental effects in animal models of systemic infection and sepsis. We sought to characterize lymphocyte apoptosis in an animal model of pneumonia due to Pneumocystis murina, an infection localized to the lungs. Methods Control mice and mice depleted of CD4+ lymphocytes were inoculated with Pneumocystis. Apoptosis of lung and spleen lymphocytes was assayed by flow cytometry and PCR assay of apoptotic proteins. Results In control mice, apoptosis of lung lymphocytes was maximal just after the infection was cleared from lung tissue and then declined. However, in CD4-depleted mice, apoptosis was also upregulated in recruited lymphocytes in spite of progressive infection. In splenic lymphocytes, apoptosis was observed early at 1 week after inoculation and then declined. Apoptosis of lung lymphocytes in control mice was associated with a decrease in mRNA for Bcl-2 and an increase in mRNA for Bim. In CD4-depleted mice, lavaged CD8+ cells did change intracellular Bcl-2 but showed increased mRNA for Bim. Conclusion Apoptosis of both pulmonary and extrapulmonary lymphocytes is part of the normal host response to Pneumocystis but is also triggered in CD4-deficient animals with progressive infection. In normal mice apoptosis of pulmonary lymphocytes may serve to terminate the immune response in lung tissue. Apoptosis of lung lymphocytes takes place via both the intrinsic and extrinsic apoptotic pathways and is associated with changes in both pro- and anti-apoptotic proteins. PMID:19558669

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

    MedlinePlus

    ... lymphocytic leukemia? What are the key statistics about acute lymphocytic leukemia? The American Cancer Society’s estimates for acute lymphocytic leukemia (ALL) in the United States for 2016 (including ...

  16. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePlus

    ... Topic Additional resources for 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 ...

  17. Successful autologous cord blood transplantation in a child with acquired severe aplastic anemia.

    PubMed

    Buchbinder, David; Hsieh, Loah; Puthenveetil, Geetha; Soni, Amit; Stites, Jill; Huynh, Van; Kirov, Ivan; Neudorf, Steve; Rubin, Elyssa; Sender, Leonard; Torno, Lilibeth; Margolis, David; Childs, Richard; Moore, Theodore; Nugent, Diane

    2013-05-01

    Over 400 cases of pediatric SAA occur annually in the United States. A growing number of children with SAA may have had their stem cells harvested through cord blood collection. We describe a nine-yr-old male with SAA treated successfully with an autologous cord blood transplant following immunoablative chemotherapy. With the increasing number of people cryopreserving autologous cord blood, the use of autologous cord blood in the treatment of SAA might be considered as initial therapy. This case serves to discuss approaches to preparative therapy as well as the potential complications in this growing cohort of patients. PMID:23464883

  18. Pregnancy after autologous bone marrow transplantation for malignant lymphomas.

    PubMed

    Brice, P; Pautier, P; Marolleau, J P; Castaigne, S; Gisselbrecht, C

    1994-10-01

    In the present paper, we report two cases of normal pregnancy after high dose chemotherapy and autologous stem cell transplantation (ASCT) in two of the 72 women belonging to a group of 188 patients transplanted in our unit for advanced malignant lymphoma. These pregnancies occurred 19 and 33 months after high dose therapy in two women aged 27 and 28, neither of whom had received previous total body irradiation or pelvic radiotherapy. There are several reasons for the relatively low frequency of pregnancies after ASCT. In particular, the median age of the patients is 35 years, most of these women are transplanted in relapse and have received previous pretreatment with alkylating agents and the disease free survival rate does not exceed 40%. The preservation of long term fertility should be taken into account when deciding therapeutic options for young women with curable disease. PMID:7892134

  19. Surgical management and autologous intestinal reconstruction in short bowel syndrome.

    PubMed

    Hommel, Matthijs J; van Baren, Robertine; Haveman, Jan Willem

    2016-04-01

    Short bowel syndrome (SBS) is a serious condition with considerable morbidity and mortality. When treatment with parenteral nutrition fails and life-threatening complications occur, autologous intestinal reconstruction (AIR) should be considered before intestinal transplantation (ITx). Single or combined ITx should be reserved for patients with severe liver disease and as last resort in the treatment of SBS. Longitudinal intestinal lengthening and tailoring (LILT) has proven its value in AIR, but its availability depends on the expertise of the surgeons. Serial transverse enteroplasty (STEP) has similar success rates as LILT and fewer patients progress to ITx. STEP is also applicable at small bowel dilatation in ultra-short bowel syndrome. The scope may be widened when duodenal dilatation can be treated as well. Spiral intestinal lengthening and tailoring (SILT) is a promising alternative. More research is needed to confirm these findings. Therefore we suggest an international data registry for all intestinal lengthening procedures. PMID:27086890

  20. An ethical framework for the disposal of autologous stem cells.

    PubMed

    Petrini, Carlo

    2013-01-01

    The disposal of haematopoietic stem cells stored for autologous transplantation purposes becomes a problem for hospitals when the conditions for their preservation cease to exist. When these cells have been stored for a considerable time the problem often becomes an ethical one involving informed consent and is linked to at least two simultaneous circumstances: (i) the indications regarding disposal contained in available informed consent papers are either absent or too generic; (ii) the person who provided the sample can no longer be traced. This article proposes and discusses some of the ethical criteria for addressing this problem on the basis of the so-called "principles" of North American bioethics, and compares them with some of the principles and values proposed in other models of bioethics. PMID:23412868

  1. Autologous cell therapies: challenges in US FDA regulation.

    PubMed

    McAllister, Todd N; Audley, David; L'Heureux, Nicolas

    2012-11-01

    Cell-based therapies (CBTs) have been hailed for the last two decades as the next pillar of healthcare, yet the clinical and commercial potential of regenerative medicine has yet to live up to the hype. While recent analysis has suggested that regenerative medicine is maturing into a multibillion dollar industry, examples of clinical and commercial success are still relatively rare. With 30 years of laboratory and clinical efforts fueled by countless billions in public and private funding, one must contemplate why CBTs have not made a greater impact. The current regulatory environment, with its zero-risk stance, stymies clinical innovation while fueling a potentially risky medical tourism industry. Here, we highlight the challenges the US FDA faces and present talking points for an improved regulatory framework for autologous CBTs. PMID:23210819

  2. Autologous Bone Marrow Aspirate Therapy in Wound Healing

    PubMed Central

    Chittoria, Ravi Kumar; Nandhagopal, Vijayaraghavan; Mohapatra, Devi Prasad; Thiruvoth, Friji Meethale; Sivakumar, Dinesh Kumar; Asokan, Arjun

    2016-01-01

    Objective: To study the role of autologous bone marrow aspirate therapy (ABMAT) in wound healing. Approach: This is a retrospective analysis of 9 patients (11 chronic nonhealing wounds) in whom ABMAT was used. Patients (wounds) were grouped into two groups. Group 1 included 4 patients (5 wounds) refusing/unfit for reconstruction and managed only with ABMAT. Group 2 included 5 patients (6 wounds) who agreed/fit for reconstruction after wound bed preparation with ABMAT. End point of the study was complete wound healing. Results: ABMAT helped in complete healing of chronic nonhealing wounds by secondary intention in group 1 patients and enhanced process of wound bed preparation for reconstruction in group 2 patients. Innovation: This study highlights the importance of ABMAT in the management of chronic nonhealing wounds. Conclusion: ABMAT helps in wound bed preparation to allow the wound to heal completely or cover by skin graft/flap. PMID:26989576

  3. Putting a price tag on novel autologous cellular therapies.

    PubMed

    Abou-El-Enein, Mohamed; Bauer, Gerhard; Medcalf, Nicholas; Volk, Hans-Dieter; Reinke, Petra

    2016-08-01

    Cell therapies, especially autologous therapies, pose significant challenges to researchers who wish to move from small, probably academic, methods of manufacture to full commercial scale. There is a dearth of reliable information about the costs of operation, and this makes it difficult to predict with confidence the investment needed to translate the innovations to the clinic, other than as small-scale, clinician-led prescriptions. Here, we provide an example of the results of a cost model that takes into account the fixed and variable costs of manufacture of one such therapy. We also highlight the different factors that influence the product final pricing strategy. Our findings illustrate the need for cooperative and collective action by the research community in pre-competitive research to generate the operational models that are much needed to increase confidence in process development for these advanced products. PMID:27288308

  4. Autologous Platelet Gel: Fad or Savoir? Do We Really Know?

    PubMed Central

    Stammers, Alfred H.; Trowbridge, Cody C.; Marko, Molly; Woods, Edward L.; Brindisi, Nicholas; Pezzuto, James; Klayman, Myra; Fleming, Sean; Petzold, Joseph

    2009-01-01

    Abstract: Autologous platelet-gel (APG) is the process of harvesting ones own cells (platelets), concentrating them most often through centrifugation, exposing them to an agonist which induces activation which releases intrinsic substances, and applying them to a target area to accelerate wound healing. APG is attractive because it concentrates a large number of biologically active substances, which are primarily proteins that participate in complex series of mechanisms involved in inflammation and wound healing. It has been used in numerous applications including sports medicine, dermatology, and surgery. However, there are few prospective randomized trials that have compared it in a rigorous manner to other techniques or to placebo. The following report is a review of APG, which includes a description of its perceived benefit, identification of the various modalities where it has been used, and criticisms concerning its use. PMID:20092084

  5. Stabilization of the Chest Wall: Autologous and Alloplastic Reconstructions

    PubMed Central

    Mahabir, Raman Chaos; Butler, Charles E.

    2011-01-01

    The goals of chest wall stabilization include maintenance of a rigid airtight cavity, protection of the thoracic and abdominal contents, optimization of respiration, and, whenever possible, an aesthetic reconstruction. Evidence suggests that bony fixation results in reduced ventilator dependence, a shorter overall hospital stay, and improved upper extremity function. We prefer to accomplish this with autologous tissue alone (such as the pectoralis major, latissimus dorsi, or rectus abdominus muscle flaps) for small to moderate defects. En bloc resection of defects larger than 5 cm or containing four or more ribs will likely benefit from chest wall stabilization. For patients previously treated with radiation, even larger defects may be tolerated owing to fibrosis. For these larger defects, methyl methacrylate composite meshes are used and covered with vascularized tissue. Contaminated wounds are generally reconstructed with bioprosthetic mesh rather than synthetic mesh. Using these principles, the reconstructive plastic surgeon can devise a comprehensive and safe plan to repair tremendous defects of the chest wall. PMID:22294941

  6. 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.

  7. Other Malignancies in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

    PubMed Central

    Tsimberidou, Apostolia-Maria; Wen, Sijin; McLaughlin, Peter; O'Brien, Susan; Wierda, William G.; Lerner, Susan; Strom, Sara; Freireich, Emil J; Medeiros, L. Jeffrey; Kantarjian, Hagop M.; Keating, Michael J.

    2009-01-01

    Purpose Other malignancies have been reported to occur with increased frequency in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The aim of this study was to determine the frequency, outcomes, and factors associated with other cancers in patients with CLL/SLL. Patients and Methods We reviewed the records of consecutive patients with previously untreated CLL/SLL seen at The University of Texas M. D. Anderson Cancer Center from 1985 to 2005. The number of second cancers observed was compared with the number expected from the Surveillance, Epidemiology, and End Results database. Results Among 2,028 patients, 324 (16%) had a history of other cancers and 227 (11.2%) developed other malignancies during the follow-up period. Overall, 625 cancers were observed in 551 patients, including skin (30%), prostate (13%), breast (9%), melanoma (8%), lymphoma (8%), gastrointestinal (9%), lung (6%), and other cancers (17%). The risk of a second cancer was 2.2 times higher than the expected risk. The response rates in patients with and without a history of other cancers were 86% and 92%, respectively (P = .04), and the 5-year survival rates were 70% and 82%, respectively (P < .001). In Cox analysis, independent factors predicting development of new cancers were older age, male sex, and elevated levels of β2-microglobulin, lactate dehydrogenase, and creatinine. In patients who were treated for CLL/SLL, the treatment regimen did not affect the risk of subsequent cancer (P = .49). Conclusion Patients with CLL/SLL have more than twice the risk of developing a second cancer and an increased frequency of certain cancer types. Awareness of risk factors could permit early detection. PMID:19114699

  8. Splenic lymphoma with circulating villous lymphocytes.

    PubMed Central

    Imbing, F; Kumar, D; Kumar, S; Yuoh, G; Gardner, F

    1995-01-01

    This report describes the occurrence of splenic lymphoma with villous lymphocytes (SLVL) in a 56 year old white female with a family history of chronic lymphocytic leukaemia. Other unusual features included a marked lymphocytosis with counts up to 224 x 10(9)/l and marked clumping of lymphocytes in EDTA anticoagulated blood. The neoplastic cells were CD19+, CD20+, CD22+, CD22+, IgM+, lambda+, kappa-, CD5-, and CD10-. The spleen had nodular infiltrates of B lymphocytes in the region of the white pulp with minimal red pulp involvement. Electron microscopy of peripheral blood lymphocytes revealed cells with polar cytoplasmic processes. This report underlines the need for detailed analysis, including morphology and immunophenotyping, for each patient with a small B cell lymphoproliferative disorder. Images PMID:7665709

  9. Different deoxyribonucleases in human lymphocytes

    PubMed Central

    Zöllner, E.Jürgen; Helm, Wolfgang; Zahn, Rudolf K.; Beck, Jörn; Reltz, Manfred

    1974-01-01

    The distribution pattern of deoxyribonuclease activities in human lymphocytes has been examined by micro-disc-electrophoresis. Four groups of deoxyribonuclease activities, differing in their electrophoretic mobility, in the nature of their optimal substrate and in their optimal incubation conditions, are characterized. There are two alkaline DNase-activities. One corresponds to DNase I (EC 3.1.4.5), the other having pH optimum of about pH 9.0, prefers denatured DNA as substrate and is not dependent on divalent cations. The fractions with an acid pH optimum can be subdivided into two groups, which differ in their activity towards native DNA, towards denatured DNA, in their activity when succinate is present and in their pH optimum. PMID:10793736

  10. Subpopulations of mouse spleen lymphocytes

    PubMed Central

    Mugraby, Lea; Gery, I.; Sulitzeanu, D.

    1974-01-01

    Fractionation on bovine serum albumin (BSA) continuous gradients or passage through anti-immunoglobulin-coated (RaMIg) columns were used to separate the populations of mouse spleen cells which react against mitogens specific for B (E. coli lipopolysaccharide (LPS)) or T cells (concanavalin A (Con A) or phytohaemagglutinin (PHA)). These manipulations could distinguish the subsets of T cells reacting toward PHA or Con A. Fractionation on BSA gradients yielded two fractions, one light and the other dense, with high reactivity toward Con A; the cells reactive to LPS were concentrated in a fraction located between these two fractions, whereas the response to PHA was distributed irregularly throughout the gradient, without any apparent correlation with the response against Con A. Lymphocytes eluted from the RaMIg columns did not react to LPS, showed increased reactivity to PHA and decreased response to Con A, as compared to the unfractionated cells. PMID:4605183

  11. Chronic Lymphocytic Leukemia: Current Concepts.

    PubMed

    Yu, Eun-Mi; Kittai, Adam; Tabbara, Imad A

    2015-10-01

    Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in adults, and while in early, asymptomatic stages treatment is not indicated, the threat to the quality of life and increased mortality of patients posed by more advanced-stage disease necessitate therapeutic intervention. Guidelines of when and how to treat are not well-established because CLL is a disease of the elderly and it is important to balance preservation of functional status and control of the disease. Advances in molecular and genetic profiling has led to the ability to identify sub-groups of patients with CLL whose disease may respond to selected therapy. This review discusses current standard therapies in the major sub-groups of CLL based on age and functional status, in both the front-line and relapsed/refractory settings. It also provides a concise review of novel agents that have shown considerable efficacy in CLL. PMID:26408673

  12. Magna-field irradiation and autologous marrow rescue in the treatment of pediatric solid tumors

    SciTech Connect

    Munoz, L.L.; Wharam, M.D.; Kaizer, H.; Leventhal, B.G.; Ruymann, R.

    1983-12-01

    Marrow ablative therapy has been given to pediatric patients with a variety of disseminated tumors. Eight patients with advanced neuroblastoma received autologous marrow reinfusion after intensive therapy. Three of eight are in continuous complete remission from 7 to 60 months. An additional four patients received allogeneic marrow transplantation and two remain in continuous complete response at 21 and 39 months. Intensive therapy and autologous marrow reinfusion have been applied to Ewing's sarcoma, but only preliminary results are available. Six patients with disseminated rhabdomyosarcoma and extra-osseous Ewing's sarcoma received conventional chemotherapy followed by sequential hemi-body irradiation. Four of six patients received autologous marrow rescue. Their median disease-free survival is 17 months. This preliminary experience demonstrates the feasibility of using marrow ablative therapy with autologous marrow transplantation in the treatment of pediatric solid tumors. Continuing Phase II studies are required to substantiate its efficacy.

  13. Preoperative Autologous Blood Donation: Waning Indications in an Era of Improved Blood Safety.

    PubMed

    Vassallo, Ralph; Goldman, Mindy; Germain, Marc; Lozano, Miguel

    2015-10-01

    A downward trend in preoperative autologous donation (PAD) continues in Europe and the Americas, with many jurisdictions only funding medically necessary collections at present. This is the result of decreasing real and perceived residual risks of allogeneic transfusion-transmitted disease and the declining need for transfusion due to patient blood management, which have also led to escalating logistical and cost constraints for PAD programs. We outline collection trends in North America, Europe, and Latin America and review the benefits, risks, effectiveness, and safety of PAD. Important elements of informed consent follow from these points. Evidence-based medical criteria for PAD and autologous transfusion are discussed as are methods to optimize autologous collection timing to regenerate donated red cells. Recommendations for identification of patients whose risk-to-benefit ratio suggests substantial benefit compared with other autologous blood salvage and anemia management alternatives conclude the review. PMID:26006319

  14. Optimizing autologous blood donation by recombinant human erythropoietin (rhu-EPO) and interleukin 3 (IL-3).

    PubMed

    Krieter, H; Frey, L; Segiet, W; Brückner, U B; Krumwieh, D; Seiler, F R; Messmer, K

    1991-12-01

    The transfusion of autologous blood protects surgical patients from both the transfusion transmitted diseases (AIDS, posttransfusion hepatitis) and the immunosuppressive effects of homologous blood. Nevertheless, the use of autologous blood is still unsatisfactory, mainly because of the elaborated logistics, organization and technique required and the often insufficient amounts of autologous blood gained. Today, the major growth-factors of erythropoiesis are available as recombinant analogues. In the studies reviewed here, we investigated the effects of rhu-EPO and IL-3 on perioperative erythropoiesis in two canine models of acute isovolemic hemodilution. Different therapeutic concepts are compared with respect to preoperative changes in hematocrit, the volume of autologous blood gained and the duration of postdilutional anemia. PMID:1801694

  15. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture

    PubMed Central

    Muir, Peter; Hans, Eric C.; Racette, Molly; Volstad, Nicola; Sample, Susannah J.; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L.; Bloom, Debra D.; Bleedorn, Jason A.; Hao, Zhengling; Amene, Ermias; Suresh, M.; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  16. Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

    PubMed

    Muir, Peter; Hans, Eric C; Racette, Molly; Volstad, Nicola; Sample, Susannah J; Heaton, Caitlin; Holzman, Gerianne; Schaefer, Susan L; Bloom, Debra D; Bleedorn, Jason A; Hao, Zhengling; Amene, Ermias; Suresh, M; Hematti, Peiman

    2016-01-01

    Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response

  17. Autologous versus unrelated donor allogeneic marrow transplantation for acute lymphoblastic leukemia.

    PubMed

    Weisdorf, D J; Billett, A L; Hannan, P; Ritz, J; Sallan, S E; Steinbuch, M; Ramsay, N K

    1997-10-15

    Bone marrow transplantation (BMT) can cure patients with high-risk or recurrent acute lymphoblastic leukemia (ALL). Those lacking a related donor can receive either autologous or histocompatible unrelated donor (URD) marrow. Autotransplantation may result in higher risk of relapse, whereas URD allografts, although associated with serious posttransplant toxicities, may reduce relapse risk. Six years (1987 to 1993) of consecutive autologous BMT (University of Minnesota, Dana Farber Cancer Institute; n = 214) were compared with URD transplants (National Marrow Donor Program; n = 337). Most transplants (70% autologous, 48% URD) were in early remission (first or second complete remission [CR1 or CR2]); 376 patients (75% autologous, 64% URD) were less than 18 years old. Autologous BMT led to significantly lower transplant-related mortality (TRM; relative risk [RR] 0.35; P = .001). URD transplantation offered greater protection against relapse (autologous RR 3.1; P = .001). Patients greater than 18 years old, women, and BMT recipients beyond CR2 had higher TRM, whereas adults, BMT recipients in CR2+, or BMT recipients during 1991 through 1993 had significantly more relapse. After 25 months median follow-up, 100 URD and 56 autologous recipients survive leukemia free. URD BMT in CR2 resulted in superior disease-free survival (DFS), especially for adult patients. Multivariate analysis showed superior DFS for children, men, and BMT during CR1 or 2. Autologous and URD BMT can extend survival for a minority of patients unlikely to be cured by chemotherapy, and the results with either technique are comparable. Greater toxicity and TRM after URD BMT are counterbalanced by better protection against relapse. Prospective studies addressing additional clinical variables are needed to guide clinical decision making about transplant choices for patients with ALL. PMID:9376576

  18. Early lymphocyte recovery after intensive timed sequential chemotherapy for acute myelogenous leukemia: peripheral oligoclonal expansion of regulatory T cells

    PubMed Central

    Kanakry, Christopher G.; Gocke, Christopher D.; Thoburn, Christopher; Kos, Ferdynand; Meyer, Christian; Briel, Janet; Luznik, Leo; Smith, B. Douglas; Levitsky, Hyam; Karp, Judith E.

    2011-01-01

    Few published studies characterize early lymphocyte recovery after intensive chemotherapy for acute myelogenous leukemia (AML). To test the hypothesis that lymphocyte recovery mirrors ontogeny, we characterized early lymphocyte recovery in 20 consecutive patients undergoing induction timed sequential chemotherapy for newly diagnosed AML. Recovering T lymphocytes were predominantly CD4+ and included a greatly expanded population of CD3+CD4+CD25+Foxp3+ T cells. Recovering CD3+CD4+CD25+Foxp3+ T cells were phenotypically activated regulatory T cells and showed suppressive activity on cytokine production in a mixed lymphocyte reaction. Despite an initial burst of thymopoiesis, most recovering regulatory T cells were peripherally derived. Furthermore, regulatory T cells showed marked oligoclonal skewing, suggesting that their peripheral expansion was antigen-driven. Overall, lymphocyte recovery after chemotherapy differs from ontogeny, specifically identifying a peripherally expanded oligoclonal population of activated regulatory T lymphocytes. These differences suggest a stereotyped immunologic recovery shared by patients with newly diagnosed AML after induction timed sequential chemotherapy. Further insight into this oligoclonal regulatory T-cell population will be fundamental toward developing effective immunomodulatory techniques to improve survival for patients with AML. PMID:20935254

  19. Age associated oxidative damage in lymphocytes

    PubMed Central

    Gautam, Nandeslu; Das, Subhasis; Mahapatra, Santanu Kar; Chakraborty, Subhankari Prasad; Kundu, Pratip Kumar

    2010-01-01

    Lymphocytes are an important immunological cell and have been played a significant role in acquired immune system; hence, may play in pivotal role in immunosenescence. Oxidative stress has been reported to increase in elderly subjects, possibly arising from an uncontrolled production of free radicals with aging and decreased antioxidant defenses. This study was aimed to evaluate the level of lipid-protein damage and antioxidant status in lymphocytes of healthy individuals to correlate between oxidative damage with the aging process. Twenty healthy individuals of each age group (11–20; 21–30; 31–40; 41–50; and 51–60 years) were selected randomly. Blood samples were drawn by medical practitioner and lymphocytes were isolated from blood samples. Malondialdehyde (MDA), protein carbonyls (PC) level were evaluated to determine the lipid and protein damage in lymphocytes. Superoxide dismutase (SOD), catalase (CAT), glutathione and glutathione dependent enzymes were estimated to evaluate the antioxidant status in the lymphocytes. Increased MDA and PC levels strongly support the increased oxidative damage in elderly subject than young subjects. The results indicated that, balance of oxidant and antioxidant systems in lymphocytes shifts in favor of accelerated oxidative damage during aging. Thus oxidative stress in lymphocytes may particular interest in aging and may play important role in immunosenescence. PMID:20972374

  20. Usefulness of the Autologous Serum Test for the Diagnosis of Chronic Idiopathic Urticaria

    PubMed Central

    Marasoğlu Çelen, Öykü; Aydemir, Ertuğrul H.

    2014-01-01

    Background The majority of chronic urticaria cases are chronic idiopathic urticaria (CIU) with no specific identifiable etiology. The role of autoantibodies in such cases remains controversial. Objective This study determined the positivity rate of autologous serum tests in CIU patients. Methods This study was performed on 30 patients with CIU and 30 individuals without any systemic or dermatologic disease. After the volar parts of right and left forearms were cleansed, 0.05 ml serum physiologic and 0.05 ml autologous serum were injected intradermally on the right forearm 5 cm apart from each other, resulting in the formation of small papules; meanwhile, 0.05 ml histamine alone was injected to the left forearm. The test results were evaluated after 30 minutes as positive in positive cases. Results The autologous serum test produced significant and non-significant results in patients with CIU and controls, respectively. The positivity rates of the autologous serum test in the CIU and control groups were 53.3% and 26.6%, respectively. There was no relationship between autologous serum test positivity and sex in either group. In male patients with CIU, positive results ranged widely with age, while in female patients, positive results were mainly observed at younger ages with a narrow age range. Conclusion The autologous serum test is a useful test in the diagnosis and treatment of CIU as well as the selection of immunotherapy, especially in patients refractory to classic therapy. PMID:25324651

  1. Cascade® Autologous System Platelet-Rich Fibrin Matrix in the Treatment of Chronic Leg Ulcers

    PubMed Central

    O'Connell, Sean M.; Hessler, Karen; Dardik, Herbert

    2012-01-01

    Problem Lower extremity ulcers (venous, diabetic) are often unresponsive to standard treatment. Various systemic and local cellular, vascular, and anatomical factors can result in nonhealing wounds that are refractory to normal healing processes and standard care. Solution Several published wound care guidelines strongly suggest that if an ulcer does not respond to standard good wound care within 4 weeks, then advanced wound therapies should be considered. These advanced therapies include wound bed preparation agents (negative wound pressure therapy, hyperbaric oxygen), recombinant growth factors, or bioengineered cell therapies. New Technology The Cascade® system produces platelet-rich fibrin matrix (PRFM), a novel autologous sterile biologic, produced at the bedside from a small volume (18 mL) of the patient's own blood by using Vacutainer® separation technology optimized for fibrin and platelet isolation. Prepared as an easy to apply, suturable membrane, without the use of exogenous thrombin, PRFM consists of a dense cross-linked fibrin lattice containing intact, viable platelets with their full complement of platelet-derived growth factors. Indications for Use From the FDA 510(k) clearance: The Cascade system “is designed to be used for the safe and rapid preparation of autologous platelet-rich plasma from a small sample of blood at the patient point of care.” PRFM has been used to successfully treat severe venous leg ulcer (VLU), neuropathic diabetic foot ulcer (DFU), mixed arterial and Charcot-deformity associated foot ulcers. Cautions When treating venous or DFUs, the Cascade system should be used together with standard wound care practice (therapeutic compression for VLU and weight off-loading, debridement, and infection control for DFU) in patients with an adequate blood supply to the lower limb. PMID:24527280

  2. Gingival Fibroblasts as Autologous Feeders for Induced Pluripotent Stem Cells.

    PubMed

    Yu, G; Okawa, H; Okita, K; Kamano, Y; Wang, F; Saeki, M; Yatani, H; Egusa, H

    2016-01-01

    Human gingival fibroblasts (hGFs) present an attractive source of induced pluripotent stem cells (iPSCs), which are expected to be a powerful tool for regenerative dentistry. However, problems to be addressed prior to clinical application include the use of animal-derived feeder cells for cultures. The aim of this study was to establish an autologous hGF-derived iPSC (hGF-iPSC) culture system by evaluating the feeder ability of hGFs. In both serum-containing and serum-free media, hGFs showed higher proliferation than human dermal fibroblasts (hDFs). Three hGF strains were isolated under serum-free conditions, although 2 showed impaired proliferation. When hGF-iPSCs were transferred onto mitomycin C-inactivated hGFs, hDFs, or mouse-derived SNL feeders, hGF and SNL feeders were clearly hGF-iPSC supportive for more than 50 passages, whereas hDF feeders were only able to maintain undifferentiated hGF-iPSC growth for a few passages. After 20 passages on hGF feeders, embryonic stem cell marker expression and CpG methylation at the NANOG and OCT3/4 promoters were similar for hGF-iPSCs cultured on hGF and SNL feeder cells. Long-term cultures of hGF-iPSCs on hGF feeders sustained their normal karyotype and pluripotency. On hGF feeders, hGF-iPSC colonies were surrounded by many colony-derived fibroblast-like cells, and the size of intact colonies at 7 d after passage was significantly larger than that on SNL feeders. Allogeneic hGF strains also maintained hGF-iPSCs for 10 passages. Compared with hDFs, hGFs showed a higher production of laminin-332, laminin α5 chain, and insulin-like growth factor-II, which have been reported to sustain the long-term self-renewal of pluripotent stem cells. These results suggest that hGFs possess an excellent feeder capability and thus can be used as alternatives to conventional mouse-derived SNL and hDF feeders. In addition, our findings suggest that hGF feeders are promising candidates for animal component-free ex vivo expansion of

  3. Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma

    ClinicalTrials.gov

    2016-02-23

    Prolymphocytic Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hodgkin Lymphoma; Refractory Non-Hodgkin Lymphoma; Refractory Small Lymphocytic Lymphoma; T-Cell Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  4. Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site.

    PubMed

    Bradley, Todd; Fera, Daniela; Bhiman, Jinal; Eslamizar, Leila; Lu, Xiaozhi; Anasti, Kara; Zhang, Ruijung; Sutherland, Laura L; Scearce, Richard M; Bowman, Cindy M; Stolarchuk, Christina; Lloyd, Krissey E; Parks, Robert; Eaton, Amanda; Foulger, Andrew; Nie, Xiaoyan; Karim, Salim S Abdool; Barnett, Susan; Kelsoe, Garnett; Kepler, Thomas B; Alam, S Munir; Montefiori, David C; Moody, M Anthony; Liao, Hua-Xin; Morris, Lynn; Santra, Sampa; Harrison, Stephen C; Haynes, Barton F

    2016-01-01

    Antibodies that neutralize autologous transmitted/founder (TF) HIV occur in most HIV-infected individuals and can evolve to neutralization breadth. Autologous neutralizing antibodies (nAbs) against neutralization-resistant (Tier-2) viruses are rarely induced by vaccination. Whereas broadly neutralizing antibody (bnAb)-HIV-Envelope structures have been defined, the structures of autologous nAbs have not. Here, we show that immunization with TF mutant Envs gp140 oligomers induced high-titer, V5-dependent plasma neutralization for a Tier-2 autologous TF evolved mutant virus. Structural analysis of autologous nAb DH427 revealed binding to V5, demonstrating the source of narrow nAb specificity and explaining the failure to acquire breadth. Thus, oligomeric TF Envs can elicit autologous nAbs to Tier-2 HIVs, but induction of bnAbs will require targeting of precursors of B cell lineages that can mature to heterologous neutralization. PMID:26725118

  5. Change in peripheral blood lymphocyte count in dogs following adoptive immunotherapy using lymphokine-activated T killer cells combined with palliative tumor resection.

    PubMed

    Mie, Keiichiro; Shimada, Terumasa; Akiyoshi, Hideo; Hayashi, Akiyoshi; Ohashi, Fumihito

    2016-09-01

    We evaluated changes in peripheral blood lymphocyte (PBL) count in dogs following adoptive immunotherapy using lymphokine-activated T killer cells (T-LAK) in combination with surgery. Fifteen tumor-bearing dogs treated with T-LAK therapy combined with palliative resection of tumors were enrolled in the present study. T-LAK were generated from autologous peripheral blood mononuclear cells (PBMC) by culture with recombinant human interleukin -2 (rhIL-2) and solid phase anti-canine cluster of differentiation (CD)3 antibody. T-LAK were administrated intravenously at 2-4-week intervals. After the first administration of T-LAK, counts of PBL and T lymphocyte subsets (CD3(+), CD4(+) and CD8(+) cells) increased and the CD4/CD8 ratio decreased, with significant increases in CD8(+) cells (P<0.05). In 8 tumor-bearing dogs that were administered sequential T-LAK, available data on changes in PBL and T lymphocyte phenotypes until the fifth administration were also analyzed. In tumor-bearing dogs administered 5 rounds of T-LAK, CD8(+) cell counts were maintained high until the fifth administration of T-LAK. Moreover, the CD4/CD8 ratio remained low until the fifth administration of T-LAK. These results indicate that T-LAK therapy combined with surgery may increase peripheral blood T lymphocytes, particularly CD8(+) cells, in tumor-bearing dogs. PMID:27436446

  6. Virus-specific HLA-restricted lysis of herpes simplex virus-infected human monocytes and macrophages mediated by cytotoxic T lymphocytes

    SciTech Connect

    Torpey, D.J. III

    1987-01-01

    Freshly-isolated peripheral blood human monocytes and 5 day in vitro cultured macrophages were infected with herpes simplex virus type 1 (HSV-1), labeled with /sup 51/Cr, and used as target cells in a 12-14 hour cell-mediated cytotoxicity assay. Mononuclear leukocytes (MNL) from HSV-1 non-immune individuals, whether unstimulated or stimulated with HSV-1 antigen, did not mediate significant lysis of either target cell. HSV-immune MNL, both freshly-isolated and cultured for 5 days without antigen, demonstrated only low levels of natural killer (NK) cell-mediate lysis. MNL from HSV-immune individuals incubated for 5 days in vitro with HSV-1 antigen mediated significant virus-specific lysis of both target cells. Mean virus-specific lysis of autologous monocytes was 8.5(/+-/2.0)% compared to a three-fold greater virus-specific lysis of autologous macrophages. Greater than 70% of this lytic activity was mediated by Leu-11-negative, T3-positive cytotoxic T lymphocytes (CTL). Allogeneic target cells lacking a common HLA determinant were not significantly lysed while T8-positive CTL mediated infrequent lysis of target cells sharing a common HLA-A and/or HLA-B determinant. T4-positive lymphocytes were demonstrated to be the predominant cell mediating lysis of autologous target cells and allogeneic target cells sharing both HLA-A and/or HLA-B plus HLA-DR determinants with the CTL; the T4-positive cell was the sole CTL mediator of lysis of allogeneic target cells having a common HLA-DR determinant.

  7. Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial

    PubMed Central

    Armand, Philippe; Nagler, Arnon; Weller, Edie A.; Devine, Steven M.; Avigan, David E.; Chen, Yi-Bin; Kaminski, Mark S.; Holland, H. Kent; Winter, Jane N.; Mason, James R.; Fay, Joseph W.; Rizzieri, David A.; Hosing, Chitra M.; Ball, Edward D.; Uberti, Joseph P.; Lazarus, Hillard M.; Mapara, Markus Y.; Gregory, Stephanie A.; Timmerman, John M.; Andorsky, David; Or, Reuven; Waller, Edmund K.; Rotem-Yehudar, Rinat; Gordon, Leo I.

    2013-01-01

    Purpose The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. Patients and Methods We conducted an international phase II study of pidilizumab, an anti–PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. Results Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E–bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. Conclusion This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease. PMID:24127452

  8. The Pathogenesis of Chronic Lymphocytic Leukemia

    PubMed Central

    Galton, D. A. G.

    1966-01-01

    The pathogenesis of chronic lymphocytic leukemia was examined in a series of 88 cases observed during a 15-year period. In untreated cases the trend of the absolute lymphocyte counts followed two main patterns. In the type I trend, the counts rose throughout the observation period; in the type II trend, the tendency to rise ceased and the counts stabilized above and below a mean value, the stationary trend being maintained for months or years. The type II trend was associated with relatively benign disease. The development of lymphocytosis was correlated with the progression of lymphadenopathy. It is suggested that lymphocytosis may result from the physiological process of recirculation and that the accumulation of lymphocytes may result from the proliferation of a single slightly abnormal cell-line. The abnormal cells might survive an unusually long time because they are unable to respond to stimuli which cause normal lymphocytes to transform. PMID:4952384

  9. Microangiectasias: Structural regulators of lymphocyte transmigration

    PubMed Central

    Secomb, Timothy W.; Konerding, Moritz A.; West, Charles A.; Su, Mei; Young, Alan J.; Mentzer, Steven J.

    2003-01-01

    The migration of lymphocytes into inflammatory tissue requires the migrating cell to overcome mechanical forces produced by blood flow. A generally accepted hypothesis is that these forces are overcome by a multistep sequence of adhesive interactions between lymphocytes and endothelial cells. This hypothesis has been recently challenged by results demonstrating wall shear stress on the order of 20 dyn/cm2 in vivo and infrequent lymphocyte–endothelial adhesion at wall shear stress >1–2 dyn/cm2 in vitro. Here, we show that lymphocyte slowing and transmigration in the skin is associated with microangiectasias, i.e., focal structural dilatations of microvessel segments. Microangiectasias are inducible within 4 days of the onset of inflammation and lead to a greater than 10-fold local reduction in wall shear stress. These findings support the hypothesis that a preparatory step to lymphocyte transmigration involves structural adaptations in the inflammatory microcirculation. PMID:12782790

  10. Lymphocytes and ischemia-reperfusion injury.

    PubMed

    Linfert, Douglas; Chowdhry, Tayseer; Rabb, Hamid

    2009-01-01

    Ischemia reperfusion injury (IRI) is a common and important clinical problem in many different organ systems, including kidney, brain, heart, liver, lung, and intestine. IRI occurs during all deceased donor organ transplants. IRI is a highly complex cascade of events that includes interactions between vascular endothelium, interstitial compartments, circulating cells, and numerous biochemical entities. It is well established that the innate immune system, such as complement, neutrophils, cytokines, chemokines, and macrophages participate in IRI. Recent data demonstrates an important role for lymphocytes, particularly T cells but also B cells in IRI. Lymphocytes not only participate in augmenting injury responses after IRI, but could also be playing a protective role depending on the cell type and stage of injury. Furthermore, lymphocytes appear to be participating in the healing response from IRI. These new data open the possibility for lymphocyte targeted therapeutics to improve the short and long term outcomes from IRI. PMID:19027612

  11. Ontogeny of Innate T Lymphocytes – Some Innate Lymphocytes are More Innate than Others

    PubMed Central

    Vermijlen, David; Prinz, Immo

    2014-01-01

    Innate lymphocytes have recently received a lot of attention. However, there are different ideas about the definition of what is “innate” in lymphocytes. Lymphocytes without V(D)J-rearranged antigen receptors are now termed innate lymphoid cells (ILCs) and include cells formerly known as natural killer (NK) cells. Also, lymphocytes that are innate should be able to recognize microbial or stress-induced patterns and react rapidly without prior sensitization, as opposed to adaptive immune responses. Formally, genuine innate lymphocytes would be present before or at birth. Here, we review the ontogeny of human and mouse innate T lymphocyte populations. We focus on γδ T cells, which are prototype lymphocytes that often use their V(D)J rearrangement machinery to generate genetically encoded predetermined recombinations of antigen receptors. We make parallels between the development of γδ T cells with that of innate αβ T cells [invariant (i)NKT and mucosa-associated invariant T cells] and compare this with the ontogeny of innate B cells and ILCs (including NK cells). We conclude that some subsets are more innate than others, i.e., innate lymphocytes that are made primarily early in utero during gestation while others are made after birth. In practice, a ranking of innateness by ontogeny has implications for the reconstitution of innate lymphocyte subsets after hematopoietic stem cell transplantation. PMID:25346734

  12. Endocrinopathies after allogeneic and autologous transplantation of hematopoietic stem cells.

    PubMed

    Orio, Francesco; Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90-99% of women and 60-90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40-50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  13. Pediatric penile reconstruction using autologous split-thickness skin graft.

    PubMed

    Diaz, E C; Corcoran, J F; Johnson, E K

    2016-06-01

    This video provides a case report of penis entrapment secondary to excessive skin removal during circumcision. It highlights the technical aspects of pediatric penile reconstruction using autologous split-thickness skin graft (STSG). Key points include: 1. Infection prevention is paramount and antibiotic prophylaxis is routine. 2. The usual harvest site for the STSG is the lateral thigh because of its source of glabrous skin and convenient proximity to the penis. The lateral thigh is also outside of the diapered area, which helps lessen postoperative pain and infectious risks. 3. A dermatome is used to harvest the STSG. Skin thickness for penis coverage at this age is usually 10-12/1000 of an inch. 4. Direct contact of the graft and wound bed is essential for graft uptake. Hemostasis of the wound bed is critical to prevent hematoma formation. Elimination of redundant tissue is also important to ensure maximal contact between the graft and underlying wound bed. 5. A pressure dressing or bolster is used to prevent shear, and provide contact between the graft and wound bed for at least the first 5 days. 6. A semi-occlusive dressing, Tegaderm, was used on the donor site and it is believed that it provides a moist environment conducive for epithelial and dermal healing. 7. Lymphedema can result if excess distal penile skin is not excised. It is prudent to limit the amount of mucosal collar or consider direct anastomosis to the glans. PMID:27155806

  14. COMPARISON OF TWIN AND AUTOLOGOUS TRANSPLANTS FOR MULTIPLE MYELOMA

    PubMed Central

    Bashey, Asad; Pérez, Waleska S.; Zhang, Mei-Jie; Anderson, Kenneth C.; Ballen, Karen; Berenson, James R.; To, L. Bik; Fonseca, Rafael; Freytes, César O.; Gale, Robert Peter; Gibson, John; Giralt, Sergio A.; Kyle, Robert A.; Lazarus, Hillard M.; Maharaj, Dipnarine; McCarthy, Philip L.; Milone, Gustavo A.; Nimer, Stephen; Pavlovsky, Santiago; Reece, Donna E.; Schiller, Gary; Vesole, David H.; Hari, Parameswaran

    2008-01-01

    Relapse is the overwhelming cause of treatment-failure after autologous transplantation for multiple myeloma (MM). For patients with a syngeneic donor, twin transplants provide a healthy graft that is free of myeloma. The relative impact of the graft on post-transplant relapse can be estimated by comparing risk of relapse after hematopoietic cell transplantation from genetically-identical twins vs. autotransplants since confounding differences in minor or major histocompatibility antigens are absent in the syngeneic transplant setting. Outcomes of 43 subjects who received twin transplants for MM were compared to 170 matched autotransplant recipients reported to the CIBMTR. Multivariate analysis was performed by fitting a Cox model stratified on matched-pairs. The matched transplant patients studied were similar with respect to subject-, disease- and transplant-related characteristics. Cumulative incidence of relapse/progression was significantly lower and progression-free survival was significantly higher following twin transplants. In multivariate analysis, the probability of relapse/progression was lower in twins (relative risk, RR=0.49, 95% confidence interval (CI) 0.28 – 0.86, p=0.011). Twin transplants have a significantly lower relapse risk than autotransplants in multiple myeloma suggesting that graft composition may impact outcomes following high-dose chemotherapy. PMID:18804041

  15. Hepcidin as a new biomarker for detecting autologous blood transfusion.

    PubMed

    Leuenberger, Nicolas; Barras, Laura; Nicoli, Raul; Robinson, Neil; Baume, Norbert; Lion, Niels; Barelli, Stefano; Tissot, Jean-Daniel; Saugy, Martial

    2016-05-01

    Autologous blood transfusion (ABT) is an efficient way to increase sport performance. It is also the most challenging doping method to detect. At present, individual follow-up of haematological variables via the athlete biological passport (ABP) is used to detect it. Quantification of a novel hepatic peptide called hepcidin may be a new alternative to detect ABT. In this prospective clinical trial, healthy subjects received a saline injection for the control phase, after which they donated blood that was stored and then transfused 36 days later. The impact of ABT on hepcidin as well as haematological parameters, iron metabolism, and inflammation markers was investigated. Blood transfusion had a particularly marked effect on hepcidin concentrations compared to the other biomarkers, which included haematological variables. Hepcidin concentrations increased significantly: 12 hr and 1 day after blood reinfusion, these concentrations rose by seven- and fourfold, respectively. No significant change was observed in the control phase. Hepcidin quantification is a cost-effective strategy that could be used in an "ironomics" strategy to improve the detection of ABT. Am. J. Hematol. 91:467-472, 2016. © 2016 Wiley Periodicals, Inc. PMID:26822428

  16. Autologous transplant in multiple myeloma with an augmented conditioning protocol.

    PubMed

    Abu Zaid, Badran; Abdul-Hai, Ali; Grotto, Itamar; Dray, Lillian; Resnick, Igor B; Tsirigotis, Panagiotis D; Samuel, Simcha; Or, Reuven; Shapira, Michael Y

    2013-11-01

    We compared the tolerability and anti-myeloma effect of two conditioning regimens for autologous stem cell transplant (auto-SCT) in consecutive groups of patients. Protocol 1 was the earlier, and consisted of the combination of three agents in a sequential manner, including etoposide, thiotepa and melphalan (n = 29), while protocol 2 employed melphalan alone (n = 34). The two groups were comparable (other than younger age in protocol 1). Conditioning with protocol 1 seemed more toxic, as expressed by the higher number of febrile days and higher demand for parenteral nutrition. This was not expressed with longer admission time. With 108 and 60 months' median follow-up, respectively, the median survival in patients treated by protocol 2 (melphalan 200 mg/m(2)) was reached at 59 months, while the median survival was not yet reached in patients treated with protocol 1 (p = 0.039). The time to progression was significantly longer with protocol 1 (median 44 months vs. 17 months with protocol 2, p = 0.033). Confounded by the small number of patients, conditioning with melphalan augmented by etoposide and thiotepa in a sequential manner is slightly more toxic than melphalan alone and may benefit patients with myeloma undergoing auto-SCT. PMID:23469964

  17. Endocrinopathies after Allogeneic and Autologous Transplantation of Hematopoietic Stem Cells

    PubMed Central

    Muscogiuri, Giovanna; Palomba, Stefano; Serio, Bianca; Sessa, Mariarosaria; Giudice, Valentina; Ferrara, Idalucia; Tauchmanovà, Libuse; Colao, Annamaria; Selleri, Carmine

    2014-01-01

    Early and late endocrine disorders are among the most common complications in survivors after hematopoietic allogeneic- (allo-) and autologous- (auto-) stem cell transplant (HSCT). This review summarizes main endocrine disorders reported in literature and observed in our center as consequence of auto- and allo-HSCT and outlines current options for their management. Gonadal impairment has been found early in approximately two-thirds of auto- and allo-HSCT patients: 90–99% of women and 60–90% of men. Dysfunctions of the hypothalamus-pituitary-growth hormone/insulin growth factor-I axis, hypothalamus-pituitary-thyroid axis, and hypothalamus-pituitary-adrenal axis were documented as later complicances, occurring in about 10, 30, and 40–50% of transplanted patients, respectively. Moreover, overt or subclinical thyroid complications (including persistent low-T3 syndrome, chronic thyroiditis, subclinical hypo- or hyperthyroidism, and thyroid carcinoma), gonadal failure, and adrenal insufficiency may persist many years after HSCT. Our analysis further provides evidence that main recognized risk factors for endocrine complications after HSCT are the underlying disease, previous pretransplant therapies, the age at HSCT, gender, total body irradiation, posttransplant derangement of immune system, and in the allogeneic setting, the presence of graft-versus-host disease requiring prolonged steroid treatment. Early identification of endocrine complications can greatly improve the quality of life of long-term survivors after HSCT. PMID:24883377

  18. Sublabial Autologous Ear Cartilage Grafting for Increasing the Nasolabial Angle

    PubMed Central

    Toncic, Dinko

    2016-01-01

    Background The loss of nasal tip support is caused by many factors and eventually results in the collapse and eventual dropping of the nasal tip. This reduces the nasolabial (NL) angle and negatively affects respiratory functions and one's appearance. Methods The aim of this retrospective study, which was conducted on 52 patients, was to present and popularize a simple and effective method for the reconstruction of a weakened columella by inserting an autologous ear cartilage graft using a sublabial approach. Results Of all the patients, three patients experienced transplant rejection. The period of follow-up observation was one to five years (mean, 27 months). The results were objectively evaluated by measuring the NL angle in standardized photos before and after the procedure at different time intervals over the follow-up period. We observed a significant increase of the NL angle (mean, 20°), and found these results to be durable over the long term. Of the 52 patients included in this study observed patients, three were dissatisfied (due to immediate infection and shifting of the strut), 28 were satisfied, and 21 were very satisfied. Conclusions The surgical method described here is simple and can be learned quickly. It has very good results with few complications, and is our method of choice for complex and serious cases seen in everyday rhinosurgical practice. PMID:26848445

  19. Older Patients with Myeloma Derive Similar Benefit from Autologous Transplantation

    PubMed Central

    Sharma, Manish; Zhang, Mei-Jie; Zhong, Xiaobo; Abidi, Muneer H.; Akpek, Görgün; Bacher, Ulrike; Callander, Natalie S.; Dispenzieri, Angela; Freytes, César O.; Fung, Henry C.; Gale, Robert Peter; Gasparetto, Cristina; Gibson, John; Holmberg, Leona A.; Kindwall-Keller, Tamila L.; Klumpp, Thomas R.; Krishnan, Amrita Y.; Landau, Heather J.; Lazarus, Hillard M.; Lonial, Sagar; Maiolino, Angelo; Marks, David I.; Mehta, Paulette; Med, Joseph R. Mikhael; Nishihori, Taiga; Olsson, Richard; Ramanathan, Muthalagu; Roy, Vivek; Savani, Bipin N.; Schouten, Harry C.; Scott, Emma; Tay, Jason; To, Luen Bik; Vesole, David H.; Vogl, Dan T.; Hari, Parameswaran

    2014-01-01

    Autologous hematopoietic cell transplantation (AHCT) for plasma cell myeloma is performed less often in people >70 years old than in people ≤70 years old. We analyzed 11,430 AHCT recipients for plasma cell myeloma prospectively reported to the Center for International Blood and Marrow Transplant Research between 2008 and 2011, representing the majority of US AHCT activity during this period. Survival (OS) was compared in 3 cohorts: ages 18 to 59 years (n = 5818), 60 to 69 years (n = 4666), and >70 years (n = 946). Median OS was not reached for any cohort. In multivariate analysis, increasing age was associated with mortality (P = .0006). Myeloma-specific mortality was similar among cohorts at 12%, indicating an age-related effect on nonmyeloma mortality. Analyses were performed in a representative subgroup comparing relapse rate, progression-free survival (PFS), and nonrelapse mortality (NRM). One-year NRM was 0% for age >70 years and 2% for other ages (P = not significant). The three-year relapse rate was 56% in age 18 to 59 years, 61% in age 60 to 69 years, and 63% age >70 (P = not significant). Three-year PFS was similar at 42% in age 18 to 59 years, 38% in age 60 to 69 years, and 33% in age >70 years (P = not significant). Postrelapse survival was significantly worse for the older cohort (P = .03). Older subjects selected for AHCT derived similar antimyeloma benefit without worse NRM, relapse rate, or PFS. PMID:25046833

  20. Quality Improvement Methodologies Increase Autologous Blood Product Administration

    PubMed Central

    Hodge, Ashley B.; Preston, Thomas J.; Fitch, Jill A.; Harrison, Sheilah K.; Hersey, Diane K.; Nicol, Kathleen K.; Naguib, Aymen N.; McConnell, Patrick I.; Galantowicz, Mark

    2014-01-01

    Abstract: Whole blood from the heart–lung (bypass) machine may be processed through a cell salvaging device (i.e., cell saver [CS]) and subsequently administered to the patient during cardiac surgery. It was determined at our institution that CS volume was being discarded. A multidisciplinary team consisting of anesthesiologists, perfusionists, intensive care physicians, quality improvement (QI) professionals, and bedside nurses met to determine the challenges surrounding autologous blood delivery in its entirety. A review of cardiac surgery patients’ charts (n = 21) was conducted for analysis of CS waste. After identification of practices that were leading to CS waste, interventions were designed and implemented. Fishbone diagram, key driver diagram, Plan–Do–Study–Act (PDSA) cycles, and data collection forms were used throughout this QI process to track and guide progress regarding CS waste. Of patients under 6 kg (n = 5), 80% had wasted CS blood before interventions, whereas those patients larger than 36 kg (n = 8) had 25% wasted CS before interventions. Seventy-five percent of patients under 6 kg who had wasted CS blood received packed red blood cell transfusions in the cardiothoracic intensive care unit within 24 hours of their operation. After data collection and didactic education sessions (PDSA Cycle I), CS blood volume waste was reduced to 5% in all patients. Identification and analysis of the root cause followed by implementation of education, training, and management of change (PDSA Cycle II) resulted in successful use of 100% of all CS blood volume. PMID:24783313

  1. First in Man: Sternal Reconstruction with Autologous Stem Cells.

    PubMed

    Khalpey, Zain; Marsh, Katherine M; Ferng, Alice; Riaz, Irbaz Bin; Hemphill, Courtney; Johnson, Kitsie; Oliva, Isabel; Friedman, Mark

    2015-01-01

    Sternal nonunion is associated with high morbidity and treated using rigid plate and screw fixation. This is the first reported example of successful sternal reconstruction using adipose-derived stromal vascular fraction (SVF) stem cells in addition to traditional techniques. Mesenchymal stem cells, one component of the SVF, play an important role in bone healing and were therefore used to promote remedial processes in a patient with sternal nonunion. A 3D printed model of the patient's sternum was used for preoperative planning of the plating. Intraoperatively, SVF was isolated using ultrasonic cavitation and previously planned sternal plating was completed. A total of 300 million cells were delivered via both local injection and intravenously before chest closure. The patient's pain dramatically decreased, commensurate with healed areas of nonunion by 3 months and maintained at 6 months postoperatively, supported by three-dimensional computed tomography imaging. Utilizing autologous stem cells from the SVF in conjunction with existing plating techniques may provide an optimal platform to stabilize the sternum and promote bone healing, although additional study is recommended. PMID:25914951

  2. Chemotaxis of large granular lymphocytes

    SciTech Connect

    Pohajdak, B.; Gomez, J.; Orr, F.W.; Khalil, N.; Talgoy, M.; Greenberg, A.H.

    1986-01-01

    The hypothesis that large granular lymphocytes (LGL) are capable of directed locomotion (chemotaxis) was tested. A population of LGL isolated from discontinuous Percoll gradients migrated along concentration gradients of N-formyl-methionyl-leucyl-phenylalanine (f-MLP), casein, and C5a, well known chemoattractants for polymorphonuclear leukocytes and monocytes, as well as interferon-..beta.. and colony-stimulating factor. Interleukin 2, tuftsin, platelet-derived growth factor, and fibronectin were inactive. Migratory responses were greater in Percoll fractions with the highest lytic activity and HNK-1/sup +/ cells. The chemotactic response to f-MLP, casein, and C5a was always greater when the chemoattractant was present in greater concentration in the lower compartment of the Boyden chamber. Optimum chemotaxis was observed after a 1 hr incubation that made use of 12 ..mu..m nitrocellulose filters. LGL exhibited a high degree of nondirected locomotion when allowed to migrate for longer periods (> 2 hr), and when cultured in vitro for 24 to 72 hr in the presence or absence of IL 2 containing phytohemagluttinin-conditioned medium. LGL chemotaxis to f-MLP could be inhibited in a dose-dependent manner by the inactive structural analog CBZ-phe-met, and the RNK tumor line specifically bound f-ML(/sup 3/H)P, suggesting that LGL bear receptors for the chemotactic peptide.

  3. Inability to Mediate Prolonged Reduction of Regulatory T Cells After Transfer of Autologous CD25-depleted PBMC and Interleukin-2 After Lymphodepleting Chemotherapy

    PubMed Central

    Powell, Daniel J.; de Vries, Christiaan R.; Allen, Tamika; Ahmadzadeh, Mojgan; Rosenberg, Steven A.

    2007-01-01

    Summary CD25+CD4+ regulatory T cells (Treg) regulate peripheral self-tolerance and possess the ability to suppress antitumor responses, which may explain the poor clinical response of cancer patients undergoing active immunization protocols, and provides the rationale for neutralizing Treg cells in vivo to strengthen local antitumor immune responses. Because interleukin-2 (IL-2) mediates tumor regression in about 15% of treated patients but simultaneously increases Treg cells, we hypothesized that transient elimination of Treg cells will enhance the clinical effectiveness of IL-2 therapy. In the current study, 5 patients with metastatic melanoma who were refractory to prior IL-2 received a lymphodepleting preparative regimen followed by the adoptive transfer of autologous lymphocytes depleted of CD25+ Treg cells and high-dose IL-2 administration. CD25+ cells were eliminated from patient leukapheresis samples using a clinical-grade, large-scale immunomagnetic system, leaving CD8+ and CD25−CD4+ T cells intact. In the early aftermath of CD25+ Treg cell-depleted cell infusion, CD25+FOXP3+ CD4+ Treg cells rapidly repopulated the peripheral blood of treated patients with 18% to 63% of CD4+ T cells expressing FOXP3. Recovering CD25+CD4+ T cells exhibited suppressive activity against CD25−CD4+ effector T-cell proliferation in vitro. No patient experienced objective tumor regression or autoimmunity. Our results indicate that in vivo transfer of autologous CD25-depleted mononuclear populations to lymphopenic patients in combination with high-dose IL-2 is not sufficient to mediate prolonged reduction of Treg cells after IL-2 administration. PMID:17457218

  4. T and B lymphocytes in myasthenia gravis.

    PubMed Central

    Itoyama, Y; Kawanami, S; Goto, I; Kuroiwa, Y

    1979-01-01

    Peripheral blood lymphocytes from seventeen non-thymectomized and nine thymectomized patients with myasthenia gravis (MG) and thirteen healthy controls were examined for the presence of surface markers characteristic of T and B lymphocytes by rosette formation with sheep red blood cells (SRBC). T cells were identified by their capacity to spontaneously form rosettes with SRBCs. The percentage of B lymphocytes was determined by the erythrocyte antibody complement (EAC) rosette-forming test. The EAC complex was prepared with either whole rabbit anti-SRBC serum or with the IgM fraction of rabbit anti-SRBC serum. The two kind of erythrocyte complement rosette-forming cells (EAC-RFC) are designated erythrocyte-haemolysin-complement RFC (EA(H)C-RFC), and erythrocyte-IgM-complement RFC (EA(M)C-RFC). The percentage of total lymphocytes and T cells was not altered in MG patients. The percentage of 'active' T cells, which have been considered to be more actively involved in cellular immunity, was also similar in MG patients and controls. A significant increase in EA(H)C-RFC occurred in both thymectomized and non-thymectomized MG patients, while in B cells detected by EA(M)C-RFC no alterations were found. The increase in EA(H)C-RFC in lymphocytes from MG patients may be due to an increase in the 19S antibody-forming B lymphocytes or to an increase in T cells which have Fc receptors on their surface. PMID:315844

  5. Effects of isolation on various lymphocyte activities

    SciTech Connect

    Jessop, J.J.

    1986-01-01

    Prolonged exposure of Sprague Dawley male rats to isolation, water scheduling, or their combination resulted in an enhanced lymphocyte proliferative response to mitogen. Time course studies of effects of isolation on mitogenic response of splenic and/or blood T and B lymphocytes and splenic NK cell activity demonstrated a suppression with short term exposure followed by an enhancement with prolonged exposure. Use of immunoperoxidase staining techniques to identify splenic T or T helper cells revealed that prolonged exposure to isolation had no significant effect on the proportion of these cell populations in the spleen. Examination of the data by Lineweaver-Burke plot and plot of the data as % maximum response showed that prolonged exposure to isolation did not alter the sensitivity of the lymphocytes to mitogen. Involvement of corticosteroids and opioid peptides in mediation of the effects of exposure to isolation on lymphocyte activity was assessed by measurement of plasma corticosterone by radioimmunoassay and by examination of the ability of the opioid antagonist naltrexone to alter the effects of isolation on lymphocyte proliferative response to mitogen. Attempts were made to mimic the effects of short-term isolation on lymphocyte activity by morphine sulfate administration.

  6. Regulation of Lymphocyte Function by Adenosine

    PubMed Central

    Linden, Joel; Cekic, Caglar

    2014-01-01

    Adenosine regulates the interaction between lymphocytes and the vasculature and is important for controlling lymphocyte trafficking in response to tissue injury or infection. Adenosine can blunt the effects of T cell receptor (TCR) activation primarily by activating adenosine A2A receptors (A2AR) and signaling via cyclic AMP and protein kinase A (PKA). PKA reduces proximal TCR signaling by phosphorylation of C-terminal Src kinase (Csk), nuclear factor of activated T cells (NF-AT) and cyclic AMP response element binding protein (CREB). PKA activation can either enhance or inhibit the survival of T cells depending on the strength and duration of signaling. Inducible enzymes such as CD73 and CD39 regulate adenosine formation and degradation in vivo. The extravasation of lymphocytes through blood vessels is influenced by A2AR-mediated suppression of Intercellular Adhesion Molecule 1 (ICAM) expression on lymphocytes and diminished production of IFNγ and IFNγ-inducible chemokines that are chemotactic to activated lymphocytes. Adenosine also decreases the barrier function of vascular endothelium by activating A2BRs. In sum, adenosine signaling is influenced by tissue inflammation and injury through induction of receptors and enzymes and has generally inhibitory effects on lymphocyte migration into inflamed tissues due to PKA-mediated effects on adhesion molecules, IFNγ production and endothelial barrier function. PMID:22772752

  7. Setting the clock for recirculating lymphocytes.

    PubMed

    Eichner, Alexander; Sixt, Michael

    2011-01-01

    In their search for antigens, lymphocytes continuously shuttle among blood vessels, lymph vessels, and lymphatic tissues. Chemokines mediate entry of lymphocytes into lymphatic tissues, and sphingosine 1-phosphate (S1P) promotes localization of lymphocytes to the vasculature. Both signals are sensed through G protein-coupled receptors (GPCRs). Most GPCRs undergo ligand-dependent homologous receptor desensitization, a process that decreases their signaling output after previous exposure to high ligand concentration. Such desensitization can explain why lymphocytes do not take an intermediate position between two signals but rather oscillate between them. The desensitization of S1P receptor 1 (S1PR1) is mediated by GPCR kinase 2 (GRK2). Deletion of GRK2 in lymphocytes compromises desensitization by high vascular S1P concentrations, thereby reducing responsiveness to the chemokine signal and trapping the cells in the vascular compartment. The desensitization kinetics of S1PR1 allows lymphocytes to dynamically shuttle between vasculature and lymphatic tissue, although the positional information in both compartments is static. PMID:22067458

  8. Use of autologous blood as part of the perfusate for cardiopulmonary bypass: a priming technique.

    PubMed

    Myers, G J; Legare, J F; Sullivan, J A; Leadon, R B; Johnstone, R; Swyer, W; Squires, C; Power, C; Hirsch, G M

    2002-05-01

    In an attempt to replace the oncotic and protein coating capabilities of serum albumin in the perfusate, we established a priming protocol that used autologous blood as part of the perfusate solution. Prior to March 1, 1999, our standard priming protocol was 1650 ml of crystalloid with 250 ml of 5% serum albumin and 5,000 units of heparin. After removing albumin from our prime, our standard protocol was altered to include 40 ml of the patient's autologous blood in 1,800 ml of crystalloid and 10,000 units of heparin. To determine the intraoperative effects of using albumin/crystalloid primes (Group A), autologous blood/crystalloid primes (Group B) and crystalloid primes (Group C), a total of 178 patients were sequentially evaluated. Intraoperative parameters evaluated were total protein (TP), colloid osmotic pressure (COP), platelets (Plts) and fluid requirements during cardiopulmonary bypass (CPB). During an overlapping 12-month period of time, 1,092 consecutive cardiac surgical cases using CPB (584 albumin prime; 508 autologous blood prime) were evaluated for clinical outcomes in terms of mortality and length of hospitalization. In addition, over a period of 15 months, 1,458 patients in both the autologous blood/crystalloid group and the crystalloid only group were evaluated for the incidence of high-pressure excursions (HPE) after going on bypass. Comparative reviews of TP, COP and Plts demonstrated no significant difference 10 min after the start of bypass between Groups A and B. However, in Group C, there was a statistically significant increase in the intraoperative fluid requirements during CPB, compared to both of the other groups. There was no significant difference in the incidence of HPE, with an occurrence of 1.04% in the crystalloid only group and 1.11% in the autologous blood/crystalloid group. Autologous blood perfusates were identical to albumin perfusates in their platelet protection and reduction of fluid shifts during the intraoperative period

  9. A Dendritic Cell Vaccine Pulsed with Autologous Hypochlorous Acid-Oxidized Ovarian Cancer Lysate Primes Effective Broad Antitumor Immunity: From Bench to Bedside

    PubMed Central

    Chiang, Cheryl Lai-Lai; Kandalaft, Lana E.; Tanyi, Janos; Hagemann, Andrea R.; Motz, Gregory T.; Svoronos, Nikolaos; Montone, Kathleen; Mantia-Smaldone, Gina M.; Nisenbaum, Harvey L.; Levine, Bruce L.; Kalos, Michael; Czerniecki, Brian J.; Torigian, Drew A.; Powell, Daniel J.; Mick, Rosemarie; Smith, Lori; Coukos, George

    2013-01-01

    Purpose Whole tumor lysates are promising antigen sources for dendritic cell (DC) therapy for they contain many relevant immunogenic epitopes to help prevent tumor escape. Two common methods of tumor lysate preparations are freeze-thaw processing and UVB-irradiation to induce necrosis and apoptosis, respectively. Hypochlorous acid (HOCl)-oxidation is a new method for inducing primary necrosis and enhancing the immunogenicity of tumor cells. Experimental Design We compared DCs’ ability to engulf three different tumor lysate preparations, produce Th1-priming cytokines and chemokines, stimulate mixed leukocyte reactions (MLR), and finally elicit T-cell responses capable of controlling tumor growth in vivo. Results We demonstrated that DCs engulfed HOCl-oxidized lysate most efficiently, stimulated robust MLRs and elicited strong tumor-specific IFN-γ secretions in autologous T-cells. These DCs produced the highest levels of Th1-priming cytokines and chemokines, including IL-12. Mice vaccinated with HOCl-oxidized ID8-ova lysate pulsed DCs developed T-cell responses that effectively controlled tumor growth. Safety, immunogenicity of autologous DCs pulsed with HOCl-oxidized autologous tumor lysate (OCDC vaccine), clinical efficacy and progression free survival (PFS) were evaluated in a pilot study of five subjects with recurrent ovarian cancer. OCDC vaccination produced few grade 1 toxicities and elicited potent T-cell responses against known ovarian tumor antigens. Circulating T regulatory cells and serum IL-10 were also reduced. Two subjects experienced durable PFS of ≥24 months after OCDC. Conclusions This is the first study demonstrating the potential efficacy of a DC vaccine pulsed with HOCl-oxidized tumor lysate, a novel approach in preparing DC vaccine that is potentially applicable to many cancers. PMID:23838316

  10. Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction

    ClinicalTrials.gov

    2016-09-09

    Adult Mixed Glioma; Adult Pineal Gland Astrocytoma; Adult Solid Neoplasm; AIDS Related Immunoblastic Lymphoma; AIDS-Related Burkitt Lymphoma; AIDS-Related Diffuse Large Cell Lymphoma; AIDS-Related Diffuse Mixed Cell Lymphoma; AIDS-Related Diffuse Small Cleaved Cell Lymphoma; AIDS-Related Hodgkin Lymphoma; AIDS-Related Lymphoblastic Lymphoma; AIDS-Related Lymphoma; AIDS-Related Primary Central Nervous System Lymphoma; Glioma; Lymphoma; Recurrent Adult Brain Neoplasm; Recurrent Adult Soft Tissue Sarcoma; Recurrent Bladder Carcinoma; Recurrent Breast Carcinoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Colorectal Carcinoma; Recurrent Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Head and Neck Carcinoma; Recurrent Lung Carcinoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Melanoma; Recurrent Pancreatic Carcinoma; Recurrent Prostate Carcinoma; Recurrent Renal Cell Carcinoma; Recurrent Thyroid Gland Carcinoma; Refractory Chronic Lymphocytic Leukemia; Refractory Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma

  11. In vivo migration of labeled autologous natural killer cells to liver metastases in patients with colon carcinoma

    PubMed Central

    Matera, Lina; Galetto, Alessandra; Bello, Marilena; Baiocco, Cinzia; Chiappino, Isabella; Castellano, Giancarlo; Stacchini, Alessandra; Satolli, Maria A; Mele, Michele; Sandrucci, Sergio; Mussa, Antonio; Bisi, Gianni; Whiteside, Theresa L

    2006-01-01

    Background Besides being the effectors of native anti-tumor cytotoxicity, NK cells participate in T-lymphocyte responses by promoting the maturation of dendritic cells (DC). Adherent NK (A-NK) cells constitute a subset of IL-2-stimulated NK cells which show increased expression of integrins and the ability to adhere to solid surface and to migrate, infiltrate, and destroy cancer. A critical issue in therapy of metastatic disease is the optimization of NK cell migration to tumor tissues and their persistence therein. This study compares localization to liver metastases of autologous A-NK cells administered via the systemic (intravenous, i.v.) versus locoregional (intraarterial, i.a.) routes. Patients and methods A-NK cells expanded ex-vivo with IL-2 and labeled with 111In-oxine were injected i.a. in the liver of three colon carcinoma patients. After 30 days, each patient had a new preparation of 111In-A-NK cells injected i.v. Migration of these cells to various organs was evaluated by SPET and their differential localization to normal and neoplastic liver was demonstrated after i.v. injection of 99mTc-phytate. Results A-NK cells expressed a donor-dependent CD56+CD16+CD3- (NK) or CD56+CD16+CD3+ (NKT) phenotype. When injected i.v., these cells localized to the lung before being visible in the spleen and liver. By contrast, localization of i.a. injected A-NK cells was virtually confined to the spleen and liver. Binding of A-NK cells to liver neoplastic tissues was observed only after i.a. injections. Conclusion This unique study design demonstrates that A-NK cells adoptively transferred to the liver via the intraarterial route have preferential access and substantial accumulation to the tumor site. PMID:17105663

  12. Carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) for corneal epithelium reconstruction: a histological study.

    PubMed

    Bardag-Gorce, Fawzia; Oliva, Joan; Wood, Andrew; Hoft, Richard; Pan, Derek; Thropay, Jacquelyn; Makalinao, Andrew; French, Samuel W; Niihara, Yutaka

    2015-04-01

    This study investigates the therapeutic effects of carrier-free cultured autologous oral mucosa epithelial cell sheet (CAOMECS) transplantation for experimentally induced severe rabbit limbal stem cell deficiency (LSCD). Buccal biopsies were performed and CAOMECS were cultured and transplanted onto diseased corneas. Six-month follow-up examinations indicated that three out of four corneas with CAOMECS grafts showed a decrease in superficial vascularization, while almost all the sham corneas did not show a similar decrease. H&E staining of corneas showed that CAOMECS transplantation reduced blood vessel invasion of central cornea, reduced lymphocyte infiltration and fibrotic tissue formation. DeltaNp63 stained markedly in the grafted cornea and to a lesser extent in the sham corneas. PCNA and Ki-67 staining were much greater in the sham corneas than in the grafted and normal corneas. K3 and K13 staining demonstrated that CAOMECS transplanted corneas had much more K3- and less K13- positive cells compared to the sham corneas. Muc5AC was decreased in the central region of grafted corneas. Very little alpha-smooth muscle actin (aSMA) staining was detected in grafted corneas, while there was a greater amount of aSMA staining in sham corneas. Staining for anti-angiogenic factor TIMP -3 was also increased, and pro-angiogenic factor MMP-3 was decreased in grafted corneas compared to sham corneas. Our results indicate that CAOMECS grafts resulted in improved epithelialization of the corneal surface and decreased vascularization and fibrosis of the diseased corneas. PMID:25881998

  13. Adenosine deaminase regulates Treg expression in autologous T cell-dendritic cell cocultures from patients infected with HIV-1.

    PubMed

    Naval-Macabuhay, Isaac; Casanova, Víctor; Navarro, Gemma; García, Felipe; León, Agathe; Miralles, Laia; Rovira, Cristina; Martinez-Navio, José M; Gallart, Teresa; Mallol, Josefa; Gatell, José M; Lluís, Carme; Franco, Rafael; McCormick, Peter J; Climent, Núria

    2016-02-01

    Regulatory T cells have an important role in immune suppression during HIV-1 infection. As regulatory T cells produce the immunomodulatory molecule adenosine, our aim here was to assess the potential of adenosine removal to revert the suppression of anti-HIV responses exerted by regulatory T cells. The experimental setup consisted of ex vivo cocultures of T and dendritic cells, to which adenosine deaminase, an enzyme that hydrolyzes adenosine, was added. In cells from healthy individuals, adenosine hydrolysis decreased CD4(+)CD25(hi) regulatory T cells. Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine receptor agonist, significantly decreased CD4(+)CD25(lo) cells, confirming a modulatory role of adenosine acting via adenosine receptors. In autologous cocultures of T cells with HIV-1-pulsed dendritic cells, addition of adenosine deaminase led to a significant decrease of HIV-1-induced CD4(+)CD25(hi) forkhead box p3(+) cells and to a significant enhancement of the HIV-1-specific CD4(+) responder T cells. An increase in the effector response was confirmed by the enhanced production of CD4(+) and CD8(+) CD25(-)CD45RO(+) memory cell generation and secretion of Th1 cytokines, including IFN-γ and IL-15 and chemokines MIP-1α/CCL3, MIP-1β/CCL4, and RANTES/CCL5. These ex vivo results show, in a physiologically relevant model, that adenosine deaminase is able to enhance HIV-1 effector responses markedly. The possibility to revert regulatory T cell-mediated inhibition of immune responses by use of adenosine deaminase, an enzyme that hydrolyzes adenosine, merits attention for restoring T lymphocyte function in HIV-1 infection. PMID:26310829

  14. Potentiation of lymphocyte proliferative responses by nickel sulfide

    NASA Technical Reports Server (NTRS)

    Jaramillo, A.; Sonnenfeld, G.

    1992-01-01

    Crystalline nickel sulfide (NiS) induced a spleen cell proliferation that resembles a mixed lymphocyte reaction (MLR). It depended on cell-cell interaction, induced high levels of interleukin-1 (IL-1) and interleukin-2 (IL-2) and the responding cell subpopulation was composed of CD4+ T lymphocytes. Furthermore, the proliferation was inhibited in a dose-dependent manner by magnesium. Crystalline NiS also increased significantly the spleen cell proliferative response to concanavalin A (Con A) and lipopolysaccharide (LPS) with magnesium potentiating the combined effects of crystalline NiS and mitogens. Interestingly, crystalline NiS did not show any effect on the induction of IL-2 by Con A. The results described herein suggest that crystalline NiS can potentiate both antigenic (MLR) and mitogenic (Con A and LPS) proliferative responses in vitro. Crystalline NiS appears to potentiate these responses by acting in the form of ionic nickel on several intracellular targets for which magnesium ions have different noncompetitive interactions. The effects of magnesium on the potentiating action of crystalline NiS are different depending upon the type of primary stimulatory signal for proliferation (mitogenic or antigenic).

  15. Abnormal immune responses of Bloom's syndrome lymphocytes in vitro.

    PubMed Central

    Hütteroth, T H; Litwin, S D; German, J

    1975-01-01

    Bloom's syndrome is a rare autosmal recessive disorder, first characterized by growth retardation and asum-sensitive facial telangiectasia and more recently demonstarted to have increased chromosome instability, a predisposition to malignancy, and increased susecptibitily to infection. The present report ocncern the immune function of Bloom's syndrom lymphoctes in vitro. Four affected homozgotes and five heterozygotes were studied. An abnormal serum concentartion of at least one class of immunoglobin was present in three out of four homozgotes. Affected homozgotes were shown capable of both a humoral and cellular response after antigenic challenge, the responses in general being weak but detectable. Blood lymphocytes from Bloom's syndrome individuals were cultured in impaired proliferavite response and synthesized less immunoglobulin at the end of 5 days than did normal controls. In contrast, they had a normal proliferative response to phytohemagglutinin except at highest concentrations of the mitogen. In the mixed lymphocte culture, Bloom's syndrome lymphocytes proved to be poor responder cells but normal stimulator cells. Lmyphoctes from the heterozgotes produced normal responses in these three systems. Distrubed immunity appears to be on of several major consequences of homozygosity for the Bloom's syndrome gene. Although the explanation for this pleiotropism is at present obscure, the idea was advanced that the aberrant immune function is, along with the major clincial feature-small body size, amanifestation of defect in cellular proliferation. PMID:124745

  16. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  17. PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer.

    PubMed

    Li, Zhongwu; Lai, Yumei; Sun, Li; Zhang, Xiaotian; Liu, Ruping; Feng, Guoshuang; Zhou, Lixin; Jia, Lin; Huang, Xiaozheng; Kang, Qiang; Lin, Dongmei; Gao, Jing; Shen, Lin

    2016-09-01

    The mechanism of carcinogenesis of gastric cancer (GC) is still unclear now. This study aimed to explore the correlations among PD-L1, Epstein-Barr virus (EBV) infection, lymphocyte infiltration, HER2 expression, HER2 gene status, histology, and other clinicopathological factors in GC. A total of 44 GC patients with massive lymphocyte infiltration (GC-MLI) and 93 GC patients without massive lymphocyte infiltration were involved in this study. Immunohistochemical analysis was used to test the expression levels of PD-L1 and HER2. Fluorescence in situ hybridization was used on HER2-positive cases with a score of 2+ to test the HER2 gene status. EBV-encoded RNA was used to test for EBV infection. In univariate analysis, PD-L1 expression was significantly associated with GC-MLI (P<.001), lower age (P=.019), EBV infection (P<.001), lower HER2 expression (P=.011), and diffuse/mixed type of histology (P=.022). EBV-encoded RNA-positive cases were significantly associated with GC-MLI (P<.001), lower age (P=.016), diffuse/mixed type of histology (P=.011), and lower HER2 expression (P=.032). In the multivariate logistic regression model, GC-MLI and the diffuse/mixed type histology were identified as 2 independent factors that affected PD-L1 expression (P<.001). Furthermore, PD-L1-positive cases have worse overall survival than do PD-L1-negative cases (P=.011). These results suggest that massive lymphocyte infiltration and the diffuse/mixed type histology of GC should be taken into consideration to select the appropriate patients for PD-L1 inhibitory treatment in the future. PMID:27260946

  18. A cost comparison of allogeneic and preoperatively or intraoperatively donated autologous blood.

    PubMed

    Roberts, W A; Kirkley, S A; Newby, M

    1996-07-01

    We determined the cost of allogeneic packed red blood cells and autologous whole blood donated either preoperatively or in the operating room during hemodilution. Direct and indirect cost estimates were based on patients requiring simple transfusion and included procurement and preparation of the blood including testing performed, materials and time used, waste, and materials for administration. Data were derived from prospective blood bank time studies, material invoice records, and retrospective review of anesthesia times. Viral infection and transfusion reaction costs were accepted from previously published sources. Direct cost of purchasing and indirect costs of preparation resulted in an overall cost of $107.26 for the first unit of allogeneic packed red blood cells transfused. A second unit was slightly less costly ($100.89), as no type and screen was required and the same delivery set and filter can be used. The total cost of acquisition, processing, and transfusion of 1 U of preoperatively donated autologous blood was $97.83. The total cost of a 2-U transfusion of autologous whole blood donated in the operating room during acute normovolemic hemodilution was $83.10. These data suggest that autologous predonation of whole blood is somewhat less expensive than allogeneic packed red blood cells, and that hemodilution may be a cost effective alternative to autologous predonation in selected patients. PMID:8659723

  19. Comorbidities, Alcohol Use Disorder, and Age Predict Outcomes after Autologous Hematopoietic Cell Transplantation for Lymphoma.

    PubMed

    Graf, Solomon A; Vaughn, Jennifer E; Chauncey, Thomas R; Storer, Barry E; Gopal, Ajay K; Holmberg, Leona A; McCune, Jeannine S; Bensinger, William I; Maloney, David G; Press, Oliver W; Storb, Rainer; Sorror, Mohamed L

    2016-09-01

    Autologous hematopoietic cell transplantation (HCT) is a treatment option for many patients diagnosed with lymphoma. The effects of patient-specific factors on outcomes after autologous HCT are not well characterized. Here, we studied a sequential cohort of 754 patients with lymphoma treated with autologous HCT between 2000 and 2010. In multivariate analysis, patient-specific factors that were statistically significantly associated with nonrelapse mortality (NRM) included HCT-specific comorbidity index (HCT-CI) scores  ≥ 3 (HR, 1.94; P = .05), a history of alcohol use disorder (AUD) (HR, 2.17; P = .004), and older age stratified by decade (HR, 1.29; P = .02). HCT-CI ≥ 3, a history of AUD, and age > 50 were combined into a composite risk model: NRM and overall mortality rates at 5 years increased from 6% to 30% and 32% to 58%, respectively, in patients with 0 versus all 3 risk factors. The HCT-CI is a valid tool in predicting mortality risks after autologous HCT for lymphoma. AUD and older age exert independent prognostic impact on outcomes. Whether AUD indicates additional organ dysfunction or sociobehavioral abnormality warrants further investigation. The composite model may improve risk stratification before autologous HCT. PMID:27311969

  20. Intrabronchial Infusion of Autologous Blood Plus Thrombin for Intractable Pneumothorax After Bronchial Occlusion Using Silicon Spigots

    PubMed Central

    Nakahara, Yasuharu; Kawamura, Tetsuji; Sasaki, Shin; Tsukamoto, Hiroaki; Mochiduki, Yoshiro

    2016-01-01

    Background: Bronchial occlusion therapy using silicon spigots is effective for intractable pneumothorax. However, sometimes the pneumothorax is refractory to bronchial occlusion because of collateral ventilation. For such difficult pneumothoraces, we attempted an intrabronchial infusion of autologous blood plus thrombin to control collateral ventilation and stop air leaks. Methods: We performed bronchial occlusions using silicon spigots in patients with spontaneous pneumothorax secondary to emphysema and refractory to chest drainage, but which was inoperable owing to each patient’s poor surgical candidacy and poor overall health condition. When bronchial occlusion proved ineffective, we undertook intrabronchial infusion of autologous blood plus thrombin, 2 to 4 days after bronchial occlusion. A catheter was inserted into the subpleural area, through a gap between the silicon spigot and the bronchial wall, using a flexible bronchoscope under fluoroscopic guidance. Autologous blood, followed by a thrombin solution, was infused using the catheter. We repeated the same infusion a total of 4 to 6 times while changing the target bronchi. All interventions were performed under local anesthesia. Results: The subjects were 9 men, aged from 61 to 88 years, with smoking histories. Three patients also had interstitial pneumonia, and 6 patients had undergone pleurodesis in vain before bronchial occlusion. For 4of the 9 patients, autologous blood plus thrombin infusions successfully stopped air leaks, and in 3 patients, intrabronchial infusions and pleurodesis halted leaks altogether. Conclusion: Intrabronchial infusion of autologous blood plus thrombin was effective for intractable pneumothoraces that could not be clinically managed, even by bronchial occlusion using silicon spigots. PMID:27454474

  1. Biochemical, mechanical, and morphological properties of a completely autologous platelet-rich wound sealant.

    PubMed

    Wu, Xiuwen; Ren, Jianan; Luan, Jianfeng; Yao, Gengong; Li, Jieshou

    2012-06-01

    The optimal composition of fibrin sealant preparations is not known. We, therefore, sought to construct a series of sealants from autologous components and compare their functioning to Bioseal a commonly used sealant. Characteristics of the platelet-rich plasma, cryoprecipitate, and thrombin were determined and compared to commercial glue from composition, function, and microscopy aspects. The concentrations of platelets as well as fibronectin in autologous fibrin glues were significantly higher than those in commercial ones (P < 0.001). Mechanical values (maximum amplitude and clot strength) obtained from thrombelastograph assays in two groups were not significantly different (P > 0.05). A dense platelet surface and fibrin net structures could be observed in the autologous samples, whereas there were only sparse fibrin nets without cellular components in Bioseal. Characterization of autologous and Bioseal fibrin sealants and their performance do not have significant difference in biochemical and mechanical properties. The entirely autologous platelet-rich gel in the present study may get wide application in future practice after confirmation of its safety, efficiency, and economic benefits. PMID:22395185

  2. Autologous fibrin sealant (Vivostat®) in the neurosurgical practice: Part I: Intracranial surgical procedure

    PubMed Central

    Graziano, Francesca; Certo, Francesco; Basile, Luigi; Maugeri, Rosario; Grasso, Giovanni; Meccio, Flavia; Ganau, Mario; Iacopino, Domenico G.

    2015-01-01

    Background: Hemorrhages, cerebrospinal fluid (CSF) fistula and infections are the most challenging postoperative complications in Neurosurgery. In this study, we report our preliminary results using a fully autologous fibrin sealant agent, the Vivostat® system, in achieving hemostasis and CSF leakage repair during cranio-cerebral procedures. Methods: From January 2012 to March 2014, 77 patients were studied prospectively and data were collected and analyzed. Autologous fibrin sealant, taken from patient's blood, was prepared with the Vivostat® system and applied on the resection bed or above the dura mater to achieve hemostasis and dural sealing. The surgical technique, time to bleeding control and associated complications were recorded. Results: A total of 79 neurosurgical procedures have been performed on 77 patients. In the majority of cases (98%) the same autologous fibrin glue provided rapid hemostasis and dural sealing. No patient developed allergic reactions or systemic complications in association with its application. There were no cases of cerebral hematoma, swelling, infection, or epileptic seizures after surgery whether in the immediate or in late period follow-up. Conclusions: In this preliminary study, the easy and direct application of autologous fibrin sealant agent helped in controlling cerebral bleeding and in providing prompt and efficient dural sealing with resolution of CSF leaks. Although the use of autologous fibrin glue seems to be safe, easy, and effective, further investigations are strongly recommended to quantify real advantages and potential limitations. PMID:25984391

  3. Using autologous peritoneal graft for portal vein injury due to blunt thoracoabdominal trauma

    PubMed Central

    Sabuncuoglu, M Z; Dandin, O; Teomete, U; Cakir, T; Kayaalp, C

    2015-01-01

    Background Autologous vein or prosthetic materials are used as patch or tube graft for portal or caval vein reconstruction after trauma or tumor resection. Preparation of autologous veins requires extra incisions and is time consuming that is crucial especially in trauma patients. This condition adversely affects postoperative morbidity and mortality, particularly in trauma cases. Prosthetic materials may not be available in some centers, and their use is associated with an increased risk of infection. Description of case A 28-year-old hemodynamically unstable man presented to the emergency room with complete transection of main portal vein, right hepatic artery and common bile duct with tissue defect on hepatoduodenal ligament due to blunt thoracoabdominal trauma. Reconstructing of the portal vein was performed using an autologous peritoneal tube graft. Conclusion Autologous peritoneal graft is a very good option in the treatment of major vascular injuries which can not be repaired with primary suturing. It is also easy to prepare and use, safe, without a need of additional incision, as an alternative to autologous veins and prosthetic materials especially under emergency conditions. Hippokratia 2015; 19 (3): 260-262. PMID:27418787

  4. Mixed Dementia

    MedlinePlus

    ... bodies , What Is Alzheimer's? NIA-Funded Memory & Aging Project Reveals Mixed Dementia Common Data from the first ... disease. For example, in the Memory and Aging Project study involving long-term cognitive assessments followed by ...

  5. Metabolic dysfunction in lymphocytes promotes postoperative morbidity.

    PubMed

    Edwards, Mark R; Sultan, Pervez; del Arroyo, Ana Gutierrez; Whittle, John; Karmali, Shamir N; Moonesinghe, S Ramani; Haddad, Fares S; Mythen, Michael G; Singer, Mervyn; Ackland, Gareth L

    2015-09-01

    Perioperative lymphopenia has been linked with an increased risk of postoperative infectious complications, but the mechanisms remain unclear. We tested the hypothesis that bioenergetic dysfunction is an important mechanism underlying lymphopenia, impaired functionality and infectious complications. In two cohorts of patients (61-82 years old) undergoing orthopaedic joint replacement (n=417 and 328, respectively), we confirmed prospectively that preoperative lymphopenia (≤1.3 x 10(9)·l(-1); <20% white cell count; prevalence 15-18%) was associated with infectious complications (relative risk 1.5 (95% confidence interval 1.1-2.0); P=0.008) and prolonged hospital stay. Lymphocyte respirometry, mitochondrial bioenergetics and function were assessed (n=93 patients). Postoperative lymphocytes showed a median 43% fall (range: 26-65%; P=0.029; n=13 patients) in spare respiratory capacity, the extra capacity available to produce energy in response to stress. This was accompanied by reduced glycolytic capacity. A similar hypometabolic phenotype was observed in lymphocytes sampled preoperatively from chronically lymphopenic patients (n=21). This hypometabolic phenotype was associated with functional lymphocyte impairment including reduced T-cell proliferation, lower intracellular cytokine production and excess apoptosis induced by a range of common stressors. Glucocorticoids, which are ubiquitously elevated for a prolonged period postoperatively, generated increased levels of mitochondrial reactive oxygen species, activated caspase-1 and mature interleukin (IL)-1β in human lymphocytes, suggesting inflammasome activation. mRNA transcription of the NLRP1 inflammasome was increased in lymphocytes postoperatively. Genetic ablation of the murine NLRP3 inflammasome failed to prevent glucocorticoid-induced lymphocyte apoptosis and caspase-1 activity, but increased NLRP1 protein expression. Our findings suggest that the hypometabolic phenotype observed in chronically lymphopenic

  6. Activation of human lymphocytes by supernatants from human thymic epithelium.

    PubMed Central

    Goust, J M; Vesole, D H; Fudenberg, H H

    1979-01-01

    Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS. PMID:160851

  7. Activation of human lymphocytes by supernatants from human thymic epithelium.

    PubMed

    Goust, J M; Vesole, D H; Fudenberg, H H

    1979-11-01

    Supernatants from human thymic epithelial cells (TS) were found to have a mitogenic effect on cultured human peripheral blood mononuclear cells and to potentiate their responses to lectins. This was not observed with culture supernatants from the human cell lines AV-3 and HeLa or from the murine cell line L-929. The maximum potentiating effects were observed with pokeweed mitogen (PWM) and phytohaemagglutinin (PHA), whereas the response to concanavalin A (Con A) was only slightly enhanced. TS also potentiated the mixed lymphocyte culture (MLC) response of normal T cells and thymocytes cultured with mitomycin C-treated B lymphoid cell lines. The mitogenic effect of TS was time-dependent and paralleled the appearance of lymphoid colonies in semi-solid agar. Chromatographical separation of concentrated serum-free TS on Sephadex G-100 yielded an active fraction of molecular weight 15,000--25,000 which had all the activities of unseparated TS. PMID:160851

  8. Regeneration of Tissues and Organs Using Autologous Cells

    SciTech Connect

    Anthony Atala, M D

    2012-10-11

    The proposed work aims to address three major challenges to the field of regenerative medicine: 1) the growth and expansion of regenerative cells outside the body in controlled in vitro environments, 2) supportive vascular supply for large tissue engineered constructs, and 3) interactive biomaterials that can orchestrate tissue development in vivo. Toward this goal, we have engaged a team of scientists with expertise in cell and molecular biology, physiology, biomaterials, controlled release, nanomaterials, tissue engineering, bioengineering, and clinical medicine to address all three challenges. This combination of resources, combined with the vast infrastructure of the WFIRM, have brought to bear on projects to discover and test new sources of autologous cells that can be used therapeutically, novel methods to improve vascular support for engineered tissues in vivo, and to develop intelligent biomaterials and bioreactor systems that interact favorably with stem and progenitor cells to drive tissue maturation. The Institute's ongoing programs are aimed at developing regenerative medicine technologies that employ a patient's own cells to help restore or replace tissue and organ function. This DOE program has provided a means to solve some of the vexing problems that are germane to many tissue engineering applications, regardless of tissue type or target disease. By providing new methods that are the underpinning of tissue engineering, this program facilitated advances that can be applied to conditions including heart disease, diabetes, renal failure, nerve damage, vascular disease, and cancer, to name a few. These types of conditions affect millions of Americans at a cost of more than $400 billion annually. Regenerative medicine holds the promise of harnessing the body's own power to heal itself. By addressing the fundamental challenges of this field in a comprehensive and focused fashion, this DOE program has opened new opportunities to treat conditions where

  9. Complication Rate of Autologous Cartilage Microtia Reconstruction: A Systematic Review

    PubMed Central

    Long, Xiao; Yu, Nanze; Huang, Jiuzuo

    2013-01-01

    Background: Autologous cartilage has been widely accepted as the frame material of ear reconstruction for patients with microtia. Although rare, there are multiple complications related with the surgical reconstruction techniques. The authors performed a systematic review of the English literature of microtia reconstruction to determine significant surgical factors that are predictors of postoperative complications. Methods: A PubMed search using the terms “ear reconstruction” and “microtia” was conducted. Articles were screened using predetermined inclusion and exclusion criteria. Data collected included patient characteristics, surgical techniques, the incidence of all kinds of complications, and the specific postoperative morbidity. Patient cohorts were pooled, and the incidence of complications was calculated. Significant predictors such as the use of tissue expander, simultaneously mid-ear reconstruction, with/without skin graft, and different fascia coverage were analyzed by chi-square test. Result: Of 320 articles found, 60 met the inclusion criteria. Totally 9415 patients with microtia were analyzed in this review with 1525 cases with complications. The overall complication incidence is 16.2% in average with a range of 0–72.9%. There was no significant difference when comparing the overall complication rate between with/without preexpansion 2-stage and multiple-stage techniques or with/without mid-ear reconstruction simultaneously. Conclusion: Although there is little agreement in literature regarding risk factors for complications, the authors were able to demonstrate several significant predictors by systematically analyzing 60 articles. Improved knowledge of the incidence of different complications related with various surgical methods can help surgeons provide improved preoperative counseling and take measures to minimize the risk. PMID:25289252

  10. Locally Advanced Breast Cancer: Autologous Versus Implant-based Reconstruction

    PubMed Central

    Prousskaia, Elena; Chow, Whitney; Angelaki, Anna; Cirwan, Cleona; Hamed, Hisham; Farhadi, Jian

    2016-01-01

    Background: Recent papers and guidelines agree that patients with locally advanced breast cancer (LABC) should be offered breast reconstruction. Yet, the type of reconstruction in this group of patients is still a point of controversy. Methods: One hundred fourteen patients, treated for LABC from 2007 to 2013, were divided into 3 groups based on the reconstructive option: no reconstruction (NR), implant-based/expander-based reconstruction (IBR), and autologous tissue reconstruction (ATR). We analyzed demographics and compared delay in adjuvant therapy, length of hospitalization, surgical complications, failure of reconstruction, local recurrence, and disease-free survival. Results: Twenty-six patients had NR, 38 had IBR, and 50 had ATR. No significant difference was found in the percentage of patients who had their adjuvant treatment delayed [16% (NR) vs 22% (IBR) vs 14% (ATR)]. Mean length of hospitalization for the NR, IBR, and ATR groups was 2.7, 6, and 7.5 days, respectively. Complication rates requiring readmission were 36% (NR), 42% (IBR), and 32% (ATR). In the IBR group, 37% of implants were removed because of complications. Failure of reconstruction was 37% and 0% for the IBR and ATR groups, respectively. Local recurrence rates in the NR and Reconstruction (groups IBR and ATR combined) groups were 7% and 2%, respectively. Mean survival times in patients were 18 (NR), 10.3 (IBR), and 12.2 (ATR) months. Conclusions: No significant difference was found in the hospital stay length, adjuvant treatment delay, and complication rates between IBR and ATR. High rates of failed reconstruction suggest that the use of implants should be considered very carefully in patients with LABC. PMID:27014551

  11. Differentiation and activation phenotypes of lung T lymphocytes differ from those of circulating T lymphocytes.

    PubMed Central

    Davidson, B L; Faust, J; Pessano, S; Daniele, R P; Rovera, G

    1985-01-01

    We used dual laser two-color flow cytometry to compare the expression of surface markers associated with activation and with differentiation in lung and peripheral blood T lymphocytes from normal subjects. T cell subsets, defined based on their reactivity with monoclonal antibodies (MAb) OKT3, OKT4, and OKT8, were analyzed for expression of activation antigens as detected by MAbs to the interleukin-2 receptor, the transferrin receptor, and HLA-DR determinants. Whereas circulating T lymphocytes expressed the three activation antigens at low levels, and the total of T4+ and T8+ cells always approximated the number of T3+ cells, lung T lymphocytes of the T3+, T4+, and T8+ populations expressed the activation antigens at variable levels in combinations not seen in circulating lymphocytes, and the sum of T4+ and T8+ cells always exceeded the T3+ total. A proportion of T4+T8+ cells was detected in lung lymphocytes. PMID:3926821

  12. Early stem cell transplantation for chronic lymphocytic leukaemia: a chance for cure?

    PubMed Central

    Dreger, P.; von Neuhoff, N.; Kuse, R.; Sonnen, R.; Glass, B.; Uharek, L.; Schoch, R.; Löffler, H.; Schmitz, N.

    1998-01-01

    B-cell chronic lymphocytic leukaemia (CLL) cannot be cured by conventional therapy. To improve the prognosis of patients with CLL, we have designed a sequential treatment strategy that comprises intensive chemotherapy for mobilization of peripheral blood progenitor cells (PBPCs) and induction of minimal disease, followed by high-dose radiochemotherapy with stem cell reinfusion and post-transplant molecular monitoring by polymerase chain reaction (PCR) amplification of the complementary determining region III (CDRIII) gene. In a prospective study, we have evaluated this protocol in 18 patients with CLL, also including early stages of the disease. The median age was 49 (29-61) years; Binet stages were A, six; B, nine; and C, three. Adverse prognostic factors [high lymphocyte count and/or diffuse bone marrow (BM) infiltration] were present in 16 out of 18 patients. All patients showed a clone-specific molecular marker as demonstrated by PCR amplification of CDRIII rearrangements. For stem cell mobilization and reduction of tumour load, one to two cycles of Dexa-BEAM chemotherapy were administered, resulting in minimal disease (circulating lymphoma cells <1 x 10(9) l(-1); BM infiltration <20%; lymphomas <2 cm) in 16 out of 18 patients, including four patients who already had minimal disease before Dexa-BEAM. Stem cell harvesting was successful in 14 patients. All grafts [three BM, 11 peripheral blood (PB)] were purged from leukaemic cells using immunomagnetic methods. Thirteen patients having achieved minimal disease were reinfused with purged autologous stem cells (ASC) after preparation with total body irradiation and cyclophosphamide. Engraftment was delayed in patients receiving BM (n = 3) but prompt [neutrophils >0.5 x 10(9) l(-1) after 10 (9-13) days, platelets >20 x 10(9) l(-1) after 11 (9-214) days] in patients restored with PBPCs (n = 10). Procedure-related deaths did not occur. Although the results of CDRIII PCR suggest persistence or recurrence of the

  13. Characterization of the atypical lymphocytes in African swine fever

    PubMed Central

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Karalyan, N. Yu; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  14. B lymphocytes: how they develop and function

    PubMed Central

    2008-01-01

    The discovery that lymphocyte subpopulations participate in distinct components of the immune response focused attention onto the origins and function of lymphocytes more than 40 years ago. Studies in the 1960s and 1970s demonstrated that B and T lymphocytes were responsible primarily for the basic functions of antibody production and cell-mediated immune responses, respectively. The decades that followed have witnessed a continuum of unfolding complexities in B-cell development, subsets, and function that could not have been predicted. Some of the landmark discoveries that led to our current understanding of B lymphocytes as the source of protective innate and adaptive antibodies are highlighted in this essay. The phenotypic and functional diversity of B lymphocytes, their regulatory roles independent of antibody production, and the molecular events that make this lineage unique are also considered. Finally, perturbations in B-cell development that give rise to certain types of congenital immunodeficiency, leukemia/lymphoma, and autoimmune disease are discussed in the context of normal B-cell development and selection. Despite the significant advances that have been made at the cellular and molecular levels, there is much more to learn, and cross-disciplinary studies in hematology and immunology will continue to pave the way for new discoveries. PMID:18725575

  15. SHARPIN Regulates Uropod Detachment in Migrating Lymphocytes

    PubMed Central

    Rantakari, Pia; Auvinen, Kaisa; Karikoski, Marika; Mattila, Elina; Potter, Christopher; Sundberg, John P.; Hogg, Nancy; Gahmberg, Carl G.

    2013-01-01

    SUMMARY Sharpin-deficient mice display a multiorgan chronic inflammatory phenotype suggestive of altered leukocyte migration. We therefore studied the role of SHARPIN in lymphocyte adhesion, polarization and migration. We found that SHARPIN localizes to the trailing edges (uropods) of both mouse and human chemokine-activated lymphocytes migrating on ICAM-1, which is one of the major endothelial ligands for migrating leukocytes. SHARPIN-deficient cells adhere better to ICAM-1 and show highly elongated tails when migrating. The increased tail lifetime in SHARPIN-deficient lymphocytes decreases the migration velocity. The adhesion, migration and uropod defects in SHARPIN deficient lymphocytes were rescued by reintroducing SHARPIN into the cells. Mechanistically we show that SHARPIN interacts directly with LFA-1, a leukocyte counter-receptor for ICAM-1, and inhibits the expression of intermediate and high-affinity forms of LFA-1. Thus SHARPIN controls lymphocyte migration by endogenously maintaining LFA-1 inactive to allow adjustable detachment of the uropods in polarized cells. PMID:24210817

  16. Total Pancreatectomy with Islet Autologous Transplantation: The Cure for Chronic Pancreatitis?

    PubMed Central

    Kesseli, Samuel J; Smith, Kerrington A; Gardner, Timothy B

    2015-01-01

    Chronic pancreatitis (CP) is a debilitating disease that leads to varying degrees of pancreatic endocrine and exocrine dysfunction. One of the most difficult symptoms of CP is severe abdominal pain, which is often challenging to control with available analgesics and therapies. In the last decade, total pancreatectomy with autologous islet cell transplantation has emerged as a promising treatment for the refractory pain of CP and is currently performed at approximately a dozen centers in the United States. While total pancreatectomy is not a new procedure, the endocrine function-preserving autologous islet cell isolation and re-implantation have made the prospect of total pancreatectomy more acceptable to patients and clinicians. This review will focus on the current status of total pancreatectomy with autologous islet cell transplant including patient selection, technical considerations, and outcomes. As the procedure is performed at an increasing number of centers, this review will highlight opportunities for quality improvement and outcome optimization. PMID:25630865

  17. The potential role of autologous stem cell transplantation in patients with systemic lupus erythematosus.

    PubMed

    Hahn, B H

    1997-05-01

    Transfer of disease by bone marrow cells has been described in experimental models of systemic lupus erythematosus (SLE). In one experiment, marrow ablation followed by transfer of T depleted allogeneic marrow resulted in prolonged survival of animals with SLE. Some experimental studies suggest a rationale for autologous stem cell transplantation indicating this intervention might "reset the thermostat" so that normal immunoregulation can control disease, while others indicate it might not be beneficial. The pros and cons of offering patients with SLE autologous hematopoietic stem cell transplantation are considered. A profile of the patient with SLE who might be considered as a candidate for autologous stem cell transplantation can be constructed by evaluating causes of death and factors that increase mortality. This profile includes life threatening disease, inadequate response to aggressive immunosuppressive therapy, and adequate function of all major organs so that risks associated with stem cell transplantation can be minimized. PMID:9150126

  18. Differential expression of CC chemokines (CCLs) and receptors (CCRs) by human T lymphocytes in response to different Aggregatibacter actinomycetemcomitans serotypes

    PubMed Central

    ALVAREZ, Carla; BENÍTEZ, Alvaro; ROJAS, Leticia; PUJOL, Myriam; CARVAJAL, Paola; DÍAZ-ZÚÑIGA, Jaime; VERNAL, Rolando

    2015-01-01

    ABSTRACT In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on LPS antigenicity. Recently, our research group has reported a differential immunogenicity when T lymphocytes were stimulated with these different serotypes. In particular, it was demonstrated that the serotype b of A. actinomycetemcomitans has a stronger capacity to trigger Th1- and Th17-type cytokine production. Objective This study aimed to quantify the expression of different CC chemokines (CCLs) and receptors (CCRs) in T lymphocytes stimulated with the different A. actinomycetemcomitans serotypes. In addition, the expression of the transcription factors T-bet, GATA-3, RORC2, and Foxp3, master-switch genes implied in the Th1, Th2, Th17, and T-regulatory differentiation, respectively, was analyzed in order to determine T-cell phenotype-specific patterns of CCL and CCR expression upon A. actinomycetemcomitans stimulation. Material and Methods Human naïve CD4+ T lymphocytes were obtained from healthy subjects and stimulated with autologous dendritic cells primed with the different A. actinomycetemcomitans serotypes. The expression levels for the chemokines CCL1, CCL2, CCL3, CCL5, CCL11, CCL17, CCL20, CCL21, CCL25, and CCL28, as well as the chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 were quantified by qPCR. Similarly, the expression levels for the transcription factors T-bet, GATA-3, RORC2, and Foxp3 were quantified and correlated with the CCL and CCR expression levels. Results Higher expression levels of CCL2, CCL3, CCL5, CCL20, CCL21, CCL28, CCR1, CCR2, CCR5, CCR6, CCR7, and CCR9 were detected in T lymphocytes stimulated with the serotype b of A. actinomycetemcomitans compared with the other serotypes. In addition, these higher expression levels of CCLs and CCRs positively correlated with the increased levels of T-bet and RORC2 when T lymphocytes were stimulated with the serotype b. Conclusion A T-lymphocyte response biased

  19. Differential expression of CC chemokines (CCLs) and receptors (CCRs) by human T lymphocytes in response to different Aggregatibacter actinomycetemcomitans serotypes.

    PubMed

    Alvarez, Carla; Benítez, Alvaro; Rojas, Leticia; Pujol, Myriam; Carvajal, Paola; Díaz-Zúñiga, Jaime; Vernal, Rolando

    2015-01-01

    In Aggregatibacter actinomycetemcomitans, different serotypes have been described based on LPS antigenicity. Recently, our research group has reported a differential immunogenicity when T lymphocytes were stimulated with these different serotypes. In particular, it was demonstrated that the serotype b of A. actinomycetemcomitans has a stronger capacity to trigger Th1- and Th17-type cytokine production. Objective This study aimed to quantify the expression of different CC chemokines (CCLs) and receptors (CCRs) in T lymphocytes stimulated with the different A. actinomycetemcomitans serotypes. In addition, the expression of the transcription factors T-bet, GATA-3, RORC2, and Foxp3, master-switch genes implied in the Th1, Th2, Th17, and T-regulatory differentiation, respectively, was analyzed in order to determine T-cell phenotype-specific patterns of CCL and CCR expression upon A. actinomycetemcomitans stimulation. Material and Methods Human naïve CD4+ T lymphocytes were obtained from healthy subjects and stimulated with autologous dendritic cells primed with the different A. actinomycetemcomitans serotypes. The expression levels for the chemokines CCL1, CCL2, CCL3, CCL5, CCL11, CCL17, CCL20, CCL21, CCL25, and CCL28, as well as the chemokine receptors CCR1, CCR2, CCR3, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 were quantified by qPCR. Similarly, the expression levels for the transcription factors T-bet, GATA-3, RORC2, and Foxp3 were quantified and correlated with the CCL and CCR expression levels. Results Higher expression levels of CCL2, CCL3, CCL5, CCL20, CCL21, CCL28, CCR1, CCR2, CCR5, CCR6, CCR7, and CCR9 were detected in T lymphocytes stimulated with the serotype b of A. actinomycetemcomitans compared with the other serotypes. In addition, these higher expression levels of CCLs and CCRs positively correlated with the increased levels of T-bet and RORC2 when T lymphocytes were stimulated with the serotype b. Conclusion A T-lymphocyte response biased towards a

  20. Bioengineered Human Pyloric Sphincters Using Autologous Smooth Muscle and Neural Progenitor Cells.

    PubMed

    Rego, Stephen Lee; Zakhem, Elie; Orlando, Giuseppe; Bitar, Khalil N

    2016-01-01

    Gastroparesis leads to inadequate emptying of the stomach resulting in severe negative health impacts. Appropriate long-term treatments for these diseases may require pyloric sphincter tissue replacements that possess functional smooth muscle cell (SMC) and neural components. This study aims to bioengineer, for the first time, innervated human pylorus constructs utilizing autologous human pyloric sphincter SMCs and human neural progenitor cells (NPCs). Autologous SMCs and NPCs were cocultured in dual-layered hydrogels and formed concentrically aligned pylorus constructs. Innervated autologous human pylorus constructs were characterized through biochemical and physiologic assays to assess the phenotype and functionality of SMCs and neurons. SMCs within bioengineered human pylorus constructs displayed a tonic contractile phenotype and maintained circumferential alignment. Neural differentiation within bioengineered constructs was verified by positive expression of βIII-tubulin, neuronal nitric oxide synthase (nNOS), and choline acetyltransferase (ChAT). Autologous bioengineered innervated human pylorus constructs generated a robust spontaneous basal tone and contracted in response to potassium chloride (KCl). Contraction in response to exogenous neurotransmitter acetylcholine (ACh), relaxation in response to vasoactive intestinal peptide (VIP), and electrical field stimulation (EFS) were also observed. Neural network integrity was demonstrated by inhibition of EFS-induced relaxation in the presence of a neurotoxin or nNOS inhibitors. Partial inhibition of ACh-induced contraction and VIP-induced relaxation following neurotoxin treatment was observed. These studies provide a proof of concept for bioengineering functional innervated autologous human pyloric sphincter constructs that generate a robust basal tone and contain circumferentially aligned SMCs, which display a tonic contractile phenotype and functional differentiated neurons. These autologous constructs have

  1. Conservative mastectomies and Immediate-DElayed AutoLogous (IDEAL) breast reconstruction: the DIEP flap

    PubMed Central

    Nestle-Krämling, Carolin; Fertsch, Sonia; Hagouan, Mazen; Munder, Beatrix; Richrath, Philip; Stambera, Peter; Abu-Ghazaleh, Alina; Andree, Christoph

    2016-01-01

    Background With the development of conservative mastectomies, there are an increasing number of women seeking immediate implant based and autologous breast reconstruction. Despite the oncologic safety of the procedures, the focus will be on the timing of reconstruction. Methods Our plastic surgery unit is focused primarily on autologous breast reconstruction and is part of an interdisciplinary breast center. We offer immediate breast reconstruction (IBR) with autologous tissue for patients with positive BRCA 1 and 2, ductal carcinoma in situ (DCIS), invasive cancer without margin problems to the skin, as well as to correct poor oncologic and aesthetic breast conserving therapy (BCT) outcomes. In the majority of cases we prefer an Immediate-DElayed AutoLogous (IDEAL) breast reconstruction concept with a two-stage procedure. Results Over the last 10 years we performed more than 1,600 breast reconstructions with free flaps, performing the deep inferior epigastric perforator (DIEP) flap as our first choice for autologous tissue. We recommend IDEAL breast reconstruction, however approximately 15% of our cases are immediate one stage conservative mastectomies and breast reconstruction with the DIEP flap. Conclusions For immediate reconstruction, the aesthetic outcome should not take precedence over oncologic considerations. Immediate one-stage, breast reconstruction with autologous tissue can be offered to the suitable patients which is most likely a healthy women with a small-to-medium sized non ptotic breast receiving a conservative mastectomy. In all other cases, we recommend an IDEAL breast reconstruction approach in order to achieve a final result that is both satisfyingly pleasing and oncologically safe. PMID:26855905

  2. Hydroxyapatite-Based Biomaterials vs. Autologous Bone Graft in Spinal Fusion: An in Vivo Animal Study.

    PubMed

    Bròdano, Giovanni Barbanti; Giavaresi, Gianluca; Lolli, Francesco; Salamanna, Francesca; Parrilli, Annapaola; Martini, Lucia; Griffoni, Cristiana; Greggi, Tiziana; Arcangeli, Elena; Pressato, Daniele; Boriani, Stefano; Fini, Milena

    2014-04-01

    Study Design. An in vivo study was designed to compare the efficacy of biomimetic Magnesium-Hydroxyapatite (MgHA) and of human demineralised bone matrix (HDBM), both dispersed in a mixture of biomimetic Mg-HA nanoparticles, with that of an autologous bone graft.Objective. The objective of this study was to evaluate two new bone substitutes as alternatives to a bone autograft for spinal fusion, determining their osteoinductive and osteoconductive properties, and their capacity of remodeling, using a large animal model.Summary of Background Data. Spinal fusion is a common surgical procedure and it is performed for different conditions. A successful fusion requires potentially osteogenic, osteoinductive and osteoconductive biomaterials.Methods. A posterolateral spinal fusion model involved 18 sheep, bilaterally implanting test materials between the vertebral transverse processes. The animals were divided into two groups: one fusion level was treated with MgHA (Group 1) or with HDBM-MgHA (Group 2). The other fusion level received bone autografts in both groups.Results. Radiographic, histological and microtomographic results indicated good osteointegration between the spinous process and the vertebral foramen for both materials. Histomorphometry revealed no significant differences between MgHA and autologous bone for all the parameters examined while significantly lower values of bone volume were observed between HDBM-MgHA and autologous bone. Moreover, the normalisation of the histomorphometrical data with autologous bone revealed that MgHA showed a significantly higher value of bone volume and a lower value of trabecular number, more similar to autologous bone, in comparison to HDBM-MgHA.Conclusion. The study showed that the use of MgHA in an ovine model of spinal fusion led to the deposition of new bone tissue without qualitative and quantitative differences with respect to new bone formed with autologous bone while the HDBM-MgHA led to a reduced deposition of newly

  3. From the cradle to enteral autonomy: the role of autologous gastrointestinal reconstruction.

    PubMed

    Bianchi, Adrian

    2006-02-01

    The short bowel state is treatable, with acceptable long-term quality of life. Management during the first 6-12 months of life is critical but, presently, frequently compromises long-term survival and prospects. At first presentation, primary caregivers, working with specialists at designated intestinal failure centers, should develop a structured individual-oriented management plan. Preservation of venous access, "hepatosparing" parenteral nutrition, and avoidance of liver sepsis are crucial to survival. Early surgery should be limited to conservation of autologous bowel, even short bowel lengths having great potential, and to facilitating natural intestinal adaptation. Bowel expansion may be relevant prior to delayed bowel reconstruction with single or combined techniques that include bowel lengthening and/or tailoring, reversed segments, and colon interposition. Bowel transplantation, as yet not recommended for primary management, offers survival and opportunity to those with no prospect of autologous bowel autonomy or following failed autologous gastrointestinal reconstruction. This paper reviews current surgery for the short bowel state and concludes that it is presently appropriate before bowel transplantation to offer autologous gastrointestinal reconstruction, with its prospect of enteral autonomy with quality life. It emphasizes the need for an individual-oriented management plan, developed jointly at the time of first presentation between the primary caregivers and a designated multidisciplinary intestinal failure center, to enhance the prospects for enteral autonomy preferably on autologous bowel. Autologous gastrointestinal reconstruction is in its infancy and requires resources, commitment, and research from dedicated bowel reconstructive surgeons toward a better opportunity for the child and family with short bowel. PMID:16473062

  4. PHENOTYPE AND POLARIZATION OF AUTOLOGOUS T CELLS BY BIOMATERIAL-TREATED DENDRITIC CELLS

    PubMed Central

    Park, Jaehyung; Gerber, Michael H.; Babensee, Julia E.

    2014-01-01

    Given the central role of dendritic cells (DCs) in directing T cell phenotypes, the ability of biomaterial-treated DCs to dictate autologous T cell phenotype was investigated. Here, we demonstrate that differentially biomaterial-treated DCs differentially directed autologous T cell phenotype and polarization, depending on the biomaterial used to pre-treat the DCs. Immature DCs (iDCs) were derived from human peripheral blood monocytes, and treated with biomaterial films of alginate, agarose, chitosan, hyaluronic acid, or 75:25 poly(lactic-co-glycolic acid) (PLGA), followed by co-culture of these biomaterial-treated DCs and autologous T cells. When autologous T cells were co-cultured with DCs treated with biomaterial film/antigen (ovalbumin, OVA) combinations, different biomaterial films induced differential levels of T cell marker (CD4, CD8, CD25, CD69) expression, as well as differential cytokine profiles [interferon (IFN)-γ, interleukin (IL)-12p70, IL-10, IL-4] in the polarization of T helper types. Dendritic cells treated with agarose films/OVA induced CD4+CD25+FoxP3+ (T regulatory cells) expression, comparable to untreated iDCs, on autologous T cells in the DC-T co-culture system. Furthermore, in this co-culture, agarose treatment induced release of IL-12p70 and IL-10 at higher levels, as compared to DC treatment with other biomaterial films/OVA, suggesting Th1 and Th2 polarization, respectively. Dendritic cells treated with PLGA film/OVA treatment induced release of IFN-γ at higher levels compared to that observed for co-cultures with iDCs or DCs treated with all other biomaterial films. These results indicate that DC treatment with different biomaterial films has potential as a tool for immunomodulation by directing autologous T cell responses. PMID:24616366

  5. Biomaterial scaffolds in cartilage-subchondral bone defects influencing the repair of autologous articular cartilage transplants.

    PubMed

    Fan, Wei; Wu, Chengtie; Miao, Xigeng; Liu, Gang; Saifzadeh, Siamak; Sugiyama, Sadahiro; Afara, Isaac; Crawford, Ross; Xiao, Yin

    2013-05-01

    The repair of articular cartilage typically involves the repair of cartilage-subchondral bone tissue defects. Although various bioactive materials have been used to repair bone defects, how these bioactive materials in subchondral bone defects influence the repair of autologous cartilage transplant remains unclear. The aim of this study was to investigate the effects of different subchondral biomaterial scaffolds on the repair of autologous cartilage transplant in a sheep model. Cylindrical cartilage-subchondral bone defects were created in the right femoral knee joint of each sheep. The subchondral bone defects were implanted with hydroxyapatite-β-tricalcium phosphate (HA-TCP), poly lactic-glycolic acid (PLGA)-HA-TCP dual-layered composite scaffolds (PLGA/HA-TCP scaffolds), or autologous bone chips. The autologous cartilage layer was placed on top of the subchondral materials. After 3 months, the effect of different subchondral scaffolds on the repair of autologous cartilage transplant was systematically studied by investigating the mechanical strength, structural integration, and histological responses. The results showed that the transplanted cartilage layer supported by HA-TCP scaffolds had better structural integration and higher mechanical strength than that supported by PLGA/HA-TCP scaffolds. Furthermore, HA-TCP-supported cartilage showed higher expression of acid mucosubstances and glycol-amino-glycan contents than that supported by PLGA/HA-TCP scaffolds. Our results suggested that the physicochemical properties, including the inherent mechanical strength and material chemistry of the scaffolds, play important roles in influencing the repair of autologous cartilage transplants. The study may provide useful information for the design and selection of proper subchondral biomaterials to support the repair of both subchondral bone and cartilage defects. PMID:22684516

  6. Injection of porous polycaprolactone beads containing autologous myoblasts in a dog model of fecal incontinence

    PubMed Central

    Kang, Sung-Bum; Lee, Hye Seung; Lim, Jae-Young; Oh, Se Heang; Kim, Sang Joon; Hong, Sa-Min; Jang, Je-Ho; Cho, Jeong-Eun; Lee, Sung-Min

    2013-01-01

    Purpose Few studies have examined whether bioengineering can improve fecal incontinence. This study designed to determine whether injection of porous polycaprolactone beads containing autologous myoblasts improves sphincter function in a dog model of fecal incontinence. Methods The anal sphincter of dogs was injured and the dogs were observed without and with (n = 5) the injection of porous polycaprolactone beads containing autologous myoblasts into the site of injury. Autologous myoblasts purified from the gastrocnemius muscles were transferred to the beads. Compound muscle action potentials (CMAP) of the pudendal nerve, anal sphincter pressure, and histopathology were determined 3 months after treatment. Results The amplitudes of the CMAP in the injured sphincter were significantly lower than those measured before injury (1.22 mV vs. 3.00 mV, P = 0.04). The amplitudes were not different between dogs with and without the injection of autologous myoblast beads (P = 0.49). Resting and squeezing pressures were higher in dogs treated with autologous myoblast beads (2.00 mmHg vs. 1.80 mmHg; 6.13 mmHg vs. 4.02 mmHg), although these differences were not significant in analyses of covariance adjusted for baseline values. The injection site was stained for smooth muscle actin, but showed evidence of foreign body inflammatory reactions. Conclusion This was the first study to examine whether bioengineering could improve fecal incontinence. Although the results did not show definite evidence that injection of autologous myoblast beads improves sphincter function, we found that the dog model was suitable and reliable for studying the effects of a potential treatment modality for fecal incontinence. PMID:23577316

  7. Nodular lymphocyte-predominant Hodgkin lymphoma.

    PubMed

    Savage, Kerry J; Mottok, Anja; Fanale, Michelle

    2016-07-01

    Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare subtype of Hodgkin lymphoma with distinct clinicopathologic features. It is typified by the presence of lymphocyte predominant (LP) cells, which are CD20(+) but CD15(-) and CD30(-) and are found scattered amongst small B lymphocytes arranged in a nodular pattern. Despite frequent and often late or multiple relapses, the prognosis of NLPHL is very favorable. There is an inherent risk of secondary aggressive non-Hodgkin lymphoma (NHL) and studies support that risk is highest in those with splenic involvement at presentation. Given disease rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma (CHL). This review provides an overview of the existing literature describing pathological subtypes, outcome and treatment approaches for NLPHL. PMID:27496311

  8. T cell immunity using transgenic B lymphocytes

    NASA Astrophysics Data System (ADS)

    Gerloni, Mara; Rizzi, Marta; Castiglioni, Paola; Zanetti, Maurizio

    2004-03-01

    Adaptive immunity exists in all vertebrates and plays a defense role against microbial pathogens and tumors. T cell responses begin when precursor T cells recognize antigen on specialized antigen-presenting cells and differentiate into effector cells. Currently, dendritic cells are considered the only cells capable of stimulating T lymphocytes. Here, we show that mature naïve B lymphocytes can be genetically programmed by using nonviral DNA and turned into powerful antigen-presenting cells with a dual capacity of synthesis and presentation of antigen to T cells in vivo. A single i.v. injection of transgenic lymphocytes activates T cell responses reproducibly and specifically even at very low cell doses (102). We also demonstrate that T cell priming can occur in the absence of dendritic cells and results in immunological memory with protective effector functions. These findings disclose aspects in the regulation of adaptive immunity and indicate possibilities for vaccination against viruses and cancer in humans.

  9. Macroautophagy in T Lymphocyte Development and Function

    PubMed Central

    He, Ming-Xiao; McLeod, Ian X.; Jia, Wei; He, You-Wen

    2011-01-01

    Macroautophagy (referred to as autophagy) is a fundamental intracellular process characterized by the sequestration of cytoplasmic compartments through double-membrane vesicles, termed autophagosomes. Recent studies have established important roles of autophagy in regulating T lymphocyte development and function. Resting T lymphocytes have basal levels of autophagy that is upregulated by T cell receptor stimulation. Several specific knockout or transgenic models have been developed during the past few years, and it has been revealed that autophagy plays an essential role in regulating thymocyte selection, peripheral T cell survival, and proliferation. The regulation of T cell development and function by autophagy is mediated through its role in regulating self-antigen presentation, intracellular organelle homeostasis, and energy production. Here we will review the current findings concerning how autophagy regulates T cell function, as well as compare different models in studying autophagy in T lymphocytes. PMID:22566906

  10. Temperature effects on lymphocyte transformation invitro.

    PubMed

    Hirsch, R L; Jeffries, B D; Gray, I

    1977-01-01

    Phytohemagglutinin (PHA)-induced transformation of normal rat peripheral lymphocytes has been studied at a wide range of culture temperatures (4 degrees C to 42 degrees C). Lymphocyte transformation was maximum at 37 degrees C while insignificant stimulation was observed between 4 degrees C and 30 degrees C. Temperatures above 37 degrees C produced sub=optimal transformation as measured by synthesis of DNA and protein, and appearance of lymphoblasts. Binding studies using 125I-PHA indicate that the low temperature inhibition of lymphocyte transformation could be a result of excess lectin (being available as a result of low temperature) bound to the cell surface, preventing the initiation of the molecular events associated with transformation. PMID:863471

  11. [T-LYMPHOCYTES AND TISSUE GROWTH FACTORS].

    PubMed

    Tishevskaya, N V; Gevorkyan, N M; Kozlova, N I

    2015-08-01

    Lympnoici regulation, in aciaition to ensuring tne protection of tne antigen, is aimecl at maintaining a qualitative, quantitative, structural and functional integrity of the body. T-lymphocytes and growth factors are involved in cell proliferation, differentiation, and tissue and organ regeneration. Lymphocyte's, sensitivity to homeostasis changes and their morphogenetic function are connected with a large number of receptors to bioactive substances and with their ability to syn- thesize and secrete hormones and tissue growth factors. At the same time tissue growth factors are involved in the development of thymocytes, in the differentiation of T helper and cytotoxic lymphocytes. Growth factors modulate the functions of Thl, Th2, Treg, Thl7, Th9. The important aspects of the interaction of T cells and EGF, TGF-P, FGF, VEGF, PlGF, HGF/SF in normal and pathological conditions are shown in this review. PMID:26591583

  12. Myeloid regeneration after whole body irradiation, autologous bone marrow transplantation, and treatment with an anabolic steroid.

    PubMed

    Ambrus, C M; Ambrus, J L

    1975-01-01

    Stumptail monkeys (Macaca speciosa) received lethal whole body radiation. Autologous bone marrow injection resulted in survival of the majority of the animals. Treatment with Deca-Durabolin, an anabolic steroid, caused more rapid recovery of colony-forming cell numbers in the bone marrow than in control animals. Both the Deca-Durabolin-treated and control groups were given autologous bone marrow transplantation. Anabolic steroid effect on transplanted bone marrow colonyforming cells may explain the increased rate of leukopoietic regeneration in anabolic steroid-treated animals as compared to controls. PMID:124758

  13. Internal and external carotid artery embolism following facial injection of autologous fat.

    PubMed

    Wang, Da-Wei; Yin, Yi-Mei; Yao, Yong-Ming

    2014-11-01

    Autologous fat injection is a common aesthetic procedure for soft-tissue augmentation of the face. Although this procedure is generally regarded as safe, several patients have experienced acute visual loss or cerebral infarction after these injections. We describe a case of internal and external carotid artery fat embolism that occurred following injection of autologous fat into the face. It appeared that the injected fat entered a branch of the left external carotid artery and that the embolus likely migrated into the left internal carotid artery and distally into the left ophthalmic artery, left anterior artery, and middle cerebral artery. LEVEL OF EVIDENCE 5: PMID:24936097

  14. The Knee Joint Loose Body as a Source of Viable Autologous Human Chondrocytes

    PubMed Central

    Melrose, J.

    2016-01-01

    Loose bodies are fragments of cartilage or bone present in the synovial fluid. In the present study we assessed if loose bodies could be used as a source of autologous human chondrocytes for experimental purposes. Histochemical examination of loose bodies and differential enzymatic digestions were undertaken, the isolated cells were cultured in alginate bead microspheres and immunolocalisations were undertaken for chondrogenic markers such as aggrecan, and type II collagen. Isolated loose body cells had high viability (≥90% viable), expressed chondrogenic markers (aggrecan, type II collagen) but no type I collagen. Loose bodies may be a useful source of autologous chondrocytes of high viability. PMID:27349321

  15. Study to evaluate the aesthetic clinical impact of an autologous antiaging serum.

    PubMed

    Pinto, Hernan; Garrido, Luis G

    2013-03-01

    Since ancient times, humans have fought a still-unwinnable battle against aging and time. The possibility of processing our own blood in order to obtain certain precious substances for a particular purpose has opened the gates for the development of new treatments, indications, and techniques. In this study, we obtained an autologous serum with very high concentrations of some growth factors and anti-inflammatory cytokines using a special syringelike device that exposed the blood to medical-grade glass spheres in a closed system. The application of this autologous conditioned antiaging serum achieved local beauty enhancement results by improving skin hydration, smoothness, and elasticity. PMID:23545916

  16. Autologous is Superior to Allogeneic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukemia in Second Complete Remission

    PubMed Central

    Chakrabarty, Jennifer L. Holter; Rubinger, Morel; Le-Rademacher, Jennifer; Wang, Hai-Lin; Grigg, Andrew; Selby, George B.; Szer, Jeffrey; Rowe, Jacob M.; Weisdorf, Daniel J.; Tallman, Martin S.

    2014-01-01

    PURPOSE To identify favored choice of transplantation in patients with acute promyelocytic leukemia in second complete remission. PATIENTS We studied 294 acute promyelocytic leukemia (APL) patients receiving allogeneic (n=232) or autologous (62) hematopoietic cell transplantation (HCT) in second complete remission (CR2) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006 including pre-HCT PML/RAR∝ status in 155 (49% of allogeneic and 66% of autologous). METHODS Patient characteristics and transplant characteristics including treatment related mortality, overall survival, and disease free survival were collected and analyzed for both univariate and multivariate outcomes. RESULTS With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous 63% (49-75%) compared to allogeneic 50% (44-57%) (p=0.10) and overall survival (OS) 75% (63-85%) vs. 54% (48-61%) (p=.002) Multivariate analysis showed significantly worse DFS after allogeneic HCT (HR=1.88, 95% CI=1.16-3.06, p=0.011) and age >40 years (HR=2.30, 95% CI 1.44-3.67, p=0.0005). OS was significantly worse after allogeneic HCT (HR=2.66, 95%CI 1.52-4.65, p=0.0006; age >40 (HR=3.29, 95% CI 1.95-5.54, p<0.001) and CR1<12 months (HR=1.56 95% CI 1.07-2.26, p=0.021). Positive pre-HCT PML-RAR∝ status in 17/114 allogeneic and 6/41 autologous transplants did not influence relapse, treatment failure or survival in either group. The survival advantage for autografting was attributable to increased 3 years TRM: allogeneic 30%; autologous 2%, and GVHD. CONCLUSION We conclude that autologous HCT yields superior overall survival for APL in CR2. Long term DFS in autologous recipients, even with MRD+ grafts remains an important subject for further study. PMID:24691221

  17. Autologous stem cell transplantation for severe autoimmune diseases: a 10-year experience.

    PubMed

    Gualandi, F; Bruno, B; Van Lint, M T; Luchetti, S; Uccelli, A; Capello, E; Mancardi, G L; Bacigalupo, A; Marmont, A

    2007-09-01

    The first autologous hematopoietic stem cell transplantation in Europe for a patient with severe refractory systemic lupus erythematosus (SLE) was performed in Genoa in 1996. Since then, 32 patients with a wide spectrum of autoimmune diseases (ADs) received autologous transplants, 22 of them with multiple sclerosis (MS). There were no fatal adverse events. All patients had complete or very good partial remissions, but relapses were frequent, especially in SLE, though never as aggressive as pretransplant. The mechanism of action of this intervention remains not completely understood, as briefly discussed here. PMID:17911461

  18. Treatment of recurrent TMJ dislocation in geriatric patient by autologous blood – A technique revisited

    PubMed Central

    Gupta, Deepak; Rana, Amar Singh; Verma, Varun Kumar

    2012-01-01

    A number of techniques have been advocated for the treatment of recurrent temporomandibular joint dislocation. Autologous blood injection around the articular capsule and/or into the articular cavity, which is one of the treatment modality, was recently reintroduced. We report a case of 82-year-old female with bilateral recurrent temporomandibular joint dislocation, treated by technique of autologous blood injection. The outcome was successful and required no further treatment in eight months follow up, thus the procedure had proven to be safe, simple, minimally invasive and cost effective. PMID:25737879

  19. CD1-restricted recognition of exogenous and self-lipid antigens by duodenal gammadelta+ T lymphocytes.

    PubMed

    Russano, Anna M; Bassotti, Gabrio; Agea, Elisabetta; Bistoni, Onelia; Mazzocchi, Alessandro; Morelli, Antonio; Porcelli, Steven A; Spinozzi, Fabrizio

    2007-03-15

    Gammadelta T cells are present in the mucosal intestinal epithelia and secrete factors necessary to maintain tissue integrity. Ags recognized by these cells are poorly defined, although in mice non-classical MHC class I molecules have been implicated. Since MHC class I-like CD1 receptors are widely expressed at the surface of epithelial and dendritic intestinal cells and have the capacity to present lipid Ags to T cells, we hypothesized that these molecules might present autologous and/or exogenous phospholipids to intestinal gammadelta T lymphocytes. Intraepithelial T lymphocytes from normal human duodenal mucosal biopsies were cloned and exposed to natural and synthetic phospholipids using CD1a-, CD1b-, CD1c- or CD1d-transfected C1R lymphoblastoid or HeLa cell lines as APCs. Their cytolytic properties and regulatory cytokine secretion were also examined. Most clones obtained from duodenal mucosa (up to 70%) were TCRalphabeta+, and either CD4+ or CD8+, whereas 20% were CD4-CD8- (6 clones) or TCRgammadelta+ (12 clones). A relevant percentage (up to 66%) of TCRgammadelta+ but few (<5%) TCRalphabeta+ T cell clones responded to synthetic and/or natural phospholipids presented by CD1 molecules, as measured by both [(3)H]thymidine incorporation and IL-4 release assays. A Th1-like cytolytic and functional activity along with the ability to secrete regulatory cytokines was observed in most phospholipid-specific gammadelta T cell clones. Thus, a substantial percentage of TCRgammadelta+ but few TCRalphabeta+ from human duodenal mucosa recognize exogenous phospholipids in a CD1-restricted fashion. This adaptive response could contribute to mucosal homeostasis, but could also favor the emergence of inflammatory or allergic intestinal diseases. PMID:17339459

  20. Alemtuzumab in chronic lymphocytic leukemia

    PubMed Central

    Fraser, G.; Smith, C.A.; Imrie, K.; Meyer, R.

    2007-01-01

    Questions With respect to outcomes such as survival, response rate, response duration, time to progression, and quality of life, is alemtuzumab a beneficial treatment option for patients with B-cell chronic lymphocytic leukemia (cll)? What toxicities are associated with the use of alemtuzumab? Which patients are more likely—or less likely—to benefit from treatment with alemtuzumab? Perspectives Evidence was selected and reviewed by one member of the Hematology Disease Site Group (dsg) of Cancer Care Ontario’s Program in Evidence-Based Care (pebc) and by methodologists. The practice guideline report was reviewed and approved by the Hema-tology dsg, which comprises hematologists, medical and radiation oncologists, and a patient representative. As part of an external review process, the report was disseminated to obtain feedback from practitioners in Ontario. Outcomes Outcomes of interest were overall survival, quality of life, response rates and duration, and adverse event rates. Methodology A systematic review of the medline, embase, HealthStar, cinahl, and Cochrane Library databases was conducted to search for primary articles and practice guidelines. The evidence informed the development of clinical practice recommendations. The evidence review and recommendations were appraised by a sample of practitioners from Ontario, Canada, and were modified in response to the feedback received. The systematic review and modified recommendations were approved by a review body within the pebc. Results The literature review found no published randomized controlled trials (rcts) that evaluated alem-tuzumab alone or in combination with other chemotherapeutic agents for the treatment of relapsed or refractory cll. One rct evaluated alemtuzumab administered to consolidate a complete or partial response to first-line fludarabine-containing chemotherapy. That study was stopped early because of excessive grades 3 and 4 infection-related toxicity in the alemtuzumab arm. Patients

  1. Human malignant melanoma-derived progestagen-associated endometrial protein immunosuppresses T lymphocytes in vitro.

    PubMed

    Ren, Suping; Chai, Lina; Wang, Chunyan; Li, Changlan; Ren, Qiquan; Yang, Lihua; Wang, Fumei; Qiao, Zhixin; Li, Weijing; He, Min; Riker, Adam I; Han, Ying; Yu, Qun

    2015-01-01

    Progestagen-associated endometrial protein (PAEP) is a glycoprotein of the lipocalin family that acts as a negative regulator of T cell receptor-mediated activation. However, the function of tumor-derived PAEP on the human immune system in the tumor microenvironment is unknown. PAEP is highly expressed in intermediate and thick primary melanomas (Breslow's 2.5mm or greater) and metastatic melanomas, correlating with its expression in daughter cell lines established in vitro. The current study investigates the role of melanoma cell-secreted PAEP protein in regulating T cell function. Upon the enrichment of CD3+, CD4+ and CD8+ T cells from human peripheral blood mononuclear cells, each subset was then mixed with either melanoma-derived PAEP protein or PAEP-poor supernatant of gene-silenced tumor cells. IL-2 and IFN-γ secretion of CD4+ T cells significantly decreased with the addition of PAEP-rich supernatant. And the addition of PAEP-positive cell supernatant to activated lymphocytes significantly inhibited lymphocyte proliferation and cytotoxic T cell activity, while increasing lymphocyte apoptosis. Our result suggests that melanoma cell-secreted PAEP protein immunosuppresses the activation, proliferation and cytotoxicity of T lymphocytes, which might partially explain the mechanism of immune tolerance induced by melanoma cells within the tumor microenvironment. PMID:25785839

  2. Studies of Two Subpopulations of Human Lymphocytes Differing in Responsiveness to Concanavalin A

    PubMed Central

    Boldt, David; Skinner, Sister Ann Marie; Kornfeld, Stuart

    1972-01-01

    We have identified two populations of human lymphocytes differing in responsiveness to the plant mitogen concanavalin A (Con-A). When peripheral blood lymphocytes are passed through a nylon column a population of lymphocytes highly responsive to Con-A adheres to the fibers while a second population of cells relatively unresponsive to Con-A emerges from the column. The untreated peripheral blood lymphocytes are termed “unfiltered” cells while the lymphocytes which pass through the column are termed “filtered” cells. Under standard assay conditions the Con-A-stimulated DNA synthesis is 6.5-fold greater, and the percentage blast formation is four-to fivefold greater in the unfiltered than in the filtered population. Mixing unfiltered with filtered cells fails to induce responsiveness in the latter indicating that a “helper” cell is not involved. The failure of filtered cells to respond to Con-A is specific for that mitogen since both populations respond nearly equally to erythroagglutinating phytohemagglutinin (E-PHA) and the poke weed mitogen (PWM). Binding studies with Con-A-131I demonstrate that the unfiltered population possesses approximately three times as many Con-A receptor sites per cell as the filtered cells, although both cell populations bind the mitogen with the same affinity (apparent association constant [K] of 1.67 × 106m−1). The relationship between Con-A binding and lymphocyte activation was determined by measuring the effect on DNA synthesis of incubating the two lymphocyte populations with increasing amounts of Con-A. The concentration of Con-A required for half-maximal stimulation of DNA synthesis was 5-14 times greater for the filtered cells. However in the presence of very high Con-A concentrations the filtered cells achieved a maximal rate of DNA synthesis approaching that of the unfiltered population. These data implicate the decreased number of Con-A receptor sites on the filtered cells in their failure to respond to low

  3. AR-42 in Treating Patients With Advanced or Relapsed Multiple Myeloma, Chronic Lymphocytic Leukemia, or Lymphoma

    ClinicalTrials.gov

    2016-03-16

    Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Prolymphocytic Leukemia; 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 Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Multiple Myeloma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Chronic Lymphocytic Leukemia; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Multiple Myeloma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large

  4. Single autologous stem-cell transplantation followed by maintenance therapy with thalidomide is superior to double autologous transplantation in multiple myeloma: results of a multicenter randomized clinical trial.

    PubMed

    Abdelkefi, Abderrahman; Ladeb, Saloua; Torjman, Lamia; Othman, Tarek Ben; Lakhal, Amel; Romdhane, Neila Ben; Omri, Halima El; Elloumi, Moez; Belaaj, Hatem; Jeddi, Ramzi; Aissaouï, Lamia; Ksouri, Habib; Hassen, Assia Ben; Msadek, Fahmi; Saad, Ali; Hsaïri, Mohamed; Boukef, Kamel; Amouri, Ahlem; Louzir, Hechmi; Dellagi, Koussay; Abdeladhim, Abdeladhim Ben

    2008-02-15

    From April 2003 to December 2006, 195 patients with de novo symptomatic myeloma and younger than 60 years of age were randomly assigned to receive either tandem transplantation up front (arm A, n = 97) or one autologous stem-cell transplantation followed by a maintenance therapy with thalidomide (day + 90, 100 mg per day during 6 months) (arm B, n = 98). Patients included in arm B received a second transplant at disease progression. In both arms, autologous stem-cell transplantation was preceded by first-line therapy with thalidomide-dexamethasone and subsequent collection of peripheral blood stem cells with high-dose cyclophosphamide (4 g/m(2)) and granulocyte colony stimulating factor. Data were analyzed on an intent-to-treat basis. With a median follow-up of 33 months (range, 6-46 months), the 3-year overall survival was 65% in arm A and 85% in arm B (P = .04). The 3-year progression-free survival was 57% in arm A and 85% in arm B (P = .02). Up-front single autologous transplantation followed by 6 months of maintenance therapy with thalidomide (with second transplant in reserve for relapse or progression) is an effective therapeutic strategy to treat multiple myeloma patients and appears superior to tandem transplant in this setting. This study was registered at www.ClinicalTrials.gov as (NCT 00207805). PMID:17875806

  5. Low-dose autologous in vitro opsonized erythrocytes. Radioimmune method and autologous opsonized erythrocytes for refractory autoimmune thrombocytopenic purpura in adults

    SciTech Connect

    Ambriz, R.; Munoz, R.; Pizzuto, J.; Quintanar, E.; Morales, M.; Aviles, A.

    1987-01-01

    Adult patients with chronic autoimmune thrombocytopenic purpura (ATP), which proved refractory to various treatments, received a single dose of autologous in vitro opsonized erythrocytes with 100 micrograms of anti-D IgG. In 1983, 30 of these patients were treated with autologous erythrocytes that had been opsonized and labeled with 25 mCi (740 MBq) of technetium Tc 99m; this treatment was designated as the radioimmune method. Favorable responses were noted in 36% of patients so treated. In 1985, another group of 16 patients with refractory ATP received therapy with autologous opsonized erythrocytes (AOPE) and 55% of these patients showed favorable responses. Five (17%) of the patients treated using the radioimmune method attained a complete, long-term (greater than 35 months) remission of their ATP, and five (31%) of the patients treated using AOPE remained in complete remission over 270 days after cessation of therapy. Major complications were not seen. We concluded that the interaction of macrophages with low-dose AOPE is a successful therapeutic approach in ATP refractory to standard treatment.

  6. What Are the Key Statistics for Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... for chronic lymphocytic leukemia? What are the key statistics for chronic lymphocytic leukemia? The American Cancer Society's ... in children. Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Last Medical Review: ...

  7. What Should You Ask Your Doctor about Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... chronic lymphocytic leukemia? What should you ask your doctor about chronic lymphocytic leukemia? As you cope with ... need to have honest, open discussions with your doctor. You should feel comfortable asking any question, no ...

  8. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... leukemia? What should you ask your doctor about acute lymphocytic leukemia? It is important to have frank, honest discussions ... answer many of your questions. What kind of acute lymphocytic leukemia (ALL) do I have? Do I have any ...

  9. What Are the Risk Factors for Acute Lymphocytic Leukemia?

    MedlinePlus

    ... lymphocytic leukemia? What are the risk factors for acute lymphocytic leukemia? A risk factor is something that affects your ... this is unknown. Having an identical twin with ALL Someone who has an identical twin who develops ...

  10. Response of lymphocytes to a mitogenic stimulus during spaceflight

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1989-01-01

    Several studies were performed that demonstrate that immunological activities of lymphocytes can be affected by spaceflight or by models that attempt to simulate some aspects of weightlessness. Included among these are the responses of lymphocytes to external stimuli such as mitogens and viruses. When cultures of lymphocytes were flown in space, the ability of the lymphocytes to respond to mitogens was inhibited. Similar results were obtained when lymphocytes from astronauts or animals just returned from space were placed into culture immediately upon return to earth, and when models of hypogravity were used. Lymphocytes placed in culture during spaceflights produced enhanced levels of interferon compared to control cultures. When cultures of lymphocytes were prepared for cosmonauts or rodents immediately upon return to earth, interferon production was inhibited. These results suggest that space flight can have profound effects on lymphocyte function, and that effects on isolated cells may be different from that on cells in the whole organism.

  11. Soft Tissue Augmentation with Autologous Platelet Gel and β-TCP: A Histologic and Histometric Study in Mice

    PubMed Central

    Ceccarelli, Maurizio; Marchetti, Massimiliano; Piattelli, Adriano; Mortellaro, Carmen

    2016-01-01

    Background. Facial aging is a dynamic process involving both soft tissue and bony structures. Skin atrophy, with loss of tone, elasticity, and distribution of facial fat, coupled with gravity and muscle activity, leads to wrinkling and folds. Purpose. The aim of the study was to evaluate microporous tricalcium phosphate (β-TCP) and autologous platelet gel (APG) mix in mice for oral and maxillofacial soft tissue augmentation. The hypothesis was that β-TCP added with APG was able to increase the biostimulating effect on fibroblasts and quicken resorption. Materials and Methods. Ten female, 6–8-week-old black-haired mice were selected. β-TCP/APG gel was injected into one cheek; the other was used as control. The animals were sacrificed at 8 weeks and histologically evaluated. Results. The new fibroblast was intensively stained with acid fuchsin and presented in contact with β-TCP. At higher magnification, actively secreting fibroblasts were observed at the periphery of β-TCP with a well differentiated fibroblast cell line and blood vessels. Acid fuchsin stained cutaneous structures in pink: no epidermal/dermal alterations or pathological inflammatory infiltrates were detected. The margins of β-TCP granules were clear and not diffused near tissues. Conclusion. APG with β-TCP preserves skin morphology, without immune response, with an excellent tolerability and is a promising scaffold for cells and biomaterial for soft tissue augmentation. PMID:27478828

  12. Soft Tissue Augmentation with Autologous Platelet Gel and β-TCP: A Histologic and Histometric Study in Mice.

    PubMed

    Scarano, Antonio; Ceccarelli, Maurizio; Marchetti, Massimiliano; Piattelli, Adriano; Mortellaro, Carmen

    2016-01-01

    Background. Facial aging is a dynamic process involving both soft tissue and bony structures. Skin atrophy, with loss of tone, elasticity, and distribution of facial fat, coupled with gravity and muscle activity, leads to wrinkling and folds. Purpose. The aim of the study was to evaluate microporous tricalcium phosphate (β-TCP) and autologous platelet gel (APG) mix in mice for oral and maxillofacial soft tissue augmentation. The hypothesis was that β-TCP added with APG was able to increase the biostimulating effect on fibroblasts and quicken resorption. Materials and Methods. Ten female, 6-8-week-old black-haired mice were selected. β-TCP/APG gel was injected into one cheek; the other was used as control. The animals were sacrificed at 8 weeks and histologically evaluated. Results. The new fibroblast was intensively stained with acid fuchsin and presented in contact with β-TCP. At higher magnification, actively secreting fibroblasts were observed at the periphery of β-TCP with a well differentiated fibroblast cell line and blood vessels. Acid fuchsin stained cutaneous structures in pink: no epidermal/dermal alterations or pathological inflammatory infiltrates were detected. The margins of β-TCP granules were clear and not diffused near tissues. Conclusion. APG with β-TCP preserves skin morphology, without immune response, with an excellent tolerability and is a promising scaffold for cells and biomaterial for soft tissue augmentation. PMID:27478828

  13. An autologous endothelial cell:peripheral blood mononuclear cell assay that detects cytokine storm responses to biologics.

    PubMed

    Reed, Daniel M; Paschalaki, Koralia E; Starke, Richard D; Mohamed, Nura A; Sharp, Giles; Fox, Bernard; Eastwood, David; Bristow, Adrian; Ball, Christina; Vessillier, Sandrine; Hansel, Trevor T; Thorpe, Susan J; Randi, Anna M; Stebbings, Richard; Mitchell, Jane A

    2015-06-01

    There is an urgent unmet need for human tissue bioassays to predict cytokine storm responses to biologics. Current bioassays that detect cytokine storm responses in vitro rely on endothelial cells, usually from umbilical veins or cell lines, cocultured with freshly isolated peripheral blood mononuclear cells (PBMCs) from healthy adult volunteers. These assays therefore comprise cells from 2 separate donors and carry the disadvantage of mismatched tissues and lack the advantage of personalized medicine. Current assays also do not fully delineate mild (such as Campath) and severe (such as TGN1412) cytokine storm-inducing drugs. Here, we report a novel bioassay where endothelial cells grown from stem cells in the peripheral blood (blood outgrowth endothelial cells) and PBMCs from the same donor can be used to create an autologous coculture bioassay that responds by releasing a plethora of cytokines to authentic TGN1412 but only modestly to Campath and not to control antibodies such as Herceptin, Avastin, and Arzerra. This assay performed better than the traditional mixed donor assay in terms of cytokine release to TGN1412 and, thus, we suggest provides significant advancement and a definitive system by which biologics can be tested and paves the way for personalized medicine. PMID:25746794

  14. CD4+ T-cell clones recognizing human lymphoma-associated antigens: generation by in vitro stimulation with autologous Epstein-Barr virus-transformed B cells.

    PubMed

    Long, Heather M; Zuo, Jianmin; Leese, Alison M; Gudgeon, Nancy H; Jia, Hui; Taylor, Graham S; Rickinson, Alan B

    2009-07-23

    Epstein-Barr virus (EBV)-specific T-cell preparations, generated by stimulating immune donor lymphocytes with the autologous virus-transformed B-lymphoblastoid cell line (LCL) in vitro, can be used to target EBV-positive malignancies. Although these preparations are enriched for EBV antigen-specific CD8(+) T cells, most also contain a CD4(+) T-cell population whose specificity is unknown. Here, we show that, although CD4(+) T-cell clones derived from such cultures recognize HLA class II-matched LCLs but not mitogen-activated B lymphoblasts, many (1) do not map to any known EBV antigen, (2) can be raised from EBV-naive as well as EBV-immune persons, and (3) can recognize a broad range of human B lymphoma-derived cell lines irrespective of EBV genome status, providing those lines to express the relevant HLA class II-restricting allele. Importantly, such CD4(+) clones not only produce IFNgamma but are also cytotoxic and can control the outgrowth of HLA-matched lymphoma cells in cocultivation assays. We infer that such CD4(+) T cells recognize cellular antigens that are preferentially up-regulated in EBV-transformed but not mitogen-activated B lymphoblasts and that are also expressed in a range of B-cell malignancies. Such antigens are therefore of potential value as targets for CD4(+) T cell-based immunotherapy. PMID:19443664

  15. Immunomodulatory drugs improve the immune environment for dendritic cell-based immunotherapy in multiple myeloma patients after autologous stem cell transplantation.

    PubMed

    De Keersmaecker, Brenda; Fostier, Karel; Corthals, Jurgen; Wilgenhof, Sofie; Heirman, Carlo; Aerts, Joeri L; Thielemans, Kris; Schots, Rik

    2014-10-01

    Multiple myeloma (MM) is characterized by a malignant proliferation of plasma cells in the bone marrow with associated organ damage. Although the prognosis of MM has improved recently, the disease remains incurable for the large majority of patients. The eradication of residual disease in the bone marrow is a main target on the road toward cure. Immune cells play a role in the control of cancer and can be tools to attack residual MM cells. However, the myeloma-associated immune deficiency is a major hurdle to immunotherapy. We evaluated ex vivo the effects of low doses of the immunomodulatory drugs (IMiDs) lenalidomide and pomalidomide on several immune cell types from MM patients after autologous stem cell transplantation and with low tumor burden. We observed that these drugs increased CD4(+) and CD8(+) T-cell proliferation and cytokine production, enhanced the lytic capacity of cytotoxic T lymphocytes and reduced the suppressive effects of regulatory T cells on CD8(+) T-cell responses. In addition, we found that functional dendritic cells (DCs) can be generated from mononuclear cells from MM patients. The presence of IMiDs improved the quality of antigen-specific T cells induced or expanded by these DCs as evidenced by a higher degree of T-cell polyfunctionality. Our results provide a rationale for the design of early phase clinical studies to assess the efficacy of DC-based immunotherapy in combination with posttransplant maintenance treatment with IMiDs in MM. PMID:24947180

  16. Cancer Statistics: Acute Lymphocytic Leukemia (ALL)

    MedlinePlus

    ... at a Glance Show More At a Glance Estimated New Cases in 2016 6,590 % of All New Cancer Cases 0.4% Estimated Deaths in 2016 1,430 % of All Cancer ... of This Cancer : In 2013, there were an estimated 77,855 people living with acute lymphocytic leukemia ...

  17. In vitro responsiveness of lymphocytes to phytohemmagglutinin.

    PubMed

    Peterson, M L; Rommo, N; House, D; Harder, S

    1978-01-01

    Peripheral blood lymphocytes from 20 human subjects exposed to 784 microgram/m3 ozone for 4 hours, and from 11 subjects exposed to clean air for the same length of time were studied for in vitro responsiveness to phytohemagglutinin (PHA). Thymus-derived (T) lymphocyte response to PHA (normal response is proliferation of lymphocytes) was significantly suppressed (P less than .01) in samples obtained immediately after subjects' exposure to ozone. Recovery of response occurred 2 weeks postexposure. Responses were unchanged in subjects exposed to clean air. Existing studies suggest that ozone exposure may generate free radicals or other reactive molecules or both, that could be responsible for immediate changes in metabolic events leading to blockage or inhibition of deoxyribonucleic acid (DNA) synthesis in T lymphocytes as shown in this study. It is possible that some prerequisite to active cell metabolism such as ribonucleic acid (RNA) may be impaired by ozone exposure. The significance of the suppression of T-cell response noted in this study is that: (1) if continuous exposures to ozone are shown to induce an immunosuppressed state for a significant time period, an important factor in carcinogenesis might be elucidated; (2) immunosuppression may cause a progression of an already present tumor; (3) immunosuppression may enable endogenous latent infections such as tuberculosis to reactivate; and (4) immunosuppression may explain in part the relationship between chronic oxidant air pollution and influenza-like illnesses in population. PMID:646458

  18. Lymphocyte Functions in Space - Related Conditions

    NASA Technical Reports Server (NTRS)

    Risin, D.; Sundaresan, A.; Pellis, N. R.; Davson, David L. (Technical Monitor)

    1999-01-01

    Our previous studies showed that modeled (MMG) and true (STS-54 and STS-56) microgravity (MG) inhibit human lymphocyte locomotion. MMG also suppresses polyclonal and antigen-specific lymphocyte activation. Analysis of the relationship between activation deficits and the loss of locomotion in MG suggested a fundamental defect in signal transduction mechanism localized either at the PKC level or upstream at the cell membrane. FACS analysis of the expression of PKC isoforms in PBMC revealed that MMG selectively inhibits the PKC isoforms expression. The decrease was most prominent in PKC epsilon, less obvious in PKC delta and almost marginal and insignificant in PKC alpha. Western blot analysis confirmed these results (PKC epsilon protein expression was downregulated at 24, 72 and 96 hours in MG). We also found a decrease in PKC epsilon mRNA expression. MMG inhibited programmed cell death (PCD) in lymphocytes. Inhibition was observed in two types of experiments: 1) when PCD was induced by gamma-radiation of PBMC, and 2) when PCD in activated T cells was triggered by PHA-M or PMA + ionomycin restimulation. The established direct effects of MG on signal transduction mechanisms as well as on PCD in lymphocytes could contribute to the impairment of the immunity in space.

  19. Functional Inactivation of EBV-Specific T-Lymphocytes in Nasopharyngeal Carcinoma: Implications for Tumor Immunotherapy

    PubMed Central

    Li, Jiang; Zeng, Xue-hui; Mo, Hao-yuan; Rolén, Ulrika; Gao, Yan-fang; Zhang, Xiao-shi; Chen, Qiu-yan; Zhang, Li; Zeng, Mu-sheng; Li, Man-zhi; Huang, Wen-lin; Wang, Xiao-ning; Zeng, Yi-Xin; Masucci, Maria G.

    2007-01-01

    Nasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV) associated malignancy with high prevalence in Southern Chinese. In order to assess whether defects of EBV-specific immunity may contribute to the tumor, the phenotype and function of circulating T-cells and tumor infiltrating lymphocytes (TILs) were investigated in untreated NPC patients. Circulating naïve CD3+CD45RA+ and CD4+CD25− cells were decreased, while activated CD4+CD25+ T-cells and CD3−CD16+ NK-cells were increased in patients compared to healthy donors. The frequency of T-cells recognizing seven HLA-A2 restricted epitopes in LMP1 and LMP2 was lower in the patients and remained low after stimulation with autologous EBV-carrying cells. TILs expanded in low doses of IL-2 exhibited an increase of CD3+CD4+, CD3+CD45RO+ and CD4+CD25+ cells and 2 to 5 fold higher frequency of LMP1 and LMP2 tetramer positive cells compared to peripheral blood. EBV-specific cytotoxicity could be reactivated from the blood of most patients, whereas the TILs lacked cytotoxic activity and failed to produce IFNγ upon specific stimulation. Thus, EBV-specific rejection responses appear to be functionally inactivated at the tumor site in NPC. PMID:17987110

  20. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics.

    PubMed

    Crompton, Joseph G; Sukumar, Madhusudhanan; Roychoudhuri, Rahul; Clever, David; Gros, Alena; Eil, Robert L; Tran, Eric; Hanada, Ken-Ichi; Yu, Zhiya; Palmer, Douglas C; Kerkar, Sid P; Michalek, Ryan D; Upham, Trevor; Leonardi, Anthony; Acquavella, Nicolas; Wang, Ena; Marincola, Francesco M; Gattinoni, Luca; Muranski, Pawel; Sundrud, Mark S; Klebanoff, Christopher A; Rosenberg, Steven A; Fearon, Douglas T; Restifo, Nicholas P

    2015-01-15

    Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) results in complete regression of advanced cancer in some patients, but the efficacy of this potentially curative therapy may be limited by poor persistence of TIL after adoptive transfer. Pharmacologic inhibition of the serine/threonine kinase Akt has recently been shown to promote immunologic memory in virus-specific murine models, but whether this approach enhances features of memory (e.g., long-term persistence) in TIL that are characteristically exhausted and senescent is not established. Here, we show that pharmacologic inhibition of Akt enables expansion of TIL with the transcriptional, metabolic, and functional properties characteristic of memory T cells. Consequently, Akt inhibition results in enhanced persistence of TIL after adoptive transfer into an immunodeficient animal model and augments antitumor immunity of CD8 T cells in a mouse model of cell-based immunotherapy. Pharmacologic inhibition of Akt represents a novel immunometabolomic approach to enhance the persistence of antitumor T cells and improve the efficacy of cell-based immunotherapy for metastatic cancer. PMID:25432172

  1. Autologous Tragal Perichondrium Transplantation: A Novel Approach for the Management of Painful Bullous Keratopathy

    PubMed Central

    Kim, Kyoung Woo; Chun, Yeoun Sook

    2013-01-01

    Purpose To introduce autologous tragal perichondrium transplantation as a novel surgical modality for the management of intractable symptomatic bullous keratopathy. Methods In three eyes of three patients with painful bullous keratopathy, autologous tragal perichondria were transplanted on the corneal surface with the human amniotic membrane transplanted above. We included an additional three eyes of three patients with painful bullous keratopathy who received amniotic membrane transplantation only to serve as controls. Clinical symptom outcomes were assessed using a visual analogue scale at postsurgical months 1, 3, 5, 7, and 9. In addition, transplanted tragal perichondrium and amniotic membrane complex tissue button obtained from one patient who underwent penetrating keratoplasty was evaluated by immunohistochemical analysis of CD34, vimentin, and alcian blue staining. Results All three patients who underwent autologous tragal perichondrium and human amniotic membrane co-transplantation showed improvements in pain and tearing. However, all three patients in the control group experienced aggravation of tearing and no further improvement of pain 3 months after surgery. In addition, one patient in the control group developed premature degradation of the amniotic membrane. Histopathologic and immunohistochemical analysis showed intact surface epithelization and positive CD34, vimentin and alcian blue staining of transplanted tragal perichondria. Conclusions The tragal perichondrium has a high mechanical structural force and high potency due to well-organized epithelization and the presence of mesenchymal stem cells. Autologous tragal perichondrium transplantation may be an effective modality for the management of painful bullous keratopathy. PMID:23730105

  2. Use of autologous fibrin glue for endoscopic treatment of esophageal lesions

    PubMed Central

    Lucas, Matthias; Seeber, Petra

    2015-01-01

    Background and study aims: Esophageal leaks are a potentially life-threatening condition. One treatment option is injection therapy with commercially available fibrin glue. We describe herein a method to close esophageal leaks by injecting autologous fibrin glue prepared exclusively with the patient's own blood. PMID:26528493

  3. Exanthem subitum (human herpesvirus-6 reactivation) after autologous stem cell transplantation.

    PubMed

    Schlaweck, S; Brägelmann, J; Brossart, P; Mayer, K

    2016-04-01

    We present the case of a 62-year-old man treated with high-dose chemotherapy and consecutive autologous stem cell transplantation for mantle cell lymphoma, who developed high fever and a rash of the trunk and both axillae 10 days after stem cell transplantation. PMID:26918962

  4. RBC aggregation dynamics in autologous plasma and serum studied with double-channel optical tweezers

    NASA Astrophysics Data System (ADS)

    Lee, Kisung; Danilina, Anna; Potkin, Anton; Kinnunen, Matti; Priezzhev, Alexander; Meglinski, Igor

    2016-04-01

    Red blood cells aggregating and disaggregating forces were measured in the autologous plasma and serum using the double-channeled optical tweezers. A significant, three-fold decrease of the both forces was observed in the serum compared to the plasma. The results of this study help to better assess the RBC aggregation mechanism.

  5. Nasal reconstruction with autologous rib cartilage: a 43-year follow-up.

    PubMed

    Horton, C E; Matthews, M S

    1992-01-01

    Autogenous costal cartilage has long been a popular material for nasal augmentation. The history of autogenous cartilage transplantation is reviewed. Two patients are presented who underwent nasal augmentation with autologous costal cartilage with a 43-year follow-up on each patient. PMID:1727245

  6. Meta-analysis on autologous stem cell transplantation in the treatment of limb ischemic

    PubMed Central

    Sun, Xiuqin; Ying, Jilin; Wang, Yunan; Li, Wei; Wu, Yaojiang; Yao, Baoting; Liu, Ying; Gao, Hongkai; Zhang, Xiaomei

    2015-01-01

    Aim: Meta-analysis on the effectiveness of the autologous stem cell transplantation in curing limb ischemic. Method: Consulting papers relate to the autologous stem cell transplantation in curing limb ischemic in PubMed, CNKI, Wan-fang Data and VIP. Based on include and exclude standards, we arrange at least 2 evaluators sifting these papers separately, doing Quality evaluation and information extraction and then cross checking. Negotiate through a third party if any disagreement comes out. Review Manager 4.2 is used in Meta-analysis. Result: Involved 7 papers, all in English version. Patients involved all diagnosed as critical limb ischemia (CLI). Results show that no adverse reaction occurred during this study. Amputation rate in patients with stem cell group treatment is lower than control group (P < 0.05). And no notable difference in improving ABI (P > 0.05). Conclusions: Applying autologous stem cell transplantation in curing limb ischemic does not have obviously effectiveness in the improvement of ABI of the limb ischemic patients. But it can dramatically reduce the rate of amputation. So autologous stem cell transplantation is a good and safe choice for patients have no choice but amputation. PMID:26309525

  7. Investigation of an autologous blood treatment strategy for temporomandibular joint hypermobility in a pig model.

    PubMed

    Stembirek, J; Matalova, E; Buchtova, M; Machon, V; Misek, I

    2013-03-01

    Many different surgical and non-surgical techniques are used for the treatment of temporomandibular joint (TMJ) hypermobility. One of these methods is autologous blood injection into the TMJ. The fate of the autologous blood used for treatment of recurring condylar dislocation is still not completely understood. The authors used 12 pigs (Sus scrota f. domestica) as a model species for autologous blood delivery into the TMJ. Blood injection was followed by histopathological analysis at different times after treatment (1h, 1, 2 and 4 weeks). Samples were examined by magnetic resonance imaging, macroscopic and histological methods. The deposition of the remaining blood was observed in the form of clots in the distal parts of the upper joint cavity 1h and 1 week after treatment. 2 weeks after treatment, small blood clots were still apparent in the distal part of the upper joint cavity. 4 weeks after surgery, no remnants of blood, changes or adhesions were apparent inside the TMJ. No morphological or histological changes were observed in the TMJ after the injection of autologous blood suggesting another mechanism is involved in the hypermobility treatment. PMID:22867740

  8. [Transfusion of autologous bone marrow for the prevention and treatment of postoperative anemia].

    PubMed

    Malakhov, S F; Men'shikova, E A; Shelukhin, V A; Bagautdinov, Sh M

    1982-12-01

    The authors have shown hyporegeneratory character of anemia developing after operations on the lungs followed by massive blood loss which was adequately compensated by conserved homologous blood. The transfusion of the autologous bone marrow prepared before operation results in a pronounced stimulation of production of erythrocytes, contributing to the quickest recovery of the circulating erythron. PMID:6762753

  9. An Exploratory Clinical Trial for Idiopathic Osteonecrosis of Femoral Head by Cultured Autologous Multipotent Mesenchymal Stromal Cells Augmented with Vascularized Bone Grafts

    PubMed Central

    Aoyama, Tomoki; Goto, Koji; Kakinoki, Ryosuke; Ikeguchi, Ryosuke; Ueda, Michiko; Kasai, Yasunari; Maekawa, Taira; Tada, Harue; Teramukai, Satoshi; Nakamura, Takashi

    2014-01-01

    Idiopathic osteonecrosis of femoral head (ION) is a painful disorder that progresses to collapse of the femoral head and destruction of the hip joint. Although its precise pathology remains unknown, the loss of blood supply causing the loss of living bone-forming cells is a hallmark of the pathophysiology of osteonecrosis. Transplantation of multipotent mesenchymal stromal cells (MSCs) is a promising tool for regenerating the musculoskeletal system. The aim of the present study was to assess the safety and efficacy of transplantation of cultured autologous bone marrow-derived MSCs mixed with β-tricalcium phosphate (β-TCP) in combination with vascularized bone grafts for the treatment of advanced stage ION in a clinical trial. Ten patients with stage 3 ION were enrolled in this study. Autologous bone marrow-derived MSCs were cultured with autologous serum, and cells (0.5–1.0×108) were transplanted after mixing with β-TCP granules in combination with vascularized iliac bone grafts. Patients were assessed 24 months after treatment. The primary and secondary endpoints were progression of the radiological stage and changes in bone volume at the femoral head, and clinical score, respectively. Nine of ten patients completed the protocol, seven of whom remained at stage 3, and the remaining two cases progressed to stage 4. The average bone volume increased from 56.5±8.5 cm3 to 57.7±10.6 cm3. The average clinical score according to the Japan Orthopaedic Association improved from 65.6±25.5 points to 87.9±19.0 points. One severe adverse event was observed, which was not related to the clinical trial. Although the efficacy of cell transplantation was still to be determined, all procedures were successfully performed and some young patients with extensive necrotic lesions with pain demonstrated good bone regeneration with amelioration of symptoms. Further improvements in our method using MSCs and the proper selection of patients will open a new approach for the

  10. Assays for B lymphocyte function.

    PubMed

    Bondada, Subbarao; Robertson, Darrell A

    2003-11-01

    This unit describes the antigenic stimulation of in vitro antibody production by B cells and the subsequent measurement of secreted antibodies. The first basic protocol is a generalized system for inducing in vitro antibody production and can accommodate various types of antigens under study. Secreted antibodies can then be measured with an enzyme-linked immunosorbent assay (ELISA) or other soluble-antibody detection systems. Alternatively, the number of antibody-producing cells can be quantified by plaque-forming cell (PFC) assays presented in this unit: the Cunningham-Szenberg and the Jerne-Nordin techniques. Both methods employ specially prepared slide chambers, described here, in which the antibody-producing B cells are mixed with complement and indicator sheep red blood cells (SRBC), or with trinitrophenol-modified SRBC (TNP-SRBC), with subsequent lysis and counting of plaques. Because IgM antibodies fix complement efficiently, whereas IgG and IgA antibodies do not, unmodified PFC assays measure only IgM antibodies. The assay can be modified, however, to measure all classes of antibodies or to enumerate total immunoglobulin-secreting B cells, as described in alternate protocols. Yet another method of measuring the number of antibody-producing B cells (in a class-specific fashion) is to use the ELISPOT technique described in UNIT 7.14. The resting B cells used in these procedures are prepared as described in the final support protocols for Percoll gradient centrifugation. PMID:18432909

  11. Autologous stem cell transplantation improves quality of life in economically challenged, Brazilian multiple myeloma patients

    PubMed Central

    Etto, Leina Y.; Morelli, Vânia Maris; Silva, Vanderleia C.; Hungria, Vania T. M.; Ciconelli, Rozana M.; Almeida, Manuella S. S.; de Oliveira, José Salvador R.; Barros, José Carlos; Durie, Brian G.; Colleoni, Gisele W. B.

    2011-01-01

    OBJECTIVES: 1) To characterize the impact of multiple myeloma on the quality of life of patients treated in two public institutions in São Paulo State, Brazil, using a generic Short Form 36 Health Survey and a questionnaire specific for oncologic patients (QLQ-C30) upon diagnosis, after the clinical treatment, and at day +100 after autologous stem cell transplantation; 2) to evaluate whether autologous stem cell transplantation can improve the quality of life of our economically challenged population aside from providing a clinical benefit and disease control. METHODS: We evaluated 49 patients with multiple myeloma (a total of 70 interviews) using the two questionnaires. The scores upon diagnosis, post-treatment/pre-autologous stem cell transplantation, and at D+100 were compared using ANOVA (a comparison of the three groups), post hoc tests (two-by-two comparisons of the three groups), and paired t-tests (the same case at two different times). RESULTS : Of the included patients, 87.8% had a family budget under US $600 (economic class C, D, or E) per month. The generic Short Form 36 Health Survey questionnaire demonstrated that physical function, role-physical, and bodily pain indices were statistically different across all three groups, favoring the D+100 autologous stem cell transplantation group (ANOVA). The questionnaire specific for oncologic patients, the QLQ-C30 questionnaire, confirmed what had been demonstrated by the Short Form 36 Health Survey with respect to physical function and bodily pain, with improvements in role functioning, fatigue, and lack of appetite and constipation, favoring the D+100 autologous stem cell transplant group (ANOVA). The post hoc tests and paired t-tests confirmed a better outcome after autologous stem cell transplantation. CONCLUSION: The questionnaire specific for cancer patients seems to be more informative than the generic Short Form 36 Health Survey questionnaire and reflects the real benefit of autologous stem cell

  12. Is Unilateral Implant or Autologous Breast Reconstruction Better in Obtaining Breast Symmetry?

    PubMed

    Cohen, Oriana; Small, Kevin; Lee, Christina; Petruolo, Oriana; Karp, Nolan; Choi, Mihye

    2016-01-01

    Unilateral breast reconstruction poses a special set of challenges to the reconstructive breast surgeon compared to bilateral reconstructions. No studies to date provide an objective comparison between autologous and implant based reconstructions in matching the contralateral breast. This study compares the quantitative postoperative results between unilateral implant and autologous flap reconstructions in matching the native breast in shape, size, and projection using three-dimensional (3D) imaging. Sixty-four patients who underwent unilateral mastectomy with tissue expander (TE)-implant (n = 34) or autologous microvascular free transverse rectus abdominus myocutaneous (TRAM; n = 18) or deep inferior epigastric artery perforator (DIEP; n = 12) flap (n = 30) reconstruction from 2007 to 2010 were analyzed. Key patient demographics and risk factors were collected. Using 3D scans of patients obtained during pre and postoperative visits including over 1 year follow-ups for both groups, 3D models were constructed and analyzed for total breast volume, anterior-posterior projection from the chest wall, and 3D comparison. No significant differences in mean age, body mass index, or total number of reconstructive surgeries were observed between the two groups (TE-implant: 52.2 ± 10, 23.9 ± 3.7, 3 ± 0.9; autologous: 50.7 ± 9.4, 25.4 ± 3.9, 2.9 ± 1.3; p > 0.05). The total volume difference between the reconstructed and contralateral breasts in the TE-implant group was insignificant: 27.1 ± 22.2 cc, similar to the autologous group: 29.5 ± 24.7 cc, as was the variance of breast volume from the mean. In both groups, the reconstructed breast had a larger volume. A-P projections were similar between the contralateral and the reconstructed breasts in the TE-implant group: 72.5 ± 3.21 mm versus 71.7 ± 3.5 mm (p > 0.05). The autologous reconstructed breast had statistically insignificant but less A-P projection compared to the contralateral breast (81.9 ± 16.1 mm versus 61

  13. [Mixed marriages].

    PubMed

    Harmsen, C N

    1998-08-01

    The author examines the extent and characteristics of mixed marriages in the Netherlands. "Nine out of ten married persons born in Turkey or Morocco have a partner who was born in the same country. The majority of married Surinamese also have a partner originating from the same country. Those who spend (a part of) their youth in Indonesia (the former Dutch East Indies), on the other hand, are mostly married to someone born in the Netherlands." (EXCERPT) PMID:12294179

  14. Autologous red blood cells potentiate antibody synthesis by unfractionated human mononuclear cell cultures.

    PubMed

    Rugeles, M T; La Via, M; Goust, J M; Kilpatrick, J M; Hyman, B; Virella, G

    1987-08-01

    We have tried to determine the most favourable conditions for the in vitro induction of specific antibody (Ab) responses to tetanus toxoid (TT) and keyhole limpet haemocyanin (KLH). Human peripheral blood mononuclear cells (PBMNC) were obtained from normal volunteers and stimulated with PWM, TT, KLH, and mixtures of PWM and antigens in the presence or absence of autologous red blood cells (RBC) (1:50 ratio of PBMNC/RBC). The cultures were harvested on day 11; immunoglobulins were determined immunonephelometrically and Ab levels by ELISA with human antibodies used for calibration. While anti-TT responses were easy to induce with PBMNC from recently boosted individuals, the production of anti-TT from PBMNC obtained from non-recently boosted individuals was only possible when PBMNC were stimulated with TT and PWM in the presence of autologous RBC. Similarly, anti-KLH responses were easier to induce with PBMNC from an immune donor; maximal response was observed after stimulation with PWM + KLH in the presence of autologous RBC. Stimulation of primary anti-KLH responses with PBMNC from non-immune donors was only successful when the cells were stimulated with KLH + PWM in the presence of autologous RBC. The potentiation of human B-cell responses with autologous RBC can be abrogated by pretreatment of PBMNC with anti-CD2 antibodies and is associated with increased expression of IL-2 receptors and increased production of gamma interferon (IFN-gamma). However, addition of IFN-gamma in different doses and at different times to PWM-stimulated PBMNC cultures was not as effective as addition of RBC in enhancing the production of immunoglobulin and antibody. PMID:3114872

  15. Autologous Umbilical Cord Blood Transfusion in Very Young Children With Type 1 Diabetes

    PubMed Central

    Haller, Michael J.; Wasserfall, Clive H.; McGrail, Kieran M.; Cintron, Miriam; Brusko, Todd M.; Wingard, John R.; Kelly, Susan S.; Shuster, Jonathan J.; Atkinson, Mark A.; Schatz, Desmond A.

    2009-01-01

    OBJECTIVE Interest continues to grow regarding the therapeutic potential for umbilical cord blood therapies to modulate autoimmune disease. We conducted an open-label phase I study using autologous umbilical cord blood infusion to ameliorate type 1 diabetes. RESEARCH DESIGN AND METHODS Fifteen patients diagnosed with type 1 diabetes and for whom autologous umbilical cord blood was stored underwent a single intravenous infusion of autologous cells and completed 1 year of postinfusion follow-up. Intensive insulin regimens were used to optimize glycemic control. Metabolic and immunologic assessments were performed before infusion and at established time periods thereafter. RESULTS Median (interquartile range [IQR]) age at infusion was 5.25 (3.1–7.3) years, with a median postdiagnosis time to infusion of 17.7 (10.9–26.5) weeks. No infusion-related adverse events were observed. Metabolic indexes 1 year postinfusion were peak C-peptide median 0.50 ng/ml (IQR 0.26–1.30), P = 0.002; A1C 7.0% (IQR 6.5–7.7), P = 0.97; and insulin dose 0.67 units · kg−1 · day−1 (IQR 0.55–0.77), P = 0.009. One year postinfusion, no changes were observed in autoantibody titers, regulatory T-cell numbers, CD4-to-CD8 ratio, or other T-cell phenotypes. CONCLUSIONS Autologous umbilical cord blood transfusion in children with type 1 diabetes is safe but has yet to demonstrate efficacy in preserving C-peptide. Larger randomized studies as well as 2-year postinfusion follow-up of this cohort are needed to determine whether autologous cord blood–based approaches can be used to slow the decline of endogenous insulin production in children with type 1 diabetes. PMID:19875605

  16. Blood lymphocyte subpopulations in breast cancer patients following radiotherapy.

    PubMed Central

    Petrini, B; Wasserman, J; Blomgren, H; Baral, E

    1977-01-01

    Both T and non-T lymphocytes decreased immediately following radiotherapy in breast cancer patients. The relative depletion of non-T lymphocytes, however, was more marked than that of T cells. 3 years later the number and the proportion of non-T lymphocytes was higher than immediately after radiotherapy, while T lymphocytes were still depressed. The proportion of cells with membrane-associated Ig was higher in patients 3 years following radiotherapy than in non-treated patients and healthy controls. There was no difference in the proportion of T and non-T lymphocytes between patients with and without metastases, respectively. PMID:330065

  17. Stimulation of human lymphocytes by Herpes simplex virus antigens.

    PubMed Central

    Starr, S E; Karatela, S A; Shore, S L; Duffey, A; Nahmias, A J

    1975-01-01

    Lymphocytes from individuals with laboratory evidence of prior infection with herpes simplex virus (HSV) type 1 or type 2 demonstrated transformation (av antigens. Higher stimulation indexes were obtained when lymphocytes were incubated with the homologous as compared with the heterologous antigen. Higher mean lymphocyte stimulation indexes were also demonstrated in seropositive as compared with seronegative individuals. Lymphocytes from children with HSV-1 stomatitis usually became responsive to HSV-1 antigen within 2 to 6 weeks after the onset of illness. Lymphocytes from infants with neonatal HSV-2 infection were stimulated by HSV-2 antigen. PMID:163788

  18. In vitro ozone exposure inhibits mitogen-induced lymphocyte proliferation and IL-2 production

    SciTech Connect

    Becker, S.; Jordan, R.L.; Orlando, G.S.; Koren, H.S.

    1989-01-01

    Human blood mononuclear cells were exposed to ozone in vitro and thereafter analyzed for competence in mitogen-induced proliferation as well as IL-1 and IL-2 production. Proliferative responses induced by phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were all depressed in lymphocytes exposed to an ozone concentration of 1 ppm for 4-6 h. The response to PWM was most sensitive to the ozone effect (38% suppression); responses to Con A and PHA were suppressed to a lesser extent, 23% and 18%, respectively, and were not significantly different from each other. PWM responses were affected at an ozone concentration as low as 0.1 ppm; however, no suppression of Con A-induced proliferation was seen below 0.18 ppm or of PHA-induced proliferation below 0.5 ppm. When lymphocytes and monocytes were exposed separately to ozone and then mixed back with control air-exposed monocytes or lymphocytes, both cell types appeared to be affected and the functional defects caused by the pollutant were additive. Monocyte IL-1 production induced by endotoxin was not affected by ozone exposure, while surface expression of HLA-DR on exposed monocytes was reduced by 40% 24 h after exposure. Moreover, lymphocytes exposed to ozone produced 46% less IL-2 while expressing similar surface density of IL-2 receptors. Taken together, these results show that exposure to ozone has distinct adverse effects on lymphocytes and monocytes, both of which are important in local immune defenses in the lung.

  19. Mixed results with mixed disulfides.

    PubMed

    Brigelius-Flohé, Regina

    2016-04-01

    A period of research with Helmut Sies in the 1980s is recalled. Our experiments aimed at an in-depth understanding of metabolic changes due to oxidative challenges under near-physiological conditions, i.e. perfused organs. A major focus were alterations of the glutathione and the NADPH/NADP(+) system by different kinds of oxidants, in particular formation of glutathione mixed disulfides with proteins. To analyze mixed disulfides, a test was adapted which is widely used until today. The observations in perfused rat livers let us believe that glutathione-6-phosphate dehydrogenase (G6PDH), i.a. might be activated by glutathionylation. Although we did not succeed to verify this hypothesis for the special case of G6PDH, the regulation of enzyme/protein activities by glutathionylation today is an accepted posttranslational mechanism in redox biology in general. Our early experimental approaches are discussed in the context of present knowledge. PMID:27095221

  20. Proteomic profiling of lymphocytes in autoimmunity, inflammation and cancer

    PubMed Central

    2014-01-01

    Lymphocytes play important roles in the balance between body defense and noxious agents involved in a number of diseases, e.g. autoimmune diseases, allergic inflammation and cancer. The proteomic analyses have been applied to identify and validate disease-associated and disease-specific biomarkers for therapeutic strategies of diseases. The proteomic profiles of lymphocytes may provide more information to understand their functions and roles in the development of diseases, although proteomic approaches in lymphocytes are still limited. The present review overviewed the proteomics-based studies on lymphocytes to headlight the proteomic profiles of lymphocytes in diseases, such as autoimmune diseases, allergic inflammation and cancer, with a special focus on lung diseases. We will explore the potential significance of diagnostic biomarkers and therapeutic targets from the current status in proteomic studies of lymphocytes and discuss the value of the currently available proteomic methodologies in the lymphocytes research. PMID:24397796

  1. Is lymphocytic (hashimoto) thyroiditis associated with suicide?

    PubMed

    Cina, Stephen J; Perper, Joshua A

    2009-09-01

    The histologic diagnosis of lymphocytic (Hashimoto) thyroiditis requires lymphocytic inflammation of the thyroid gland in combination with Hourthle cell metaplasia of follicular epithelial cells. Clinically, this autoimmune process has been associated with hypothyroidism and psychiatric conditions including depression. This retrospective study was designed to quantify the incidence and severity of lymphocytic thyroiditis in a series of nonconsecutive suicides compared with a cohort of motor vehicle accident victim controls. Eighty-one suicide victims (61 male, 20 female; age range 13-79 years, average 43) were compared with 88 age and gender matched controls (64 males, 24 females; age range 19-85 years, average 36). The degree of lymphocytic inflammation of the thyroid gland was graded on a scale of 0 to 3 (0 = no inflammation, 1 = mild inflammation, 2-3 moderate-to-marked inflammation with Hourthle cell metaplasia). Slides from each case were reviewed while blinded to the cause and manner of death in each case. Of these 169 total cases, 8 (4.7%) received a score of 3, whereas additional 7 (4.1%) received a grade of 2. Eighty-six percent of all of the cases showed no significant inflammation and recorded a score of 0. Of the 81 suicides, 3 had a score of 3, and 3 had a score of 2 (combined incidence of 7.4%). Within the control group, 5 of 88 cases scored 3 and another 4 scored 2 (combined incidence = 10.2%). Three males and 5 females scored 3 with an age range of 23 to 63 years, average 42. Incidental data tabulated showed that 19% of suicide victims were on psychoactive medications compared with 6% in the motor vehicle accident control group. No one on this study was on thyroid hormone replacement therapy. Depression is strongly linked to suicide and lymphocytic thyroiditis may be a cause of depression. Based on this study, however, the presence of lymphocytic thyroiditis cannot be used as a histologic adjunct to discriminate between suicide and accident in

  2. Cell Death Mechanisms Induced by Cytotoxic Lymphocytes

    PubMed Central

    Chávez-Galán, L; Arenas-Del Angel, M C; Zenteno, E; Chávez, R; Lascurain, R

    2009-01-01

    One of the functions of the immune system is to recognize and destroy abnormal or infected cells to maintain homeostasis. This is accomplished by cytotoxic lymphocytes. Cytotoxicity is a highly organized multifactor process. Here, we reviewed the apoptosis pathways induced by the two main cytotoxic lymphocyte subsets, natural killer (NK) cells and CD8+ T cells. In base to recent experimental evidence, we reviewed NK receptors involved in recognition of target-cell, as well as lytic molecules such as perforin, granzymes-A and -B, and granulysin. In addition, we reviewed the Fas-FasL intercellular linkage mediated pathway, and briefly the cross-linking of tumor necrosis factor (TNF) and TNF receptor pathway. We discussed three models of possible molecular interaction between lytic molecules from effector cytotoxic cells and target-cell membrane to induction of apoptosis. PMID:19254476

  3. Methionine dependency of cultured human lymphocytes.

    PubMed

    Hall, C A; Begley, J A; Chu, R C

    1986-06-01

    Human peripheral blood lymphocytes stimulated with phytohemagglutinin and a lymphocyte model consisting of the RPMI 6410 cell, a human virus-transformed B cell, required added methionine (Met) for growth of the cultures. This failure to meet all needs for Met via endogenous synthesis, which is characteristic of oncogenic transformation, occurred even in the presence of adequate homocysteine, methylfolate (5-CH3-H4PteGlu) and cobalamin (Cbl)-dependent methionine synthetase activity. Folinic acid (5-CHO-H4PteGlu), which provides available folate independently of Cbl, improved growth only slightly in the absence of Met. Free Cbl at 222 nM, an amount great enough to alter other intracellular events, failed to increase growth in the absence of Met, but 0.22 nM Cbl bound to transcobalamin II did, however, enhance growth. PMID:3703873

  4. Lymphocyte transformation in presumed ocular histoplasmosis

    SciTech Connect

    Ganley, J.P.; Nemo, G.J.; Comstock, G.W.; Brody, J.A.

    1981-08-01

    Lymphocytes from individuals with inactive macular disciform lesions of presumed ocular histoplasmosis challenged with three histoplasmin antigens incorporated tritiated thymidine at a significantly higher rate than histoplasmin-stimulated lymphocytes of matched control and peripheral scar groups. This finding is consistent with the etiologic association of the disciform ocular syndrome and previous systemic infection with Histoplasma capsulatum. The disciform group had a higher mean response than the other two groups to pokeweed mitogen but not to phytohemagglutinin and had higher mean counts per minute to the specific antigens Toxoplasma gondii, Blastomyces dermatitidis, Cryptococcus neoformans, Mycobacterium tuberculosis, M battery, and M gaus, but not to Candida albicans. These data would suggest that individuals with the disciform lesion of presumed ocular histoplasmosis have a hyperreactive cellular immune response; this response may play an important role in the development of the disciform.

  5. Lymphocytes subsets reference values in childhood.

    PubMed

    Tosato, F; Bucciol, G; Pantano, G; Putti, M C; Sanzari, M C; Basso, G; Plebani, M

    2015-01-01

    Immunophenotyping of blood lymphocyte subsets and activation markers is a basic tool in the diagnostic process of primary immunodeficiency diseases, its use becoming more and more widespread as the knowledge about these illnesses increases. However, the availability of reliable reference values, which need to be age-matched for the pediatric population, is a pre-requisite for the reliable interpretation of immunophenotyping data. Aim of this study is to analyze the lymphocyte subsets and activation markers distribution in children aged 0-18 years referring to the University Hospital of Padova and to create age-matched reference values expressed by percentiles, thus providing a valuable guideline for the interpretation of the immunophenotype. PMID:25132325

  6. Effect of weightlessness on lymphocyte proliferation

    NASA Technical Reports Server (NTRS)

    Cogoli, A.

    1981-01-01

    An experiment to study the effect of weightlessness on lymphocyte proliferation to detect possible alteration of the cells responsible for the immune response during long-duration space flights is described. Human lymphocytes in culture medium will be delivered shortly before launch in an incubator which will be kept at 37C. Mitogen will be added to the culture. A control without mitogen will be run in parallel. After 70 hours of incubation, radioactive thymidine will be added. After two hours, cellular activity will be stopped by fixation and incubator power switched off. Later, the amount of incorporated thymidine will be determined and the cell morphology and the distribution of cell organelles will be investigated.

  7. Skewed T cell receptor repertoire of Vδ1+ γδ T lymphocytes after human allogeneic haematopoietic stem cell transplantation and the potential role for Epstein–Barr virus-infected B cells in clonal restriction

    PubMed Central

    Fujishima, N; Hirokawa, M; Fujishima, M; Yamashita, J; Saitoh, H; Ichikawa, Y; Horiuchi, T; Kawabata, Y; Sawada, K-I

    2007-01-01

    The proliferation of Vδ1+ γδ T lymphocytes has been described in various infections including human immunodeficiency virus (HIV), cytomegalovirus (CMV) and malaria. However, the antigen specificity and functions of the human Vδ1+ T cells remain obscure. We sought to explore the biological role for this T cell subset by investigating the reconstitution of T cell receptor (TCR) repertoires of Vδ1+ γδ T lymphocytes after human allogeneic haematopoietic stem cell transplantation (HSCT). We observed skewed TCR repertoires of the Vδ1+ T cells in 27 of 44 post-transplant patients. Only one patient developed EBV-associated post-transplant lymphoproliferative disorder in the present patient cohort. The -WGI- amino acid motif was observed in CDR3 of clonally expanded Vδ1+ T cells in half the patients. A skew was also detected in certain healthy donors, and the Vδ1+ T cell clone derived from the donor mature T cell pool persisted in the recipient's blood even 10 years after transplant. This T cell clone expanded in vitro against stimulation with autologous EBV–lymphoblastoid cell lines (LCL), and the Vδ1+ T cell line expanded in vitro from the same patient showed cytotoxicity against autologous EBV–LCL. EBV-infected cells could also induce in vitro oligoclonal expansions of autologous Vδ1+ T cells from healthy EBV-seropositive individuals. These results suggest that human Vδ1+ T cells have a TCR repertoire against EBV-infected B cells and may play a role in protecting recipients of allogeneic HSCT from EBV-associated disease. PMID:17425654

  8. Remission With Donor Lymphocyte Infusion in a Child With Marrow Relapse After Haploidentical Stem Cell Transplantation for Relapsed Stage 4 Neuroblastoma.

    PubMed

    Liu, A P Y; Leung, R Y Y; Cheuk, K L; Lee, P P W; Chiang, A K S; Ha, S Y; Chan, G C F

    2016-08-01

    A 7-year-old male with Stage 4 neuroblastoma was treated with chemotherapy and autologous hematopoietic stem cell transplantation (HSCT), resulting in partial response with residual bone and marrow disease. He proceeded to haploidentical-HSCT with his mother as donor and achieved remission. The patient developed marrow relapse 2 years after haploidentical-HSCT with cytopenia and dropping donor chimerism. Donor lymphocyte infusion (DLI) using mother's whole blood was given resulting in clearance of marrow disease, resolution of cytopenia, and full donor chimerism. This is the first report of successful treatment for neuroblastoma relapse after haploidentical-HSCT using DLI alone, supporting the role of adoptive cell therapy post-HSCT in neuroblastoma. PMID:27100283

  9. Novel agents for chronic lymphocytic leukemia

    PubMed Central

    2013-01-01

    Chronic lymphocytic leukemia (CLL) is a heterogeneous group of B-cell neoplasm. CLL is typically sensitive to a variety of cytotoxic agents, but relapse frequently occurs with conventional approaches. The treatment of CLL is evolving rapidly with the introduction of novel drugs, such as bendamustine, ofatumumab, lenalidomide, ibrutinib, idelalisib, veltuzumab, XmAb5574, navitoclax, dasatinib, alvespimycin, and TRU-016. This review summarizes the most current clinical experiences with these agents in the treatment of CLL. PMID:23680477

  10. Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive traet

    PubMed Central

    Liang, Wei; Wang, Hui; Sun, Tie-Mie; Yao, Wen-Qing; Chen, Li-Li; Jin, Yu; Li, Chun-Ling; Meng, Fan-Juan

    2003-01-01

    AIM: To treat patients with stage I-IV malignant tumors of digestive tract using autologous tumor cell vaccine and NDV (Newcastle disease virus) vaccine, and observe the survival period and curative effect. METHODS: 335 patients with malignant tumors of digestive tract were treated with autologous tumor cell vaccine and NDV vaccine. The autologous tumor cell vaccine received were assigned for long-term survival observation. While these failed to obtain the autologous tumor tissue were given with NDV vaccine for a received short-term observation on curative effect. RESULTS: The colorectal cancer patients treated with autologous tumor cell vaccine were divided into two groups: the controlled group (subjected to resection alone) (n = 257), the vaccine group (subjected to both resection and immunotherapy) (n = 310). 25 patients treated with NDV immunotherapy were all at stage IV without having resection. In postoperation adjuvant therapy patients, the 5, 6 and 7-year survival rates were 66.51%, 60.52%, 56.50% respectively; whereas in patients with resection alone, only 45.57%, 44.76% and 43.42% respectively. The average survival period was 5.13 years (resection alone group 4.15 years), the median survival period was over 7 years (resection alone group 4.46 years). There were significant differences between the two groups. The patients treated with resection plus vaccine were measured delayed-type hypersensitivity (DTH) reactions after vaccination, (indurative scope > 5 mm). The magnitude of DTH was related to the prognosis. The 5-year survival rate was 80% for those with indurations greater than 5 mm, compared with 30% for those with indurations less than 5 mm. The 1-year survival rate was 96% for 25 patients treated with NDV immunotherapy. The total effective rate (CR+PR) was 24.00% in NDV immunotherapy; complete remission (CR) in 1 case (4.00%), partial remission (PR) in 5 cases (20.00%), stabilizedin in 16 cases (64.00%), progression (PD) in 1 case (4.00%). After

  11. Effectiveness of Autologous Stem Cell Therapy for the Treatment of Lower Extremity Ulcers

    PubMed Central

    Jiang, Xupin; Zhang, Hengshu; Teng, Miao

    2016-01-01

    Abstract Primary studies in animal models and humans have suggested the therapeutic potential of autologous stem cell for treating chronic lower extremity ulcers. However, the results of pilot randomized controlled trials (RCTs) in humans have been inconsistent. A meta-analysis of RCTs was performed to evaluate the role of autologous stem cell-based therapy for lower extremity ulcers. Studies were identified during a systematic search of Medline, Embase, Cochrane's library, and references cited in related reviews and studies. Studies were included if they were RCTs published in English, recruited patients with lower extremity ulcers who were assigned to either a group for the topical therapy with autologous stem cells, and reported data regarding the healing of the ulcers. Relative risks (RRs) for healing rate and standardized mean differences (SMDs) for the changes in the mean sizes of ulcers were evaluated with a random-effects model. Overall, autologous stem cell-based therapy was associated with better healing of lower extremity ulcers (12 comparisons, 290 patients, RR for partial healing = 3.07, 95% confidence interval [CI] = 1.14–8.24, P = 0.03; RR for complete healing = 2.26, 95% CI = 1.48–3.16, P < 0.001) with little heterogeneity (I2 = 0%). Moreover, autologous stem cell-based therapy was associated with a greater reduction in mean ulcer size (SMD = −0.63, 95% CI = −1.03 to −0.22, P = 0.002). Subgroup analyses indicated that stem cells from peripheral blood and bone marrow seemed to exert similar beneficial effects on the healing of ulcers. Stem cell therapy was not associated with any increased risks for adverse events. The optimized sources, amounts, and delivery methods of stem cell -based therapy for patients with chronic lower extremity ulcers need to be determined, and the long-term effects of stem cell-based therapy on clinical outcomes need further exploration. Autologous stem cell-based therapy is

  12. Predictive Value of Neutrophil Lymphocyte Ratio and Platelet Lymphocyte Ratio in Patients with Coronary Slow Flow

    PubMed Central

    Çetin, Mustafa; Kiziltunc, Emrullah; Elalmış, Özgül Uçar; Çetin, Zehra Güven; Demirçelik, Muhammed Bora; Çiçekçioğlu, Hülya; Kurtul, Alparslan; Özkan, Selçuk; Avan, Candan Mansuroğlu; Örnek, Ender; Ulusoy, Feridun Vasfi

    2016-01-01

    Background Increased microvascular resistance due to chronic inflammation is assumed to be one of the mechanisms associated with coronary slow flow (CSF). Previous studies have shown that the platelet-to-lymphocyte ratio (PLR) and the neutrophil-lymphocyte ratio (NLR) are markers of inflammation for various diseases. In this study we aimed to evaluate the relationship between CSF and PLR-NLR. Methods Seventy-eight patients with CSF and 50 patients with normal coronary flow were enrolled into this study. The study subjects underwent medical examination and testing, after which their platelet-to-lymphocyte ratios and NLR values were calculated. An independent observer measured the coronary flow rate by Thrombolysis in Myocardial Infarction Frame Count (TFC) method. The platelet-to-lymphocyte ratio and NLR values were compared between the groups and correlation analysis was performed to explore the relationship between mean TFC with PLR and NLR. Results Platelet-to-lymphocyte ratio and NLR values were significantly higher in patients with CSF (p < 0.001). There was a positive significant correlation between TFC with NLR and PLR (Spearman’s Rho: 0.59, p < 0.001 and Spearman’s Rho: 0.30, p = 0.001, respectively). Multivariate logistic regression analysis revealed that NLR is the one independent predictor for CSF. Conclusions This study demonstrated an association between CSF and PLR-NLR. Although the exact mechanism could not be explained, our findings support the possible role of inflammation in CSF physiopathology. PMID:27274171

  13. Imaging collagen remodeling and sensing transplanted autologous fibroblast metabolism in mouse dermis using multimode nonlinear optical imaging

    NASA Astrophysics Data System (ADS)

    Zhuo, Shuangmu; Chen, Jianxin; Cao, Ning; Jiang, Xingshan; Xie, Shusen; Xiong, Shuyuan

    2008-06-01

    Collagen remodeling and transplanted autologous fibroblast metabolic states in mouse dermis after cellular injection are investigated using multimode nonlinear optical imaging. Our findings show that the technique can image the progress of collagen remodeling in mouse dermis. It can also image transplanted autologous fibroblasts in their collagen matrix environment in the dermis, because of metabolic activity. It was also found that the approach can provide two-photon ratiometric redox fluorometry based on autologous fibroblast fluorescence from reduced nicotinamide adenine dinucleotide coenzyme and oxidized flavoproteins for sensing the autologous fibroblast metabolic state. These results show that the multimode nonlinear optical imaging technique may have potential in a clinical setting as an in vivo diagnostic and monitoring system for cellular therapy in plastic surgery.

  14. Effective implantation of autologous chondrocytes in a patient suffering from a painful and invalidating rizoarthrosis: a case report

    PubMed Central

    Sgherzi, Stefano; Sillani, Alessandro; Magris, Cecilia

    2009-01-01

    A 45-year-old patient, caucasian, affected by severe, painful and invalidating rizoarthrosis has been treated by implanting autologous chondrocytes, normally used for degenerative joint diseases of the knee and ankle. PMID:19918494

  15. Effective implantation of autologous chondrocytes in a patient suffering from a painful and invalidating rizoarthrosis: a case report.

    PubMed

    Carelli, Francesco; Sgherzi, Stefano; Sillani, Alessandro; Magris, Cecilia

    2009-01-01

    A 45-year-old patient, caucasian, affected by severe, painful and invalidating rizoarthrosis has been treated by implanting autologous chondrocytes, normally used for degenerative joint diseases of the knee and ankle. PMID:19918494

  16. Primary immunodeficiencies of the B lymphocyte.

    PubMed

    Moise, Ana; Nedelcu, Filofteia Daniela; Toader, Maria Adela; Sora, Steluta Mihaela; Tica, Anca; Ferastraoaru, Denisa Elena; Constantinescu, Ileana

    2010-01-01

    The immune response consists of two main components: humoral immunity represented by B lymphocytes and cellular immunity maintained by the T lymphocytes. Immunoglobulins, produced by B-lymphocytes, are the main mediators of humoral immunity, and deficiencies at this level affect the body's response to infection. Plasmocytes produce nine antibody izotypes: immunoglobulins G (IgG1, IgG2, IgG3, IgG4), immunoglobulins M (IgM), immunoglobulins A (IgA1, IgA2), immunoglobulins D (IGD) and immunoglobulins E (IgE). Primary hypogammaglobulinemias are characterized by the occurrence of recurrent infections and, paradoxically, by the occurrence of autoimmune diseases. Characteristic for these diseases is that symptoms occur at 7-9 months after birth, when transplacental antibody titers transmitted from the mother decrease, and the infant's body is unable to synthesize them to normal levels. Primary hypogammaglobulinemias are transmitted genetically, but mutations at the molecular level are still not fully understood. The most common are: Bruton agammaglobulinemia, transient newborn hypogammaglobulinemia, selective immunoglobulin deficiency and variable common immunodeficiency. Treatment consists of monthly antibiotics and immunoglobulins, depending on antibody titers (except for IgA deficiency). PMID:20302197

  17. Lymphocyte reactivity in patients with gonococcal urethritis.

    PubMed Central

    Rosenthal, L; Sandström, E

    1978-01-01

    Lymphocyte reactivity to virulent gonococcal antigen T2 and the non-pathogenic Neisseria pharyngis (NPN) has been studied by using the 14C-thymidine uptake in cell cultures from 42 patients with gonococcal urethritis and from 18 controls. The DNA synthesis in cell cultures with T2 antigen was higher in 21 female patients than in the 18 controls. No differences in DNA synthesis were observed in antigen-stimulated cell cultures from patients with single or multiple infections, from patients with urogenital complication, or from controls. Gonococcal antibodies in the serum were detected by the gonococcal complement-fixation test (GCFT). A study of the possible correlation between the outcome of the serological test and the cellular response to gonococcal antigen showed that 14C-thymidine uptake in lymphocyte cultures from male patients with negative GCFT, stimulated with T2 antigen, was much lower than the thymidine uptake in stimulated cell cultures from all the other male and female patients (P less than 0.001). The DNA synthesis was higher in cell cultures from seronegative women than from seronegative men (P less than 0.01). A significant difference (P less than 0.01) was also noted in the lymphocyte reactivity to gonococcal antigen between controls and all patients, except in those men who gave negative results to the serological tests. There were no differences between these two groups with respect to the thymidine uptake in NPN-stimulated cell cultures. PMID:678955

  18. ACTIVATION OF T LYMPHOCYTES IN ATHEROSCLEROTIC PLAQUES

    PubMed Central

    Grivel, Jean-Charles; Ivanova, Oxana; Pinegina, Natalia; Blank, Paul S.; Shpektor, Alexander; Margolis, Leonid B.; Vasilieva, Elena

    2011-01-01

    Objective To decipher the immunological mechanisms of plaque maturation and rupture, it is necessary to analyze the phenotypes and distribution of individual lymphocytes which migrate to the plaques as well as their activation at different stages of plaque formation. Methods and Results We developed a protocol to isolate plaque-residing immune cells and analyze their status using polychromatic flow cytometry. We found that the composition and phenotype of T lymphocytes in the plaques differs from that in blood. CD4 and, in particular, CD8+ T cells in plaques are highly activated; the fraction of CD8 T cells co-expressing CD25 and HLA-DR in plaques was 10 times larger than in blood. Conclusions The first flow-cytoanalysis of individual T cells in atherosclerotic plaques indicates that plaques represent a separate immunological compartment from blood with lymphocytes characterized by a high level of T cells activation, which is compatible with the presence of antigen(s) that trigger infiltration activation of these cells. The ability to isolate and characterize these cells may lead to the identification of such antigens. PMID:21960562

  19. Microgravity and Cellular Consequences in Lymphocyte Function

    NASA Technical Reports Server (NTRS)

    Pellis, Neal R.; Sundaresan, Alamelu

    2004-01-01

    Mammalian cells adapt to the environment of low gravity and express a series of responses, some possibly from direct effects on cells and others based on environmental conditions created by microgravity. Human lymphocytes in microgravity culture are functionally diminished in activation and locomotion. Both processes are integral to optimal immune response to fight pathogens. The NASA Rotating-wall vessel (RWV) is a well-accepted analog for microgravity culture on the ground. Gene array experiments and immunoblotting identified upstream events in human lymphocytes adapting to microgravity analog culture. Microgravity induces selective changes, many of which are cell membrane related. Results showed that upstream of PKC in the T cell activation cascade, PLC-gamma and LAT are significantly diminished. ZAP 70 which controls LAT activation is also down regulated in modeled microgravity. Thus events governing cell shape might warrant attention in microgravity conditions. The goal of this study is to delineate response suites that are consequential, direct or indirect effects of the microgravity environment and which of these are essential to lymphocytes

  20. Shigella impairs T lymphocyte dynamics in vivo

    PubMed Central

    Salgado-Pabón, Wilmara; Celli, Susanna; Arena, Ellen T.; Nothelfer, Katharina; Roux, Pascal; Sellge, Gernot; Frigimelica, Elisabetta; Bousso, Philippe; Sansonetti, Philippe J.; Phalipon, Armelle

    2013-01-01

    The Gram-negative enteroinvasive bacterium Shigella flexneri is responsible for the endemic form of bacillary dysentery, an acute rectocolitis in humans. S. flexneri uses a type III secretion system to inject effector proteins into host cells, thus diverting cellular functions to its own benefit. Protective immunity to reinfection requires several rounds of infection to be elicited and is short-lasting, suggesting that S. flexneri interferes with the priming of specific immunity. Considering the key role played by T-lymphocyte trafficking in priming of adaptive immunity, we investigated the impact of S. flexneri on T-cell dynamics in vivo. By using two-photon microscopy to visualize bacterium–T-cell cross-talks in the lymph nodes, where the adaptive immunity is initiated, we provide evidence that S. flexneri, via its type III secretion system, impairs the migration pattern of CD4+ T cells independently of cognate recognition of bacterial antigens. We show that bacterial invasion of CD4+ T lymphocytes occurs in vivo, and results in cell migration arrest. In the absence of invasion, CD4+ T-cell migration parameters are also dramatically altered. Signals resulting from S. flexneri interactions with subcapsular sinus macrophages and dendritic cells, and recruitment of polymorphonuclear cells are likely to contribute to this phenomenon. These findings indicate that S. flexneri targets T lymphocytes in vivo and highlight the role of type III effector secretion in modulating host adaptive immune responses. PMID:23417297

  1. Intra-arterial Autologous Bone Marrow Cell Transplantation in a Patient with Upper-extremity Critical Limb Ischemia

    SciTech Connect

    Madaric, Juraj; Klepanec, Andrej; Mistrik, Martin; Altaner, Cestmir; Vulev, Ivan

    2013-04-15

    Induction of therapeutic angiogenesis by autologous bone marrow mononuclear cell transplantation has been identified as a potential new option in patients with advanced lower-limb ischemia. There is little evidence of the benefit of intra-arterial cell application in upper-limb critical ischemia. We describe a patient with upper-extremity critical limb ischemia with digital gangrene resulting from hypothenar hammer syndrome successfully treated by intra-arterial autologous bone marrow mononuclear cell transplantation.

  2. Idelalisib for the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma.

    PubMed

    Barrientos, Jacqueline C

    2016-09-01

    Idelalisib is a first-in-class selective oral PI3Kδ inhibitor for the treatment of patients with relapsed chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma, a predominantly elderly population with high comorbidity. The drug promotes apoptosis in primary CLL cells ex vivo, independent of common prognostic markers and inhibits CLL cell homing, migration and adhesion to cells in the microenvironment. Idelalisib has shown efficacy with acceptable safety as monotherapy and combination therapy in relapsed/refractory CLL. Idelalisib has clinical activity in patients with CLL with del(17p). The development of other novel B-cell-targeted agents provides the opportunity to evaluate additional idelalisib treatment combinations for their potential to further improve outcomes in CLL/small lymphocytic lymphoma. PMID:27324214

  3. Blood leukocyte and spleen lymphocyte immune response of spleen lymphocytes and whole blood leukocytes of hamsters

    SciTech Connect

    Peters, B.A.; Sothmann, M.; Wehrenberg, W.B. )

    1989-01-01

    This study was designed to evaluate the effects of chronic physical activity on the immune response of spleen lymphocytes and whole blood leukocytes of hamsters. Animals were kept sedentary or allowed to exercise spontaneously on running wheels for eight weeks. Physically active animals averaged 12 kilometers per day. The immune response of spleen lymphocytes whole blood leukocytes was evaluated by {sup 3}H-thymidine incorporation in response to Concanavalin A or lipopolysaccharide. There was no treatment effect between physically active and sedentary hamster in response of spleen lymphocytes. The immune response of whole blood leukocytes to these mitogens was significantly greater in physically active vs. sedentary hamsters. These results demonstrate that chronic physical activity has the capacity to modulate immunoresponses.

  4. Clinical evaluations of autologous fibrin glue and polyglycolic acid sheets as oral surgical wound coverings after partial glossectomy.

    PubMed

    Kouketsu, Atsumu; Nogami, Shinnosuke; Fujiwara, Minami; Mori, Shiro; Yamauchi, Kensuke; Hashimoto, Wataru; Miyashita, Hitoshi; Kurihara, Jun; Kawai, Tadashi; Higuchi, Keisuke; Takahashi, Tetsu

    2016-08-01

    Polyglycolic acid (PGA) sheets and commercial fibrin glue are commonly used to cover open wound surfaces in oral surgery. Compared to commercial fibrin glue composed of pooled allogeneic blood, autologous fibrin glue is less expensive and poses lower risks of viral infection and allergic reaction. Here, we evaluated postoperative pain, scar contracture, ingestion, tongue dyskinesia, and postoperative bleeding in 24 patients who underwent partial glossectomy plus the application of a PGA sheet and an autologous fibrin glue covering (autologous group) versus 11 patients in whom a PGA sheet and commercial fibrin glue were used (allogeneic group). The evaluated clinical measures were nearly identical in both groups. Remarkable wound surface granulation was recognized in two cases in the autologous group. No complications were observed in either group, including viral infection or allergic reaction. Abnormal postoperative bleeding in the wound region was observed in one case in the allogeneic group. Coagulation and adhesion of the autologous fibrin glue were equivalent to those of conventional therapy with a PGA sheet and commercial fibrin glue. Thus, our results show that covering wounds with autologous fibrin glue and PGA sheets may help avoid the risks of viral infection and allergic reaction in partial glossectomy cases. PMID:27341770

  5. [Pregnancy outcome in five women after autologous bone marrow transplantation for acute lymphoblastic leukaemia].

    PubMed

    Hołowiecka, Aleksandra; Zielińska, Monika; Rozmus, Wioletta; Krzemień, Sławomira; Hołowiecki, Jerzy

    2005-10-01

    There are reports of successful pregnancies in women with haematological malignancies after either autologous or allogeneic bone marrow transplantation (BMT). We report six cases of uncomplicated pregnancies in five women treated with high-dose chemotherapy, radiotherapy and autologous bone marrow transplantation (ABMT) for acute lymphoblastic leukaemia. One patient was diagnosed as having leukaemia during pregnancy. The pregnancy ended with medical termination. Each woman received conditioning regimens without total body irradiation (TBI). Of five women, who received AMBT, all resumed spontaneous cyclical menstruation post transplantation. All of them conceived naturally between 15-52 months following ABMT. We noted one miscarriage in our 29-year-old patient. Six pregnancies went to term and each resulted in the successful delivery of a full-term baby. We did not notice any case of relapse of leukaemia in pregnancy. PMID:16417095

  6. [Monomorphic post-transplant T-lymphoproliferative disorder after autologous stem cell transplantation for multiple myeloma].

    PubMed

    Ishikawa, Tetsuya; Shimizu, Hiroaki; Takei, Toshifumi; Koya, Hiroko; Iriuchishima, Hirono; Hosiho, Takumi; Hirato, Junko; Kojima, Masaru; Handa, Hiroshi; Nojima, Yoshihisa; Murakami, Hirokazu

    2016-01-01

    We report a rare case of T cell type monomorphic post-transplant lymphoproliferative disorders (PTLD) after autologous stem cell transplantation. A 53-year-old man with multiple myeloma received autologous stem cell transplantation and achieved a very good partial response. Nine months later, he developed a high fever and consciousness disturbance, and had multiple swollen lymph nodes and a high titer of Epstein-Barr (EB) virus DNA in his peripheral blood. Neither CT nor MRI of the brain revealed any abnormalities. Cerebrospinal fluid contained no malignant cells, but the EB virus DNA titer was high. Lymph node biopsy revealed T cell type monomorphic PTLD. Soon after high-dose treatment with methotrexate and cytosine arabinoside, the high fever and consciousness disturbance subsided, and the lymph node swelling and EB virus DNA disappeared. Given the efficacy of chemotherapy in this case, we concluded that the consciousness disturbance had been induced by central nervous system involvement of monomorphic PTLD. PMID:26861102

  7. [Autologous hematopoietic stem cell transplantation followed by oral bexarotene in a patient with advanced mycosis fungoides].

    PubMed

    Pérez-Barrio, S; Izu, R; García-Ruiz, J C; Acebo, E; Martínez de Lagrán, Z; Díaz-Pérez, J L

    2008-09-01

    We describe the case of a 17-year-old patient with rapidly progressing and aggressive mycosis fungoides, with multiple cutaneous tumors and large cell transformation. She was initially treated with 3 cycles of high-dose chemotherapy with mega-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) without response, leading to the decision to undertake autologous hematopoietic stem cell transplantation. Partial remission of the disease was achieved with this treatment and subsequent introduction of oral bexarotene led to complete remission, which has been maintained for more than 3 years with good tolerance of oral therapy. We discuss the advantages and disadvantages of autologous hematopoietic stem cell transplantation and the use of oral bexarotene. PMID:18682170

  8. Autoimmune thrombocytopenia following autologous hematopoietic cell transplantation: review of literature and treatment options.

    PubMed

    Jillella, A P; Kallab, A M; Kutlar, A

    2000-10-01

    Autoimmune thrombocytopenia after high-dose chemotherapy and autologous bone marrow/peripheral blood stem cell transplantation occurs infrequently and only six cases meeting the criteria have been reported in the literature. All six of these patients had either acute myelogenous leukemia (AML) or lymphoblastic lymphoma (LBL). Immune thrombocytopenia following autologous transplantation in solid tumors has not been reported. We report the first case of autoimmune thrombocytopenia after high-dose chemotherapy and peripheral blood stem cell transplantation in a patient with breast cancer. A review of the literature has been conducted and treatment options are discussed. In two patients the condition resolved with treatment and in a third patient it improved. Immune-mediated thrombocytopenia in the post-transplant period is one of the causes of a low platelet count. It should be recognized promptly and treated. PMID:11081398

  9. Total Single-Stage Autologous Breast Reconstruction with Free Nipple Grafts.

    PubMed

    Schwartz, Jean-Claude D; Skowronski, Piotr P

    2015-12-01

    Outstanding results are difficult to achieve in postmastectomy reconstructions in obese ptotic patients. We describe an autologous single-stage reconstruction with free nipple grafts that is best suited for these difficult patients. This technique allows for delayed volume supplementation with implants or fat grafting but does not commit the patient to additional surgery. It avoids the common complications of immediate implant-based reconstructions. This technique is also an excellent option in patients with a known requirement for radiotherapy as it does not sacrifice a valuable autologous flap nor does it subject the patient to capsular contracture, infection, and extrusion. It also obviates the psychological trauma that many women suffer awaiting a reconstruction after radiotherapy. We believe it should be considered as a first-line reconstructive option. PMID:26894012

  10. Autologous blood donation in a small general acute-care hospital.

    PubMed Central

    Mott, L. S.; Jones, M. J.

    1995-01-01

    Increased public concerns about infectious risk associated with homologous blood transfusions have led to a significant increase in autologous blood collections. In response, blood banks and large hospitals have implemented autologous blood donation programs (ABDPs). Small hospitals lack the technical resources and patient case loads to effectively institute ABDPs. A preoperative ABDP designed to increase availability and patient convenience--and, therefore, utilization--is described. The program created in a rural 90-bed general acute-care hospital processed 105 donors and collected 197 units over a 38-month period. The percentage of the collected units that were transfused was 44.7%, and only 6.1% of participating patients required homologous transfusions. Comparisons of hematological and clinical data with previously published results indicate that small-scale preoperative ABDPs are clinically effective, safe, and provide cost-efficient utilization of the safest blood supply available. PMID:7674344

  11. Autologous staged fat tissue transfer in post-traumatic lower extremity reconstruction.

    PubMed

    Benjamin, Martin A; Schwarzman, Garrett; Eivazi, Mariet; Zachary, Lawrence

    2015-01-01

    Autologous fat tissue transfer for aesthetic reconstruction has been described in the literature for soft tissue damage as early as 1893. One area that has yet to be described is the role of fat grafting in post-traumatic lower extremity injuries. In this case report, we present a patient who had significant injury to her right lower extremity and presented for reconstruction. The patient is a 52-year-old female who presented to clinic after a right lower extremity traumatic injury that required multiple re-operations, which lead to dense scarring and volume loss along the extremity inferior to the knee joint. The patient received two staged autologous fat injections and reported positive outcomes. Our case report demonstrates the utility of fat transfer in reconstruction of the lower extremity in staged fashion. Further research in the refinement of this technique and patient follow-up will lead to better graft survival and reconstructive outcomes. PMID:26572154

  12. Autologous Fat Grafting in the Treatment of Painful Postsurgical Scar of the Oral Mucosa

    PubMed Central

    Lisa, Andrea; Summo, Valeria; Bandi, Valeria; Maione, Luca; Murolo, Matteo; Klinger, Francesco; Klinger, Marco

    2015-01-01

    Background. Persistent pain as a consequence of surgical treatment has been reported for several common surgical procedures and represents a clinical problem of great magnitude. Material and Methods. We describe the case of a 47-year-old female who presented a retractile scar that adhered to deep planes at the upper right of the vestibule due to surgical removal of maxillary exostosis, which determined important pain symptoms extending till the right shoulder during both chewing and rest. We subsequently treated her with autologous fat grafting according to Coleman's technique. Results. Clinical assessments were performed at 5 and 14 days, 1, 3, and 6 months, and 1 year after surgical procedure. We observed a progressive release of scar retraction together with an important improvement of pain symptoms. Conclusion. The case described widens the possible application of autologous fat grafting on a new anatomical site as buccal vestibule and in one specific clinical setting confirming its promising biological effects. PMID:26064132

  13. Allogeneic and autologous mode of stem cell transplantation in regenerative medicine: which way to go?

    PubMed

    Mamidi, Murali Krishna; Dutta, Susmita; Bhonde, Ramesh; Das, Anjan Kumar; Pal, Rajarshi

    2014-12-01

    Stem cell transplantation is a generic term covering different techniques. However there is argument over the pros and cons of autologous and allogeneic transplants of mesenchymal stem cells (MSCs) for regenerative therapy. Given that the MSCs have already been proven to be safe in patients, we hypothesize that allogeneic transplantation could be more effective and cost-effective as compared to autologous transplantation specifically in older subjects who are the likely victims of degenerative diseases. This analysis is based on the scientific logic that allogeneic stem cells extracted in large numbers from young and healthy donors could be physiologically, metabolically and genetically more stable. Therefore stem cells from young donors may be expected to exhibit higher vigor in secreting trophic factors leading to activation of host tissue-specific stem cells and also be more efficient in remodeling the micro-environmental niche of damaged tissue. PMID:25456787

  14. The use of bone anchors for autologous flap fixation in perineal reconstruction: a case report.

    PubMed

    Saad, Adam; Cece, John A; Arvanitis, Michael L; Elkwood, Andrew I

    2013-01-01

    The purpose of this case report is to demonstrate the use of bone anchors with an autologous flap in perineal reconstruction. This technique has not been reported before. A 64-year-old female presented to our office with a chief complaint of perineal hernia 1.5 years after abdominoperineal resection. She had a history of recurrent rectal cancer for which she received chemotherapy, radiation and surgery. To repair the hernia, a standard vertical rectus abdominismyocutaneous was harvested and de-epithelialized. It was secured into place in the pelvis utilizing several bone anchors. Mesh was used to repair the donor site defect. At 18 month follow-up, there was good healing of all the wounds and no recurrence of the hernia. She was pain free and able to resume her activities of daily living. Bone anchor fixation is a viable technique for fixation of autologous flaps in perineal reconstruction. PMID:24964462

  15. The use of bone anchors for autologous flap fixation in perineal reconstruction: a case report

    PubMed Central

    Saad, Adam; Cece, John A.; Arvanitis, Michael L.; Elkwood, Andrew I.

    2013-01-01

    The purpose of this case report is to demonstrate the use of bone anchors with an autologous flap in perineal reconstruction. This technique has not been reported before. A 64-year-old female presented to our office with a chief complaint of perineal hernia 1.5 years after abdominoperineal resection. She had a history of recurrent rectal cancer for which she received chemotherapy, radiation and surgery. To repair the hernia, a standard vertical rectus abdominismyocutaneous was harvested and de-epithelialized. It was secured into place in the pelvis utilizing several bone anchors. Mesh was used to repair the donor site defect. At 18 month follow-up, there was good healing of all the wounds and no recurrence of the hernia. She was pain free and able to resume her activities of daily living. Bone anchor fixation is a viable technique for fixation of autologous flaps in perineal reconstruction. PMID:24964462

  16. A new cost-effective and fast method of autologous fat grafting.

    PubMed

    Sorin, T; Rausky, J; Rem, K; Ozil, C; Nguyen Van Nuoi, V; Revol, M; Mazouz Dorval, S

    2016-08-01

    Due to the increasing number of fat grafting procedures, several laboratories have developed their own fat processing system (Puregraft(®), LipiVage(®), Viafill(®), etc.), such as closed harvesting systems, centrifugation or washing and filtration devices, or even simple decantation techniques. However, all these tissue-engineering systems are expensive. Our team has developed a simple and fast autologous fat grafting system, useable even for a large volume of lipofilling, and based on low-pressure suction and a sterile closed-system for processing the harvested fat tissue. It is a cost-effective system, as it only costs 9.28Eur (10.52USD) for a 500milliliters autologous fat graft procedure. PMID:27181064

  17. Autologous staged fat tissue transfer in post-traumatic lower extremity reconstruction

    PubMed Central

    Benjamin, Martin A.; Schwarzman, Garrett; Eivazi, Mariet; Zachary, Lawrence

    2015-01-01

    Autologous fat tissue transfer for aesthetic reconstruction has been described in the literature for soft tissue damage as early as 1893. One area that has yet to be described is the role of fat grafting in post-traumatic lower extremity injuries. In this case report, we present a patient who had significant injury to her right lower extremity and presented for reconstruction. The patient is a 52-year-old female who presented to clinic after a right lower extremity traumatic injury that required multiple re-operations, which lead to dense scarring and volume loss along the extremity inferior to the knee joint. The patient received two staged autologous fat injections and reported positive outcomes. Our case report demonstrates the utility of fat transfer in reconstruction of the lower extremity in staged fashion. Further research in the refinement of this technique and patient follow-up will lead to better graft survival and reconstructive outcomes. PMID:26572154

  18. Safety Concern between Autologous Fat Graft, Mesenchymal Stem Cell and Osteosarcoma Recurrence

    PubMed Central

    Perrot, Pierre; Rousseau, Julie; Bouffaut, Anne-Laure; Rédini, Françoise; Cassagnau, Elisabeth; Deschaseaux, Frédéric; Heymann, Marie-Françoise; Heymann, Dominique; Duteille, Franck; Trichet, Valérie; Gouin, François

    2010-01-01

    Background Osteosarcoma is the most common malignant primary bone tumour in young adult treated by neo adjuvant chemotherapy, surgical tumor removal and adjuvant multidrug chemotherapy. For correction of soft tissue defect consecutive to surgery and/or tumor treatment, autologous fat graft has been proposed in plastic and reconstructive surgery. Principal Findings We report here a case of a late local recurrence of osteosarcoma which occurred 13 years after the initial pathology and 18 months after a lipofilling procedure. Because such recurrence was highly unexpected, we investigated the possible relationship of tumor growth with fat injections and with mesenchymal stem/stromal cell like cells which are largely found in fatty tissue. Results obtained in osteosarcoma pre-clinical models show that fat grafts or progenitor cells promoted tumor growth. Significance These observations and results raise the question of whether autologous fat grafting is a safe reconstructive procedure in a known post neoplasic context. PMID:20544017

  19. Hip Arthroscopic Osteochondral Autologous Transplantation for Treating Osteochondritis Dissecans of the Femoral Head

    PubMed Central

    Kubo, Takanori; Utsunomiya, Hajime; Watanuki, Makoto; Hayashi, Hidetoshi; Sakai, Akinori; Uchida, Soshi

    2015-01-01

    Osteochondritis dissecans (OCD) of the femoral head is not a common source of hip pain. Hip arthroscopy is becoming a more frequent indication for intra-articular pathologies of the hip. Osteochondral autologous transplantation is a promising technique that theoretically can reconstruct osteochondral lesions of the femoral head. We describe our technique for arthroscopic antegrade osteochondral autologous transplantation for the treatment of OCD of the femoral head. The advantages of this technique include that it is a less invasive method with the ability to assess and treat intra-articular pathologies associated with OCD of the femoral head at same time. Case series and outcomes after this technique are not currently reported in the literature; however, it could be a less invasive method and provide favorable clinical outcomes for patients with OCD lesions of the femoral head. PMID:26870645

  20. One-step treatment of proximal hypospadias by the autologous graft of cultured urethral epithelium.

    PubMed

    Romagnoli, G; De Luca, M; Faranda, F; Franzi, A T; Cancedda, R

    1993-10-01

    Surgical management of severe proximal hypospadias or long strictures of the posterior urethra is a difficult clinical task. Often, the therapeutic approach involves the autologous graft of free flaps of bladder or oral mucosa. We recently reported the use of autologous graft of cultured squamous urethral epithelium during urethroplasty in patients with severe proximal hypospadias. The main limitation to the widespread use of cultured epithelium was the long hospitalization due to the requirement of 2 surgical steps. We now report a substantial modification of the surgical procedure which allows for rapid 1-step urethroplasty. Cultured squamous urethral epithelium is tubularized in vitro with the aid of a tubular polytetrafluoroethylene (Gore-Tex) support and 1-step urethroplasty is performed within 30 minutes. Results obtained in 8 patients are presented. PMID:8371392

  1. Total Single-Stage Autologous Breast Reconstruction with Free Nipple Grafts

    PubMed Central

    Schwartz, Jean-Claude D.; Skowronski, Piotr P.

    2015-01-01

    Summary: Outstanding results are difficult to achieve in postmastectomy reconstructions in obese ptotic patients. We describe an autologous single-stage reconstruction with free nipple grafts that is best suited for these difficult patients. This technique allows for delayed volume supplementation with implants or fat grafting but does not commit the patient to additional surgery. It avoids the common complications of immediate implant-based reconstructions. This technique is also an excellent option in patients with a known requirement for radiotherapy as it does not sacrifice a valuable autologous flap nor does it subject the patient to capsular contracture, infection, and extrusion. It also obviates the psychological trauma that many women suffer awaiting a reconstruction after radiotherapy. We believe it should be considered as a first-line reconstructive option. PMID:26894012

  2. Transplantation of autologously derived mitochondria protects the heart from ischemia-reperfusion injury.

    PubMed

    Masuzawa, Akihiro; Black, Kendra M; Pacak, Christina A; Ericsson, Maria; Barnett, Reanne J; Drumm, Ciara; Seth, Pankaj; Bloch, Donald B; Levitsky, Sidney; Cowan, Douglas B; McCully, James D

    2013-04-01

    Mitochondrial damage and dysfunction occur during ischemia and modulate cardiac function and cell survival significantly during reperfusion. We hypothesized that transplantation of autologously derived mitochondria immediately prior to reperfusion would ameliorate these effects. New Zealand White rabbits were used for regional ischemia (RI), which was achieved by temporarily snaring the left anterior descending artery for 30 min. Following 29 min of RI, autologously derived mitochondria (RI-mitochondria; 9.7 ± 1.7 × 10(6)/ml) or vehicle alone (RI-vehicle) were injected directly into the RI zone, and the hearts were allowed to recover for 4 wk. Mitochondrial transplantation decreased (P < 0.05) creatine kinase MB, cardiac troponin-I, and apoptosis significantly in the RI zone. Infarct size following 4 wk of recovery was decreased significantly in RI-mitochondria (7.9 ± 2.9%) compared with RI-vehicle (34.2 ± 3.3%, P < 0.05). Serial echocardiograms showed that RI-mitochondria hearts returned to normal contraction within 10 min after reperfusion was started; however, RI-vehicle hearts showed persistent hypokinesia in the RI zone at 4 wk of recovery. Electrocardiogram and optical mapping studies showed that no arrhythmia was associated with autologously derived mitochondrial transplantation. In vivo and in vitro studies show that the transplanted mitochondria are evident in the interstitial spaces and are internalized by cardiomyocytes 2-8 h after transplantation. The transplanted mitochondria enhanced oxygen consumption, high-energy phosphate synthesis, and the induction of cytokine mediators and proteomic pathways that are important in preserving myocardial energetics, cell viability, and enhanced post-infarct cardiac function. Transplantation of autologously derived mitochondria provides a novel technique to protect the heart from ischemia-reperfusion injury. PMID:23355340

  3. Differentiation within autologous fibrin scaffolds of porcine dermal cells with the mesenchymal stem cell phenotype

    SciTech Connect

    Puente, Pilar de la

    2013-02-01

    Porcine mesenchymal stem cells (pMSCs) are an attractive source of cells for tissue engineering because their properties are similar to those of human stem cells. pMSCs can be found in different tissues but their dermal origin has not been studied in depth. Additionally, MSCs differentiation in monolayer cultures requires subcultured cells, and these cells are at risk of dedifferentiation when implanting them into living tissue. Following this, we attempted to characterize the MSCs phenotype of porcine dermal cells and to evaluate their cellular proliferation and differentiation in autologous fibrin scaffolds (AFSs). Dermal biopsies and blood samples were obtained from 12 pigs. Dermal cells were characterized by flow cytometry. Frozen autologous plasma was used to prepare AFSs. pMSC differentiation was studied in standard structures (monolayers and pellets) and in AFSs. The pMSCs expressed the CD90 and CD29 markers of the mesenchymal lineage. AFSs afforded adipogenic, osteogenic and chondrogenic differentiation. The porcine dermis can be proposed to be a good source of MSCs with adequate proliferative capacity and a suitable expression of markers. The pMSCs also showed optimal proliferation and differentiation in AFSs, such that these might serve as a promising autologous and implantable material for use in tissue engineering. -- Highlights: ► Low fibrinogen concentration provides a suitable matrix for cell migration and differentiation. ► Autologous fibrin scaffolds is a promising technique in tissue engineering. ► Dermal cells are an easily accessible mesenchymal stem cell source. ► Fibrin scaffolds afforded adipogenic, osteogenic and chondrogenic differentiation.

  4. Autologous transplantation for diffuse aggressive non-Hodgkin lymphoma in first relapse or second remission.

    PubMed

    Vose, Julie M; Rizzo, Douglas J; Tao-Wu, Jing; Armitage, James O; Bashey, Asad; Burns, Linda J; Christiansen, Neal Paul; Freytes, Cesar O; Gale, Robert Peter; Gibson, John; Giralt, Sergio A; Herzig, Roger H; Lemaistre, Charles F; McCarthy, Philip L; Nimer, Stephen D; Petersen, Finn B; Schenkein, David P; Wiernik, Peter H; Wiley, Joseph M; Loberiza, Fausto R; Lazarus, Hillard M; van Biesen, Koen; Horowitz, Mary M

    2004-02-01

    We evaluated the results of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with diffuse aggressive non-Hodgkin lymphoma (NHL) in first relapse (Rel 1) or second complete remission (CR 2). Data were evaluated from the Autologous Blood and Marrow Transplant Registry on 429 patients with diffuse aggressive NHL who underwent transplantation in Rel 1 or CR 2. Transplantations were performed between 1989 and 1996 and were reported to the Autologous Blood and Marrow Transplant Registry by 93 centers in North and South America. The probability of 3-year survival was 44% (95% confidence interval [CI], 33%-55%). The probability at 3 years of progression-free survival was 31% (95% CI, 27%-36%). Patients who underwent transplantation in CR 2 had a 3-year probability of progression-free survival of 38% (95% CI, 30%-46%) compared with 28% (95% CI, 22%-33%) for those who were not in remission at the time of transplantation (P <.001). In multivariate analysis, chemotherapy resistance, increased lactic dehydrogenase at diagnosis, an interval of <12 months from diagnosis to relapse, age >or=40 years, and use of myeloid growth factors to accelerate posttransplantation bone marrow recovery were adverse predictors of survival. High-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with diffuse aggressive NHL in CR 2 or Rel 1 resulted in better outcome for patients with chemotherapy-sensitive disease, longer relapse-free intervals, and age <40 years. Exposure to myeloid growth factors to accelerate recovery for recipients of bone marrow grafts may increase the risk of disease progression or death. PMID:14750077

  5. [Determination of kinetic parameters lymphocyte populations in cows with chronic lymphocytic leukemia].

    PubMed

    Kuznetsov, V A; Feofanova, T V; Busol, V A; Nikolaeva, N V

    1995-01-01

    We analyzed changes in the number of lymphocytes in the blood of cows with chronic lymphoid leukemia using the Gomperts equation of population dynamics. The parameters of this equation were determined. Coefficients beta and gamma proved to be the most variable. The former reflects the delay and the latter characterizes the maximum rate of growth of the lymphocyte population. According to these parameters, three groups of animals were distinguished with different kinetics of leucosis and different correlations between immuno-hematological indices. PMID:7670356

  6. Aryl hydrocarbon mono-oxygenase activity in human lymphocytes

    SciTech Connect

    Griffin, G.D.; Schuresko, D.D.

    1981-06-01

    Aryl hydrocarbon mono-oxygenase (AHM), an enzyme of key importance in metabolism of xenobiotic chemicals such as polynuclear aromatic hydrocarbons (PNA), is present in human lymphocytes. Studies investing the relation of activity of AHM in human lymphocytes to parameters such as disease state, PNA exposure, in vitro mitogen stimulation, etc. have been summarized in this report. Some studies have demonstrated increased AHM activity in lymphocytes from cigarette smokers (compared to nonsmokers), and in lung cancer patients when compared to appropriate control groups. These observations are confused by extreme variability in human lymphocyte AHM activities, such variability arising from factors such as genetic variation in AHM activity, variation in in vitro culture conditions which affect AHM activity, and the problematical relationship of common AHM assays to actual PNA metabolism taking place in lymphocytes. If some of the foregoing problems can be adequately addressed, lymphocyte AHM activity could hold the promise of being a useful biomarker system for human PNA exposure.

  7. Dural repair using autologous fat: Our experience and review of the literature

    PubMed Central

    Di Vitantonio, Hambra; De Paulis, Danilo; Del Maestro, Mattia; Ricci, Alessandro; Dechordi, Soheila Raysi; Marzi, Sara; Millimaggi, Daniele F.; Galzio, Renato J.

    2016-01-01

    Background: Various materials have been proposed to obliterate dead spaces and to reconstruct dural defects during a neurosurgical approach. This study describes our technique of using the abdominal autologous fat graft and evaluates the complications and characteristics related to the use of this tissue during cranial procedures. Methods: Autologous fat grafts were used in 296 patients with basicranial and convexity extraaxial tumors from April 2005 to January 2015. The adipose tissue was removed from the paraumbilical abdominal region and was transformed into a thin foil. When possible, a watertight suture was made between the dural or bone edge with a fat graft. We always used fibrin glue to reinforce the dural closure. Results: Complications occurred between 2 days and 1 year following procedure. Cerebrospinal fluid leaks were found in 11 cases. No case of mortality, pseudomeningoceles, fistula, infections, bacterial meningitides, or lipoid meningitides was reported. No patient required removal of the graft. No adhesion was observed between the brain and the autologous fat. Other fat-related complications observed were 2 cases of fat necrosis in the abdomen and 2 cases of abdominal hemorrhage. Conclusion: The technique of harvesting and applying fat grafts is fairly simple, although it must be performed meticulously to be effective. Our experience has led us to believe that the use of fat grafts presents low morbidity and mortality. However, a neurosurgeon should never forget the possible late or early complications related to the use of fat grafts. PMID:27500007

  8. Periorbital Lipogranuloma after Facial Autologous Fat Injection and Its Treatment Outcomes

    PubMed Central

    Park, Jun Young

    2016-01-01

    Purpose To investigate periorbital lipogranuloma cases that developed after autologous fat injection and to determine various treatment outcomes from these cases. Methods This retrospective study involved 27 patients who presented with periocular mass (final diagnosis of lipogranuloma) and had history of facial autologous fat injection. The collected data included information on patient sex, age, clinical presentation, number and site of fat injections, interval between injections, duration from injection to symptom onset, fat harvesting site, use of cryopreservation, and treatment outcome. Results The most common presenting symptom was palpable mass (92.6%), followed by blepharoptosis and eyelid edema. The mean time from injection to symptom onset was 13.6 ± 29.2 months (range, 2 to 153 months). Patients were managed by intralesional triamcinolone injection (six patients) and surgical excision (three patients); 18 patients were followed without treatment. Among the six patients who underwent intralesional triamcinolone injection, five showed complete resolution, and one showed partial resolution. Among the 18 patients who were followed without management, three showed spontaneous resolution over a 5-month follow-up period. Conclusions Lipogranuloma can develop in the eyelid after autologous fat injection into the face. Both surgical excision and intralesional triamcinolone injection yield relatively good outcomes. Simple observation can be a good option because spontaneous resolution can occur in a subset of patients. PMID:26865798

  9. Autologous and allogeneic hematopoietic stem cell transplantation for Multiple Sclerosis: perspective on mechanisms of action.

    PubMed

    Van Wijmeersch, Bart; Sprangers, Ben; Dubois, Bénédicte; Waer, Mark; Billiau, An D

    2008-07-15

    Multiple Sclerosis (MS) is a frequent demyelinating immune-mediated disease of the central nervous system (CNS) that affects principally young adults and leads to severe physical and cognitive impairment. The current standard treatment makes use of the immune modulators beta-interferon, glatiramer acetate and natalizumab, or immunosuppressants such as mitoxantrone. However, these agents are only partially effective and in a number of patients fail to achieve satisfactory disease control. Autologous hematopoietic stem cell transplantation (HSCT) is being explored in the treatment of severe MS as a means of delivering high-dose immunosuppression followed by 'rescue' of the immuno-hematopoietic system with autologous HSC. The potential therapeutic benefit is based on the concept of so-called 'resetting' the immune system. The use of allogeneic HSCT as a possible therapeutic approach for severe MS is inspired by case reports of MS patients that underwent allogeneic HSCT for a concomitant hematological malignancy, and subsequently is supported by data from rodent models of MS. Allogeneic HSCT may offer specific therapeutic effects, such as the replacement of the autoreactive immune compartment by healthy allogeneic cells and the development of a graft-versus-autoimmunity (GVA) effect. Here, we review the currently available experimental and clinical evidence to support the role of autologous and allogeneic HSCT in MS. PMID:18541311

  10. Platelet storage in PAS-2 or autologous plasma: impact on functional parameters.

    PubMed

    Bunescu, A; Hild, M; Lundahl, J; Egberg, N

    2001-04-01

    Currently, several platelet additive solutions for long-term platelet storage have been introduced. The aim of this study was to compare the deterioration of functional status of platelets stored for up to 5 days in autologous plasma (AP) only, with platelet stored in PAS-2, a salt solution containing acetate, citrate and sodium chloride. Change in platelet adhesion, aggregation and activation was measured by flow cytometric technique. In addition, beta-Thromboglobulin (beta-TG), lactate and glucose were determined. After 5 days of storage, the expression of P-Selectin was significantly higher, the production of lactate and the consumption of glucose were significantly lower, in platelets stored in PAS-2 than in autologous plasma. No significant differences were detected on day 5 between the two groups with regard to fibrinogen, von Willebrand factor binding capacity, or to beta-TG release. It can be concluded that neither storage medium was consistently better for the parameters tested. However, it must be emphasized that platelets stored in autologous plasma exhibited less lesion, in terms of P-Selectin expression compared with platelets stored in PAS-2. PMID:11299027

  11. Autologous mesenchymal stem cell-derived dopaminergic neurons function in parkinsonian macaques.

    PubMed

    Hayashi, Takuya; Wakao, Shohei; Kitada, Masaaki; Ose, Takayuki; Watabe, Hiroshi; Kuroda, Yasumasa; Mitsunaga, Kanae; Matsuse, Dai; Shigemoto, Taeko; Ito, Akihito; Ikeda, Hironobu; Fukuyama, Hidenao; Onoe, Hirotaka; Tabata, Yasuhiko; Dezawa, Mari

    2013-01-01

    A cell-based therapy for the replacement of dopaminergic neurons has been a long-term goal in Parkinson's disease research. Here, we show that autologous engraftment of A9 dopaminergic neuron-like cells induced from mesenchymal stem cells (MSCs) leads to long-term survival of the cells and restoration of motor function in hemiparkinsonian macaques. Differentiated MSCs expressed markers of A9 dopaminergic neurons and released dopamine after depolarization in vitro. The differentiated autologous cells were engrafted in the affected portion of the striatum. Animals that received transplants showed modest and gradual improvements in motor behaviors. Positron emission tomography (PET) using [11C]-CFT, a ligand for the dopamine transporter (DAT), revealed a dramatic increase in DAT expression, with a subsequent exponential decline over a period of 7 months. Kinetic analysis of the PET findings revealed that DAT expression remained above baseline levels for over 7 months. Immunohistochemical evaluations at 9 months consistently demonstrated the existence of cells positive for DAT and other A9 dopaminergic neuron markers in the engrafted striatum. These data suggest that transplantation of differentiated autologous MSCs may represent a safe and effective cell therapy for Parkinson's disease. PMID:23202734

  12. The sGAP flap: rare exception or second choice in autologous breast reconstruction?

    PubMed

    Baumeister, Steffen; Werdin, Frank; Peek, Alberto

    2010-05-01

    Various flaps are available for autologous breast reconstruction. However, there is no accepted standard. The superior gluteal artery perforator (sGAP) flap is one possible option for autologous breast reconstruction. Eighty-one sGAP flaps were performed for breast reconstruction. Patient data regarding age, body mass index, medical history, timing of reconstruction, operating time, success of the operation, and complications were retrospectively analyzed. The success rate was 93% ( N = 75). Thrombosis occurred in nine flaps, and three revisions were successful. There was no partial necrosis. All but one bilateral breast reconstruction was performed in two stages. The average time between the reconstructions was 3 and 5 months (2 to 6). The average operating time was 7 hours 36 minutes (5'45 to 9'33). For autologous breast reconstruction, there is no universally accepted standard and no flap meets all the requirements. The deep inferior epigastric perforator flap is our first choice. We favor the sGAP as a second choice particularly for larger breast sizes. For a staged bilateral reconstruction, the sGAP flap advances to be our first choice. The sGAP flap is a safe and reliable perforator flap providing a good breast projection, cosmetically pleasing outcome on the breast, and an acceptable outcome on the buttock with the disadvantage of a demanding dissection. PMID:20169527

  13. A Novel Method of Orbital Floor Reconstruction Using Virtual Planning, 3-Dimensional Printing, and Autologous Bone.

    PubMed

    Vehmeijer, Maarten; van Eijnatten, Maureen; Liberton, Niels; Wolff, Jan

    2016-08-01

    Fractures of the orbital floor are often a result of traffic accidents or interpersonal violence. To date, numerous materials and methods have been used to reconstruct the orbital floor. However, simple and cost-effective 3-dimensional (3D) printing technologies for the treatment of orbital floor fractures are still sought. This study describes a simple, precise, cost-effective method of treating orbital fractures using 3D printing technologies in combination with autologous bone. Enophthalmos and diplopia developed in a 64-year-old female patient with an orbital floor fracture. A virtual 3D model of the fracture site was generated from computed tomography images of the patient. The fracture was virtually closed using spline interpolation. Furthermore, a virtual individualized mold of the defect site was created, which was manufactured using an inkjet printer. The tangible mold was subsequently used during surgery to sculpture an individualized autologous orbital floor implant. Virtual reconstruction of the orbital floor and the resulting mold enhanced the overall accuracy and efficiency of the surgical procedure. The sculptured autologous orbital floor implant showed an excellent fit in vivo. The combination of virtual planning and 3D printing offers an accurate and cost-effective treatment method for orbital floor fractures. PMID:27137437

  14. Autologous adipose stem cells in treatment of female stress urinary incontinence: results of a pilot study.

    PubMed

    Kuismanen, Kirsi; Sartoneva, Reetta; Haimi, Suvi; Mannerström, Bettina; Tomás, Eija; Miettinen, Susanna; Nieminen, Kari

    2014-08-01

    The purpose of our study was to find out whether transurethral injections of autologous adipose stem cells (ASCs) are an effective and a safe treatment for female stress urinary incontinence (SUI). We treated five SUI patients with ASCs combined with bovine collagen gel and saline. Prior to the treatment, the ASCs were isolated from subcutaneous fat and expanded for 3 weeks in a good manufacturing practice-level laboratory. The mixture of ASCs and collagen was injected transurethrally via cystoscope. Additionally, viability, multipotency, and surface marker profile of ASCs were analyzed in vitro. We followed up with patients 3, 6, and 12 months after the injections. The primary endpoint was a cough test to measure objectively the effect of the treatment. Validated questionnaires were used to determine the subjective cure rate. After 6 months, 1 of 5 patients displayed a negative cough test with full bladder filled with 500 ml of saline. At 1 year, the cough test was negative with three patients; two of them were satisfied with the treatment and did not wish further treatment for SUI. Validated questionnaires showed some subjective improvement in all five patients. This is the first study describing the use of autologous ASCs in combination with collagen gel for female SUI treatments. Thus far, the treatment with autologous ASCs has proven safe and well tolerated. However, the feasibility and efficacy of the treatment were not optimal; therefore, additional research is needed to develop SUI injection therapies. PMID:24985079

  15. Upper airway oedema following autologous blood transfusion from a wound drainage system.

    PubMed

    Woda, R; Tetzlaff, J E

    1992-03-01

    We report a case of a 70-yr-old white woman who underwent a revision of a total hip arthroplasty under general anaesthesia. The intraoperative course was stable without any complications and the estimated blood loss was 2500 ml. The patient received an autologous transfusion of blood from a wound drainage system in the recovery room. The transfusion was followed immediately by marked respiratory distress and upper airway oedema. She required emergency tracheal intubation and mechanical pulmonary ventilation. A coagulopathy also developed which was treated and resolved within 12 hr of the capillary leak phenomenon. The trachea was extubated on the first postoperative day and she had an uneventful course until discharge from the hospital two days later. We discuss the possible, aetiology of such a reaction to autologous blood including complement and platelet activation. It is suggested that reinfusion of nonwashed shed blood from a wound drainage system may present a hazard even though the fluid was autologous in origin. PMID:1551163

  16. [Autologous fat grafting in the surgical management of painful scar: preliminary results].

    PubMed

    Baptista, C; Iniesta, A; Nguyen, P; Legré, R; Gay, A-M

    2013-10-01

    The purpose of this study was to report our experience about the effectiveness of autologous fat injections in the management of painful scars. Between 2010 and 2012, all patients with persistent incisional pain despite a well-conduced 6 months medical treatment received an autologous fat graft according to the technique originally described by Coleman. Results interpretation was based on pain improvement thanks to a Visual Analogic Scale (VAS), postoperative patient satisfaction, reduction on analgesics intake and quality of life improvement. Eleven patients were included, the mean quantity of fat injected was 11cm(3). Nine patients (1.5%) benefited from a complete or significant pain decrease, 74.5% reported being very satisfied or satisfied with the result. The mean reduction of VAS was 3.5 points. We did not observe any complication. Autologous fat grafting is an innovative therapeutic approach and appears to be an attractive concept in the management of scar neuromas resistant to drug treatment, by providing an easy effective and safe surgical treatment. PMID:24035685

  17. Advanced therapies using autologous bone marrow cells for chronic liver disease.

    PubMed

    Takami, Taro; Terai, Shuji; Sakaida, Isao

    2012-07-01

    The radical treatment currently for decompensated liver cirrhosis is still liver transplantation. However, liver transplants are not widely performed worldwide and development of genuine regeneration therapy for liver cirrhosis is an urgent task. We have developed a novel murine model [the green fluorescent protein (GFP)/carbon tetrachloride (CCl4) model], and reported that infused GFP-positive bone marrow cells repopulated cirrhotic liver. Moreover, repopulated bone marrow cells ameliorated liver fibrosis through higher expression of matrix metalloproteinase-9, consistent with improved liver functions and better survival rate. Based on these findings, we started a clinical trial of autologous bone marrow cell infusion (ABMi) therapy for decompensated liver cirrhotic patients, and reported the efficacy and the safety of this approach. On the other hand, various other clinical studies for liver disease have been also reported, including hepatic administration of autologous CD34-positive cells induced by granulocyte colony-stimulating factor (G-CSF), portal vein administration of CD133-positive mononuclear cells, and administration of autologous bone marrow derived mesenchymal stem cells (MSCs). Effectiveness of these approaches has been shown in some patients. We provided here an overview of the current status of liver regeneration therapies including our results of the murine GFP/CCl4 model and ABMi therapy for liver cirrhosis and future prospects. PMID:22846198

  18. Autologous Peritoneum Graft Repair of a Superior Mesenteric Vein Defect During Pancreaticoduodenectomy.

    PubMed

    Kayaalp, Cuneyt; Sumer, Fatih; Polat, Yilmaz; Kutlu, Ramazan

    2015-01-01

    Pancreatic cancers frequently invade the portomesenteric veins. Venous resection during pancreaticoduodenectomy with curative intent is more common now than it was in the past. Most venous resections can be repaired primarily, but some require vascular grafts. Here, we describe the use of an autologous parietal peritoneum graft instead of vascular grafts for repairing a superior mesenteric vein (SMV) defect. Pylorus-preserving pancreaticoduodenectomy combined with en bloc resection of the SMV lateral wall was performed in a 70-year-old woman with cancer of the pancreatic head. The SMV defect was 2 cm long and its width was half the SMV circumference. The defect was covered with a 3 × 2 cm parietal autologous peritoneum graft obtained from the left subcostal area and using running 6/0 polypropylene suture. Tension-free patching was performed, and we retained slight bulging of the graft. Her postoperative course was uneventful. She was discharged on Day 11 after computed tomography confirmed the patency of the SMV, despite slight narrowing. She was well after 10 months of follow-up. Autologous parietal peritoneum grafts can be used for repairing partial venous defects during pancreaticoduodenectomy. They are effective and are easy, fast, and cheap to obtain. PMID:26594604

  19. Delayed improvement of insulin secretion after autologous islet transplantation in partially pancreatectomized patients.

    PubMed

    Jung, Hye Seung; Choi, Seong-Ho; Kim, Sung-Joo; Choi, Dong-Wook; Heo, Jin-Seok; Lee, Kyu Taek; Lee, Jong Kyun; Jang, Kee-Taek; Lee, Byung-Wan; Jee, Jae-Hwan; Noh, Jung-Hyun; Jeong, In Kyung; Yang, Tae-Young; Oh, Seung-Hoon; Ahn, You-Ran; Kim, Young-Seok; No, Heesung; Lee, Moon-Kyu; Kim, Kwang-Won

    2009-11-01

    The purpose of this study was to evaluate the effects of autologous islet transplantation (ITx) on glucose homeostasis and insulin secretory function after partial pancreatectomy (Px). Fourteen nondiabetic patients who underwent distal Px and autologous ITx for benign pancreatic tumors were enrolled in the study (Px + ITx group). Fourteen normal glucose-tolerant controls and 6 Px without ITx controls were recruited, and all groups were followed over a 24-month period. They performed the 75-g oral glucose tolerance test and the 1-mg glucagon stimulation test. Hemoglobin A(1c) was measured, and indices of insulin secretion were calculated. In the Px + ITx group, insulin secretion increased after a nadir at 6 months. Glucose tolerance, which had been abruptly impaired immediately after Px, recovered until 6 months and stabilized thereafter. As a result, differences in glucose intolerance emerged between the subjects in the Px group and those in the Px + ITx group at 24 months after Px. Characteristic variables in the better insulin secretory subjects in the Px + ITx group included younger age, less extensive pancreas resection, and a greater number of total islets. In summary, delayed amelioration of glucose intolerance was induced by autologous ITx after partial Px, even with a small number of islets. PMID:19604519

  20. Human Neoplasms Elicit Multiple Specific Immune Responses in the Autologous Host

    NASA Astrophysics Data System (ADS)

    Sahin, Ugur; Tureci, Ozlem; Schmitt, Holger; Cochlovius, Bjorn; Johannes, Thomas; Schmits, Rudolf; Stenner, Frank; Luo, Guorong; Schobert, Ingrid; Pfreundschuh, Michael

    1995-12-01

    Expression of cDNA libraries from human melanoma, renal cancer, astrocytoma, and Hodgkin disease in Escherichia coli and screening for clones reactive with high-titer IgG antibodies in autologous patient serum lead to the discovery of at least four antigens with a restricted expression pattern in each tumor. Besides antigens known to elicit T-cell responses, such as MAGE-1 and tyrosinase, numerous additional antigens that were overexpressed or specifically expressed in tumors of the same type were identified. Sequence analyses suggest that many of these molecules, besides being the target of a specific immune response, might be of relevance for tumor growth. Antibodies to a given antigen were usually confined to patients with the same tumor type. The unexpected frequency of human tumor antigens, which can be readily defined at the molecular level by the serological analysis of autologous tumor cDNA expression cloning, indicates that human neoplasms elicit multiple specific immune responses in the autologous host and provides diagnostic and therapeutic approaches to human cancer.

  1. The Results of Autologous Skin Test in Patients with Chronic Urticaria in Hamadan, Iran

    PubMed Central

    Safari, Mojgan; Sayemiri, Hooshyar

    2016-01-01

    Introduction The etiology of chronic urticaria is unknown in many cases. In this study, we demonstrated the presence of autoimmune antibodies in patients with chronic urticaria by using of the Autologous Serum Skin Test (ASST). Methods We performed a cross-sectional study to detect the presence of autologous antibodies in the serum of 38 patients (25 females and 13 males) with idiopathic chronic urticaria who were referred to the Hamedan Allergy Clinic in 2014. All of the necessary tests for demonstrating chronic urticaria were performed, including complete blood count (CBC), thyroid and liver functionality tests, and the prick test but they did not confirm the cause of chronic urticaria. We conducted the Autologous Serum Skin Test on the patients and analyzed the results. Results In 15 patients (39%), the ASST was positive. Of the 15 patients with positive autoimmune chronic urticaria, five patients (33%) were males, and 10 patients (67%) were females. Conclusion We concluded that many patients with chronic urticaria have autoimmune urticaria. It is the reason for the lack of the response to treatment with common medications for urticaria. New ways of treatment must be considered for them. PMID:27504169

  2. Autologous pubovaginal slings: back to the future or a lost art?

    PubMed Central

    Bang, Shieh-Ling; Belal, Mohammed

    2016-01-01

    Stress urinary incontinence (SUI) is an under-diagnosed problem affecting up to 50% of women worldwide. SUI is a source of psychological distress to the individual and also imposes a financial burden to the individual and the health care system. The role of surgery in the treatment in SUI has evolved steadily in the last two decades. The synthetic mid-urethral sling and its different insertion methods have gained widespread popularity and are now the most frequently used surgical interventions for women with SUI in Europe. As the use of synthetic slings becomes more widespread, an increasing number of complications are being reported. With the recent concerns surrounding the use of synthetic transvaginal meshes in organ prolapse surgery, synthetic slings have been put under further scrutiny. It is imperative for health care providers to be aware of the current issues associated with synthetic slings and the alternative surgical options available. Traditional autologous pubovaginal slings (PVS) have re-emerged as a viable alternative to synthetic slings in light of the issues with synthetic slings. The re-adoption of autologous PVS has however, been slow due to the technical difficulty of the surgery and perceived higher morbidity rates. In this article, we will discuss the various aspects of autologous PVS and its indications as an alternative to synthetic slings. We will also touch on the current evidence and controversies for synthetic mesh slings. PMID:26848479

  3. Natural History Study of Monoclonal B Cell Lymphocytosis (MBL), Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Lymphoplasmacytic Lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), and Splenic Marginal Zone Lymphoma (SMZL)

    ClinicalTrials.gov

    2016-08-31

    B-Cell Chronic Lymphocytic Leukemia; Monoclonal B-Cell Lymphocytosis; Lymhoma, Small Lymphocytic; Chronic Lymphocytic Leukemia; Lymphoplasmacytic Lymphoma; Waldenstrom Macroglobulinemia; Splenic Marginal Zone Lymphoma

  4. Do lymphocytes from Chagasic patients respond to heart antigens?

    PubMed Central

    Todd, C W; Todd, N R; Guimaraes, A C

    1983-01-01

    Lymphocyte transformation studies of nonadherent lymphocytes from chronic Chagasic and uninfected persons demonstrated that responses of all individuals to a mouse heart homogenate showed a correlation with responses to streptococcal antigens. Considering the known cross-reactions between streptococcal and cardiac antigens and the high reactivity of Chagasic patients to streptococcal antigens, it is possible that positive lymphocyte transformation to unfractionated heart antigen preparations may not represent specific reactivity to heart antigens. PMID:6404836

  5. Dental pulp stem cells suppress the proliferation of lymphocytes via transforming growth factor-β1.

    PubMed

    Ding, Gang; Niu, Jianyi; Liu, Yi

    2015-04-01

    Dental pulp stem cells (DPSCs) possess self-renewal capability, multi-lineage differentiation potential, and can generate a dentin-pulp-like tissue in vivo, which is promising for tooth regeneration. To enlarge the cells resource of DPSCs and explore the feasibility of DPSCs-mediated immune therapy, it is prerequisite to investigate the immunological properties of DPSCs and the underlying mechanisms. Human DPSCs and peripheral blood mononuclear cells were isolated and cultured. Then we used lymphocytes proliferation assays, cytokines detection, Transwell cultures, neutralization experiments, and flow cytometry to examine the in vitro immune characteristics of DPSCs. We found that DPSCs failed to stimulate allogeneic T cells proliferation and suppressed T cells proliferation, B cells proliferation, and mixed lymphocyte reaction. In addition, DPSCs could up-regulate IL-10, down-regulate the production of IL-2, IL-17, and IFN-γ, and did not affect the production of IL-6. Monoclonal antibody against transforming growth factor-β1 restored the T cells proliferation inhibited by DPSCs. Moreover, the population of regulatory T cells increased significantly and T-helper 17 cells decreased significantly in peripheral blood mononuclear cells co-cultured with DPSCs. These data confirmed that DPSCs are low immunogenic, could inhibit the proliferation of lymphocytes, regulate the production of cytokines in vitro, and the secretion of transforming growth factor-β1 may be involved in this event. PMID:25605036

  6. Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection

    PubMed Central

    Cabral-Piccin, M P; Guillermo, L V C; Vellozo, N S; Filardy, A A; Pereira-Marques, S T; Rigoni, T S; Pereira-Manfro, W F; DosReis, G A; Lopes, M F

    2016-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute T. cruzi infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both in vitro and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to T. cruzi. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence. PMID:27195678

  7. Apoptotic CD8 T-lymphocytes disable macrophage-mediated immunity to Trypanosoma cruzi infection.

    PubMed

    Cabral-Piccin, M P; Guillermo, L V C; Vellozo, N S; Filardy, A A; Pereira-Marques, S T; Rigoni, T S; Pereira-Manfro, W F; DosReis, G A; Lopes, M F

    2016-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi. CD8 T-lymphocytes help to control infection, but apoptosis of CD8 T cells disrupts immunity and efferocytosis can enhance parasite infection within macrophages. Here, we investigate how apoptosis of activated CD8 T cells affects M1 and M2 macrophage phenotypes. First, we found that CD8 T-lymphocytes and inflammatory monocytes/macrophages infiltrate peritoneum during acute T. cruzi infection. We show that treatment with anti-Fas ligand (FasL) prevents lymphocyte apoptosis, upregulates type-1 responses to parasite antigens, and reduces infection in macrophages cocultured with activated CD8 T cells. Anti-FasL skews mixed M1/M2 macrophage profiles into polarized M1 phenotype, both in vitro and following injection in infected mice. Moreover, inhibition of T-cell apoptosis induces a broad reprogramming of cytokine responses and improves macrophage-mediated immunity to T. cruzi. The results indicate that disposal of apoptotic CD8 T cells increases M2-macrophage differentiation and contributes to parasite persistence. PMID:27195678

  8. Control of intestinal Nod2-mediated peptidoglycan recognition by epithelium-associated lymphocytes.

    PubMed

    Duerr, C U; Salzman, N H; Dupont, A; Szabo, A; Normark, B H; Normark, S; Locksley, R M; Mellroth, P; Hornef, M W

    2011-05-01

    Innate immune recognition of the bacterial cell wall constituent peptidoglycan by the cytosolic nucleotide-binding oligomerization domain 2 (Nod2) receptor has a pivotal role in the maintenance of intestinal mucosal homeostasis. Whereas peptidoglycan cleavage by gut-derived lysozyme preserves the recognition motif, the N-acetylmuramoyl-L-alanine amidase activity of the peptidoglycan recognition protein 2 (PGLYRP-2) destroys the Nod2-detected muramyl dipeptide structure. PGLYRP-2 green fluorescent protein (GFP) reporter and wild-type mice were studied by flow cytometry and quantitative RT-PCR to identify Pglyrp-2 expression in cells of the intestinal mucosa and reveal a potential regulatory function on epithelial peptidoglycan recognition. CD3(+)/CD11c(+) T lymphocytes revealed significant Pglyrp-2 expression, whereas epithelial cells and intestinal myeloid cells were negative. The mucosal Pglyrp-2-expressing lymphocyte population demonstrated a mixed T-cell receptor (TCR) αβ or γδ phenotype with predominant CD8α and less so CD8β expression, as well as significant staining for the activation markers B220 and CD69, presenting a typical intraepithelial lymphocyte phenotype. Importantly, exposure of peptidoglycan to PGLYRP-2 significantly reduced Nod2/Rip2-mediated epithelial activation. Also, moderate but significant alterations of the intestinal microbiota composition were noted in Pglyrp-2-deficient animals. PGLYRP-2 might thus have a significant role in regulation of the enteric host-microbe homeostasis. PMID:20980996

  9. The use of autologous serum for the treatment of ocular surface disease at a Swedish tertiary referral center

    PubMed Central

    von Hofsten, Joanna; Egardt, Maria; Zetterberg, Madeleine

    2016-01-01

    Purpose The study aims to describe an intact cohort with mixed ocular surface disease (OSD) treated with autologous serum (AS) eye drops in a tertiary eye center. Patients and methods All cases (n=32 eyes, 24 patients) treated with AS for OSD at the Department of Ophthalmology, Sahlgrenska University Hospital, Mölndal, between 2002 and 2013 were included and medical records were reviewed retrospectively. Results Mean duration of treatment with 20% AS was 28.3±56.1 (median: 12, range: 3–217) days. The most common indication for AS treatment was a persistent epithelial defect (PED), which was seen in 16 eyes of 14 patients. Mean duration of PED prior to treatment was 19.3±18.9 (median: 10, range: 5–68) days. Complete or partial epithelial healing occurred in nine eyes (56.2%). The remaining seven eyes (44%) did not respond to treatment or data were missing. The second group consisted of nine eyes of five patients with superficial punctate keratitis (SPK) secondary to dry eye syndrome. Complete or partial healing of the epithelium occurred in five eyes (56%), and the remaining four eyes (44%) were lost to follow-up. A third group included five eyes with AS as an adjuvant treatment after corneal perforation, whereas a fourth group consisted of one patient with dry eye after laser-assisted in situ keratomileusis (LASIK). Conclusion In this cohort, patients with PED or SPK responded well to treatment with AS. Standardized preparation protocols, defined optimal serum concentrations for various indications, and large randomized clinical trials are needed to fully comprehend the role of AS in the treatment of OSD. PMID:27042143

  10. Comparison of automated haematology analysers for detection of apoptotic lymphocytes.

    PubMed

    Taga, K; Sawaya, M; Yoshida, M; Kaneko, M; Okada, M; Taniho, M

    2002-06-01

    Automated haematology analysers can rapidly provide accurate blood cell counts and white blood cell differentials. In this study, we evaluated four different haematology analysers for the detection of apoptotic lymphocytes in peripheral blood: MAXM A/L Retic, H*2, Cell-Dyn 3500 and NE-8000. With the MAXM A/L Retic haematology analyser, the apoptotic lymphocyte cluster appeared below the original lymphocyte cluster on the volume/DF1, and to the right under the original lymphocyte cluster on the volume/DF2 scattergrams. With the H*2 haematology analyser, the apoptotic polymorphonuclear lymphocytes produced a higher lobularity index on the BASO channel. With the Cell-Dyn 3500 haematology analyser, the apoptotic lymphocyte cluster appeared to the right side of the original lymphocyte cluster on the 0D/10D scattergram and to the left side of the polymorphonuclear cluster on the 90D/10D scattergram. With the NE-8000 haematology analyser, the apoptotic lymphocyte cluster was not distinguishable. Thus, apoptotic lymphocytes are readily detected on scattergrams generated by selected haematology analysers. PMID:12067276

  11. Mechanisms of inhibition of Cryptococcus neoformans by human lymphocytes.

    PubMed Central

    Levitz, S M; North, E A; Dupont, M P; Harrison, T S

    1995-01-01

    Recently, our laboratory and others have demonstrated that human peripheral blood T and NK lymphocytes directly inhibit the growth of Cryptococcus neoformans. In this study, we further define the conditions under which lymphocyte-mediated fungistasis against C. neoformans occurs and examine whether mechanisms implicated in lymphocyte-mediated activities against other target cells are also involved in anticryptococcal activity. The addition of whole or broken heat-killed C. neoformans modestly inhibited lymphocyte-mediated fungistasis, whereas other particulates had no effect. The hydroxyl radical scavenger catechin, but not diethyl urea or propyl gallate, profoundly inhibited fungistasis. Salicylic acid inhibited fungistasis in a dose-dependent fashion. However, two other cyclooxygenase inhibitors, piroxicam and indomethacin, had no effect, suggesting that the mechanism of inhibition by salicylic acid was cyclooxygenase independent. Reagent prostaglandin E2, at concentrations shown by others to inhibit NK cell-mediated bactericidal and tumorlytic activities, had no effect on lymphocyte-mediated fungistasis. The addition of selected monoclonal antibodies or ligands reactive with receptors on human lymphocytes had no significant effect on lymphocyte-mediated fungistasis. Acapsular, small-capsuled, and large-capsuled C. neoformans organisms were inhibited by lymphocytes to an approximately equal extent. These data demonstrate that lymphocyte-mediated activity against C. neoformans proceeds regardless of the presence of capsule and by mechanisms at least in part dissimilar from those seen with other target cells. PMID:7642290

  12. In vitro effects of flunarizine on human lymphocytes.

    PubMed

    Brohée, D; Piro, P; Kennes, B; Nève, P

    1986-01-01

    Flunarizine, a slow-channel calcium entry blocker used as a vasodilator, interferes in vitro with human lymphocyte functions. It prevents lymphocytes from capping sheep erythrocytes, an effect which is probably due to the disconnection of the membrane from its cytoskeletal control. Flunarizine antagonizes both colchicine and cytochalasin B effects upon capping. Although the mitogen-induced lymphocyte stimulation has been shown to be sensitive to calcium depletion or calcium entry blocking by Verapamil, an enhanced response to phytohaemagglutinin A was observed with flunarizine. This suggests a differential sensitivity of the lymphocytes to calcium-entry blockers. PMID:3731875

  13. Increased mitogenic response in lymphocytes from chronically centrifuged mice

    NASA Technical Reports Server (NTRS)

    Mueller, Otfried; Hunzinger, E.; Cogoli, Augusto; Bechler, B.; Lee, J.; Moore, J.; Duke, J.

    1990-01-01

    The effects upon the mitogenic response of splenic lymphocytes when exposing mice to prolonged hypergravity conditions (3.5 G for 1 year) were studied. Cultures of splenic lymphocytes isolated from both centrifuged and control (1 G) animals were stimulated with Concanavalin A and the response measured using both morphological and biochemical means. Lymphocytes obtained from centrifuged mice exhibited much higher activation rates (as measured by the incorporation of H-3 thymidine) and larger cell aggregates consisting of more lymphoblasts and mitotic figures than those observed in non centrifuged control animals. Isolated splenic lymphocytes thus appear to have been conditioned by hypergravity state.

  14. B-lymphocyte populations in Xenopus laevis.

    PubMed

    Hadji-Azimi, I; Coosemans, V; Canicatti, C

    1990-01-01

    Two-color immunofluorescence technique was used to show the development and distribution of surface mu- cytoplasmic mu+ (s mu- c mu+) pre-B, s mu+ B- and s mu+ cIg+ plasma cells in metamorphic, postmetamorphic, and adult Xenopus. Generation of pre-B cells was evident in hematopoietic liver and spleen, but not in bone marrow, thymus, and duodenal mucosa. Surface immunoglobulin positive small lymphocytes were the most abundant in the spleen while plasma cells were detected in the thymus, duodenal mucosa, spleen, and liver. We had shown previously the appearance of s mu- c mu+ pre-B cells in the liver of Xenopus larvae at developmental stage 46 and later at stage 49 in the spleen. The frequency of pre-B cells dropped to zero at stage 58, the climax of metamorphosis. Pre-B cells start to reappear slowly as a second wave, at stage 60 through early postmetamorphic life in the liver and spleen. The percentage of surface Ig+ (sIg+) cells in the spleen of developing animals from stage 60 onward is comparable to that observed in adult life. In adult animals, the periphery of the liver continues to be active in hematopoiesis and contains some IgM producing plasma cells and rare sIg+ small lymphocytes while the pre-B cells are almost nonexistent in this region. The spleen, which is also active in some hematopoiesis, constitutes the main site of B-cell differentiation. Three ontogenic stages of pre-B, B-, and plasma cells are present in this organ. Pre-B and plasma cells are of low density and heterogeneous in size while small sIg+ B lymphocytes are of high density and much more homogeneous in size. The bone marrow in these lower anuran amphibia is rudimentary and is not a lymphopoietic tissue; in adult animals it is active only in differentiation of neutrophilic granulocytes. PMID:2338158

  15. Renal function in high dose chemotherapy and autologous hematopoietic cell support treatment for breast cancer.

    PubMed

    Merouani, A; Shpall, E J; Jones, R B; Archer, P G; Schrier, R W

    1996-09-01

    Autologous and allogeneic bone marrow grafting both require cytoreductive therapy but only the allogeneic procedure requires immunosuppressive agents. Allogeneic bone marrow transplantation has been reported to be associated with a high incidence of both renal failure and veno-occlusive disease (VOD) of the liver, the combination of which is associated with a high morbidity and mortality. There is less known about the frequency and severity of these complications in patients undergoing autologous bone marrow transplantation. In the present study renal, hepatic and other complications were examined in 232 patients with Stages II/III and IV breast cancer who were treated with high-dose chemotherapy and autologous hematopoietic cell support with either marrow or peripheral blood progenitor cells. The post-treatment severity of the renal dysfunction was classified as follows: Grade 0, normal renal function [< 25% decrement in glomerular filtration rate (GFR)]; Grade 1. mild renal dysfunction (> 25% decrement in GFR but < a twofold increase in serum creatinine); Grade 2, > twofold rise in serum creatinine but no need for dialysis; Grade 3 > than twofold rise in serum creatinine and need for dialysis. There were 102 patients (44%) who were classified as Grade 0 and 81 patients (35%) who were classified as Grade 1 renal dysfunction. Severe renal dysfunction (Grades 2 and 3) was observed in 49 of the 232 patients (21%). This severe renal dysfunction of 21% compares with a previously reported 53% incidence of severe renal dysfunction for allogeneic bone marrow transplantation. Similarly, the frequency of hepatic VOD was less (4.7% or 11 of 232 patients) in this autologous bone marrow transplant study as compared to a reported incidence of hepatic VOD ranging from 22 to 53% in large series of allogeneic bone marrow transplant patients. The severe renal dysfunction (Grades 2 and 3) in the present autologous hematopoietic cell support study correlated most significantly with

  16. Intravenous immune globulin in chronic lymphocytic leukaemia.

    PubMed Central

    Gamm, H; Huber, C; Chapel, H; Lee, M; Ries, F; Dicato, M A

    1994-01-01

    The most common complication of chronic lymphocytic leukaemia (CLL) is infection, which occurs mainly in advanced stages of disease or in those patients with hypogammaglobulinaemia. Intravenous immune globulin (IVIG) has been shown to be a useful prophylactic therapy against infections in such patients. A randomized, double-blind study on 36 patients receiving either 500 mg/kg or 250 mg/kg IVIG every 4 weeks was undertaken to determine the dose regimen required. There was no significant difference in the two treatment groups and we found that CLL patients were equally protected with low-dose IVIG. PMID:8033428

  17. B cell conducts the lymphocyte orchestra.

    PubMed

    Youinou, Pierre

    2007-01-01

    The interest for B cells has recently been revived. They normally play a role in the development, the regulation, as well as the activation of lymphoid architecture: they regulate dendritic cells and T-cell subsets function through cytokine production. Receptor editing is also essential in B cells and aids in preventing autoimmunity. Both abnormalities in the distribution of B-cell subsets and clinical benefit response to B-cell depletion in autoimmune states illustrate their importance. A new area has thus been reached, whereby B lymphocytes return as a significant contributor to autoimmune disorders. PMID:17363215

  18. Therapeutic Autologous Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2011-07-12

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

  19. Thymic influence on the T-lymphocyte self MHC repertoire. II. Cytotoxic T-lymphocyte precursors.

    PubMed

    Jenski, L J; Miller, B A

    1988-01-01

    We measured the frequency and specificity of thymic alloantigen-reactive cytotoxic T-lymphocyte precursors in spleens of allogeneic thymus-grafted nude mice tolerant to thymic alloantigens. Under our conditions of limiting dilution analysis we found no selective loss of cytotoxic T-lymphocyte precursors in allogeneic thymus-grafted mice. Upon analysis of individual cytotoxic T-lymphocyte clones, we found that lysis of specific and third party targets was mediated by distinct clones specific for H-2 antigens. Precursors from allogeneic thymus-grafted nudes stimulated at limiting dilutions with thymic alloantigens tended to lyse fewer targets than were lysed by normal cytotoxic T-lymphocytes or allogeneic thymus-grafted nude precursors stimulated with third party alloantigens, but the reduction in lytic activity was not statistically significant. Specific suppression was not demonstrated, but could not be ruled out unequivocally. We conclude that intrathymic deletion of thymic alloantigen-reactive pCTL is not necessary to achieve specific tolerance to thymic alloantigens. PMID:3259029

  20. Anchorage and lymphocyte function. Spreading-capacity distinguishes common thymocytes and peripheral T lymphocytes.

    PubMed Central

    Otteskog, P; Sundqvist, K G

    1983-01-01

    Contact of T-enriched human blood lymphocytes with an adhesive surface in the presence of Concanavalin A (Con A) almost immediately induced a sequence of motile changes in virtually all cells. The initial event in this spreading process was the formation of filopodia distinct from the microvilli of lymphocytes in suspension. The filopodia were accompanied by lamellipodia, ruffles and flattening of the nucleus. Contact with a nonadhesive substratum in the presence of Con A did not trigger this sequence of changes. Cytochalasin B and D or low temperature inhibited the contact-induced changes. With the exception of a small number of cells (5-15%), T-enriched lymphocytes that were allowed to settle in the absence of Con A showed a radius of action (area occupied by the cells/translational movement per hr) of 39 micrometers 2/ less than 1 micrometer. The small 'motile' population showed a radius of action of 74 micrometers 2/8 micrometers. The Con-A-mediated spreading-process yielded a radius of action of the lymphocytes of 117 micrometers 2/6 micrometers. This augmented radius of action markedly facilitated cell-cell interaction in a high frequency of the cells and appeared to be a prerequisite for such interactions at 'low' cell density. Thymocytes reactive with OKT 6 antibodies or belonging to the 'high-density' fraction of cells attached to a Con-A-coated surface to the same extent as peripheral OKT 3 positive lymphocytes, but did not exhibit the morphological changes characteristic of a spreading-process. In contrast, OKT 6 negative thymocytes or thymocytes with a relatively low density showed spreading indistinguishable from that of OKT 3 positive peripheral lymphocytes. These results characterize the spreading-process in human T lymphocytes and demonstrate its functional importance for interactions with the environment. Spreading-capacity appears to reflect the stage of maturation of T cells. Images Figure 1 Figure 2 Figure 3 Figure 4b Figure 4c Figure 7 PMID