Search PubMed⌕ Search

Biomedical subjects

E Barker

Publications and source records attributed to E Barker.

At least 55 records · Page 3Linked to original sources
PubMed1994

Immunologic abnormalities associated with chronic fatigue syndrome.

Several aspects of cellular immunity in patients with clinically defined chronic fatigue syndrome (CFS) were evaluated and compared with those in healthy individuals. Flow cytometric analyses revealed normal expression of total T (CD3+), B (CD19+), and NK (natural killer) (CD16+, CD56+) markers on the surface of peripheral blood mononuclear cells (PMC) from patients with CFS. However, compared with those of healthy individuals, patients' CD8+ T cells expressed reduced levels of CD11b and expressed the activation markers CD38 and HLA-DR at elevated levels. In many of the individuals in whom expression of CD11b was reduced the expression of CD28 was increased. These findings indicate expansion of a population of activated CD8+ cytotoxic T lymphocytes. A marked decrease in NK cell activity was found in almost all patients with CFS, as compared with that in healthy individuals. No substantial abnormalities in monocyte activity or T cell proliferation were observed. The results of this study suggest that immune cell phenotype changes and NK cell dysfunction are common manifestations of CFS.

Adult↗
PubMed1993

A mechanism for neutrophil-mediated lysis of human neuroblastoma cells.

Neutrophils mediate the lysis of human neuroblastoma cells coated with human/mouse chimeric anti-GD2 ganglioside antibody ch14.18. This study examined the mechanism(s) by which this occurs. Neutrophil degranulation was found to be a required step for lysis, since release of granular enzymes from neutrophils correlated with the lysis of antibody-coated neuroblastoma cells. In addition, agents which block degranulation specifically inhibited this process. Antibody-dependent lysis of neuroblastoma cells was enhanced by exposing neutrophils to granulocyte-macrophage colony stimulatory factor. An increased release of lytic granular molecules was found to be responsible for this lymphokine-mediated phenomenon. Among the molecules released from neutrophil granules that were shown to be involved in neuroblastoma cell lysis were defensins, M(r) 3000-4000 neutrophil granular proteins which are known to bind and permeabilize tumor cells. In addition, cathepsin-G, a neutrophil granular protease, was demonstrated for the first time to mediate the lysis of human neuroblastoma cells. The enzymatic activity of cathepsin-G was found to be required for the lysis of these tumor cells, since phenylmethylsulfonyl fluoride blocks the lytic ability of this protein.

Antibodies, Neoplasm↗
PubMed1993

Clinical experience with a fiberoptic intracranial pressure monitor.

Retrospective clinical experience with our first 46 patients monitored with a fiberoptic intracranial pressure device is described. In 43 of 46 patients, the transducer was introduced into brain parenchyma. A ventriculostomy system was used in 3 of 46 patients. The monitoring system was generally characterized by ease of placement and system maintenance and by technical simplicity. Several problems were encountered, including breakage of system components (12%), erroneous readings requiring transducer repositioning (8.6%), epidural hematoma (3.4%), and infection (1.7%). No infections or hematomas occurred in the 3 cases in which the ventriculostomy system was used. Overall, our experience with the Camino intracranial pressure fiberoptic monitoring system confirms previous reports of its favorable features.

Brain Injuries↗
PubMed1992

Successful treatment of failed AID cases by use of gamete intra-fallopian transfer using donor semen (GIFT (D)).

Over a 13-month period in a newly opened assisted conception unit at the Women's Hospital, Liverpool, gamete intra-fallopian transfer using donor semen, GIFT (D) was offered to eighteen couples who had failed to conceive after numerous cycles of treatment with artificial insemination by donor semen (AID). The indication for the use of donor semen was either azo- or severe oligoaesthenospermia, and, in addition, the female partners have been exhaustively investigated with no major cause found to account for the couple's infertility. Using a basic clomiphene citrate and human menopausal gonadotrophin protocol it was possible to achieve a pregnancy rate of 56% per GIFT (D) cycle. As a consequence of these results it is now our policy to treat couples whose infertility is due to an unresolvable male factor with AID for 12 cycles only. If they have been unsuccessful in achieving a pregnancy after this time, they are offered GIFT (D).

Adult↗
PubMed1992

Cutaneous T-cell lymphoma. Evaluation of pretreatment skin biopsy specimens by a panel of pathologists.

BACKGROUND AND DESIGN: Cutaneous T-cell lymphoma (CTCL) frequently presents a difficult diagnostic challenge for the clinician and pathologist. To assess the diagnostic validity of conventional histopathologic findings in CTCL, pretreatment skin biopsy specimens were scored prospectively and independently by a panel of five to seven dermatopathologists and pathologists. Scores were compared with disease outcome. Repeatability of these scores was examined among observers and for the same observer. The study population consisted of 165 subjects, initially referred for suspected mycosis fungoides or Sézary syndrome. Ninety-two patients determined to have CTCL have been followed up for 6.3 +/- 3.5 years (mean +/- SD) and are categorized according to disease outcome: 22 are in complete remission, 35 are in partial remission, three have progressive lymphoma, 15 died of disease, 13 died of other causes, and four were unavailable for follow-up. Seventy-three patients determined not to have CTCL have been followed up for 5.3 +/- 3.2 years without subsequent clinicopathologic evidence of CTCL. These longitudinal data allowed comparisons of the clinical course with the original histologic interpretations. RESULTS: Data showed that the histologic scores rendered by the pathology panel did not correlate with stage of disease and were not an accurate predictor of clinical outcome, because the histologic ratings did not discriminate between patients who eventually had complete remission and those with either progressive lymphoma or who have died of disease. The results also substantiate the low inherent reliability of histopathologic findings in CTCL. Large differences existed among pathologists in scoring the study populations and repeated reading of selected cases by the same panel member resulted in a change of diagnosis 15% of the time. Among the histologic features evaluated, only the presence of mitoses in the infiltrating cells showed a trend toward an unfavorable outcome. CONCLUSION: Pathologic diagnosis in the CTCL disease spectrum should be interpreted with caution and then only in conjunction with the clinical evaluation. As expected, the use of an average value from a panel of readers added a component of stability to the histologic interpretation.

Biopsy↗
PubMed1991

Effect of a chimeric anti-ganglioside GD2 antibody on cell-mediated lysis of human neuroblastoma cells.

An anti-GD2 ganglioside human/mouse chimeric monoclonal antibody, ch14.18, like its murine counterpart, 14.G2a, was shown to bind to human neuroblastoma cells. This chimeric antibody proved to be more effective than 14.G2a in mediating the lysis of neuroblastoma cells with human effector cells, such as granulocytes and natural killer cells within the peripheral blood mononuclear cell population. A comparison of these two effector cell populations isolated from the same donor revealed granulocytes to be more effective than peripheral blood mononuclear cells in lysing neuroblastoma cells, which were coated with monoclonal antibody ch14.18. Addition of recombinant human granulocyte-macrophage colony-stimulatory factor increased ch14.18-mediated lysis of neuroblastoma cells by granulocytes but not by peripheral blood mononuclear cells. In fact, granulocytes were effective in mediating lysis of neuroblastoma cells coated with ch14.18 irrespective of whether they were obtained from normal adults or from neuroblastoma patients.

Animals↗
PubMed1991

Phorbol ester-induced enhancement in lytic activity of CD8+ splenic T cells from low-dose melphalan-treated MOPC-315-tumor bearers.

We have previously shown that while spleen cells from untreated mice bearing a large MOPC-315 tumor are not cytotoxic in vitro for MOPC-315 tumor cells, spleen cells obtained from such mice on day 7 after low-dose melphalan (L-phenylalanine mustard); L-PAM therapy exert a substantial anti-MOPC-315 cytotoxicity [Mokyr et al. (1989) Cancer Res 49: 4597]. Here we show that this anti-MOPC-315 lytic activity is evident by day 5, and peaks on day 7 after the low-dose chemotherapy, at a time when the mice are actively engaged in tumor eradication. Short-term exposure of spleen cells from mice bearing a MOPC-315 tumor and treated with low-dose L-PAM (L-PAM TuB mice) to phorbol 12-myristate 13-acetate (PMA) was found to enhance greatly the ability of these spleen cells to lyse MOPC-315 tumor cells. The highest level of anti-MOPC-315 cytotoxicity was obtained when spleen cells from tumor-bearing mice that had received chemotherapy 7 days earlier were exposed to PMA at a concentration of 1-10 ng/ml. The exertion of the enhanced anti-MOPC-315 lytic activity by L-PAM TuB spleen cells exposed to PMA was found to require CD8+, but not CD4+, T cells. The apparent specificity of the lytic activity exerted by the PMA-stimulated L-PAM TuB spleen cells was illustrated not only by the inability of the spleen cells to lyse an allogeneic, antigenically unrelated thymoma (EL4), but also by their relatively weak lytic activity for two antigenically related syngeneic plasmacytomas. In addition, when EL4 target cells were admixed with MOPC-315 tumor cells, the lytic activity triggered in the L-PAM TuB spleen cells by the MOPC-315 tumor cells plus PMA was not effective in lysing the antigenically unrelated target cells. Moreover, even in the presence of the calcium-specific ionophore, ionomycin, L-PAM TuB spleen cells exposed to PMA were unable to lyse the EL4 target cells. Thus, fresh CD8+ splenic T cells from L-PAM TuB mice that are in the process of eradicating a large MOPC-315 tumor as a consequence of low-dose L-PAM therapy can be triggered with PMA to exert enhanced lytic activity against MOPC-315 tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Low nm23 protein expression in infiltrating ductal breast carcinomas correlates with reduced patient survival.

Protein levels corresponding to nm23 were determined in normal and neoplastic breast tissues by immunoperoxidase staining. Nm23 protein levels were highest in normal breast epithelium, and lower in intraductal carcinomas. Based on nm23 staining, 39 infiltrating ductal carcinomas were separated into two groups: tumors with homogeneously high nm23 protein content, and tumors with low staining in either a homogeneous or heterogeneous pattern. Patients with low nm23 staining tumors, determined by three pathologists independently, had reduced survival times (alpha = 0.034, alpha = 0.012, alpha = 0.052 by the log rank test). Nm23 expression approached significance as an independent predictor of survival in Cox's proportional hazards model. The data provide the first correlation of low nm23 protein expression and reduced breast carcinoma patient survival.

Breast Neoplasms↗
PubMed1990

Eradication of a large MOPC-315 tumor in athymic nude mice by chemoimmunotherapy with Lyt2+ splenic T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor.

We have previously shown that spleen cells from BALB/c mice that are in the process of eradicating a large MOPC-315 tumor following low-dose (2.5 mg/kg) melphalan (L-phenylalanine mustard) therapy are effective in preventing tumor progression upon adoptive transfer into BALB/c mice bearing a barely palpable tumor that had been treated with a subcurative dose of melphalan [Mokyr et al. (1989) Cancer Res 49:4597]. Here we show that such spleen cells in conjunction with a subcurative dose of drug (adoptive chemoimmunotherapy, ACIT) can cause the complete regression of a large (15-20 mm) s.c. MOPC-315 tumor in a large percentage of T-cell-deficient (athymic nude) tumor-bearing mice. Spleen cells that were effective in ACIT of athymic nude mice displayed in vitro a substantial direct lytic activity against MOPC-315 tumor cells, and the lytic activity was greatly enhanced when the spleen cells were cultured for 5 days with or without mitomycin-C-treated MOPC-315 stimulator tumor cells. The cells responsible for the therapeutic effectiveness of the spleen cells in ACIT of athymic nude mice, as well as the cells responsible for the direct in vitro anti-MOPC-315 lytic activity of the spleen cells, were of the Lyt 2 and not the L3T4 phenotype. Most of the athymic nude mice that completely eradicated a large MOPC-315 tumor as a consequence of ACIT were capable of rejecting a challenge with 30-100 times the minimal lethal tumor dose for 100% of normal BALB/c mice administered more than 1 month after the ACIT. The ability of these athymic nude mice to resist the tumor challenge was associated with the presence of a greatly elevated percentage of cells expressing T cell surface markers in their spleens. Thus, it is conceivable that splenic Lyt 2+T cells from melphalan-treated BALB/c mice bearing a large MOPC-315 tumor mediate their therapeutic effectiveness in ACIT of athymic nude mice bearing a large MOPC-315 tumor, at least in part, through direct cytotoxicity for MOPC-315 tumor cells. In addition, eradication of a large MOPC-315 tumor through cooperation between antitumor immunity and melphalan toxicity endues the athymic nude mice with an elevated percentage of T cells in their secondary lymphoid organs, and these T cells are probably responsible for the long-lasting protective antitumor immunity exhibited by these mice.

Animals↗
PubMed1990

Peripheral blood-derived stem cell collections for use in autologous transplantation after high dose chemotherapy: an alternative approach.

Peripheral blood-derived hematopoietic stem cells (PBHSC) can be utilized to reconstitute hematopoiesis in patients after high dose myeloablative chemotherapy. We have performed PBHSC reinfusion in 18 patients who have or had a history of tumor involving the bone marrow or a hypocellular bone marrow. The PBHSC were collected by continuous flow leukapheresis and subsequently cryopreserved. A median of 31.9 X 10(9) (range 18 X 10(9)-67.2 X 10(9)) mononuclear cells or a median of 4.85 X 10(8) mononuclear cells/kg (range 2.7 X 10(8)-11.0 X 10(8)) were collected. Fifteen patients had in vitro assays of granulocyte-monocyte colony-forming cells (CFU-GM) performed with a median of 2.7 X 10(4) (range 0-11.5 X 10(4)) CFU-GM/kg. To date, of the 18 patients collected, all have undergone high dose chemotherapy and PBHSC reinfusion. For the evaluable patients, granulocyte recovery (greater than 500 X 10(6)/ml) has occurred in a median of 15 days and platelet recovery (greater than 50 X 10(9)/ml without transfusion support) has occurred in a median of 43 days. Four patients have had prolonged thrombocytopenia and still require platelet transfusion at 80+, 97+, 124+, and 270+ days. PBHSC collection is safe and effective for hematopoietic reconstitution after high dose chemotherapy in the majority of patients; however incomplete hematopoietic reconstitution has been observed in 4/18 evaluable patients. This procedure requires further investigation.

Adult↗
PubMed1989

Reduced Nm23/Awd protein in tumour metastasis and aberrant Drosophila development.

Tumour metastasis is the principal cause of death for cancer patients. We have identified the nm23 gene, for which RNA levels are reduced in tumour cells of high metastatic potential. In this report we identify the cytoplasmic and nuclear Nm23 protein, and show that it also is differentially expressed in metastatic tumour cells. We also find that the human Nm23 protein has sequence homology over the entire translated region with a recently described developmentally regulated protein in Drosophila, encoded by the abnormal wing discs (awd) gene. Mutations in awd cause abnormal tissue morphology and necrosis and widespread aberrant differentiation in Drosophila, analogous to changes in malignant progression. The metastatic state may therefore be determined by the loss of genes such as nm23/awd which normally regulate development.

Amino Acid Sequence↗