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Biomedical subjects

J Bryant

Publications and source records attributed to J Bryant.

At least 109 records · Page 6Linked to original sources

Apolipoprotein E (ApoE), a novel heparin-binding protein inhibits the development of Kaposi's sarcoma-like lesions in BALB/c nu/nu mice.

Recombinant apolipoprotein E-3 (ApoE-3), expressed in Escherichia coli, was purified and used in an in vitro and an in vivo model system for acquired immunodeficiency syndrome-associated Kaposi's sarcoma (AIDS-KS). This protein blocked cell proliferation and chemotaxis of AIDS-KS cells in response to activated lymphocyte conditioned medium (AL-CM) and oncostatin M (OSM). ApoE-3 also inhibited the formation of neoangiogenic lesions induced in BALB/c nu/nu mice by AIDS-KS cells. These findings represent a novel and potentially less toxic therapeutic approach for the treatment of AIDS-KS.

Acquired Immunodeficiency Syndrome↗

Effects of therapy with interferon-alpha on peripheral blood lymphocyte subsets and NK activity in patients with chronic hepatitis C.

Longitudinal changes in lymphocyte subpopulations, including total and activated T cells, B cells, and NK cells as well as NK activity and 2',5'-oligoadenylate synthetase (2'5' AS) levels were determined in peripheral blood before, during, and after therapy with human recombinant interferon-alpha (HurIFN-alpha) in 39 patients with serologically and biopsy-confirmed chronic hepatitis C. Immunologic data obtained at baseline and during IFN-alpha administration were correlated with the clinical response to IFN-alpha therapy defined as a normalization of the serum alanine aminotransferase level. There were 23 responders (R) and 13 nonresponders (NR) to IFN-alpha and 3 patients were not evaluable. Prior to the use of IFN-alpha, the patients tended to have higher numbers of activated (DR+) T and NK cells but a lower number of CD3+CD25+ T cells than normal controls. During IFN-alpha therapy, highly significant induction of 2'5'AS was observed. The numbers of circulating WBC, total lymphocytes, and T and B cells were reduced during IFN-alpha therapy. In contrast, both the absolute number and percentage of activated CD3+CD25+ and CD4+DR+ T cells increased in response to the IFN-alpha therapy. The percentage of activated CD56+DR+ NK cells was also significantly elevated over the pretreatment baseline. IFN-alpha therapy had no effect on NK activity in peripheral blood mononuclear cells. No differences in the immunologic profile of R vs NR were noted, except that the number of IL2R+ T cells was increased transiently early during IFN-alpha therapy but only in the NR group. It was not possible to reliably discriminate between R vs NR to IFN-alpha therapy on the basis of longitudinal changes in the phenotype or function of immune effector cells.

2',5'-Oligoadenylate Synthetase↗

Characteristics of porcine T lymphocytes and T-cell lines.

Monoclonal antibodies (mAb) against leucocyte differentiation antigens have altered the way in which immunologists examine the immune system. These mAb allow us to identify distinct surface molecules on leucocyte populations, by which these cells can be classified, isolated and studied for their functional properties. This review summarizes the knowledge about differentiation antigens useful in the characterization of porcine T lymphocytes. Furthermore, it focuses on several properties of porcine T lymphocytes, T-lymphocyte subpopulations and the generation of porcine antigen-specific T-cell lines.

Animals↗

Carpet beetle larval parts in Pap smears: report of two cases.

We describe the cases of two asymptomatic patients who had carpet beetle larval parts in routine cervical Pap smears. The diagnosis was made by finding pathognomonic hastisetae in the smears. The evidence suggests that contamination occurred at or around the time of sampling.

Adult↗

In vitro cytokine production by normal human peripheral blood mononuclear cells as a measure of immunocompetence or the state of activation.

Measurements of cytokine levels in serum may not adequately reflect the cytokine-producing potential of immune cells because of the short half-lives of cytokines and the presence of various inhibitors in human sera. In vitro cytokine production by peripheral blood mononuclear cells (PBMCs) can be an important and reliable measure of immunocompetence. Also, spontaneous in vitro release of cytokines by PBMCs may serve as a measure of their activation in vivo. In the present study, normal ranges for the in vitro production by PBMCs of interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF-alpha), IL-2, and gamma interferon (IFN-gamma) were established; the feasibility of using cryopreserved PBMCs for assays of in vitro cytokine production was evaluated; and spontaneous (unstimulated) versus induced production of cytokines by fresh and cryopreserved PBMCs from healthy donors was compared. Supernatants obtained from paired fresh and frozen PBMCs were quantitated for IL-1 beta, TNF-alpha, IL-2, and IFN-gamma by using enzyme-linked immunosorbent assay or a radioimmunoassay standardized against World Health Organization cytokine standards. Fresh or cryopreserved PBMCs activated with lipopolysaccharide produced comparable levels of IL-1 beta. However, the mean levels of stimulated production of TNF-alpha, IFN-gamma, and IL-2 were significantly higher in cryopreserved versus fresh PBMCs (P < or = 0.0004). Correlations between the level of production of each cytokine by fresh versus cryopreserved in vitro-stimulated PBMCs were statistically significant, although of moderate magnitude. Spontaneous cytokine release by fresh versus cryopreserved cells was not significantly different.

Adult↗

Successful transfusion in the presence of anti-K4 (anti-Kpb).

A 71-year-old group A, DC female, with anti-K4(-Kpb), -E, and -S was admitted for her second coronary artery surgery. Four units of autologous red blood cells (1BCs) were transfused perioperatively, and four units of homologous K:-4, E-, S- RBCs were transfused over the next 24 hours. Ten units of fresh frozen plasma and 28 units of platelets were also transfused. Continued bleeding necessitated calling donors from other states in AUStralia and from the International Panel of Donors of Rare Type, Bristol, UK, maintained by the World Health Organization. Four units of group 0, K:4, E-, S- KHCs were transfused in the next 24 hours while the K:-4 blood was in transit. No immediate signs of a transfusion reaction were noted. Blood pressure, temperature, bilirubin, and urinary output were normal, and an increase in hemoglobin was observed. A positive direct antiglobulin test was evident 3 days posttransfusion of the incompatible units and was still present 8 days later. Anti-A and anti-K4 were eluted from the patient's RBCs. The titer of anti-K4 increased from 8 preoperatively to 2,048 19 days posttransfusion of K:4 RBCs. Subsequent transfusions were not required, and the patient was discharged 3 weeks after the operation without further incident.

Journal Article↗

Evidence for local and systemic activation of immune cells by peritumoral injections of interleukin 2 in patients with advanced squamous cell carcinoma of the head and neck.

Interleukin 2 (IL2) was injected peritumorally and intranodally in 36 patients with unresectable squamous cell carcinoma of the head and neck enrolled in an Eastern Cooperative Oncology Group-sponsored phase Ib trial (EST P-Z388). Groups of 6 patients received escalating doses(200, 2 x 10(3), 2 x 10(4), 2 x 10(5), 2 x 10(6), and 4 x 10(6) units) of IL2 daily 5 times/week for 2 weeks. Tumor biopsies were obtained before and after IL2 therapy. Tumor tissue was provided for histology, and the remaining fresh tissue was divided for snap-freezing in -75 degrees C and for separation of tumor-infiltrating lymphocytes (TIL) and tumor cells. Immunophenotyping of TIL performed on cryostat sections of paired pre- and post-IL2 biopsy tissues showed increases after IL2 therapy in the number of T-cells (P = 0.005), natural killer (NK; CD16+) cells (P = 0.0001), CD25+ cells (P = 0.004), and HLA-DR+ cells (P = 0.001) accumulating in the tumor stroma. In the tumor parenchyma, NK cells (P = 0.0001) and HLA-DR+ cells (P = 0.003) were increased after IL2 therapy. The T:NK cell ratios in the tumor stroma and parenchyma were decreased after therapy, suggesting selective accumulation of NK cells. By flow cytometry, TIL recovered from post-IL2 biopsy tissues were enriched (P < 0.05) in CD3-CD56+ (NK) cells. In situ hybridization with [35S] cDNA probes for cytokines and IL2 receptors indicated that the numbers of cells expressing mRNA for IL2, tumor necrosis factor alpha, IL1-beta, gamma-interferon, transforming growth factor beta, and IL2 receptor p55 or p70 were increased in post-IL2 biopsy tissues as compared to pre-IL2 tissues. Cytolytic activity of TIL isolated from post-IL2 tissues was also increased, as determined in 4-h 51Cr release assays against K562 targets (12 +/- 3 mean lytic units/10(7) cells +/- SEM pre-IL2 versus 46 +/- 13 post-IL2; n = 16) and against autologous tumor (13 +/- 8 versus 68 +/- 26; n = 9). Fresh TIL of one clinical responder showed relatively high levels (195 lytic units) of autotumor cytotoxicity after IL2 therapy versus no activity prior to therapy. In the blood, NK and lymphokine-activated killer cell activity, and percentages of CD3-CD56+ NK cells and of activated (CD25+) T-lymphocytes were increased for all doses of IL2.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma, Squamous Cell↗

Dangerous dogs.

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Animals↗

Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study.

In an effort to determine if cell cycle active agents are augmented when given after non-cell cycle active agents, 104 patients with either multiply relapsed or refractory acute nonlymphocytic leukemia or blast crisis of chronic myelogenous leukemia were treated with mitoxantrone. Patients whose bone marrow did not show significant cytoreduction received 5-azacytidine. Twenty-seven of the 93 evaluable patients (23%) with ANLL achieved a complete remission. A total of 28% of patients receiving mitoxantrone alone achieved remission compared to 15% for those receiving mitoxantrone and 5-azacytidine. Relapsed patients had a higher CR rate (36%) than refractory patients (15%). Nausea, vomiting, and stomatitis were common but rarely severe. The median duration of remission was 3.7 months and patients with abnormal karyotypes had longer remission durations than those with normal karyotypes. In this patient population, there was no evidence that 5-azacytidine given after mitoxantrone increased the complete remission rate.

Adult↗

Developing a primary health care management information system that supports the pursuit of equity, effectiveness and affordability.

A key set of goals of primary health care (PHC) includes equity, effectiveness and affordability. By equity, we mean universal coverage and care according to need; by effectiveness, that the system has a favorable impact on mortality and serious morbidity; by affordability, that the system is within the budgetary reach of government and communities. There are other requirements of PHC as well: that the system be socially and culturally acceptable, and that communities are active participants in the development and implementation of the system. Further, the PHC system should be compatible with larger system of a region or country, and possibly serve as a prototype for the development of larger health systems. With these requirements in mind, the Aga Khan University has developed a series of community-based, urban PHC systems, each serving a population of about 10,000, in the katchi abadis (squatter settlements) of Karachi. These communities are severely deprived, with high infant, child and maternal mortality rates. The PHC systems are designed to achieve equity, effectiveness and affordability, and within 3-5 years have advanced substantially toward those goals. A key factor in those developments has been the management information system (MIS), which has served as a basis for planning, managing and evaluating the PHC systems. Central questions about such an MIS are: What kind of MIS design is necessary to support the pursuit of those goals? What problems arise in the MIS as such a system is implemented? What kinds of changes and adaptations need to be considered in the MIS as the PHC system itself matures? What does the PHC system cost, and what part of the total cost of the PHC system is attributable to the MIS? How practical is this kind of MIS, developed in small prototype PHC systems, for replicability in larger health systems? What are the possibilities and requirements for simplification in order to be used in health systems that are less intensively managed? The experience of AKU in Pakistan in the development of PHC systems, with associated management information systems, helps to answer these questions.

Community Health Services↗

Preparation of viable tumour cell vaccine from human solid tumours: relationship between tumour mass and cell yield. The Tissue Bank, Pittsburgh Cancer Institute.

Active specific immunotherapy for cancer often requires the use of autologous or allogeneic tumour cells as immunizing antigen. Tumours were obtained for such a protocol. However, estimation of viable cell yield from pre-processed fresh tumour mass was difficult, and initially there did not appear to be a direct relationship between pre-processed tumour mass and viable cells obtained after processing. We therefore analysed all of 293 tumour specimens processed to attempt to discern such a relationship. Of these 137 were melanoma, 14 were sarcoma, 48 were adenocarcinoma, 59 were renal cell carcinoma and 35 were classified as other. A positive correlation was found between pre-processed tumour mass and viable cell yield, with Spearman correlation values varying from r = 0.49 (adenocarcinoma) to r = 0.84 (melanoma). For all tumours the Spearman correlation was r = 0.70 (p = 0.0001). Not surprisingly, the most frequent site of removal associated with bacterial contamination was bowel. In conclusion, this study provides useful curves for predicting viable tumour cell yield from pre-processed tumour mass of given histology.

Adenocarcinoma↗

Acidified chloroquine treatment for the removal of class I HLA antigens.

With the aim of reducing the damage to platelets while effectively removing class I HLA antigens from their surfaces, we developed a new method using acidified chloroquine diphosphate. Platelets were treated with a 0.2 M solution of chloroquine diphosphate (pH 4.0). More than 90% of the platelets remained viable after treatment. While a marked reduction in reactions of acidified chloroquine-treated platelets with multispecific HLA antisera was noted in comparison with phosphate-buffered-saline-(PBS)-treated platelets, reactions with platelet-specific antibodies were preserved. This was demonstrated by immunofluorescence tests and solid-phase and monoclonal antibody immobilization of platelet antigen assays. Aggregation responses, though reduced in comparison with PBS-treated platelets, were still preserved after acidified chloroquine treatment. Ultrastructural analysis did not show any significant difference from PBS-treated platelets. We conclude that treatment of platelets with acidified chloroquine diphosphate is a simple and effective method for removing class I HLA antigens from their surfaces with minimal damage to their structure and function.

Blood Platelets↗

Calculation of lytic units for the expression of cell-mediated cytotoxicity.

Over the past 10 years, the lytic unit has become the most common means by which activity is expressed in cell-mediated cytotoxicity assays. The strengths and weaknesses of the lytic unit as a summary of cytotoxicity are discussed, and computational methods reviewed. The fundamental "assumption of proportional effect" which is implicit in the interpretation of lytic units is described and empirically tested. Based on extensive data from the assay of human natural killer (NK) activity against K562 targets, simplified computational methods are recommended. The proposed methods are easily explained, may be made robust to occasional erratic data, and permit a reasonable interpretation of lytic units even when the assumption of proportional effect breaks down.

Cytotoxicity Tests, Immunologic↗

The contamination of pork with spoilage bacteria during commercial dressing, chilling and cutting of pig carcasses.

Swab samples from the surfaces of carcasses and cuts were obtained at various stages of the dressing, chilling and cutting operations in three pig processing plants. The aerobic microflora obtained from those swabs were enumerated and characterized. The flora on the skins of carcasses exiting the scalding tanks were dominated by Gram-positive organisms, with numbers about 10(3)/cm2. After dehairing, numbers were about 10(4)/cm2 with major fractions of Gram-negative organisms. Flora numbers and compositions were largely unaltered after the singeing operations, but lesser numbers were recovered after the carcasses were polished. Carcass dressing did not change the numbers on the skin. During the chilling of carcasses, the flora at two large plants altered little, but drying of the carcass surfaces at a smaller plant reduced the Gram-negative fraction of the flora. Numbers on serous and fat surfaces exposed during the dressing and cutting of carcasses were initially about 10(2)/cm2. That number was approximately maintained on finished skinned cuts produced at the smaller plant, but further contamination with lactobacilli and Brochothrix thermosphacta occurred during cutting. At the larger plants, the flora on skinned cuts were similar to those on skins, although further contamination with B. thermosphacta occurred at one plant.

Abattoirs↗