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Biomedical subjects

D Char

Publications and source records attributed to D Char.

15 recordsLinked to original sources
PubMed1991

Transformation of T-lymphocyte subsets by Marek's disease herpesvirus.

Marek's disease herpesvirus (MDV)-transformed lymphoblastoid tumor cell lines were characterized for the presence of the surface markers. Monoclonal antibodies were used for CD3 (T-cell receptor [TCR] complex), TCR1, TCR2, and TCR3, CD4, CD8, and Ia antigen by indirect fluorescence staining followed by microscopic examination or flow cytometry. The lymphoblastoid cell lines were obtained from tumors from chickens infected with MDV (n = 44) or from local lesions induced by inoculation of allogeneic, MDV-infected chick kidney cells (n = 56). Lymphocytes were harvested from these lesions between 4 and 16 days postinoculation and cultured in vitro to establish cell lines. All cell lines expressed Ia antigen and CD3 and/or TCR and thus are activated T cells. Most of the cell lines developed from tumors were CD4+ CD8-; only one cell line was negative for both markers. Sixteen percent of the cell lines were TCR3+, while the remainder were TCR2+. The cell lines developed from local lesions were much more heterogeneous: 45% were CD4- CD8+, 34% were CD4- CD8-, and only 21% were CD4+ CD8-. The number of TCR3+ cell lines was larger than expected for the CD4- CD8+ and CD4- CD8- cell lines, as judged from the presence of these cells in the blood. These results indicate that several subsets of T lymphocytes can be transformed by MDV, depending on the pathogenesis of infection. Activation of T cells as a consequence of the normal pathogenesis or by allogeneic stimulation seem to be a first important step in the process of transformation.

Animals↗
PubMed1990

A third sublineage of avian T cells can be identified with a T cell receptor-3-specific antibody.

Avian homologues of mammalian gamma delta and alpha beta TCR, termed TCR1 and TCR2, have been identified in the chicken with specific mAb. A third TCR, dubbed TCR3, has been identified on a subpopulation of T cells that lack the TCR1 or TCR2 epitopes. We have now produced a mAb that identifies this TCR3 molecule. The anti-TCR3 antibody immunoprecipitates a CD3-associated heterodimer with a relative Mr of 88,000, composed of 48,000 and 40,000 disulfide-linked chains. The Mr 40,000 chains of TCR3 and TCR2 exhibited the same isoelectric points of 5.6 to 6.5 and had core proteins of 34,000. Although the Mr 48,000 chain of TCR3 and the Mr 50,000 chain of TCR2 had the same basic isoelectric point of 6.2 to 7.6, their core proteins were different in size, 31,000 vs 29,000. Immunofluorescence analysis reveals that the TCR3 was present on all of the CD3+ T cells not identified by antibodies specific for TCR1 or TCR2. Thymocytes that expressed the surface CD3/TCR3 complex at relatively low levels were predominantly CD4+ and CD8+, whereas those with higher levels of surface CD3/TCR3 were predominantly CD4+ and CD8+ singles. Mature TCR3+ cells in the periphery were also either CD4+ (80%) or CD8+ (20%). The TCR1+, TCR2+, and TCR3+ subsets of T cells were generated sequentially in the thymus and seeded to the periphery in the same order. Intrathymic development of the TCR3+ cells was selectively inhibited by embryonic treatment with the anti-TCR3 mAb. The pattern of histologic localization of TCR3+ cells in the periphery was similar to the TCR2 subset of cells except that the TCR3+ cells were rarely seen in the intestine. Cross-reactivity patterns of the anti-chicken TCR antibodies suggested that other gallinaceous species share the three types of TCR. We conclude that TCR2 and TCR3 in gallinaceous birds may represent alpha beta subfamilies of TCR that are sequentially expressed on developmentally discrete sublines of T cells.

Animals↗
PubMed1990

Effect of cyclosporin A on the ontogeny of different T cell sublineages in chickens.

We have used a panel of murine mAb against chicken TCR and associated molecules to study the effect of cyclosporin A (CsA) on the ontogeny of the different sublineages of T cells. After injection of CsA (20 mg/kg/day from day 0 to 20) we observed a significant suppression of the normal maturation of the TCR2 (alpha beta TCR) cells in their transition from cortical CD4+CD8+ thymocytes to the mature single positive cells in the thymus medulla. The TCR3 subpopulation, a distinct form of alpha beta-like TCR in chickens, was inhibited from initially developing within the cortex by CsA, indicating that the TCR3 subpopulation is functionally distinct from the TCR2+ cells. In contrast, the maturation and peripheral emigration of TCR1 (gamma delta TCR) cells was unaffected by CsA treatment. Mature splenic T cells sorted for either TCR1+ or TCR2+ subsets were equally sensitive to CsA blockade of Con A-stimulated mitogenesis, indicating that there is no inherent difference in CsA sensitivity between these sublineages. Furthermore, no difference was detected in the expression of class II MHC Ag in thymi of birds treated with olive oil vs CsA. Inasmuch as the mechanism of CsA action appears to involve inhibition of TCR initiated signal transduction for lymphokine synthesis, these data indicate that a similar signaling is involved in thymic repertoire selection for TCR2. The lack of an effect on TCR1 cell maturation suggests that the TCR1 repertoire may not undergo selection in the thymus as do TCR2+ cells.

Animals↗
PubMed1990

Long-term results of helium ion irradiation of uveal melanoma.

Between 1978 and 1988, 307 patients with uveal melanoma were irradiated using helium ions at Lawrence Berkeley Laboratory. The length of follow-up ranged from 1-115 months (median 42 months). The 5-year actuarial treatment results were: local control rate, 96.8%, determinate survival rate, 81%, freedom from distant metastases, 76%, eye retention rate, 83%, and risk of developing neovascular glaucoma, 36%. Long-term vision outcome was analyzed in 81 patients with a minimum follow-up of 5 years. Forty-seven percent of patients retained vision of 20/200 or better. The median change in vision was a loss of four lines on the standard eye chart. Thirty-eight percent of patients had visual acuity either improve or remain within two lines of their pretreatment vision. A multivariate analysis identified tumor size as the only independently significant risk factor affecting survival, development of neovascular glaucoma, or the risk of enucleation; no risk factor correlated with local recurrence. Tumor size, tumor-fovea distance, and pretreatment visual acuity were independently significant risk factors influencing vision outcome. These results confirm that helium ion irradiation is an effective treatment for uveal melanoma which combines high rates of local control, survival, and eye retention with a substantial likelihood of long-term vision preservation.

Adult↗
PubMed1990

Ciliary body melanoma treated with helium particle irradiation.

Melanoma involving the ciliary body is a rare tumor which carries a poor prognosis when compared to all uveal melanoma. We have treated 54 patients with ciliary body melanoma using helium ions from 1978 to 1985. Because of the high rate of metastatic disease, the 5-year disease specific survival rate is only 59% despite a 5-year local control rate of 98%. The greatest diameter of the tumor was predictive of loss of vision and enucleation (p = .05, p = .04, respectively). Multivariate analysis showed that the greatest diameter of the tumor was the most important predictor of death from metastases. The incidence of neovascular glaucoma at 5 years is 43%. The 5-year actuarial rate of enucleation is 26%. Enucleation was done for pain and/or neovascular glaucoma. Univariate analysis showed treatment volume to be a statistically significant predictor for the development of neovascular glaucoma (p = .0017) and enucleation (p = .0078). Seventy percent of neovascular glaucoma occurred in patients with treatment volume greater than 5.5 cc. Seventy-four percent occurred in patients with an initial ultrasound height greater than 9.2 mm. Using this information, patients at high risk for neovascular glaucoma could be considered for prophylactic treatment with panretinal photocoagulation.

Adult↗
PubMed1989

Analysis of the first two waves of thymus homing stem cells and their T cell progeny in chick-quail chimeras.

Chick-quail chimeras were used to study precursor/progeny relationships of hemopoietic stem cells (SC) that enter the embryonic thymus in waves to give rise sequentially to the TCR-1+, TCR-2+, and TCR-3+ lineages of T cells. The first wave of SC and their progeny were examined by grafting thymus from 9-d chick embryos (E9) into E3 quails. mAbs specific for chick T cell antigens were used to trace the development of T cells in the recipients. All three lineages of TCR-bearing cells were generated from the first wave of SC. The cortico-medullary transit time was several day shorter for the TCR-1 subpopulation than for the TCR-2 subpopulation, and the peripheral seeding of TCR-2 cells also occurred later in development. The duration of thymocyte production from the first wave of SC that entered the thymus was approximately 3 wk, during which gradual cortical to medullary replacement by second wave SC progeny occurred. When the latter was examined, after transplantation of E7 quail thymus into E3 chick embryos, a sequential generation pattern for the TCR-1 and TCR-2 cell progeny was not evident. Finally, recirculation of T cells to the thymus medulla was defined in this avian model.

Age Factors↗
PubMed1989

Cytoplasmic CD3+ surface CD8+ lymphocytes develop as a thymus-independent lineage in chick-quail chimeras.

We have analyzed the embryonic development of a population of lymphoid cells that express a CD3 antigenic determinant in the cytoplasm but not on the cell surface. Since these cells lack T cell receptor (TcR) molecules, we have provisionally named them TCRO cells. Their development, expansion and distribution was investigated following transplantation of splenic and bursal fragments from chicken embryos into quail embryos. Since quail cells are not recognized by our panel of monoclonal antibodies against chicken TcR1, TcR2, TcR3, CD3, CD4 and CD8 molecules, these antibodies provided reliable markers for donor chick lymphocytes in the tissues of the quail recipients. Transplanted spleen and bursa both generated CD3+ cells, the number of which increased as a function of age. Notably, approximately half of these CD3+ cells expressed surface CD8, but none acquired TcR1 (gamma/delta), TcR2 (alpha/beta) or TcR3 expression. Since TCRO cells normally appear first in the spleen of 8-day chick embryos (E8), their generation in E6 splenic transplants indicated an extrathymic origin. The TCRO cells of chick splenic origin migrated to the spleen, bursa and thymus of the quail recipients. In six of seven chimeras acquiring CT3+ cells in the recipient thymus, these cells were restricted to the medulla and displayed the typical TCRO phenotype: CD3+CD8+TcR1-TcR2-TcR3-. These intrathymic TCRO cells also lacked the CT1 thymocyte antigen. We conclude that the TCRO cells represent a thymus-independent lineage of lymphoid cells that can migrate into a receptive thymus by rarely, if ever, differentiate into conventional T cells.

Animals↗
PubMed1989

Computer assisted treatment planning for 125I ophthalmic plaque radiotherapy.

This paper describes a computer program for planning the treatment of ocular tumors with 125I plaques. The program permits the input of the tumor configuration into a model eye and facilitates the viewing of the relative geometry of the tumor and various eye structures in different perspectives. Custom-designed 125I plaques can be localized onto the globe, and dose distributions can be calculated and superimposed on the eye structures in any plane or on the inner eye surface. The program allows efficient evaluation of the plaque design in terms of radiation dose distribution relative to the tumor and critical structures.

Brachytherapy↗
PubMed1989

Primary liposarcoma of the orbit. Problems in the diagnosis and management of five cases.

The clinicopathologic features and the results of diagnostic studies were reviewed in five patients with primary orbital liposarcoma. The major clinical complaints were diplopia and proptosis; visual function was typically well maintained. In three cases, computed tomographic (CT) scans displayed lesions with a central fat density rimmed by a variably radiodense pseudocapsule, leading to the erroneous clinical impression that the lesions were cystic in character. Ultrasonography ruled out a truly cystic tumor by demonstrating internal acoustic interfaces. Magnetic resonance imaging (MRI) in one case showed hyperintense signals in T-1-weighted images, suggesting the presence of fat within the lesional tissue. In the other two cases, CT scans showed reticulated densities accentuating the septa of the orbital fat in the absence of clear-cut circumscription. A potentially useful feature pointing to a neoplasm was bowing of an involved extraocular muscle, which is usually straightened and splinted in either Graves' disease or inflammatory pseudotumor. Histopathologically, two lesions were well-differentiated liposarcomas and three were myxoid liposarcomas, all featuring univacuolar signet ring lipoblasts. Scattered bizarre hyperchromatic mesenchymal cells without prominent lipidization were present in the lesions. None of the patients has experienced regional or distant metastases with follow-ups from onset of 1 to 7 years (mean, 5.2 years); three required orbital exenteration after local recurrence; and two who refused exenteration received only orbital radiotherapy.

Adult↗
PubMed1975

Rubella vaccination: fertility control in a large-scale vaccination program for postpubertal women.

Despite nationwide immunization programs, rubella infections during pregnancy continue. To solve this serious health problem direct immunization of women of reproductive age may be required. On a clinic basis, using nonphysician personnel, we vaccinated 404 susceptible women, ages 18 to 33; half were sexually active. Since pregnancy is proscribed for 2 to 3 months following rubella vaccination, a full range of family-planning services and a variety of contraceptive methods were used to ensure sustained fertility control. Sixteen vaccinees presented with possible conceptions in a 3 month follow-up. Of these, only five required treatment: two received diethylstilbestrol, two had menstrual inductions, and one an abortion. Administration of vaccine during a menstrual period was effective in preventing inadvertent vaccination of pregnant women. It was concluded that contraceptive counseling with adequate pregnancy termination backup makes it feasible to give rubella vaccine to highly motivated women.

Contraception↗
PubMed1975

Cell-mediated immunity in human acute leukemia.

The general cell-mediated immunological reactivity of patients with acute leukemia has been found to be intact, although it may be depressed by extensive disease or by chemotherapy. Patients with acute leukemia also have cellular immune reactivity against tumor associated antigens, as measured by skin tests for delayed hypersensitivity, lymphocyte stimulation, and 51Cr release cytotoxicity. Skin reactions to autologous and allogeneic crude membrane extracts of blast cells correlated with disease state, positive in many patients in remission and negative in most patients in relapse. Extracts of human lymphoid tissue culture cell lines derived from lymphomas or leukemia also gave positive reactions in patients with acute leukemia, and also in patients with lymphoma and nasopharyngeal carcinoma. The antigens detected in the skin tests with the lymphoid cell lines appear to be different from those associated with Epstein-Barr virus (EBV) and from those detected in the 51Cr release assay. Evidence is presented which suggests a complex variety of antigens on blast cells and on the cell lines. Although leukemia associated antigens were also detected by lymphocyte stimulation and by cytotoxicity assays, the results did not correlate with the skin tests nor with each other. The possible use of these assays for monitoring the chemotherapy and immunotherapy of acute leukemia patients is discussed.

Acute Disease↗
PubMedDate not supplied

Induction of Fc alpha receptor expression on T cells from murine Peyer's patch, spleen and thymus.

It has been shown that Fc alpha receptor-positive (Fc alpha R) lymphocytes function in the regulation of IgA responses. In the present study, we have compared the frequency of Fc alpha R+ T cells in IgA inductive sites, e.g., the Peyer's patches (PP) with a systemic tissue, the spleen (SP), and the progenitor tissue, thymus. CD3+, Thy-1+ T cells were incubated with purified IgA and then counterstained with fluorescence conjugated anti-mouse alpha-chain specific antibody. Flow cytometry (FACS) analysis showed a distinct subset of Fc alpha R+ T cells in both PP (5-10%) and SP (1-4%), while essentially no Fc alpha R+ T cells were found among isolated thymocytes. The Fc alpha R+ T cells in PP were associated with the population of large, blast cells as determined by forward angle light scatter analysis. The expression of the Fc alpha R could be induced or augmented by activation of T cells with anti-CD3 antibody. Incubation of thymocytes with anti-CD3 antibody resulted in the induction of thymocyte blasts and in Fc alpha R expression in this large cell population. Treatment of splenocytes with anti-CD3 also induced T cell blasts and enhanced the frequency of Fc alpha R+ T cells in this large cell population. Furthermore, when splenic T cells were separated into large blasts and small, resting T cell fractions on Percoll-gradients and then incubated with anti-CD3 antibody, the enhancement of Fc alpha R+ T cells was only noted in the latter cell population.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Microscope sterility system.

The problem of microscope sterility during ophthalmic microsurgery has generally been managed by using sterilizable handle protectors, or by using some form of plastic sterilizable drape for the entire microscope. Both of these systems have disadvantages. A simple and effective alternative which has been designed for Zeiss operating microscopes and can be modified for other types of instruments is presented. No modification of the microscope is required. The instrument consists of two pieces: a metal bracket which mounts in the accessory shoe of the operating microscope, and a rigid plastic sterilizable portion which is readily attached on the microscope from below with three sterilizable screws. The entire assembly can be attached within 15 seconds. It affords complete sterility protection of the operative field; it provides a sterile surface for handling and moving the microscope; it does not interfere with accessory lighting systerms; and it allows open access to external accessories such as cameras and observer tubes.

Methods↗