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Biomedical subjects

S M Baird

Publications and source records attributed to S M Baird.

At least 19 recordsLinked to original sources
PubMed1992

Epstein-Barr virus-induced human B-cell lymphomas in SCID mice reconstituted with human peripheral blood leukocytes.

Epstein-Barr virus (EBV) infection is associated with immunoblastic B-cell lymphomas in immunosuppressed or human immunodeficiency virus-infected individuals and in SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors. The risk of tumors appearing in the hu-PBL-SCID mice differs among EBV-seropositive donors. Four different outcomes have been noted: (a) no tumors appear (no incidence donors); (b) tumors appear in a fraction of hu-PBL-SCID mice with a 10-20 week latent period (low- and intermediate-incidence donors); or (c) tumors appear in all hu-PBL-SCID mice within 6-10 weeks (high-incidence donors). The latter category of rapidly appearing tumor invariably involved activation of EBV replication, whereas more slowly growing tumors rarely activated EBV. The results indicate that prospective screening of high-risk individuals in the hu-PBL-SCID model may predict the risk of EBV-associated lymphoma development.

Animals↗
PubMed1992

Heterogeneity among Epstein-Barr virus-seropositive donors in the generation of immunoblastic B-cell lymphomas in SCID mice receiving human peripheral blood leukocyte grafts.

Epstein-Barr virus (EBV) is associated with B-cell malignancy in immunosuppressed humans and SCID mice receiving human peripheral blood leukocyte grafts (hu-PBL-SCID). We have further characterized the process of lymphoma development in hu-PBL-SCID mice. We report that EBV-seropositive donors differ markedly in the capacity of their PBL to give rise to immunoblastic lymphomas in SCID mice; some donors (high incidence) generated tumors rapidly in all hu-PBL-SCID mice, other donors (intermediate-low incidence) gave rise to sporadic tumors after a longer latent period (greater than 10 weeks), and some donors failed to produce tumors. B-cell lymphomas arising from high incidence donors were multiclonal in origin, and EBV replication was detected in all tumors. Tumors derived from intermediate-low incidence donors were monoclonal or oligoclonal and often had no evidence of viral replication. All tumors, regardless of the donor, resembled EBV-transformed lymphoblastoid cell lines in surface phenotype but differed from lymphoblastoid cell lines by having less Epstein-Barr nuclear antigen 2 and CD23 expression. The variable patterns of lymphomagenesis seen among different EBV-sero-positive donors may be explained by lower levels of specific immunity to EBV in high incidence donors, permitting activation of EBV replication and potential transformation of secondary B-cell targets. In addition, there may be differences in the transforming potential of EBV infecting different donors. The use of the hu-PBL-SCID model may help predict patients at high risk for posttransplant or acquired immunodeficiency syndrome-associated lymphomas.

Age Factors↗
PubMed1992

EBV-induced human B cell lymphomas in hu-PBL-SCID mice.

Epstein-Barr virus (EBV) infection is associated with Burkitt's lymphoma (BL) in normal individuals and immunoblastic B cell lymphomas in immunosuppressed or HIV-infected individuals. SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors also may develop spontaneous B cell lymphomas which histologically and phenotypically resemble post-transplant tumors, and are distinct from BL. These tumors always contain EBV DNA. We have noted three different reproducible outcomes depending upon the EBV-seropositive donor used for generation of hu-PBL-SCID mice: (i) no tumors appear; (ii) tumors appear in a fraction of hu-PBL-SCID mice with a 10-20 wk. latent period; or (iii) tumors appear in all hu-PBL-SCID mice within 6-10 wk. Southern blot analysis of late versus early tumors using a probe specific for the EBV terminal repeat sequences (BamNJ), which allows distinction between circular latent and linear replicating genomes, shows that late tumors do not involve active EBV replication but that early tumors do show replicating genomes. In addition, EBV genomes were monoclonal in late tumors but polyclonal in early tumors. These data suggest two mechanisms for EBV lymphomagenesis, slow outgrowth of rare latently-infected B cells, and more rapid transformation of uninfected bystander B cells by replicating virus. The latter process may be highly amenable to therapy in patients at risk for EBV-related lymphomas. In addition, prospective screening of EBV-seropositive transplant recipients in the hu-PBL-SCID model may predict the risk of post-transplant lymphoma development.

Animals↗
PubMed1992

Cardiopulmonary resuscitation during pregnancy.

Cardiopulmonary arrest during pregnancy, although relatively rare, poses a unique challenge to the obstetric nurse. Resuscitation measures attempt to restore maternal hemodynamic stability and promote fetal well-being. Prognosis is improved when those caring for such women possess the knowledge and skills necessary to implement basic and advanced resuscitation protocols. This chapter reviews significant physiologic alterations in pregnancy that have an impact on resuscitation and cardiopulmonary resuscitation (CPR) algorithms for selected pulseless rhythms. As critical care capabilities continue to develop within obstetric units, it is reasonable to predict that obstetric nurses will face this challenge with increasing frequency.

Cardiopulmonary Resuscitation↗
PubMed1991

Break for SCIDs.

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Animals↗
PubMed1991

Human immunodeficiency virus infection of human-PBL-SCID mice.

Severe combined immunodeficient (SCID) mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID mice) have inducible human immune function and may be useful as a small animal model for acquired immunodeficiency syndrome (AIDS) research. Hu-PBL-SCID mice infected with human immunodeficiency virus-1 (HIV-1) contained virus that was recoverable by culture from the peritoneal cavity, spleen, peripheral blood, and lymph nodes for up to 16 weeks after infection; viral sequences were also detected by in situ hybridization and by amplification with the polymerase chain reaction (PCR). Mice could be infected with multiple strains of HIV-1, including LAV-1/Bru, IIIB, MN, SF2, and SF13. HIV-1 infection affected the concentration of human immunoglobulin and the number of CD4+ T cells in the mice. These results support the use of the hu-PBL-SCID mouse for studies of the pathogenesis and treatment of AIDS.

Animals↗
PubMed1990

Characteristics of CD11c+CD5+ chronic B-cell leukemias and the identification of novel peripheral blood B-cell subsets with chronic lymphoid leukemia immunophenotypes.

Previous studies have indicated that chronic lymphocytic leukemias (CLL) are characterized by the coexpression of CD5 and B-cell antigens, while hairy cell leukemias (HCL) typically express CD11c+CD5- B-cell immunophenotypes. In this report we describe the features of B-cell leukemias with CD11c+CD5+ immunophenotypes and the identification of novel circulating B-cell subsets defined by the expression of CD20, CD5, and CD11c antigens. Morphologic evaluation of 14CD11c+CD5+ B-cell leukemias showed that they generally had larger cellular diameters (14 to 21 microns) and lower nuclear:cytoplasm ratios than typical small lymphocyte CLL. These cases did not exhibit the well-defined nucleoli characteristic of prolymphocytic leukemia (PLL). The presenting clinical features of CD11c+CD5+ B-cell leukemias were most consistent with CLL or PLL, and none of the evaluated cases had pancytopenia, splenomegaly, and cytoplasmic villi characteristic of HCL. Examination of normal peripheral blood (n = 6) by three-color flow cytometry identified four novel B-cell subsets with the following immunophenotypes (mean percent of total CD20+ B cells +/- SE): CD20+CD5+CD11c+ (8.0 +/- 1.6); CD20+CD5-CD11c+ (12.0 +/- 2.0); CD20+CD5+CD11c- (35.0 +/- 4.9); and CD20+CD5-CD11c- (44.0 +/- 5.0). Our findings suggest that CD11c+CD5+ B-cell leukemias with atypical morphologic features represent forms of CLL or PLL rather than HCL. In addition, we have identified novel subsets of circulating B cells defined by patterns of CD20, CD5, and CD11c expression that correspond to the immunophenotypes of chronic B-cell leukemias.

Adult↗
PubMed1989

On the SCIDs?

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Animals↗
PubMed1989

Studies of HIV infection and the development of Epstein-Barr virus-related B cell lymphomas following transfer of human lymphocytes to mice with severe combined immunodeficiency.

Mice with severe combined immunodeficiency (C.B-17 scid, hereafter SCID) accept xenografts of adult human peripheral blood leukocytes (PBL). The transplanted human PBL expand in number and survive for at least thirteen months and have been shown to reconstitute human immune function at both the T and B cell levels. Human immunoglobulin production is restored, and secondary antibody responses to antigens such as tetanus toxoid can be induced. All SCID mice reconstituted with 50 x 10(6) or more PBL from donors with evidence of exposure to Epstein-Barr virus (EBV) have developed human B cell lymphomas at 8-16 weeks after PBL engraftment, whereas mice reconstituted with PBL from EBV-seronegative donors fail to develop tumors. These tumors involve both lymphatic and non-lymphatic organs, and histologically they resemble large cell or immunoblastic lymphomas. The tumors are associated with high levels of human immunoglobulin secretion and serum electrophoresis reveals oligoclonal immunoglobulin banding patterns. Analysis of tumor DNA shows the presence of EBV genomes and oligoclonal patterns of immunoglobulin JH gene rearrangement. Taken together, these observations suggest an EBV-related proliferation of B lymphocytes leading to the rapid appearance of oligoclonal B cell malignancies following transfer of B lymphocytes from "normal" donors to SCID mice. SCID mice reconstituted with PBL from EBV-seronegative donors have been infected with the LAV-1 strain of human immunodeficiency virus (HIV-1). Virus has been recovered from most infected animals by co-culture of mouse tissue with human T lymphoblasts. Some mice with high virus titers have developed an acute wasting syndrome and depletion of human T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Thymidine kinase obliteration: creation of transgenic mice with controlled immune deficiency.

The cell-specific expression of herpes simplex virus 1 thymidine kinase (HSV-1-tk) has provided a simple and highly efficient technique to achieve conditional ablation of targeted cell types in transgenic mice. The ablation is induced by treating transgenic animals expressing HSV-1-tk with the antiherpetic drug ganciclovir. In lymphoid tissues of mice expressing HSV-1-tk from an immunoglobulin promoter, administration of ganciclovir leads to massive destruction of B- and T-cell lineages. Tissues not expressing HSV-1-tk are insensitive to drug treatment. After depletion of greater than 99% of total thymocytes, a number of progenitor cells remain that are able to repopulate all T-cell lineages within 7 days. The ability to control and direct ablation allows for creation of conditional mutant phenotypes at precise periods of development. This technique also provides a potential means to enrich stem cell populations as well as permitting the creation of animal models for particular pathological conditions.

Acyclovir↗
PubMed1989

Peripheral white blood cells and HPA axis neurohormones in major depression.

Alterations in peripheral blood leukocyte distribution in major depression, including leukocytosis, neurotrophilia and lymphopenia, have been described. To assess peripheral white blood cells and the hypothalamic-pituitary (HP) axis in drug-free patients with major depression, we measured the total white blood cell count (WBC), and percentage of lymphocytes, and the plasma levels of cortisol, adrenocorticotropic hormone (ACTH), growth hormone (GH) and prolactin (PRL). Twenty male patients with major depression had relative lymphopenia and leukocytosis when compared with 20 age, sex and racematched control subjects. Elevated Beck and Hamilton depression scores correlated with a decreased percentage of lymphocytes, in a group of all subjects combined. There was a weak tendency for elevated growth hormone to correlate with relative lymphopenia in the control subjects only. Relative lymphopenia and leukocytosis may be a part of the psychobiology of major depression.

Adrenocorticotropic Hormone↗
PubMed1988

Transfer of a functional human immune system to mice with severe combined immunodeficiency.

The pressing need for a better experimental system for AIDS research has brought into sharp focus the shortcomings of available animal models and the practical and ethical limitations of studies of immune responses and viral pathogenesis in humans. Current studies of the human immune responses are limited to relatively restrictive in vivo experiments and several in vitro systems that, although useful, allow only short-term studies and support responses to a few antigens. Neither model is particularly amenable to studies of the pathogenesis of diseases of the immune system. We report here that injection of human peripheral blood leukocytes (PBL) can result in the stable long-term reconstitution of a functional human immune system in mice with severe combined immunodeficiency (SCID). Human PBL transplanted to SCID mice increase in number and survive for at least six months; reconstituted mice show spontaneous secretion of human immunoglobulin and a specific human antibody response is induced following immunization with tetanus toxoid. All of the major cell populations present in PBL are found in the lymphoid tissue and blood of SCID recipients, although the relative proportions of B cells, T-cell subsets and monocytes/macrophages in long-term recipients differ from those found in normal PBL and, in mice transplanted with 50 x 10(6) or more PBL from Epstein-Barr virus (EBV)-seropositive donors, EBV-positive B-cell lymphomas often develop. Our results suggest that xenogeneic transplantation of human lymphoid cells into SCID mice may provide a useful model for the study of normal human immune function, the response of the immune system to pathogenic agents and early events in lymphomagensis.

Animals↗
PubMed1988

Neutrophilia and lymphopenia in major mood disorders.

Alterations in peripheral blood leukocyte distribution in major depression, including lymphopenia, neutrophilia, eosinopenia, and monocytopenia, have been described. The present study was designed to replicate these results, but with methodological improvements, including age-, sex-, and race-matched control subjects; DSM-III and Research Diagnostic Criteria diagnoses based on the Schedule for Affective Disorders and Schizophrenia interview; objective and subjective severity of depression measured quantitatively; and consideration of psychosocial stressors (DSM-III, Axis IV). We found relative lymphopenia and absolute neutrophilia and leukocytosis in depression, but did not find decreased numbers of eosinophils or monocytes. The relative lymphopenia and absolute neutrophilia were present in the subgroup of only unipolar depressed patients, but not in the bipolar, currently depressed subgroup. However, these blood cell changes were not found in a subgroup of patients who had been medication free greater than or equal to 1 month but only in the subgroup of patients using medication at the time of phlebotomy. Groups formed on the basis of psychosocial stress levels were not found to have significant significant intergroup differences in white blood cell (WBC) counts. The clinical significance of these findings needs study. While leukocytosis and neutrophilia can be found in major depression, these changes are perhaps secondary to medication use.

Adult↗
PubMed1988

A human monoclonal antibody to cytokeratin intermediate filament antigens derived from a tumor draining lymph node.

Human lymphocytes derived from a lymph node draining a primary breast adenocarcinoma were fused with the mouse myeloma P3X63Ag8.653 to generate human-mouse hybridomas secreting human monoclonal antibodies (MAbs) to tumor associated antigens (TAAs). One of the resulting human MAbs, YBB 190 (IgM) is described. Enzyme-linked immunosorbent assays (ELISA) employing membrane and cytosol fractions of human tissues demonstrated YBB 190 reactivity against cytosol but not membrane components of malignant and normal epithelial tissues. When tested by an indirect immunoperoxidase staining method against fresh frozen human tissue sections, YBB 190 reacted with malignant cells in 26 of 28 epithelial cancers and with normal epithelia in 11 different benign tissues. Preliminary western blot antigen characterization indicated that YBB 190 recognizes cytokeratin intermediate filaments, or a protein that is closely associated with cytokeratins. These data indicate that B cells with specificity for intermediate filaments are present in tumor draining lymph nodes. Our findings provide insights into the nature of potential autoimmune responses in cancer patients and suggest that improved tumor directed sensitization procedures may be required to more effectively utilize lymphocytes from tumor draining lymph nodes to generate therapeutically useful human MAbs to TAAs.

Adenocarcinoma↗
PubMed1986

Tissue distribution and serum kinetics of T101 monoclonal antibody during passive anti-cancer therapy.

We have administered fifty-six 24 hr infusions of the anti-human T-cell monoclonal antibody T101 to 10 patients with cutaneous T-cell lymphoma (CTCL) and 6 patients with chronic lymphocytic leukemia (CLL) in doses of 10, 50, 100, 150, and 500 mg. The larger doses of T101 resulted in higher, more persistent serum T101 concentrations, and CTCL patients generally developed higher serum T101 levels than CLL patients given equivalent doses. The presence of host anti-mIgG antibodies prior to infusion was associated with decreased serum concentrations of T101. Treatments that demonstrated measurable serum T101 levels were also associated with in vivo T101 binding and cytodestruction of circulating target cells. Immunofluorescence analysis of bone marrow and lymph node biopsies in CLL, and skin biopsies in CTCL, suggested that T101 had reached extravascular tumor sites. Infusion of 111In-conjugated T101 showed uptake in the liver, spleen, lymph nodes, and (in CTCL) skin infiltrates. Our data demonstrate the tissue distribution of T101 and suggest that immunoconjugates of T101 with toxins, drugs, or radioisotopes may result in better therapeutic responses.

Antibodies, Monoclonal↗
PubMed1986

Continuous infusion of T101 monoclonal antibody in chronic lymphocytic leukemia and cutaneous T-cell lymphoma.

We report results of 24-h continuous infusions of murine monoclonal antibody T101 in six patients with chronic lymphocytic leukemia (CLL), and 10 with cutaneous T-cell lymphoma (CTCL), at doses of 10, 50, 100, or 500 mg. Similar side-effects were seen in CLL and CTCL, including direct toxic effects of therapy, such as fever, sweats, and chilling, and a 30% frequency of allergic manifestations. In vivo binding of T101 to target cells in blood, skin, lymph nodes, tumor masses, and bone marrow was demonstrated. Antigenic modulation occurred rapidly in all cases, and persisted throughout the infusion period. Peak serum T101 levels for equivalent doses were somewhat higher, and persisted longer in CTCL, perhaps because of differences in the number of circulating target cells. Antimouse antibodies were demonstrated in 5 of 10 CTCL vs. 0 of 6 CLL patients. In all five cases, there was a substantial component of T101 specificity in the antimouse response. Brief objective clinical responses were observed in 4 of 10 CTCL and 2 of 6 CLL patients. Acute anti-tumor effects of T101 were substantially more dramatic in CTCL than CLL, but appeared limited by antigenic modulation and the emergence of antimouse antibodies. In view of the in vivo binding and modulation, more durable anti-tumor effects may be achievable with cytotoxic immunoconjugates of this monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1985

Glycophorin A on normal and leukemia cells detected by monoclonal antibodies, including a new monoclonal antibody reactive with glycophorins A and B.

A new hemagglutinating monoclonal antibody, MoAb31, detected glycophorins A and B in Western blots. Results with enzyme-modified erythrocytes indicated the MoAb31 determinants were sialic acid dependent, and resided on glycophorin A on the trypsin-resistant, ficin-sensitive segment, and on glycophorin B on the ficin-sensitive segment. Another new monoclonal antibody, MoAb36, detected the Wrb antigen, located on the non-glycosylated segment of glycophorin A near its insertion into the lipid bilayer. Immunofluorescent staining of normal hematopoietic and leukemia cells with these and other monoclonal antibodies to glycophorin A demonstrated glycophorin A on erythroid cells only. Cytofluorograph analysis showed the majority of cells of the erythroleukemia cell lines K562 and HEL expressed glycophorin A, as indicated by reactivity with the monoclonal glycophorin A antibodies R10, R18, 6A7 and 10F7. However, reactivity with monoclonal antibodies to glycosylated determinants (MoAb31 and R1.3) and to the non-glycosylated segment near the membrane insertion (MoAb36, and R7.1) was reduced or absent. Expression of "missing" glycophorin A antigens on K562 and HEL could not be induced using a variety of chemical and biologically active modifiers. We conclude that glycophorin A of erythroleukemia cell lines K562 and HEL differs from glycophorin A at the surface of normal, mature erythrocytes with respect to reactivity with monoclonal glycophorin A antibodies.

Animals↗