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Biomedical subjects

C M Baum

Publications and source records attributed to C M Baum.

At least 19 recordsLinked to original sources

CD34+ progenitor cells from asymptomatic patients are not a major reservoir for human immunodeficiency virus-1.

Controversy exists as to whether hematopoietic progenitor cells are infected by human immunodeficiency virus-1 (HIV-1) in vivo. Most studies have focused on patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex, and little data are available on asymptomatic patients with well preserved CD4+ T-cell counts. To determine if CD34+ hematopoietic progenitor cells are infected early in the course of HIV-1 disease, we evaluated 10 asymptomatic HIV-1 seropositive (HIV-1+) patients. The CD34+ cell fraction was purified by a two-step procedure consisting of both affinity chromatography and fluorescence-activated cell sorting that resulted in a median purity of over 99%. Using conventional and nested polymerase chain reaction (PCR) assays, we evaluated the presence and frequency of HIV-1 proviral DNA. Both bone marrow mononuclear cells and CD34- cells from all 10 patients were strongly positive for the HIV-1 pol and/or gag gene sequences. In contrast, sorted CD34+ cells from only two of 10 patients were positive, and the number of copies of proviral DNA in these samples was estimated to be from 2 to 5 per 250,000 cells. To test the in vitro functional capacity of CD34+ progenitors, these cells were assayed in both methylcellulose and long-term stromal culture. We found no significant reduction in the number of colony-forming unit-erythroid (CFU-E), burst-forming unit-erythroid (BFU-E), or colony-forming unit-granulocyte macrophage (CFU-GM) colonies, or in the frequency of cobblestone area forming cells from limit dilution analysis in HIV-1+ asymptomatic patients. Pooled methylcellulose colonies generated from CD34+ cells were HIV-1- in nine of 10 samples. All progeny from long-term cultures of CD34+ cells were HIV-1-. We conclude that the CD34+ hematopoietic progenitor compartment is not infected in the majority of asymptomatic HIV-1+ patients, and that these cells may represent a suitable target for strategies designed to protect developing CD4+ T cells from infection.

Adult

Potent interleukin 3 receptor agonist with selectively enhanced hematopoietic activity relative to recombinant human interleukin 3.

A systematic evaluation of structure-activity information led to the construction of genetically engineered interleukin 3 (IL-3) receptor agonists (synthokines) with enhanced hematopoietic potency. SC-55494, the most extensively characterized member of this series, exhibits 10- to 20-fold greater biological activity than recombinant human IL-3 (rhIL-3) in human hematopoietic cell proliferation and marrow colony-forming-unit assays. In contrast, SC-55494 is only twice as active as rhIL-3 in priming the synthesis of inflammatory mediators such as leukotriene C4 and triggering the release of histamine from peripheral blood leukocytes. The enhanced hematopoietic activity of SC-55494 correlates with a 60-fold increase in IL-3 alpha-subunit binding affinity and a 20-fold greater affinity for binding to alpha/beta receptor complexes on intact cells relative to rhIL-3. SC-55494 demonstrates a 5- to 10-fold enhanced hematopoietic response relative to its ability to activate the priming and release of inflammatory mediators. Therefore, SC-55494 may ameliorate the myeloablation of cancer therapeutic regimens while minimizing dose-limiting inflammatory side effects.

Amino Acid Sequence

Detecting cumulative trauma disorders in workers performing repetitive tasks.

On-site testing of 157 poultry processors disclosed that 50% had three or more abnormal upper extremity findings out of a total of 22 possibles. The average worker had five to six abnormal findings. Impaired pinch strength, decreased vibration sensitivity in the fingertips, and reports of current numbness were the most prevalent. Of workers with signs, 25% reported no symptoms, whereas only 8% of workers reported symptoms but had no signs. The investigators concluded that this measurement method has utility for assessments of worker populations to determine prevalence of CTDs and, potentially, for preclinical detection of these disorders to permit early intervention, reduce medical costs, and minimize disability. The need for accurate measurement to enhance early detection and prevention is discussed.

Adult

Isolation of a candidate human hematopoietic stem-cell population.

We have identified a rare (0.05-0.1%) subset of human fetal bone marrow cells that contains multipotent hematopoietic precursors. The population of human precursor cells that express Thy-1 and CD34 but no known lineage markers is enriched for clonogenic activity that establishes long-term, multilineage (myelomonocytic and B lymphoid) cultures on mouse marrow stromal lines. Further, the Thy-1+CD34+ subset that takes up little of the fluorescent mitochondrial dye rhodamine 123 contains virtually all the cells that establish long-term cultures. In human fetal thymus transplanted into SCID (severe combined immunodeficiency) mice, Thy-1+CD34+ fetal bone marrow cells differentiate into T lymphocytes. In two of nine cases, allogeneic Thy-1+CD34+ cells could engraft intact human fetal bone marrow grown in SCID mice, resulting in donor-derived myeloid and B cells. By extrapolation, the rare human Thy-1+Lin-CD34+ cell population contains pluripotent hematopoietic progenitors; we propose that it is highly enriched for candidate hematopoietic stem cells.

Animals

Implantation and maintenance of functional human bone marrow in SCID-hu mice.

Human fetal bone fragments implanted in the immunodeficient C.B-17 scid/scid (SCID) mouse were shown to sustain active human hematopoiesis in vivo. Human progenitor cell activity was maintained for as long as 20 weeks after implantation and was associated with multilineage differentiation in the engrafted bone. Thus, the bone implants provided stem cells as well as the microenvironment requisite for their long-term maintenance and multilineage differentiation. Administration of human erythropoietin (Epo) stimulated human erythropoiesis in human bone implants. This animal model may facilitate direct analysis of a wide variety of physiologic and pathologic conditions of human bone marrow (BM) in vivo.

Animals

Monoclonal antibodies specific for novel murine cell surface markers define subpopulations of germinal center cells.

A panel of mAbs has been generated which selectively, but not exclusively, recognizes populations of cells within germinal centers of immunized mice. All four mAbs stain B cell populations as defined by flow cytometry. The mAbs FH9.5 and C3.5 also stain T cell subsets (CD4+ and CD8+, respectively). Following density gradient centrifugation of spleen cells from immunized mice the majority of FH9.5+ and C3.5+ B cells are found in the low density, activated fractions. The cells bearing the epitope(s) recognized by the C6C3 and the A6A2 mAbs are less frequent, and from flow cytometric analysis the cells stained with these mAbs are B cells and myeloid cells. The surface markers defined by the four mAbs are not induced following mitogen stimulation of small resting B cells suggesting that these molecules are not general activation markers. Cell lines from a variety of hematopoietic lineages expressing the four markers have been identified. The cell surface molecule immunoprecipitated by the FH9.5 mAb is a polypeptide of 23-28 kDa. The C3.5 antigen is an 85- to 95-kDa protein. These mAbs will be useful in elucidating the complex events involved in B cell differentiation and maturation which occur within germinal centers.

Animals

Addressing the needs of the cognitively impaired elderly from a family policy perspective.

Management of the cognitively impaired elderly person in the community is presumed to be cost-efficient and the American way. Although this is what should be done, most would agree that paying for the services that make it possible to do so is not currently within the means of the median income of the family ($25,986) or of the female head of household ($15,350) in this country. This paper reviews the changes in the family, current family policies, and practices of our businesses and government and proposes the services that could be used to support both the impaired person and the family in the management of this evolving societal issue. Strategies for development of payment mechanisms for the proposed services are presented.

Aged

Certification: serving the public interest.

The certification program has undergone an exciting change. The AOTA leadership and AOTA members are to be applauded for making this important step. The AOTCB is still a fledgling organization; nonetheless, it has already made great strides in carrying out its mission. The AOTCB will continue to build on the very excellent foundation AOTA has laid for the certification program. The AOTCB welcomes questions, comments, and suggestions concerning the certification program. To contact AOTCB, write to AOTCB, 1383 Piccard Drive, Rockville, MD 20850-4375 or call (301) 948-9626.

Certification

Study of the DBA/2Ha immunodeficiency: X-chromosome mosaicism and in vivo immunoresponses.

DBA/2Ha mice have an X-chromosome-linked immunodeficiency and lack the receptor to a TRF (T cell replacing factor) on a subpopulation of B cells. Their immunodeficiency is considered to resemble that of CBA/N, another X-chromosome-linked immunodeficiency. To facilitate direct comparisons of the two immunodeficiencies and to study the in vivo manifestations of DBA/2Ha immunodeficiency, we measured phenotypes and functions of B cells of DBA/2Ha mice. We found that the expression of sIgM among B cells is normal in DBA/2Ha mice, heterozygous females equally express both affected and normal B cell subpopulations, and DBA/2Ha mice respond well to a TI-2 antigen (TNP-Ficoll) and a polyclonal activator (LPS). Unlike CBA/N, DBA/2Ha mice demonstrate very little in vivo immunodeficiencies.

Animals

Polymorphism of Fc receptor on murine B cells is Igh-linked.

Analysis of mouse IgG binding to Fc receptors on mouse B cells indicates that the IgG1, IgG2a, and IgGb subclasses bind to the same receptor. No differences in affinity were detected among subclass or between mouse strains. This same receptor bound rat IgG with an affinity that differed between mouse strains. This polymorphism in affinity for rat IgG maps to chromosome 12 distal to the Igh locus.

Animals

Growth, renewal, and challenge: an important era for occupational therapy.

Occupational therapy is facing some important decisions as it approaches a changing health care system. By understanding the prospective payment system it is possible to promote occupational therapy services to a changing marketplace while avoiding major problems. Specific opportunities and strategies are defined to promote occupational therapy to new markets.

Delivery of Health Care

B-cell subsets: functional and structural characteristics.

The review will examine B-cell differentiation with an emphasis on B-cell subpopulations. We will begin with an analysis of current evidence concerning B-cell ontogeny. The development of the B-cell repertoire will be traced from stem cell to effector cells. The CBA/N mouse, which expresses an X-linked immunodeficiency, will serve as a basis for discussing the delineation of B cells into subpopulations. The CBA/N mouse provides evidence for distinct populations of B cells which can be differentiated by cell surface antigens as well as function. We intend to focus on the functional diversity of B-cell subpopulations and how they develop. The CBA/N mouse is not the only evidence for distinct B cell subpopulations and we will attempt to organize these data into a coherent story of B-cell subsets.

Animals

Initiating occupational therapy clinical research.

The purpose of research is to give us indications of what the effectiveness of particular treatments are on groups of people. The similarities between what we accept as a standard of education and practice and what we conceive to be research are striking. In both cases, these are disciplined methods of collecting and analyzing data, and acting upon the results of it. Those of us with clinical populations have unanswered questions and thus, good reasons for conducting research. The professional who wants answers must be willing to work for them knowing that the rewards and personal satisfaction will be great. Hopefully, the membership will recognize the importance of providing support to research and will be generous in their contribution to the American Occupational Therapy Foundation. The AOTF provides the necessary seed money to answer the questions that we are all facing.

Foundations

Deregulation.

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Health Planning