Biomedical subjects

C Rosse

Publications and source records attributed to C Rosse.

At least 37 records · Page 2Linked to original sources

PubMed1997

The digital anatomist information system and its use in the generation and delivery of Web-based anatomy atlases.

Advances in network and imaging technology, coupled with the availability of 3-D datasets such as the Visible Human, provide a unique opportunity for developing information systems in anatomy that can deliver relevant knowledge directly to the clinician, researcher or educator. A software framework is described for developing such a system within a distributed architecture that includes spatial and symbolic anatomy information resources, Web and custom servers, and authoring and end-user client programs. The authoring tools have been used to create 3-D atlases of the brain, knee and thorax that are used both locally and throughout the world. For the one and a half year period from June 1995-January 1997, the on-line atlases were accessed by over 33,000 sites from 94 countries, with an average of over 4000 "hits" per day, and 25,000 hits per day during peak exam periods. The atlases have been linked to by over 500 sites, and have received at least six unsolicited awards by outside rating institutions. The flexibility of the software framework has allowed the information system to evolve with advances in technology and representation methods. Possible new features include knowledge-based image retrieval and tutoring, dynamic generation of 3-D scenes, and eventually, real-time virtual reality navigation through the body. Such features, when coupled with other on-line biomedical information resources, should lead to interesting new ways for managing and accessing structural information in medicine.

Anatomy↗

PubMed1996

Visualization and mapping of neurosurgical functional brain data onto a 3-D MR-based model of the brain surface.

The Human Brain Project was initiated with the goal of developing methods for managing and sharing information about the brain. As a prototype Human Brain Project application we are developing a system for organizing, visualizing, integrating and sharing information about human language function. The goal of the brain mapping component of our work, described in this article, is to generate the 3D location and extent of cortical language sites with respect to a uniform, 3D patient coordinate system. The language sites of individual patients can then be combined with or related to other patient data in terms of a Talairach, surface-based, or other deformable coordinate systems. Language site mapping is done by visually comparing an intraoperative photograph with the rendered image (from MRI data). The techniques outlined in this article have been utilized to map cortical language sites of six patients. Preliminary results point to the adequacy of our volume visualizations for language mapping. The strength of the visualization scheme lies in the combination of interactive segmentation with volume and surface visualization. We are now in the process of acquiring more patient data to further validate the usefulness of our method.

Brain Mapping↗

PubMed1995

The potential of computerized representations of anatomy in the training of health care providers.

The purpose of anatomy education is to develop the skills for anatomical reasoning, which is a requirement for performing a number of clinical tasks. Anatomical reasoning integrates an understanding of the three-dimensional (3-D) geometry of the body and its parts (the spatial domain of anatomical information) with an understanding of functional, developmental, pathological, and other relationships among anatomic entities (the symbolic domain of anatomical information). Traditional methods in anatomy have substantial shortcomings for representing and integrating these two information domains. Computer-based methods of knowledge representation have a great potential for overcoming the shortcomings and for promoting anatomical reasoning. To realize this potential, there is a need for (1) establishing 3-D electronic atlases of the human body; (2) generating models of symbolic anatomical information, and (3) developing computer programs (user interfaces) that integrate these knowledge sources and serve the needs of trainees and practitioners in different fields of the health sciences. The Digital Anatomist Program at the University of Washington has begun to build such a client-server framework for anatomical information, and its application for biomedical education is being evaluated.

Anatomy↗

PubMed1995

Web-based access to an online atlas of anatomy: the Digital Anatomist Common Gateway Interface.

A World Wide Web Common Gateway Interface package is described for accessing existing online interactive atlases of anatomy. The Web interface accesses the same 2-D and 3-D images of human neuroanatomy, knee anatomy and thoracic viscera that are currently accessed by a custom interactive atlas in distance learning courses. Although the Web interface is too slow to replace the existing atlas, it provides a parallel access path that has much broader potential for development of a distributed distance learning network in anatomy. By maintaining both access methods to the same information sources we continue to satisfy the fast interactivity needs for our local courses, while at the same time providing a migration path to the Web as the capabilities of Web browsers evolve.

Anatomy, Artistic↗

PubMed1995

Enhancements of anatomical information in UMLS knowledge sources.

Although anatomical terminology forms a part of biomedical structured vocabularies, available sources lack the requisite granularity, semantic types and relationships for comprehensively and consistently representing anatomical concepts in machine readable form. Thoracic angiology was selected as a proof of concept experiment for in depth representation of symbolic information in gross anatomy through the enhancement of semantic types, concepts and relationships in UMLS. Provided the representation of concepts is comprehensive, hierarchies generated with four types of simple relationships are capable of displaying anatomical information from the systemic view point with sufficient detail to meet the needs of applications in basic science education and in the practice of surgical subspecialties.

Anatomy↗

PubMed1993

In vivo and in vitro suppression of primary B lymphocytopoiesis by tumor-derived and recombinant granulocyte colony-stimulating factor.

Transplantation of a granulocytosis-inducing murine CE mammary carcinoma into mice suppresses primary B lymphopoiesis in the marrow. The mechanisms of this tumor-induced B-cell suppression were investigated using Whitlock-Witte-type lymphoid cultures. When seeded with normal marrow progenitors, stromal cells of tumor-bearing mice supported the production of B220+ cells as well as did either stomal cells derived from control mice or the stromal cell line S17. Cultured over normal stroma, marrow cells of tumor-bearing mice depleted of adherent cells and B220+ cells generated B220+ cells as effectively as a similar cell population from control mice. However, interleukin-7-responsive progenitors, were completely depleted from the marrow of tumor-bearing mice. When conditioned medium (CM) of cloned CE tumor cells known to produce granulocyte colony-stimulating factor (G-CSF) and macrophage-CSF, or recombinant murine G-CSF was added to the cultures established with S17 cells, B220+ cell production was significantly diminished. Antiserum to murine G-CSF blocked these effects. These in vitro observations were corroborated by the elimination of marrow B220+ cells in mice injected with G-CSF. These in vitro and in vivo studies suggest that G-CSF plays an inhibitory role in primary B lymphopoiesis by blocking stromal cell-mediated differentiation of early B-cell progenitors into phenotypically recognizable B220+ pre-B cells.

Animals↗

PubMed1992

Production and differentiation of NK lineage cells in long-term bone marrow cultures in the absence of exogenous growth factors.

Neither lytic NK cells nor IL-2-responsive NK precursors were produced in myeloid (Dexter) long-term bone marrow cultures (LTBMC). However, when myeloid LTBMC were switched to lymphoid (Whitlock-Witte) conditions and reseeded ("recharged") with fresh bone marrow cells (BMC), nonadherent cells with NK lytic activity and NK 1.1+ phenotype were produced within 1-2 weeks without the addition of exogenous IL-2 to the cultures. NK- and T cell-depleted BMC proliferated extensively in switched cultures and in 2 weeks generated cells that lysed the NK target YAC-1 but not the LAK target P815. The presence of NK precursors in the cultures was confirmed by reculturing nonadherent cells harvested from recharged LTBMC in fresh medium containing 50 U rIL-2/ml. High levels of NK lytic activity were generated. Sequential expression of NK 1.1 and IL-2 responsiveness followed by lytic activity was demonstrated by harvesting cells early after recharge, prior to the appearance of lytic cells. Elimination of NK 1.1+ cells depleted the ability to respond to IL-2 in secondary culture. Our studies demonstrate that myeloid-to-lymphoid switched LTBMC support the proliferation and differentiation of NK lineage cells from their NK 1.1-, nonlytic progenitors in the absence of an exogenous source of growth factors.

Animals↗

PubMed1991

The role of hematogenous and intrinsic precursor cells in lymphocyte production in murine bone marrow and thymus.

It is well recognized that the bone marrow contains cells that can repopulate a depleted thymus as well as cells that can be induced to express phenotypic markers characteristic of T cells. It is not known, however, to what extent thymocytopoiesis in the normal thymus relies on immigrant, bone marrow-derived cells, nor whether some T cell precursors have entered the bone marrow from the circulation. We used the parabiotic system to test whether thymocytopoiesis relies on progenitors intrinsic to the thymus or on cells that enter the organ from the circulation. In the same system, we have also investigated whether Thy-1- bone marrow lymphocytes that respond to phytohemagglutinin (PHA) by proliferation and Thy-1 expression are produced by myelogenous or hematogenous progenitors. Syngeneic CBA/HT6 and CBA/CaJ mice were joined in parabiotic union at 4-6 weeks of age. Cross circulation between the two partners was verified by the equilibration of Evans' blue dye injected into one partner and by the equilibration of PHA-responsive T cells in the spleen of the parabionts. Chromosome spreads were prepared from the PHA-stimulated T cell-depleted bone marrow and from spontaneously proliferating thymocytes as well as from thymocytes stimulated by PHA or Concanavalin A (Con A). The exchange of spleen colony-forming units (CFU-S) in the femoral marrow was assessed by karyotyping individual spleen colonies. Regardless of the length of parabiotic union, ranging from 4 to 20 weeks, Thy-1-, PHA-responsive bond marrow lymphocytes remained predominantly of the host type with only 3% being derived from the opposite partner.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Altered lymphocyte populations in sphha/sphha mice with chronic hemolytic anemia.

Lymphocyte kinetics and phenotype were examined in mutant anemic sphha/sphha mice that manifest a lifelong lymphocytosis which accompanies their chronic hemolytic anemia. Anemic mice have significant increases in CD4+, CD8+, and sIgM+ lymphocytes in peripheral blood. Pulse and continuous infusion studies with [3H]TdR suggest that this apparent lymphoid expansion is not due to increased production of lymphocytes in bone marrow or thymus but rather to a redistribution of lymphocytes from the spleen to other peripheral lymphoid tissue sites as well as increased proliferation of T and B lymphocytes in lymph nodes. This murine model could be useful to examine lymphocyte perturbations that may accompany chronic hemolytic anemia in humans.

Anemia, Hemolytic, Congenital↗

PubMed1989

Modulation of murine natural killer cells by a granulocytosis-inducing tumor.

The nonmetastatic neutrophilia-inducing murine mammary carcinoma CE1460 has been shown previously to have profound effects on hemopoiesis and lymphopoiesis. In this report we examined the effects of progressive growth of CE1460 on natural killer (NK) cell activity both in the bone marrow, the site of primary NK cell production, and in a peripheral site, the spleen. (BALB/c x CE)F1 mice were injected subcutaneously with trypsinized cells from in vivo passaged CE1460 or from B66, a BALB/c mammary carcinoma that does not induce neutrophilia. 3 days posttumor implantation, NK activity in bone marrow cells or spleen cells was greatly enhanced compared to normal controls. In B66 tumor-bearing mice, NK activity returned to normal by Day 7 and remained there through Day 14. In contrast, however, NK activity in CE1460 tumor-bearing mice decreased to only 10-20% of normal by Day 14. Excision of the tumor on Day 14, when WBC counts were three times normal, was followed by a rapid return of the WBC count to the normal range. NK activity in bone marrow and in spleen cells recovered somewhat but was still significantly suppressed 7 days after tumor excision. Limiting dilution analysis revealed a 3-5-fold decrease in frequency of NK precursors in bone marrow cells of mice bearing CE1460 for 7 or 14 days. The dramatic changes in NK activity observed in these experiments may reflect perturbation in production as well as an initial activation and subsequent suppression of mature NK cells.

Animals↗

PubMed1987

The primary role of murine bone marrow in the production of natural killer cells. A cytokinetic study.

The normal steady state production of natural killer (NK) cells in the bone marrow and spleen was characterized with cytokinetic technics. We developed a protocol to enrich for NK cells in bone marrow and demonstrate that target binding can be used as a criterion for marrow NK cells if nonspecifically "sticky" cells are eliminated. The selected population of B cell-depleted bone marrow lymphoid cells was comprised mainly of lymphocytes, of which 80% were NK-1.1+. B cell-depleted bone marrow lymphocytes that bound to YAC-1 could be characterized as two populations on the basis of morphology and proliferative status: large, proliferating target-binding cells (TBC), of which 25% were in S phase of the mitotic cycle, and small postmitotic TBC. Pulse and chase studies indicated that the small TBC in bone marrow were derived from an immediate proliferating precursor, presumably the large TBC, which were, in turn, derived from a precursor population that was more rapidly proliferating. In contrast, few if any splenic TBC were labeled after a 30-min pulse with [3H]TdR and significant numbers of labeled TBC did not appear in the spleen until 2 or more days after the pulse label. Surprisingly, some of the splenic TBC were relatively long lived and survived 2 mo or longer. These studies are the first to directly characterize the production of NK cells in situ in normal marrow. We demonstrate that the marrow is the primary site of production of NK cells and that little, if any, proliferation of NK cells occurs in the periphery of unstimulated mice. The data suggest the existence in the bone marrow of at least three compartments in the NK lineage: a rapidly proliferating NK precursor population, a less rapidly proliferating population of large TBC, and a population of small postmitotic TBC.

Animals↗

PubMed1985

Effects of the motheaten gene on murine B-cell production.

The rapidly fatal autoimmune disease in the mutant mouse known as motheaten is caused by an autosomal recessive gene and is characterized by hypergammaglobulinemia and autoantibody production, among other defects. The cellular kinetics of B-cell maturation were investigated in three-week-old motheaten mice and their normal littermates to determine whether any abnormality in cell production of the B lineage could be correlated with B-cell hyperactivity. The production rates and renewal times of newly produced bone marrow, splenic small B-lymphocytes, and splenic plasma cells were examined by in vivo tritiated-thymidine administration using a pulse-chase protocol and radioautography of immunofluorescence-stained cells. Because small B-lymphocytes in both organs were produced at comparable rates in the mutant mice and in their normal littermates, primary B-cell production was unaffected in the mutant mice. In contrast, splenic plasma cells were produced 10-30 times faster in motheaten mice than in normal mice. The enhanced rate of plasma cell production in motheaten mice could be correlated with a concurrent increased loss of labeled large B-lymphocytes, presumably rapidly dividing activated B cells. Thus, the excessive antibody production in motheaten mice may be reflected by the increased plasma cell production.

Animals↗

PubMed1985

A granulocytosis-inducing tumor inhibits the production of B lymphocytes in murine bone marrow.

Mice bearing a transplantable CE mammary carcinoma have been shown to have greatly augmented rates of neutrophil production coupled with a marked diminution of bone marrow lymphocytes. The objective of the present study was to test whether the loss of lymphocytes, and especially of B cells, from the bone marrow and spleen of tumor-bearing animals was due to a reduced rate of cell production and if so, at what level this response was regulated. A modified 3H-TdR pulse and chase analysis was used to assess the rates of production of small lymphocytes and B cells (stained for c mu and s mu) at weekly intervals after CE tumor transplantation. 3H-TdR was infused continuously for 24 hr, and radioautographs were prepared of bone marrow and spleen cells 0, 24, and 48 hr after termination of the infusion. Pre-B cells (c mu+s mu-) essentially disappeared from the femoral bone marrow by the end of 1 wk of tumor growth, followed by a great reduction in the number of c mu+s mu+ cells in the marrow and s mu + cells in the spleen. Although pre-B cells appeared in the peripheral marrow (caudal vertebrae, metatarsal bones) and spleen of tumor-bearing mice, these cells could not compensate for the continued decrease in the numbers of more mature B cells. In normal mice, during the 48-hr chase period, newly formed, 3H-TdR-labeled, small lymphocytes and s mu+ cells continued to emerge from the prelabeled precursor compartment at a steady rate, but after 1 wk of tumor growth, the number of small lymphocytes and s mu+ cells emerging from the precursor compartment fell steadily during the 48-hr chase period. During the second and third weeks of tumor growth, a steady state appears to have been reached in B cell production, which was at a level approximately 10 times below that of normal. Because pre-B cells are normally maintained by a less mature precursor population (2), the initial disappearance of c mu+s mu- cells suggests that the CE mammary carcinoma exerts its modulatory influence on primary B cell production by inhibiting or eliminating the cells that eventually feed into the pre-B compartment. The nature of the regulatory factors apparently secreted by the tumor and the more precise identity of the target cells are under investigation.

Adenocarcinoma↗

PubMed1985

Induction of granulocytic hyperplasia, thymic atrophy, and hypercalcemia by a selected subpopulation of a murine mammary adenocarcinoma.

Three tumor cell subpopulation lines derived from a single, spontaneously occurring BALB/cfC3H mammary tumor were evaluated for their ability to cause a leukemoid effect in mice. One of the BALB/cfC3H tumor cell lines (410.4) produced leukocytosis with neutrophilia, hypercalcemia, and thymic atrophy. A second line (66) produced none of these effects. The third line (168) was intermediate in its ability to affect neutrophil counts and splenomegaly but did not produce thymic atrophy or hypercalcemia. These studies demonstrated that the hemopoietic effect of tumor cells derived from a single tumor was variable and that a tumor cell line which caused neutrophilia also induced hypercalcemia and thymic atrophy, the same association that was reported previously in the case of murine CE mammary carcinoma. These observations will be useful in the further investigation of pathophysiology of tumor-induced leukemoid reactions, hypercalcemia, and other paraneoplastic syndromes.

Adenocarcinoma↗

PubMed1982

Distribution and identity of the earliest proliferating progeny of colony-forming cells in regenerating murine spleen and bone marrow.

A study was made of the sites of development and the types of cells found in very early hemopoietic colonies in the mouse spleen. Two, 3, and 4 days after transplantation, the proliferating descendants of transplanted bone-marrow cells were identified on radioautographs of spleen sections and on spleen and bone-marrow smears of supralethally irradiated recipient mice which were injected with 3H-TdR at 12, 6, and 0.5 hours before sacrifice. Surprisingly the spleens of nontransplanted, irradiated mice contained proliferating medium and large lymphocytes in the white pulp which increased in numbers during the observation period. The early descendants of transplanted cells that lodged in the spleen could be clearly distinguished from the labeled indigenous cells because they formed discrete nodules or colonies beneath the splenic capsule or in the vicinity of venules and trabeculae of the red pulp. These cells were identifiable on day 2 as transitional cells or unknown hemopoietic blasts and on day 4 included early erythroid cells and small lymphocytes. There was evidence for the traffic of 3H-TdR-labeled cells through the splenic sinusoids.

Animals↗

PubMed1982

Physical, biologic, and phenotypic properties of natural regulatory cells in murine bone marrow.

A lymphocyte-enriched fraction of murine bone marrow (BML) contains natural regulatory cells (NRC) that can inhibit, on a dose-dependent basis, proliferative and cytotoxic responses to alloantigens in a mixed lymphocyte culture. The objective of this study was to investigate the characteristics of the cells responsible for this phenomenon in CBA mice. Maximal suppression was obtained with BML cells themselves rather than cell products. Light-scatter analysis of NRC on the fluorescence-activated cell sorter demonstrated them to be larger than small lymphocytes, and their sedimentation in discontinuous Percoll gradients showed the cells to be of heterogeneous density. This heterogeneity is further reflected by the fact that both plastic adherent and nonadherent BML are suppressive. NRC must be viable in order to mediate suppression; they are cortisone-resistant and are not affected by doses of gamma irradiation up to 1,000 R. NRC are not T or B lymphocytes or Ia-bearing macrophages. The involvement of mature granulocytes and macrophages in natural suppression is unlikely in that NRC do not bear Fc receptors. Elimination of cells from BML with the natural killer (NK) surface marker Asialo GM1 does not abrogate suppression. NRC are capable of mediating suppression across major and minor histocompatibility complex barriers. While lymphoid cells are prominent in BML, the contamination of this marrow fraction with immature granulocytes and monocytes makes a morphologic identification of NRC difficult. These characteristics are most consistent with NRC begin immature marrow cells of undetermined lineage. The relationship of NRC to naturally occurring marrow suppressor cells described in other systems is not yet clear and awaits experimental clarification.

Adrenal Cortex Hormones↗

PubMed1982

Abnormal in vitro proliferation of splenic mononuclear phagocytes from autoimmune motheaten mice.

Motheaten mice develop combined immunodeficiency and fatal autoimmune disease that follow autosomal recessive inheritance. In splenocyte cultures of motheaten mice, supplemented with 5% normal serum proliferating cells (MP) were present exhibiting morphologic characteristics of mononuclear phagocytes at light and electron microscopic levels. The macrophage nature of these cells was confirmed by the lack of Thy-1 antigen and immunoglobulins; the expression of Mac-1 antigen, FcR for IgG, and Ia antigens on their cell surfaces; their ability to phagocytize EA and adhere to plastic; the presence of nonspecific esterase and lysomal enzymes in their cytoplasm; and the pattern of peroxidase localization similar to monocyte-derived macrophages. MP from motheaten mice exponentially grew in culture in the absence of exogenous growth factors with a doubling time of approximately 76 hr. Although these cells were present in splenocyte cultures of normal controls, their number did not increase during the culture period under the same conditions. The addition of dextran sulfate further enhanced the proliferation of MP from motheaten mice, and induced exponential growth of these cells from normal controls, reaching only the level of unstimulated cells from motheaten mice. Radioautographic analysis demonstrated that MP substantially contributed to the elevated spontaneous and dextran sulfate-induced DNA synthesis in splenocyte cultures. Therefore, the in vitro abnormality of MP may be indicative of in vivo aberrancies of macrophages from motheaten mice and lends credence for investigating the role of macrophages in immunodeficiency and autoimmunity that develop very early in motheaten mice.

Animals↗

PubMed1982

Depletion of lymphocyte subpopulations in primary and secondary lymphoid organs of mice by a transplanted granulocytosis-inducing mammary carcinoma.

Transplanted CE mammary carcinoma causes a marked increase in the production of neutrophilic granulocytes in mice associated with the expansion of hemopoietic marrow into the peripheral skeleton. Changes in lymphocyte populations in the femoral marrow, the expanding peripheral marrow, and the spleen were examined for a period of 3 weeks post-tumor transplantation using fluoresceinated antisera specific for B- and T-cells. As tumor growth and granulocytic hyperplasia progressed, B- and T-cells became reduced in femoral marrow and the spleen, but lymphocytes of undefined function, devoid of T- and B-cell surface antigens (null cells), transiently increased in femoral marrow and in the spleen. In the expanding peripheral marrow, such null cells increased and remained as the predominant cell type until granulocytic hyperplasia took place. These changes suggest shifts in the site of myelogenous lymphocyte production or in the differentiation program of lymphocytes. The thymus invariably showed marked atrophy which, as shown in adrenalectomized animals, could not be explained entirely by tumor-induced stress. Thus, the massive granulocytopoietic effects of CE mammary carcinoma are coupled with marked changes in lymphocyte populations due, most likely, to the tumor's influence on primary lymphoid organs.

Adrenalectomy↗