Carol Reinisch

Carol Reinisch
Tufts University | Tufts · Department of Environmental and Population Health

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95
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Publications (95)
Article
Full-text available
Transmissible cancers, in which cancer cells themselves act as an infectious agent, have been identified in Tasmanian devils, dogs, and four bivalves. We investigated a disseminated neoplasia affecting geographically distant populations of two species of mussels (Mytilus chilensis in South America and M. edulis in Europe). Sequencing alleles from f...
Article
Full-text available
Transmissible cancers, in which cancer cells themselves act as an infectious agent, have been identified in Tasmanian devils, dogs, and four bivalves. We investigated a disseminated neoplasia affecting geographically distant populations of two species of mussels (Mytilus chilensis in South America and M. edulis in Europe). Sequencing alleles from f...
Article
Most cancers arise from oncogenic changes in the genomes of somatic cells, and while the cells may migrate by metastasis, they remain within that single individual. Natural transmission of cancer cells from one individual to another has been observed in two distinct cases in mammals (Tasmanian devils1 and dogs2, 3), but these are generally consider...
Article
Outbreaks of fatal leukemia-like cancers of marine bivalves throughout the world have led to massive population loss. The cause of the disease is unknown. We recently identified a retrotransposon, Steamer, that is highly expressed and amplified to high copy number in neoplastic cells of soft-shell clams (Mya arenaria). Through analysis of Steamer i...
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Bivalve mollusks of the North Atlantic, most prominently the soft shell clam Mya arenaria, are afflicted with an epidemic transmissible disease of the circulatory system closely resembling leukemia. The disease is characterized by a dramatic expansion of blast-like cells in the hemolymph with high mitotic index. Examination of hemolymph of diseased...
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##Assembly-Data-START## Sequencing Technology :: Sanger dideoxy sequencing ##Assembly-Data-END##
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Intensive farming of potatoes in Prince Edward Island (PEI) relies on the repeated and widespread application of fertilizers and pesticides. In PEI the main potato farming areas are in close proximity and drain directly to estuaries. Runoff from high agricultural activity watersheds could impact benthic organism health in the depositional zone of d...
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Author Posting. © National Research Council Canada, 2005. This article is posted here by permission of National Research Council Canada for personal use, not for redistribution. The definitive version was published in Canadian Journal of Fisheries and Aquatic Sciences 62 (2005): 2055-2066, doi:10.1139/F05-119. Evaluating patterns of expression of p...
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Environmental contaminants pose a signifi cant risk to organisms at all stages of life. This risk is perhaps most pronounced during the early embryonic period when rapid changes are occurring during development. These images show how early embryonic exposure to a common mixture of polychlorinated biphenyls (PCBs) can lead to a decrease in neurite o...
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Polychlorinated biphenyls (PCBs) are persistent environmental contaminants that have documented neurological effects in children exposed in utero. To better define neuronally linked molecular targets during early development, zebrafish embryos were exposed to Aroclor 1254, a mixture of PCB congeners that are common environmental contaminants. Micro...
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The p53 family of transcription factors has been implicated in many vertebrate cancers. Altered p53 and p73 protein expression observed in leukemic cells of molluscs suggests that these transcription factors might be involved in invertebrate cancers as well. Here, we fully characterize the mRNA of four novel p53-like variants in the bivalve mollusc...
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Members of the hemoglobin (Hb) superfamily are present in nerve tissue of several vertebrate and invertebrate species. In vertebrates they display hexacoordinate heme iron atoms and are typically expressed at low levels (microM). Their function is still a matter of debate. In invertebrates they have a hexa- or pentacoordinate heme iron, are mostly...
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The extent to which humans and wildlife are exposed to anthropogenic challenges is an important focus of environmental research. Potential use of p53 gene family marker(s) for aquatic environmental effects monitoring is the long-term goal of this research. The p53 gene is a tumor suppressor gene that is fundamental in cell cycle control and apoptos...
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Using the surf clam embryo, we investigated the effects of the combination of bromoform, chloroform, and tetrachloroethylene, three pollutants found in high concentrations in the municipal water supply in Brick, New Jersey. Exposure produced an increase in an isoform of the regulatory subunit (RII) of cAMP-dependent protein kinase, demonstrated by...
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To understand the role of p53 gene family members during invertebrate embryonic development, we used polymerase chain reaction (PCR) to identify p63/73 homologues in the marine mollusc Spisula solidissima. Here, we report the sequences of two distinct p63/73-like homologues, both cloned from Spisula embryos. The first, Ssp63/73alpha is 2699 nucleot...
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The cell-cycle checkpoint protein p53 both directs terminal differentiation and protects embryos from DNA damage. To study invertebrate p53 during early development, we identified three differentially expressed p53 family members (p53, p97, p120) in the surf clam, Spisula solidissima. In these mollusks, p53 and p97 occur in both embryonic and adult...
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We have defined the development of the serotonergic and dopaminergic components of the central nervous system in the early Spisula solidissima (surf clam) embryo using HPLC and immunocytochemistry. HPLC analysis reveals norepinephrine, dopamine, and serotonin are present at 24 h post-fertilization. Immunocytochemistry shows that the serotonergic ne...
Article
In coastal locations, marine invertebrates, primarily molluscs, develop fatal leukemias in their blood or hemolymph. In the clam Mya arenaria, non-adhesive, mitotic, spherical leukemia cells replace adhesive, motile, normal hemocytes as leukemia progresses. End-stage leukemia cells express a unique antigen, IE10, while normal cells express the 2A4...
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Homologues for human p53 (Hsp53) and p73 (Hsp73) genes were cloned and expression patterns for their corresponding proteins analysed in tissues from normal and leukemic softshell clams (Mya arenaria). These are the first structural and functional data for p53 and p73 cDNAs and gene products in a naturally occurring, non-mammalian disease model. Cor...
Article
Polychlorinated biphenyls (PCBs) are ubiquitous environmental pollutants that accumulate to toxic levels in the food chain. Using Spisula solidissima (surf clam) embryos as a developmental model, it was shown that Aroclor 1254 specifically targets two neuronal structures during embryonic development. Embryos were exposed to 1, 10), or 100 ppm Arocl...
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Full-text available
Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that exert neurotoxic effects during embryonic development. The present study demonstrates that early embryonic exposure to a mixture of PCBs (Aroclor 1254) results in a decrease in serotonergic cell growth. Using a novel, marine invertebrate embryo model, Spisula solidissim...
Article
Hemocytic neoplasia (HN) develops in soft shell clams (Mya arenaria L.) in coastal locations throughout the world. However, the prevalence of this neoplasm is higher than background levels when clams are collected from a polychlorinated biphenyl (PCB)-contaminated site, New Bedford Harbor (NBH), MA. Immunohistochemistry was used to examine the rela...
Article
Leukemia in the soft-shell clam, Mya arenaria, is characterized by tumor cells which are detected initially in the hemolymph. This disease is much more common in clams inhabiting polluted waters, suggesting an environmental component to its pathogenesis. In this study, leukemia cells were identified using a murine monoclonal antibody, 1E10, which r...
Article
Leukemia of the soft shell clam, Mya arenaria, is characterized by circulating tumor cells detected initially in the hemolymph and, as the disease progresses, in solid tissue. Because they are estuarine filter-feeders, clams are exposed to a wide variety of environmental pollutants. Genotoxic pollutants may react directly in vivo with DNA. Genotoxi...
Article
Bivalve molluscs such as the soft shell clam (Mya arenaria) develop leukemias in the hemolymph which are fatal. The prevalence of leukemia in Mya was evaluated using a murine monoclonal antibody which recognizes a leukemia-specific protein expressed by tumor cells. The reactivity with a polyclonal antibody to polychlorinated biphenyls (PCBs) of bot...
Article
The ontogeny of circulating hemocytes and tumor cells in mollusks has been approached using monoclonal antibodies to normal cells. A monoclonal antibody, previously shown to identify an adhesion related protein (p130), has been used to define the reactivity of cells in tissues from normal soft-shell clams (Mya arenaria) and soft-shell clams with le...
Article
Molluscs have circulating cells in the hemolymph which are both adherent and phagocytic. Mya arenaria, the soft-shell clam, is particularly interesting because it develops a leukemia detected first in the hemolymph and, as the disease progresses, in solid tissue. We have previously described a leukemia-specific protein (Miosky et al., 1989) identif...
Article
MRL/1pr mice demonstrate anatomic specificity in their development of vasculitis including the small- and medium-sized muscular arteries of the mesentery. To define the functional role of endothelium in vasculitis, we have cloned endothelial cells derived from inflamed small- and medium-sized arteries. Primary cells were derived by enzymatic disper...
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The pathogenesis of autoimmune vasculitis is poorly understood. Understanding the immunologic mechanisms governing this disease requires precise identification of the cells which comprise the lesion. In this report, we have evaluated tissue sections from MRL/lpr mice from 16 to 45 weeks of age, representing all stages of clinical vasculitis. We dem...
Article
Vascular smooth muscle cells were cultured from the mesenteric arteries of MRL lpr/lpr, MRL +/+, CBA/J, or C3H/HeJ mice and evaluated for their ability to synthesize a range of cytokines. Vascular smooth muscle cells of MRL +/+, MRL lpr/lpr, and CBA/J origin released biologically significant amounts of CSF-1 and IL-6 and relatively low but detectab...
Article
A field survey of hematopoietic neoplasia (Hn) in the soft shell clamMya arenaria (L.) was undertaken using an immunoperoxidase diagnostic technique. Monthly collections ofM. arenaria were made at two sites: Little Buttermilk Bay and New Bedford Harbor, both in Buzzards Bay, Massachusetts, USA, from May 1986 to October 1987. Clams were diagnosed fo...
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Four sites in Dorchester Bay, Boston Harbor were selected to gather baseline data on the prevalence of leukemia in soft-shell clams. Mya arenaria. Prevalence studies were conducted from September 1986 to December 1987 using two techniques to evaluate hemolymph: (1) Indirect immunoperoxidase (IP) staining using monoclonal antibodies specific for leu...
Article
Identifying the evolutionary origin of inducible, specific immune recognition represents a major objective in developmental immunology. In order to address this issue from an overall phylogenetic perspective, major studies of cellular and humoral immune function are being undertaken using lower vertebrate and invertebrate models. Here, C. Reinisch...
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The destruction of vascular smooth muscle cells (VSMC) in autoimmune arteritis is a poorly understood phenomenon. To approach this problem, VSMC cultures were established. The interaction of these cells (from normal or autoimmune mice) with lymphocytes was then evaluated. Specifically, splenocytes from MRL/1pr or C3H mice were co-cultivated with MR...
Article
A leukemic disease of the soft shell clam, Mya arenaria, has been identified along the east coast of the United States since 1977. This disease, first called hematopoietic neoplasia, is characterized by circulating tumor cells which are found in the hemolymph even before significant tissue invasion or localization of the cells can be demonstrated....
Article
Soft shell clams, Mya arenaria, develop leukemias in the hemolymph which are fatal. Tissue sections and hemolymph samples from normal and tumor-bearing clams were tested with an antileukemic cell specific monoclonal antibody (Mab) “IEII.” Evaluation of leukemic cells and normal hemocytes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis...
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The cellular mechanisms governing the expression of mononuclear cell vasculitis are poorly understood. For determination of the precise sequence of events in the development of vasculitis in autoimmune MRL/lpr mice, histologic sections from 4-20-week-old mice were evaluated with a panel of cytochemical and immunohistochemical stains. The results sh...
Article
Two cytological methods are primarily used to diagnose hematopoietic neoplasia (HN) in the soft shell clam, Mya arenaria. These methods involve (1) the examination of fresh hemocytes by using a hemocytometer or (2) the evaluation of fixed hemocyte preparations stained with Feulgen Picromethyl Blue. This paper presents a new method which uses indire...
Article
ORA I-a, a cloned Ia+ monocyte tumor line, interacts with distinct immunoregulatory T-cell subsets. ORA cells present soluble and alloantigen to primed lymph node T cells and alloantigen to antigen-activated T-cell clones. However, they induce dose-dependent suppression during primary mixed lymphocyte cultures. Activation of a mixed lymphocyte resp...
Article
How and where erythropoiesis is maintained during advanced leukemic disease is an important and, as yet, unresolved question in hematology. To address the potential role of T-lymphocytes as cells that regulate CFU-E differentiation during leukemogenesis, an experimental model of disease has been developed in inbred Balb/c mice. Specifically, three-...
Article
Full-text available
The destruction of vascular smooth muscle cells (VSMCs) in autoimmune arteritis is a poorly understood phenomenon. For evaluation of the cellular interactions that may contribute to vasculitis, the immunobiology of VSMCs and lymphocytes was explored in vitro. Primary VSMC cultures were established, and the interaction of these cells (from normal or...
Article
The MRL/lpr mouse is an inbred strain widely accepted as a model for autoimmune disease both in murine and human systems. Developed from a series of crosses involving four strains of mice, the MRL/lpr (H-2k) genome is a composite estimated to contain approximately 75% of its parental LG/J (H-2d) genome. To explore the cellular mechanism underlying...
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A series of Thy-1.2+ Ly-1+ Qa-1+ malignant T cell clones have been isolated from murine sarcoma virus-murine leukemia-Moloney (MSV-MuLV-M)-induced B cell lymphomas or from MSV-MuLV-M-infected B6 mice. These T cell clones enhance both antigen-independent and -dependent lymphocyte differentiation and function. They also induce the differentiation of...
Article
Ia+ immature malignant monocyte clones were isolated from retrovirus-induced lymphomas. These lymphomas contained a predominant population of Ly-1+ T cells. In order to explain this anomaly, the functional capacity of one of these clones, ORA I-a, was assessed. The results indicated that ORA I-a could present protein antigen to syngeneic and semisy...
Article
Soft shell clams (Mya arenaria) were collected from tidal flats in southeastern New England, and their haemolymph analyzed for the presence of neoplastic cells. The prevalence of neoplasia varied from 10-90% with the highest prevalence found in New Bedford Harbor, a site containing high levels of pollutants, including PCBs, heavy metals and industr...
Article
Soft shell clams () are commonly found in coastal waters of both the eastern and western United States. These invertebrates, which have an open circulatory system, may develop neoplasms of the haemolymph which ultimately kill the host. In this study we have 1) recorded the prevalence of hematopoietic neoplasms (HN) in within a 50 mile radius of Woo...
Article
Soft shell clams (Mya arenaria) are commonly found in coastal waters of both the eastern and western United States. These invertebrates, which have an open circulatory system, may develop neoplasms of the haemolymph which ultimately kill the host. In this study we have 1) recorded the prevalence of hematopoietic neoplasms (HN) in Mya arenaria withi...
Article
BALB/cBy (Qa-2–) mice injected with the syngeneic tumor, ORA I-a (Qa-2+), produced antibodies to Qa-2 and a newly discovered antigen, Qa-6. Specific antisera against Qa-6, in the presence of complement, lyses approximately 40% of lymph-node lymphocytes and splenocytes. Strain distribution analyses indicate that Qa-6 is specified by a gene within th...
Article
Qa2+ tumor cell lines were previously isolated from individual BALB/cBy (Qa2-) splenic lymphomas induced by murine sarcoma virus-murine leukemia virus-Moloney (MSV-MuLV-M). Two clonally derived cell lines, ORA I-a and Thorbly, and one noncloned cell line, BOMS, expressed Qa2, but neither Ly-1 nor Ly-2 were detected. In order to determine whether ei...
Article
Recent work has shown that established B-cell tumours, previously thought to proliferate independently of immune regulation, may activate, and be regulated by, helper or suppressor T-cell subpopulations1-7. We now report a unique model of a murine sarcoma virus (MSV) induced B-cell lymphoma which is closely associated with a population of pre-malig...
Article
The migration of highly purified null lymphocytes to murine sarcoma virus (MSV)-induced rhabdomyosarcomas was investigated. Spleen cell populations were obtained from normal mice as well as from B6 mice which had been injected with MSV. Either fractionated spleen cells or immunoabsorbent column-purified null cells were radiolabeled with sodium chro...
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Three tumor cell lines isolated from individual murine sarcoma virus-infected BALB/cBy (Qa2-) mice were established. BOMS, ORA I, and Thorbly I were analyzed for the expression of Qa2 and Ly surface differentiation antigens. By Cytofluorograf analysis and absorption techniques, all 3 cell lines were found to be Qa2+, Ly1-, Ly2-. This cell surface p...
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Thymectomy of young adult mice has been found to prevent virus-induced lymphomas which develop as the animals age. Thymectomy protects mice by removing a source of suppressor T cells which inhibit the generation of cytolytic T cells against autochthonous tumors. Furthermore, suppression is specific since T cells are regulated in their capacity to r...
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The ontogeny of thymus-dependent lymphoid tumors induced by murine sarcoma-murine leukemia virus (MSV-MuLV) was investigated. Tumors that developed in spleens of infected mice 6 or more months after the injection of virus were diagnosed as immunoblastic T cell sarcomas. Cells derived from the tumors and established as a continuous cell line express...
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Adult thymectomy prevents the development of suppressor T cells without impairing the induction of immunologic tolerance to the same antigenic determinant. This finding demonstrates that the cellular mechanisms underlying immune suppression and immune tolerance are different.
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Splenic lymphocytes from nude (nu/nu), heterozygous/nude (+/nu), or wild type (+/+) mice were examined for their capacity to secrete immunoglobulin (Ig) in the absence of exogenous antigenic stimulation. Using the reverse hemolytic plaque assay, which measures spontaneous Ig secretion in vitro, whole spleen populations from both heterozygous/nude (...
Article
The susceptibility of mouse lymphocytes from various organs to infection by murine leukemia virus (MuLV) (Friend) was studied both in vivo and in vitro by using either Friend virus complex (FV) or lymphatic leukemic virus (LLV), the helper virus isolated from FV. Productively infected cells releasing infectious MuLV were identified as infectious ce...
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Adult thymectomy has been shown to result in the enhanced capacity of splenic T cells to respond to and lyse syngeneic tumor cells in vitro. In addition, T cells from thymectomized mice which kill syngeneic tumor cells do not lyse either normal lymphoid or mitogen-stimulated syngeneic lymphoblast target cells. These findings indicate that the thymu...
Article
The effect of adjuvant on the generation of suppressor cells in the thymus was investigated. C57Bl/6 mice were injected i.p. with complete Freund's adjuvant (CFA), and the capacity of thymocytes and splenic T cells to suppress the in vitro generation of cytolytic T cells was studied. Suppressor thymocytes were detected within two days after CFA ino...
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The regulatory role of the adult thymus on the appearance of cytotoxic and suppressor T cells (thymus-derived lymphocytes) to allogeneic and autochthonous virus-induced tumors in mice was investigated. It was demonstrated that C57BL/6 mice challenged with allogeneic P815 mastocytoma cells and complete Freund's adjuvant failed to develop cytotoxic c...
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The migration of splenic T and B lymphocytes into syngeneic tumors undergoing immunologic rejection was investigates. Spleen cells were obtained from normal BALC/c mice or BALB/c mice bearing tumors induced by murine sarcoma virus (MSV). Either whole spleen cells or immunoabsorbent purified T and B cells were radiolabeled with sodium chromate-51 an...
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Inoculation of C57BL/6J mice with allogeneic P815 mastocytoma cells in the presence of simian virus 40 (SV40), a DNA tumor virus, led to an enhanced cytolytic T-cell response to P815 in vivo. Cytotoxic function was also augmented if SV40 was given subsequent to a primary immunization, even when mice were given a suboptimal dose of immunizing cells....
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The effect of complete Freund's adjuvant (CFA) on distinct T cell functions was investigated. Adjuvant was found to suppress the generation of cytolytic T cells in vivo when mixed with allogeneic P815 cells before immunization of C57BL/6 mice. Inoculation of the mice with either adjuvant or adjuvant emulsified with allogeneic cells resulted in whol...
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BDF1 mice were made tolerant by a single i.v. injection of 1 mg of DNAP-gamma1 or by weekly i.v. injections of 0.2 mg of DNP-gamma1 given for a month. In both instances, spleen cells of tolerant animals were fractionated to obtain pure populations of T cells (nonimmunoglobulin-bearing cells), referred to as tolerant T cells, and B cells (immunoglob...
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The ability of T and B lymphocytes to migrate into skin allografts undergoing rejection was studied in mice. Spleen cells from CBA/J mice sensitized to transplantation antigens of A/J or C57BL/6 mice were separated on immunabsorbent columns into purified populations of T and B cells, labeled in vitro with 3H-uridine and injected intravenously into...
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SINCE Metchnikoff (quoted in ref. 1) showed that amoebocytes, the circulating cells in invertebrates, are capable of phagocytosis1, it has become increasingly apparent that they have various immunological functions. For example, amoebocytes mediate resistance to infection2,3 and rejection of xenogeneic grafts4,5.
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A cytopathic effect was induced by the Schmidt-Ruppin strain of Rous sarcoma virus (RSV-SR) in five of nine rat tumor cell lines tested in vitro. The cells showed irreversible cytopathic change as early as 24-48 h after infection. Of the leukemogenic and tumorigenic viral agents tested, only RSV-SR induced the rapid Rous cytopathic effect. Virus wa...
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SIMIAN virus SV40, a DNA tumour virus, causes a productive infection in both monkey and human cells, leading to lysis of the cells and release of infectious virus. In murine systems, however, the virus transforms the cells, leading to new virus-specific antigens on the transformed cells1. These transformed cells induce tumours in mice which then re...
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Recognition of self and non-self by invertebrates apparently varies from species to species and as yet there is no general understanding of this variation within the phylum. Injection of Arbacia (sea urchin) cells, about half of which are deeply pigmented, into Asterias (sea star) in vivo was followed by an abrupt drop in the number of circulating...