BackgroundXenotropic MurineLeukemia Virus-related (XMRV) virus is a recently identified mouse gammaretrovirus that has the ability to infect certain human cells. In this study,...Full Text Available
The integration sites for viral DNA in cells infected with Moloney murineleukemia virus (M-MuLV) were studied by restriction endonuclease cleavage of cellular DNA followed by electrophoresis in agarose...Full Text Available
Previous studies have revealed marked differences in the incidence of leukemia between rats and mice exposed to 1,3-butadiene that do not appear to be readily explained on the basis of pharmacokinetics...Full Text Available
For more information about this message, please visit this page: About CDC.gov. XMRV (Xenotropic MurineLeukemia Virus-related Virus) XMRV Home Questions & Answers Updates...
Chronic HTLV-I (human T cell lymphotropic virus type I) infection may cause adult T cell leukemia/lymphoma (ATL), a disease with dismal long-term prognosis. The HTLV-I transactivator, Tax, initiates...Full Text Available
The accepted model of retroviral reverse transcription includes a circular DNA intermediate which requires strand displacement synthesis for linearization and creation of an integration-competent, long...Full Text Available
The AKR mouse strain is characterized by a high incidence of spontaneous thymic lymphoma that appears in older animals (greater than 6 months of age) and is associated with novel provirus integrations...Full Text Available
The Moloney murineleukemia virus (MMLV) belongs to the Retroviridae family of enveloped viruses, which is known to acquire minute amounts of host cellular proteins both on the surface...Full Text Available
XMRV or xenotropic murineleukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs....Full Text Available
Xenotropic murineleukemia virus-related virus (XMRV) was discovered in human prostate tumors and later in some chronic fatigue syndrome (CFS) patients. However, subsequent studies have identified various sources of potential contamination with XMRV and other murineleukemia virus (MLV)-related sequences in test samples. Biological and nucleotide sequence analysis indicates that XMRV is distinct from known xenotropic MLVs and has a broad host range and cell tropism including human cells. Therefore, it is prudent to minimize the risk of human exposure to infection by evaluating XMRV contamination in cell lines handled in laboratory research and particularly those used in the manufacture of biological products. Nested DNA PCR assays were optimized for investigating XMRV gag and env sequences in various cell lines, which included MRC-5, Vero, HEK-293, MDCK, HeLa, and A549, that may be used in the ...
Abstract Recent reports showed many patients with chronic fatigue syndrome (CFS) harbor a retrovirus, xenotropic murineleukemia-related virus (XMRV), in blood; other studies could not replicate this finding. A useful next step would be to examine cerebrospinal fluid, because in some patients CFS is thought to be a brain disorder. Finding a microbe in the central nervous system would have greater significance than in blood because of the integrity of the blood-brain barrier. We examined cerebrospinal fluid from 43 CFS patients using polymerase chain reaction techniques, but did not find XMRV or multiple other common viruses, suggesting that exploration of other causes or pathogenetic mechanisms is warranted. Ann Neurol 2011;
Two cellular DNA regions representing common domains for proviral DNA integration ( Mlvi -1 and Mlvi -2) have been identified in Moloney murineleukemia virus-induced rat thymic lymphomas. Cellular...Full Text Available
A series of translocation break points found in a subset of human acute leukemias have one of the breaks on human chromosome 11q23. This region has recently been cloned and a large gene, ALL-1, with...Full Text Available
The gammaretrovirus, xenotropic murineleukemia virus-related virus (XMRV), replicates to high titers in some human cell lines and is able to infect non-human primates. To determine whether APOBEC3 (A3) proteins restrict XMRV infections in a non-human primate model, we sequenced proviral DNA from peripheral blood mononuclear cells of XMRV-infected rhesus macaques. Hypermutation characteristic of A3DE, A3F and A3G activities was observed in the XMRV proviral sequences in vivo. Furthermore, expression of rhesus A3DE, A3F, or A3G in human cells inhibited XMRV infection and caused hypermutation of XMRV DNA. These studies show that some rhesus A3 isoforms are highly effective against XMRV in the blood of a non-human primate model of infection and in cultured human cells. PMID:21982221
BACKGROUND: Since the identification of xenotropic murineleukemia virus-related virus (XMRV) in prostate cancer patients in 2006 and in chronic fatigue syndrome patients in 2009, conflicting findings have been reported regarding its etiologic role in human diseases and prevalence in general populations. In this study, we screened both plasma and peripheral blood mononuclear cells (PBMNCs) collected in Africa from blood donors and human immunodeficiency virus Type 1 (HIV-1)-infected individuals to gain evidence of XMRV infection in this geographic region. STUDY DESIGN AND METHODS: A total of 199 plasma samples, 19 PBMNC samples, and 50 culture supernatants from PBMNCs of blood donors from Cameroon found to be infected with HIV-1 and HIV-1 patients from Uganda were screened for XMRV infecti...
A technique for delivering genes carried by recombinant retroviruses into specific cell types could have numerous applications in oncology, developmental biology, and gene therapy. As a first step toward this remote goal the authors designed a procedure allowing in vitro cell targeting by retroviruses. Biotinylated antibodies against the viral envelope protein on one side, and against specific cell membrane markers on the other side, were bridged by streptavidin and used to link the virus to the host. The method was successfully used to infect human cells with ecotropic murine retroviruses by means of major histocompatibility complex class I and class II antigens and appears easily adaptable to other cell, membrane markers. Moreover, the sequential protocol they design, although allowing infection of human cells, requires less stringent safety constraints than would handling of amphotropic virus stocks.
Erythroid differentiation regulator (Erdr1) was first discovered in mouse leukemia cell lines and functions as a stress-related survival factor. This study investigated whether Erdr1 regulates murine melanoma progression, as well as the mechanism involved in Erdr1-regulated metastasis. The expression of Erdr1 is negatively correlated with IL-18 expression, which has a pro-cancer effect in melanoma. To study the role of Erdr1 as an anti-cancer factor, cell migration, invasion, and proliferation were measured. Erdr1 overexpression markedly inhibited the level of cell migration, invasion, and proliferation in B16F10 cells in vitro. In addition, Erdr1 overexpression significantly suppressed melanoma lung colonization, metastasis, and tumor growth in vivo. To identify the factors involved in Er...
XMRV or xenotropic murineleukemia virus-related retrovirus, a recently discovered retrovirus, has been linked to both prostate cancer and chronic fatigue syndrome (CFS). Recently, the teams of Drs. Shyh-Ching Lo and Harvey Alter discovered the presence of sequences closely related to XMRV in the blood of 86.5% of patients with CFS [1]. These findings are important because since the initial discovery of XMRV in CFS, several studies have failed to find XMRV in specimens collected from CFS patients. While the current study also did not find XMRV in CFS, Lo et al. did detect sequences that belong to polytropic mouse endogenous retroviruses (PMV), which share considerable similarity with XMRV. Criteria for future studies that will help bring greater clarity to the issue of retroviral sequences in CFS are proposed below. PMID:21994623
Retroviruses are well known pathogens of mammals, birds and fish. Their potential to induce cancer in chickens was already described almost 100 years ago and murine retroviruses have been a subject of study for 50 years. The first human retroviruses, HTLV and HIV, were discovered more than 30 years ago, surprising researchers and physicians by the profound differences in the diseases they cause. HTLV-1 is able to induce, after decades of infection, lymphomas/leukemia or neuroimmune disorders whereas untreated HIV infection leads almost inevitably to AIDS. The recently described XMRV (xenotropic murineleukemia virus-related virus) appeared to possess many of the features known for HTLV and was regarded by some to be the third human retrovirus. However, recent publications by Knox et al. [1] and Paprotka et al. [2] have shed new light on this gammaretrovirus. Knox and colleagues clearly demonstrate that ...
An overall hypothesis for benzene-induced leukemia is proposed. Key components of the hypothesis include a) activation of benzene in the liver to phenolic metabolites; b) transport of these metabolites...Full Text Available
BackgroundXMRV (xenotropic murineleukemia virus-related virus) is the first known example of an exogenous gammaretrovirus that can infect humans. A limited number of reports suggest that XMRV is intrinsically resistant to many of the antiretroviral drugs used to treat HIV-1 infection, but is sensitive to a small subset of these inhibitors. In the present study, we used a novel marker transfer assay to directly compare the antiviral drug sensitivities of XMRV and HIV-1 under identical conditions in the same host cell type.ResultsWe extend the findings of previous studies by showing that, in addition to AZT and tenofovir, XMRV and HIV-1 are equally sensitive to AZddA (3'-azido-2',3'-dideoxyadenosine), AZddG (3'-azido-2',3'-dideoxyguanosine) and adefovir. These results indicate that specific 3'-azido or acyclic nucleoside analog inhibitors of HIV-1 reverse transcriptase (RT) also block XMRV infection with comparable efficacy in vitro. Our data ...
These studies have addressed firstly the effect of single small doses of x-ray upon murine hematopoietic stem cells to obtain a better estimate of the D/sub q/. It is small, of the order of 20 rads. Secondly, a dose fractionation schedule tht does not kill or perturb the kinetics of hemopoietic cell proliferation was sought in order to investigate the leukemogenic potential of low level radiation upon an unperturbed hemopoietic system. The studies reported herein show tht 1.25 rads every other day decrease the CFU-S content of bone marrow by the time 40 rads are accumulated. Studies on the effect of 0.5, 1.0, 2.0, and 3.0 rads 3 times per week are under way. Two rads 3 times per week produced a modest decrease in CFU-S content of bone marrow after an accumulation of 68 rads. With 3.0 rads 3 times per week an accumulation of 102 rads produces a significant decrease in CFU-S content of bone marrow. Dose fractionation at 0.5 and 1.0 rad 3 times per week has not ...
Thus far there are relatively few data on the risk of leukemia among those who were exposed to external radiation during cleanup operations following the Chornobyl nuclear accident, and results...Full Text Available
To delineate the mechanisms of bovine leukemia virus (BLV) pathogenesis, four full-length BLV clones, 1, 8, 9, and 13, derived from the transformed cell line FLK-BLV and a clone construct, pBLV913,...Full Text Available
Antibodies against feline leukemia virus (FeLV) and the feline oncornavirus-associated cell membrane antigen (FOCMA) were transferred from pregnant cats to their suckling kittens. All of these kittens...Full Text Available
BackgroundAllogeneic hematopoietic cell transplantation is a potentially curative treatment for patients with acute lymphoblastic leukemia. However, the majority of older adults...Full Text Available
In 1871, the observation of yellowish nodules in the enlarged spleen of a cow was considered to be the first reported case of bovine leukemia. The etiological agent of this lymphoproliferative disease,...Full Text Available
A Legionella-like organism, strain 1677-MI-H, was isolated from the bronchoscopy washings of a patient with pneumonia who had a 2-year history of progressive, chronic lymphocytic leukemia. The growth...Full Text Available
DNA from the peripheral blood mononuclear cells of 17 different individuals infected with human T-cell lymphoma/leukemia virus type II (HTLV-II) was successfully amplified by the polymerase chain reaction...Full Text Available
The purpose of this study was to determine the effects of bovine leukemia virus (BLV) infection on production, reproduction and longevity in dairy cattle. The study population was a commercial Holstein...Full Text Available
Possible associations between environmental hazards and the occurrence of childhood leukemia were investigated in Woburn, MA, for the period 1969-79. Residents of Woburn were concerned over what they...Full Text Available
...treated for leukemia. B' s physician, who is employed by the HMO, is considering a treatment plan that includes six-mercaptopurine, a drug for treating leukemia in most children. However, the drug could be fatal if taken by a small percentage of...
PurposeThe goal of this study was to clarify the dynamics of tumor oxygen (partial pressure of oxygen, pO2) in SCC VII murine tumors in mice after X-ray...Full Text Available
We investigated the role of early portal hypotensive pharmacotherapy in preventing the development of portal-systemic shunting in a portal hypertensive model of chronic murine schistosomiasis induced...Full Text Available
IntroductionThe murine air pouch is a bursa-like space that resembles the human synovial membrane. Injection of monosodium urate (MSU) crystals into the pouch elicits an acute inflammatory...Full Text Available
The murine cytomegalovirus (MCMV) M33 gene is conserved among all betaherpesviruses and encodes a homologue of seven-transmembrane receptors (7TMR) with the capacity for constitutive signaling. Previous...Full Text Available
The identification of the protein targets for dengue virus-specific T lymphocytes may be useful for planning the development of subunit vaccines against dengue. We studied the recognition by murine...Full Text Available
BackgroundCerebral malaria (CM) is a neurological syndrome that includes coma and seizures following malaria parasite infection. The pathophysiology is not fully understood and cannot...Full Text Available
Murine cytomegalovirus (MCMV) is an important animal model of human cytomegalovirus (HCMV), a β-Herpesvirus that infects the majority of the world's population and causes disease in neonates...Full Text Available
In t(15;17) acute promyelocytic leukemia, all-trans retinoic acid (RA) induces leukemic cell maturation in vitro and remission in acute promyelocytic leukemia patients, but in vivo treatments invariably...Full Text Available
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and other diseases....Full Text Available
Bovine leukemia virus (BLV), a retrovirus related to human T-cell leukemia virus types 1 and 2, can induce persistent nonneoplastic expansion of the CD5+ B-cell population, termed...Full Text Available
A case is presented in which the diagnosis of acute myelomonocytic leukemia was made 16 months after the start of irradation and chemotherapy for Ewing's sarcoma. The association of these two diseases is rare. The etiologic role of therapy in the development of leukemia is speculative in this case. However, there is need for surveillance for secondary neoplasms of all types so that the benefits of therapy may be properly weighed against the risks.
Recent improvements in cell purification and transplantation techniques have contributed to the identification of cell populations known as tumor-initiating cells (TIC). This discovery has led to the -cancer stem cell hierarchy- concept, which holds that tumors are organized as a hierarchy of malignant tissues sustained by such TIC. However, this concept remains controversial. In this review, we examine recent advances in cancer stem cell research that have been generated from studies of Philadelphia (Ph) chromosome-positive leukemia. The abnormal Ph chromosome, which arises from a translocation creating the BCR-ABL1 fusion gene, is most commonly associated with chronic myelogenous leukemia (CML) and precursor B cell acute lymphoblastic leukemia (B-ALL). Examination of the pathophysiology ...
Flow cytometry (FCM) is widely used in health research and in treatment for a variety of tasks, such as in the diagnosis and monitoring of leukemia and lymphoma patients, providing the counts of helper-T...Full Text Available
The presence of a high number of activated T cells in the bloodstream and spontaneous proliferation of peripheral blood mononuclear cells in vitro are striking characteristics of human T-cell leukemia...Full Text Available
HIX, a recombinant derived from Moloney leukemia virus, has an envelope glycoprotein different from that of the Moloney virus. HIX and Moloney viruses share the majority of the large T1 oligonucleotides...Full Text Available
Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the...Full Text Available
Lysozyme activities of serum and urine in normal subjects, patients with various leukemias, and a-bomb survivors were determined. The lysozyme activity was increased in the majority of the leukemia patients. Urinary lysozyme of a-bomb survivors could not be detected.
Bovine leukemia virus (BLV) is a complex B-lymphotrophic retrovirus of cattle and the causative agent of enzootic bovine leukosis. Serum antibody in infected animals does not correlate with protection...Full Text Available
Developing markets in the Pacific Basin depend heavily on the production and export of consumer goods. The generation of hazardous waste as a by-product of industrial production can be linked to adverse health outcomes, such as childhood leukemia, in ways that are presently unknown. In California, exposures resulting from hazardous waste disposal are of concern in the etiology of childhood cancer. Approximately 63% of the 57 hazardous waste sites that the U.S. Environmental Protection Agency (USEPA) included in the national priority list under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) statute were in the six-county San Francisco Bay area. This area includes California`s Silicon Valley, where a disproportionate majority of these sites are located. Although only one study links hazardous waste disposal to childhood leukemia evidence is accumulating that in utero and maternal pesticide exposures as well as ...
The xenotropic murine leukaemia virus-related virus (XMRV), a gammaretrovirus, was discovered in prostate cancer tumours by Virochip technology in 2006. It was subsequently detected in chronic fatigue patients in 2009. The association between XMRV and chronic fatigue has proved to be controversial. No study has confirmed these findings and many have refuted them. Here, we present the evidence for our contention that XMRV is not a human pathogen. PMID:21978843
Several early genes of murine cytomegalovirus (MCMV) encode proteins that mediate immune evasion by interference with the major histocompatibility complex class I (MHC-I) pathway of antigen presentation...Full Text Available
Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp...Full Text Available
We evaluated 190 children with very high-risk leukemia, who underwent allogeneic hematopoietic cell transplantation in 2 sequential treatment eras, to determine whether those treated with contemporary protocols had a high risk of relapse or toxic death, and whether non-HLA-identical transplantations yielded poor outcomes. For the recent cohorts, the 5-year overall survival rates were 65% for the 37 patients with acute lymphoblastic leukemia and 74% for the 46 with acute myeloid leukemia; these rates compared favorably with those of earlier cohorts (28%, n = 57; and 34%, n = 50, respectively). Improvement in the recent cohorts was observed regardless of donor type (sibling, 70% vs 24%; unrelated, 61% vs 37%; and haploidentical, 88% vs 19%), attributable to less infection (hazard ratio [HR] = 0.12; P = .005), regimen-related toxicity (HR = 0.25; P = .002), and leukemia-related death (HR = 0.40; P = .01). ...
Hepatocellular carcinoma (HCC) represents a major health problem as it afflicts an increasing number of patients worldwide. Albeit most of the risk factors for HCC are known, this is a deadly syndrome with a life expectancy at the time of diagnosis of less than 1?year. Definition of the molecular principles governing the neoplastic transformation of the liver is an urgent need to facilitate the clinical management of patients, based on innovative methods to detect the disease in its early stages and on more efficient therapies. In the present study, we have combined the analysis of a murine model and human samples of HCC to identify genes differentially expressed early in the process of hepatocarcinogenesis, using a microarray-based approach. Expression of 190 genes was impaired in murine ...
SUMMARYThe biologic and clinical significance of KIT overexpression that associates with KIT gain-of- function mutations occurring in subsets...Full Text Available
BackgroundSome epidemiologic studies have suggested an association between electromagnetic field exposure induced by high voltage power lines and childhood leukemia, but null results...Full Text Available
OBJECTIVES: This article uses meta-analysis methodology to examine the statistical consistency and importance of random variation among results of epidemiologic studies of residential magnetic field...Full Text Available
In addition to its role in megakaryocyte production, signaling initiated by thrombopoietin (TPO) activation of its receptor, myeloproliferative leukemia virus protooncogene (c-Mpl, or Mpl), controls...Full Text Available
The RNA packaging process for retroviruses involves a recognition event of the genome-length viral RNA by the viral Gag polyprotein precursor (PrGag), an important step in particle morphogenesis. The...Full Text Available
BackgroundThe immunoregulatory enzyme indoleamine 2,3-dioxygenase, which catalyzes the conversion of tryptophan into kynurenine, is expressed in a significant subset of patients...Full Text Available
The dielectrophoretic (DEP) crossover method has been applied to the detection of cell responses to toxicants. Time and dose responses of the human cultured leukemia (HL-60) line were measured...Full Text Available
A survey is presented of the consequences of the irradiation of the population with ionizing radiation. There is an increased incidence of leukemia in irradiated population groups. Among the inhabitants of Hiroshima and Nagasaki maximum death of leukemia was observed in the years 1951 to 1952. The results are summed up of the observation of carcinoma of the breast, lungs and bronchi, bones, and carcinoma of the thyroid. The effect of radiation on experimental animals is described. It was found that the scatter of the dependence of the incidence of various types of cancer on the dose equivalent apparently reflects differences in the biological mechanism of this incidence and that a proportional relationship cannot be expected between the primary damage of cells during irradiation and the actual manifestation of the disease. (E.S.).
We report the case of a 22-year-old man with Ewing's sarcoma who attained a complete remission (CR) after combination radiotherapy and chemotherapy. Secondary acute lymphoblastic leukemia with multiple cytogenetic abnormalities involving chromosome 5 and 7 developed 16 years later. The patient underwent induction chemotherapy and entered a CR. Peripheral blood stem cell transplantation from a matched sibling was performed successfully and he is in complete remission of both ALL and Ewing's sarcoma. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)
A new simple multi-well plate-based assay to determine monocyte differentiation-inducing activity was developed. It is based on the increase of macrophage adherence after the induction of monocyte differentiation. The assay was conducted using a human monocytic leukemia cell line, THP-1, treated with either 12-O-tetradecanoylphorbol 13-acetate or cytokines, such as tumor necrosis factor-alpha and interferon-gamma. This method is sensitive and easy to perform, especially in case of analyzing a large number of samples. PMID:17920620
A new simple multi-well plate-based assay to determine monocyte differentiation-inducing activity was developed. It is based on the increase of macrophage adherence after the induction of monocyte differentiation. The assay was conducted using a human monocytic leukemia cell line, THP-1, treated with either 12-O-tetradecanoylphorbol 13-acetate or cytokines, such as tumor necrosis factor-? and interferon-?. This method is sensitive and easy to perform, especially in case of analyzing a large number of samples.
Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2, gelatinase A) are associated with syndromes that include abnormal facial appearance, short stature, and severe bone...Full Text Available
Cysticercosis is an infection with larval cysts of the cestode Taenia solium. Through pathways that are incompletely understood, dying parasites initiate a granulomatous reaction that,...Full Text Available
We have studied the functions of the intracellular RNAs of mouse mammary tumor virus (MMTV) by purification and translation in vitro. Two major size classes of MMTV RNA, 35S and 24S RNA, were isolated...Full Text Available
Osterix (Osx) is a zinc-finger-containing transcription factor that is expressed in osteoblasts of all endochondral and membranous bones. In Osx null ...Full Text Available
Retroviruses are well known pathogens of mammals, birds and fish. Their potential to induce cancer in chickens was already described almost 100 years ago and murine retroviruses have been a subject...Full Text Available
Borrelia burgdorferi produces potent cell-activating molecules capable of stimulating polyclonal proliferation and immunoglobulin production by murine B lymphocytes and cytokine production by a variety...Full Text Available
Experimental metastases in the brain of mice are infiltrated by microglia, and parabiosis experiments of green fluorescent protein (GFP+) and GFP- mice revealed that these microglia...Full Text Available
We have characterized the kinetic response of gene targets throughout the murine genome to transcriptional modulation by the glucocorticoid receptor (GR). In contrast to a model in which multiple genes...Full Text Available
The effectiveness of chemotherapy in human schistosomiasis varies from one area to another, and limited data from experimentally infected animals suggest inherent differences in the susceptibility...Full Text Available
The murine γ-herpesvirus-68 (γHV68) establishes viral latency in dendritic cells (DCs). In the present study, we examined the specific consequences...Full Text Available
Enteric infections with attaching/effacing lesion-inducing bacterial pathogens are a worldwide health problem. A murine infection model with one such pathogen, Citrobacter rodentium,...Full Text Available
BackgroundAnimals carrying genetic mutations have provided powerful insights into the role of interstitial cells of Cajal (ICC) in motility. One classic model is...Full Text Available
Francisella tularensis requires iron (Fe) for growth, but the biologic sources of Fe for this organism are largely unknown. We found that Francisella sp. growing in...Full Text Available
BackgroundSevere sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic...Full Text Available
BackgroundNeurofibromatosis type 1 (NF1) is a common monogenic tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1....Full Text Available
Evaluation of the protective efficacy of recombinant T-cell-reactive proteins of Coccidioides posadasii in a murine model of coccidioidomycosis has led to the discovery of potential...Full Text Available
The influence of pretreatment of Escherichia coli and Staphylococcus aureus with sub-MICs of the new beta-lactam antibiotic imipenem on phagocytosis and killing by murine peritoneal macrophages and...Full Text Available
Colistin is increasingly used as last-line therapy against Gram-negative pathogens. The pharmacokinetic (PK)/pharmacodynamic (PD) index that best correlates with the efficacy of colistin remains undefined....Full Text Available
Definition of the T-lymphocyte responses to dengue viruses should aid in the development of safe and effective vaccines and help to explain the pathophysiology of dengue hemorrhagic fever and dengue...Full Text Available
The cellular receptor for murine coronavirus mouse hepatitis virus (MHV)-A59 is a member of the carcinoembryonic antigen (CEA) family of glycoproteins in the immunoglobulin superfamily. We isolated...Full Text Available
Chondroitin sulphate (CS) is a glycosaminoglycan widely distributed in animal tissues, which has anti-inflammatory and chondroprotective properties. We reported previously that chondroitin 4-sulphate...Full Text Available
IntroductionBRAF (v raf murine sarcoma viral oncogene homologue B1) is a serine-threonine kinase involved in the mitogen-activated protein kinase (MAPK) signalling pathway, known...Full Text Available
AimsThe experiments explored for atrial arrhythmogenesis and its possible physiological background in recently developed hetero-(RyR2+/S) and homozygotic...Full Text Available
Cultured mouse or human embryonic stem (ES) cells provide access to all of the genes required to elaborate the fundamental components and physiological systems of a mammalian cell. Chemical or insertional...Full Text Available
This study investigated the effect of copper as an antibacterial agent on the infectivity of Salmonella enterica serovar Typhimurium. Mice were infected orally with a standardized dose...Full Text Available
In August 1982, a 44-year-old man was diagnosed as having rectal cancer, histologically diagnosed as well differentiated adenocarcinoma, and abdominoperineal resection and colostomy were performed. Postoperatively, he received chemotherapy with mitomycin C up to a total dose of 100 mg. In September 1986, lung metastasis occurred and he was treated with a combination chemotherapy consisting of cisplatin, pirarubicin and 5-fluorouracil. In the following year, radiation treatment (total: 6900 rad) was given for a recurrent pelvic lesion. Peripheral blood on April 30, 1988, showed anemia, thrombocytopenia and appearance of myeloblasts, and a diagnosis of acute myelogenous leukemia (FAB: M1) was made. Combination chemotherapy (including aclarubicin, vincristine, behenoyl ara-C, daunorubicin, 6-mercaptopurine, cytarabine, etoposide and prednisolone) failed to induce remission and the patient died in June 1988. This case was thought to be one of secondary ...
Much progress has been made in the clinical, biological and technical aspects of the T-cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT). Our experience demonstrates that infusing a megadose of extensively T-cell-depleted hematopoietic peripheral blood stem cells after an immuno-myeloablative conditioning regimen in acute leukemia patients ensures sustained engraftment with minimal GvHD without the need of any post-transplant immunosuppressive treatment. Since our first successful pilot study, our efforts have concentrated on developing new conditioning regimens, optimizing the graft processing and improving the post-transplant immunological recovery. The results we have so far achieved in high risk acute leukemia patients show that haploidentical transplantation ...
Allogeneic stem-cell transplantation (SCT) is potentially curative therapy in AML by providing both dose-intensive chemo-radiotherapy and induction of graft-versus-leukemia (GvL) effect. Historically, more emphasis was given to the intensity of conditioning. Over the last decade the pendulum turned more towards induction of GvL as the primary goal. A plethora of non-myeloablative (NMA) and reduced-intensity conditioning regimens (RIC) were introduced trying to reduce transplant-related toxicities and allow SCT in elderly and medically infirm patients. In addition, reduced-toxicity myeloablative regimens (RTC) based on fludarabine and myeloablative alkylating-agent doses were designed to allow safer administration of dose-intensive therapy. Conditioning dose-intensity is highly correlated w...
Abstract: The ability of melatonin as a potent antioxidant was used as a rationale for testing its antiapoptotic ability in normal cells. Recently, melatonin was shown to possess proapoptotic action by increasing reactive oxygen species in certain cancer cells. The modification of radiation-induced apoptosis by melatonin and the expression of apoptosis-associated upstream regulators were studied in normal mice splenocytes and Jurkat T leukemia cells. C57BL/6 mice were exposed to a single whole body X-ray radiation dose of 2 Gy with or without 250 mg/kg melatonin pretreatment. The Jurkat cells were divided into four groups of control, 1 mm melatonin alone, 4 Gy irradiation-only and melatonin pretreatment before irradiation. The highest level of apoptosis in the normal splenic white pulp was...
Background The 2003 outbreak of severe acute respiratory syndrome (SARS) infected over 8000 people and killed 774. Transmission of SARS occurred through direct and indirect contact and large droplet nuclei. The World Health Organization recommended the use of household disinfectants, which have not been previously tested against SARS coronavirus (SARS-CoV), to disinfect potentially contaminated environmental surfaces. There is a need for a surrogate test system given the limited availability of the SARS-CoV for testing and biosafety requirements necessary to safely handle it. In this study, the antiviral activity of standard household products was assayed against murine hepatitis virus (MHV), as a potential surrogate for SARS-CoV. Methods A surface test method, which involves drying an amo...
From the frequency of diagnostic radiologic examinations and their radiation dose delivered to the population the risk of cancer induction and genetic damage is calculated on the basis of the risk factors given by the ICRP. Thus 0.38 % and 3 % of the total mortality for cancer and leukemia, resp., can be attributed to X-ray diagnostics. Chest examinations alone result in 0.07-0.7 damages per 100,000 persons depending on the imaging technique applied. (author).
Human T cell leukemia/lymphoma virus Type 1 and 2 (HTLV-1 and HTLV-2), together with their simian counterparts (STLV-1, STLV-2), belong to the Primate T lymphotropic viruses group (PTLV). The high percentage...Full Text Available
Amplification of oncogenes has been found to be an important prognostic factor in behavior of patients' malignancies. In this study we have used new gel electrophoresis techniques to follow the location...Full Text Available
BackgroundGene mutation is an important mechanism of myeloid leukemogenesis. However, the number and combination of gene mutated in myeloid malignancies is still a matter of investigation.MethodsWe...Full Text Available
Arsenic trioxide (As2O3), used to treat promyelocytic leukemia, triggers cell death via unknown mechanisms. To further our understanding of As2O3-induced...Full Text Available
The ζ chain-associated 70-kDa protein (ZAP-70) of tyrosine kinase plays a critical role in T cell receptor-mediated signal transduction and the immune response. A high level of ZAP-70 expression...Full Text Available
CAP18 (an 18-kDa cationic antimicrobial protein) is a granulocyte-derived protein that can bind lipopolysaccharide (LPS) and inhibit various activities of LPS in vitro. The present study examined the...Full Text Available
Anti-TAG-72 monoclonal antibodies target the tumor-associated glycoprotein (TAG)-72 in various solid tumors. This study evaluated the use of anti-TAG-72 monoclonal antibodies, both murine CC49...Full Text Available
The long pentraxin PTX3 has multiple roles in innate immunity. For example, PTX3 regulates C1q binding to pathogens and dead cells and regulates their uptake by phagocytes. It also inhibits P-selectin-mediated...Full Text Available
Oestrogen has been reported to modulate tumour necrosis factor (TNF), interleukin (IL)-1 and IL-6 cytokine levels in human mononuclear cell cultures. In the present study, the effects of exogenous oestrogen...Full Text Available
BackgroundThe Ras and Notch signaling pathways are frequently activated during development to control many diverse cellular processes and are often dysregulated during tumorigenesis....Full Text Available
The prototypic pituitary hormone prolactin (PRL) exerts a wide variety of bioregulatory effects in mammals and is also found in extrapituitary sites, including murine skin. Here, we show by reverse...Full Text Available
Murine embryonic stem (ES) cells have unusually long telomeres, much longer than those in embryonic tissues. Here we address whether hyper-long telomeres are a natural property of pluripotent stem cells,...Full Text Available
The present study treats only the collective risk of ex-utero leukaemia associated with the routine releases of the nuclear industrial installations of the North Cotentin (0.0009 cases over the considered period) the uncertainty on the contribution to the collective risk of the incidents and the accidents of the nuclear installations (notably the drilling of the pipe of release in sea arisen in 1979-1980 and the fire of the waste silo on January 6. 1981, for the reprocessing plant of La Hague has not been considered. Only 45% of the risk are taken into account by the study. Every calculated value remains very inferior to the number of leukemia cases observed (4 cases observed for two expected cases) and to the risk of radioinduced leukemia any merged exposure sources, that is to say 0.84 cases. It appears thus not very probable that the nuclear installations of the North - Cotentin can explain the tendency to the excess of observed leukaemia. ...
By applying the linear-dose effect relation, the weighting factors for total risks recommended by IRCP can be transformed to weighting factors for somatic effects. Another weighting factor Msub(s) has to be used which takes into account the dependence of the latent period for occurrence of malignant disease and the variation of the incidence with time. On this basis a somatically significant dose equivalent can be defined as 'the dose equivalent which if received by every member of the population, would be expected to produce the same total somatic injury to the population as does the actual dose equivalent received by the various individuals', and an approximation has been derived for this. Tables are presented of the somatic effective dose equivalents calculated for different x-ray examinations for various organs and tissues. The S.E.D. equivalents have also been calculated for some of the most frequent radiopharmaceutical examinations, together with the absorbed dose to some ...
The aim of this pilot study was to evaluate the feasibility of long-term subcutaneous application of low-dose IL-2 in children with malignancies at very high risk of relapse who underwent highly T cell and B cell depleted HLA-identical (MUD) or full haplotype mismatched related hematopoetic stem cell transplantation. We studied 11 patients with acute leukemias/myelodysplastic syndrome and juvenile myelomonocytic leukemia (active disease and/or second stem cell transplantation, n = 8; >=CR 2, n = 2) and relapsed or progressive Ewings sarcoma (n = 2) who received prophylactic IL-2 treatment for a high probability of disease recurrence after allo-HSCT. Toxicities from IL-2 were transient fever, fatigue and local inflammation. In one patient GvHD grade III with no clear association to IL-2 adm...
It may result in acute radiation syndrome after body is exposed to ionizing radiation. The one of long-term effects of irradiation injury is leukemia. The bone marrow cells (BMC) transplantation including stem cells is the only effective therapy for acute radiation syndrome patients. Recently, with the advancement of stem cell research that the stem cells have multipotential and can convert each other, it may supply the new stem source for the irradiation injury patients. At the same time with the further research of radioprotective reagents, the hematopoietic stem cells proliferation after irradiation injury is promoted
The authors describe the production of two mouse hybridomas secreting monoclonal antibodies to antigenic determinants of the surface membranes of human neutrophils, activated T lymphocytes, and acute leukemic blast cells. The degree of lymphocyte stimulation was estimated from incorporation of /sup 3/H-thymidine with parallel microculture. Monoclonal antibodies of supernatants of hybridoma cultures shown here reacted in both immunofluorescence test and cytotoxicity test with surface membrane antigens on the majority of neutrophils and PHA-activated peripheral blood lymphocytes from healthy subjects, but did not give positive reactions with unactivated lymphocytes, adherent monocytes, erythrocytes, and alloantigen-stimulated lymphocytes.
The genetically and leukemia-significant doses (GSD and LSD) were calculated from the average gonad and bone marrow doses caused by the most frequently applied radiopharmaceuticals in Bulgaria in 1976. Because of the lack of information about the age groups of the patients examined assumptions have been made which led to estimated values of 0.97 mrad for GSD and 2.0 mrad for LSD which must be considered as the upper limit of the real GSD and LSD. The influence of the different radiopharmaceuticals on the average radiation exposure of the population is discussed. (author).
The tissue distribution of "1"3"1I-transferrin ("1"3"1I-Tf) was studied in athymic nude mice having s.c. human colonic adenocarcinoma HT-29 xenografts. Four days after "1"3"1I-Tf injection, the "1"3"1I specific activity measured in the HT-29 tumor, i.e. amount of radioactivity per gram of fresh tissue, represented 0.31 #+-# 0.09% of the injected radioactivity and was 1.90 fold more than that measured in the murine colon (P < 0.05). After correction for intravascular "1"3"1I-Tf as estimated by mean of "9"9"mTc-Sn in vivo labeling of red blood cells, the "1"3"1I specific activity observed in the HT-29 tumor was 7.21 fold more than that observed in the murine colon. This subtracting method enabled us to localize a HT-29 tumor xenograft by #gamma# scintigraphy of the entire animal and demonstrated that "1"3"1I-Tf could be a non-specific but potent marker for human colon cancer. (author).
A competitive repopulation assay utilizing chromosome markers was used to assay the reconstituting potential of hematopoietic populations. The test populations consisted of tibial murine marrow locally irradiated with doses ranging from 1.5 Gy to 8.5 Gy and of marrow generated from either murine splenic or marrow stem cells. The purpose of this assay was to assess the innate proliferative potential and microenvironmental influences on the ability to repopulate. Regardless of origin, spleen repopulating ability consistently agreed with spleen colony-forming unit (CFU-s) content. Doses of radiation from 5 Gy to 8.5 Gy diminished, by a factor of 2, the ability to repopulate marrow despite maintenance of CFU-s levels. Marrow generated from splenic stem cells had one-fifth the repopulating ability of marrow derived from marrow stem cells, even though CFU-s levels were equivalent. The results imply that the splenic environment can only maintain stem ...
The studies reported here used genetic differences in susceptibility of C57BL/6N and C3H/HeN mice and exacerbation of the disease by nitrogen dioxide (NO/sub 2/) as tools in assessing the role of early host responses in the pathogenesis of MRM. The two strains did not differ in susceptibility to infection, but C3H/HeN mice were more susceptible to and had increased severity of lung lesions 14 days after intranasal inoculation as determined by 50% biological endpoints and morphometric analysis of tissues. Exposure to NO/sub 2/ for 4 hours prior to exposure to infectious aerosols exacerbated murine respiratory mycoplasmosis (MRM) by 7 days after exposure in both mouse strains. NO/sub 2/ appeared to affect host lung defense mechanisms responsible for limiting mycoplasmal growth in the lungs. The NO/sub 2/ exposure concentration required for this effect varied with the genetic background of the host, the dose of mycoplasmas administered, and the endpoint measured. ...
Total skin electron beam therapy (TSEB) was used in the treatment of 33 patients with lymphoma and 13 patients with leukemia involving extensive segments of the skin surface. Twenty-two of 23 had lesions as a primary manifestation of lymphoma (primary cutaneous lymphoma-PCL) and 11 developed cutaneous lesions following disseminated nodal lymphoma (secondary cutaneous lymphoma-SCL). A once weekly fractionation scheme was employed to irradiate the entire skin surface with 3.5 to 4 MeV electron beam from a 6 MeV linear accelerator. During each weekly session, 400 rad were delivered to the entire skin and a complete course consisted of 4-6 consecutive weekly sessions. The majority of patients have been previously treated elsewhere for various periods and all patients have been at risk for a median of 12 months, range from 12-117 months following TSEB. Striking predominance of the diffuse pattern (76%) was demonstrated in both the PCL and SCL. There was extracutaneous ...
The risks of genetic, leukemia and malignant diseases from medical X-ray diagnostic examinations were estimated using the frequency of radiographic and fluoroscopic exposures per diagnostic examination, child expectancy, leukemia and malignancy significant factors, and using a weighting factor determined on the basis of data concerning the cancer mortality among atomic bomb survivors in Nagasaki and of a recommendation of International Commission of Radiological Protection. The organ or tissue doses with respect to the stochastic risks were determined with ionization chambers and thermoluminescent dosimeters placed at the positions of the organs or tissues in a RANDO woman phantom which was exposed to diagnostic X-rays according to technical factors of typical radiographic and fluoroscopic examinations obtained from a nationwide survey. The resultant risks by age-group and type of radiographic and fluoroscopic examination are tabulated in terms ...
In the medical and occupational exposures, there is a tradition to use the genetically significant dose as an index of harm to the population although it only includes the genetical effects from ionizing radiations. A similar significant dose for somatic effects such as radiation leukemogenesis and carcinogenesis should be added to the genetically significant dose in order to approach an index of total harm to the population from medical and occupational exposures. For this purpose, leukemia and malignant significant factors were determined based on the induction of malignant diseases including leukemia for the atomic bombs in Hiroshima and Nagasaki and the life expectancy of individuals subject to medical examinations or treatments as well as radiation workers, taking account of the possibility of their deaths due to other diseases or accidents during a latent period of malignant diseases. The resultant significant factors were tabulated as a ...
Influenza virus infection during pregnancy has been implicated as one of cause of premature delivery, abortion and stillbirth. We have reported that cultured human fetal membrane chorion cells undergoing apoptosis by influenza virus infection secrete unidentified heat-stable monocyte differentiation-inducing (MDI) factors. In this study, cellular, biological and immunochemical characteristics of MDI factors were investigated using human monocytic leukemia THP-1 cells by nitroblue tetrazolium reduction and cell adhesion assays. The treatment of THP-1 cells with culture supernatants from the influenza virus-infected chorion cells induced the nitroblue tetrazolium reduction ability, which was inhibited by the addition of superoxide dismutase and diphenyleneiodonium chloride, an inhibitor for reduced nicotinamide adenine dinucleotide phosphate oxidase. The phenomenon was also observed in human peripheral blood monocytes and histiocytic leukemia ...
The authors have found that heat-inactivated serum (57/sup 0/C for 1 hour) from normal chickens reduces the proliferation of mitogen-stimulated chicken and murine splenocytes as well as some transformed mammalian lymphoblastoid cell lines. Greater than a 50% reduction in /sup 3/H-thymidine incorporation was observed when concanavalin A (Con A)-activated chicken splenocytes that were cultured in the presence of 10% autologous or heterologous serum were compared to mitogen-stimulated cells cultured in the absence of serum. Normal chicken serum (10%) also caused greater than 95% suppression of /sup 3/H-thymidine incorporation by bovine (EBL-1 and BL-3) and gibbon ape (MLA 144) transformed lymphoblastoid cell lines. The only cell line tested that was not inhibited by chicken serum was an IL-2-dependent, murine cell line. Chicken serum also inhibited both /sup 3/H-thymidine incorporation and IL-2 synthesis by Con A-activated ...
Background: Recent studies have developed a murine model of IgE-mediated food allergy based on oral coadministration of antigen and cholera toxin (CT) to establish a maximal response for studying immunopathogenic mechanisms and immunotherapeutic strategies. However, for studying subtle immunomodulating factors or factors effective during response initiation, this maximal response-based model is less suitable due to a lack of sensitivity. Therefore, in attempts to identify essential parameters to fine-tune the immune response towards a submaximal level, potentially more sensitive, we were interested in characterizing the individual effects of the parameters in the CT-based model: CT dose, antigen type and dose, and number of immunizations. Methods: BALB/c mice were orally sensitized weekly for 3 or 7 weeks with graded doses of CT and various food antigens (soy-trypsin inhibitor, ovalbumin or ovomucoid). Antigen-specific lgG1, IgG2a, IgA and IgE were monitored by ...
The genetically significant dose (GSD), per Caput mean bone marrow dose (CMD), leukemia significant dose (LSD) and malignancy significant dose (MSD) from medical diagnostic X-ray examinations in Japan were estimated based on a 1979 nationwide survey of randomly sampled hospitals and clinics. The population risk estimates were carried out using the resultant values of GSD, LSD and MSD. In the risk estimates, the significant factors, namely, the relative child expectancy, the leukemia significant factor and the malignancy significant factor, for patients were assumed to be same as those of general population. The risk factors used were 185 x 10"-"6 rad"-"1 for genetic risk of all generations, 20 x 10"-"6 rad"-"1 for fatal leukemia and 165 x 10"-"6 rad"-"1 for fatal malignant diseases, respectively. The resultant annual population doses per person were 15 mrad (0.15 mGy) for GSD, 107 mrad (1.07 mGy) for CMD, 86 mrad (0.86 mGy) ...
The most advanced frontier of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is represented by the use of an HLA-partially matched relative as donor. In this type of transplantation, donor-derived natural killer (NK) cells, which are alloreactive towardtoward recipient cells, significantly contribute to the eradication of leukemia blasts. Alloreactive NK cells may also kill host dendritic cells and T lymphocytes, thus preventing graft-versus-host disease and graft rejection, respectively. Sophisticated strategies of adoptive infusion of T-cell lines/clones specific for the most life-threatening pathogens (namely cytomegalovirus, Epstein-Barr virus, Aspergillus and Adenovirus) have been envisaged, and successfully tested in a few pilot trials, to protect the recipient in the...
Abstract Septins are highly conserved cytoskeletal GTP-binding proteins implicated in numerous cellular processes from apoptosis to vesicle trafficking. Septins have been associated with leukemia and solid tumor malignancies, including breast, ovarian, and prostate. We previously reported that high SEPT9_i1 expression in human mammary epithelial cell lines (HMECs) led to malignant cellular phenotypes such as increased cell proliferation, invasiveness, motility, and genomic instability. Our goal here was to better understand how SEPT9_i1 expression might contribute to genomic instability and malignant progression. First, we confirmed that even transient expression of SEPT9_i1 was sufficient to increase aneuploidy in HMECs. We then analyzed SEPT9_i1 by immunoprecipitation and immunofluoresce...
This study investigated the occurrence of free-living amoebae (FLA) in immunodeficiency wards of hospitals in Tehran, Iran. A total of 70 dust and biofilm samples from wards serving transplant, pediatric (malignancies), HIV, leukemia and oncology patients of five university hospitals were collected and examined for the presence of FLA using culturing and molecular approaches. Based on the morphology of the amoebae in plate cultures, primer sets were applied for molecular identification of Acanthamoeba, vahlkampfiid amoebae and Hartmannella. Out of 70 samples, 37 (52.9%) were positive for FLA. Acanthamoeba belonged to the T4 genotype was the most prevalent isolate. Presence of the T4 genotype on medical instruments, including an oxygen mask in an isolation room of an immunodeficiency pediat...
Abstract Herpesvirus saimiri (HVS) causes acute lymphoma and leukemia upon experimental infection of various monkey species. HVS strain C488 is also capable of transforming human T-lymphocytes to stable growth in culture. The most susceptible species for oncogenesis are New World primates, in particular the cottontop tamarin (Saguinus oedipus). However, Old World monkeys such as macaques are the most used animal model for the close-to-human situation. The limited data on HVS infection in Old World monkeys prompted us to investigate susceptibility to infection and disease induction by HVS in macaques. After having established that rhesus macaques can be infected productively, and that rhesus T-cells can be transformed in vivo by HVS, we observed induction of lymphoma in all inoculated anima...
Abstract Imatinib mesylate is the first of a novel group of drugs that specifically target protein tyrosine kinases, which are central to the pathogenesis of human cancer. It has been approved for the treatment of chronic myeloid leukemia and gastrointestinal stromal tumor and has been found efficacious in other neoplastic diseases. Nilotinib and dasatinib, a second-generation of tyrosine kinase inhibitors (TKIs), were developed in response to findings of emerging imatinib resistance or intolerance to the drug. Cutaneous reactions are the most common nonhematologic side effect of these drugs, and their management is challenging especially in the absence of alternative anticancer agents. The present review focuses on the clinical characteristics and the hypothesized molecular pathogenesis o...
Nano- and microstructured surfaces are known to impact on the binding and differentiation of cells, but the detailed basic understanding of the underlying regulatory mechanisms is still scarce, which impedes the rational design of smart biomaterials. Towards a comprehensive analysis of the interplay between topographical parameters such as feature design and lateral and vertical dimensions we here report on a combinatorial screening approach, BioSurface Structure Array (BSSA) of test squares each with a distinct topography. Using such BSSA libraries of 504 topographically distinct surface structures, we have identified combinations of size, gap and height of structures which enhance mineralization as well as the expression of osteogenic markers of a preosteoblastic murine cell line. This g...
ObjectiveExtended periods of muscle disuse, physical inactivity, immobilization, and bedrest result in a loss of muscle mass and a decrease in muscle force, which are accompanied by an increase in oxidative stress. We investigated the effects of the intake of green tea catechins on unloading-induced muscle dysfunction in tail-suspended mice. MethodsTen-week-old male BALB/c mice were fed a purified control diet or a diet containing 0.5% tea catechins for 14 d. Thereafter, the mice were subjected to continuous tail suspension for 10 d. On the final day, muscle mass, contractile force production, antioxidant potential, and carbonylated protein levels were evaluated. ResultsHind limb unloading caused a loss of soleus muscle weight and muscle force. Intake of tea catechins significantly inhibit...
A better understanding of the immune processes in the pathogenesis and progression of prostate cancer (CaP) may point the way towards improved treatment modalities. The challenge is to amplify immune responses to combat tumour escape mechanisms. Infection and inflammation may have a role in prostate carcinogenesis, including the newly discovered xenotropic murine leukaemia virus (XMRV). These inflammatory states damage defence mechanisms and induce a high proliferative state favouring further mutation and impaired immune surveillance. With this knowledge we are able to explore the use of immunotherapy to rejuvenate the immune system in combating CaP. Recently Sipuleucel-T, an immunotherapeutic agent for metastatic androgen independent CaP, has resulted in improved survival and might be the...
Olfactory memory dysfunctions were investigated in the triple-transgenic murine model of Alzheimer's disease (3x Tg-AD). In the social transmission of food preference test, 3x Tg-AD mice presented severe deficits in odor-based memory, without gross changes in general odor-ability. Ab and tau immunoreactivity was not observed in the primary processing regions for odor, the olfactory bulbs (OBs), whereas marked immunostaining was present in the piriform, entorhinal, and orbitofrontal cortex, as well as in the hippocampus. Our results suggest that the impairment in olfactory-based information processing might arise from degenerative mechanisms mostly affecting higher cortical regions and limbic areas, such as the hippocampus.
Toxigenic Clostridium sordellii strains are increasingly recognized to cause highly lethal infections in humans that are typified by a toxic shock syndrome (TSS). Two glucosylating toxins, lethal toxin (TcsL) and hemorrhagic toxin (TcsH) are believed to be important in the pathogenesis of TSS. While non-toxigenic strains of C. sordellii demonstrate reduced cytotoxicity in vitro and lower virulence in animal models of infection, there are few data regarding their behavior in humans. Here we report a non-TSS C. sordellii infection in the context of a polymicrobial bacterial cholangitis. The C. sordellii strain associated with this infection did not carry either the TcsL-encoding tcsL gene or the tcsH gene for TcsH. In addition, the strain was neither cytotoxic in vitro nor lethal in a murine...
Objective To evaluate the inhibitory property of de-glycyrrhizinated extract of Glycyrrhiza glabra root and its phytoconstituents (glabridin, isoliquiritigenin and glycyrrhizin) on LPS-induced production of pro-inflammatory mediators. Materials and methods Inhibitory effect of G. glabra extract and its phytoconstituents were studied on lipopolysaccharide (LPS)-induced nitric oxide (NO), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) levels in J774A.1 murine macrophages. Results G. glabra and isoliquiritigenin significantly inhibited LPS stimulated NO, IL-1 beta and IL-6 production. Glabridin showed significant inhibition of NO and IL-1 beta release, but failed to attenuate IL-6 levels at the tested concentrations. In addition, glycyrrhizin did not exhibit inhibitory response towar...
The potential association between xenotropic murine leukaemia virus-related gammaretrovirus (XMRV) and prostate cancer (PCa) has been documented since 2006. It is important for furthering our understanding of the biological mechanisms of PCa to ascertain whether this association is causal. To summarize the available information on the epidemiological and laboratory findings of the association, we conducted a literature search of the PubMed electronic database (from March 2006 to February 2011) to identify relevant published studies that examined the association between XMRV and PCa. Although several studies showed the positive association between XMRV and PCa, more recent studies did not support this conclusion. The positive findings might be due to contamination of human samples. Further ...
Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot ...
Please cite this paper as: Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder - a preliminary study. Experimental Dermatology 2008; 17: 203-207. Abstract: Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6-/- mice. Three groups were fed a specific di...
Internal amplification controls (IACs) were constructed for incorporation into real-time nucleic acid amplification assays for bovine polyomavirus, hepatitis A virus, hepatitis E virus, human adenovirus, human norovirus genogroup I, human norovirus genogroup II, murine norovirus and porcine adenovirus. The addition of optimised amounts of IAC into the assays did not affect the limits of detection for each specific target virus. A poorly performed extraction of viral nucleic acids was simulated, and the effectiveness of IACs in identifying failed assays was demonstrated. The IACs constructed in this study can be reliably used in their specific assays to provide a robust control that can be routinely applied in the analysis of foods for viruses.
Background. Reports of positive patch test and photopatch test reactions to the chemical ultraviolet filter octocrylene have increased during the last decade. Little is known about the reason for octocrylene's allergenic activity. Objectives. To present and discuss the results of patch tests and photopatch tests with octocrylene, and to investigate the possible cause of its allergenic properties. Methods. Results of patch tests and photopatch tests with octocrylene in patients with adverse skin reactions to sunscreen products and/or ketoprofen were collected. The allergenic potency of octocrylene was investigated in the murine local lymph node assay (LLNA). Chemical reactivity assays were used to mimic octocrylene's interaction with biomolecules. Results. We report 23 cases of positive tes...
An exposure chamber is described for the quantifiable addition of fine and ultrafine aerosol particulate matter directly to cells and used to demonstrate the in vitro cytotoxicity of fine 1,4-naphthoquinone particles to murine lung epithelial cells. The electrostatic particulate dosage and exposure system (EPDExS) operates on the principle of electrostatic precipitation and is shown to deposit fine and ultrafine aerosol particles directly to cells with 100% efficiency for particle diameters in the range of 40-530nm. This range is not limited by the EPDExS, but rather by the aerosolization method used for this study. Numbers of particles deposited onto the cells are counted with a condensation particle counter, negating any need to calculate or estimate particle exposure. The process of par...
We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-? (TNF-?) and Interferon-gamma (IFN-?) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092
Objective: To survey the data for the state of health in the ambient residents of Daya Bay Nuclear Power Plant, and provide the background data to evaluate the state of health affected by fallout of nuclear power plant. Methods: The datas were collected by a radiation epidemiology. The investigation was carried out in the area within 20 km of radius from Daya Bay Nuclear' Power Plant, and the subjects who had lived there for three years or longer before January. 1,1993 and covered by the Household Registry were recruited to a cohort. Results: The mortality rate of overall cancer (per 100 000 PYr) was 88.57 (the standard mortality rate was 79.77 ), the mortality rate of leukemia (per 100 000 PYr) was 3.24 (the standard mortality rate was 2.94), the palpation rate of the goiter in 7-14 years old was 8.34%(9.69% in B ultrasonic), the morbidity rate of newborn's defect (per 100 00 P) was 82.33. The mortality of all cancers or leukemia was similar ...
The development of leukemia and thyroid cancer is characterized by activation of the abl oncogene and ret oncogene, respectively. In order to clarify the relationship between these gene aberrations and radiation, the pro-myelogenous leukemia-derived cell line HL60 and the thyroid cancer-derived cell line 8505C, were irradiated in vitro with 100Gy of X-rays. RNA was then extracted from 10"8 cells of the respective cell lines and examined by the reverse transcription PCR method for rearrangements of abl and ret genes. Five kinds of positive bands were observed in the HL-60 cells irradiated with 100Gy of X-ray. Similarly, six positive bands were also observed in the 8505C cells irradiated with 100Gy. In vitro X-irradiation activation of oncogenes found in radiation induced cancers imply that gene rearrangement by X-rays is involved in the development of malignant tumors. Furthermore, in an experiment to detect radiation effects in A-bomb ...
The neuronal nicotinic acetylcholine receptor {alpha}7 subunit is a member of a family of ligand-gated ion channels, and is the only subunit know to bind {alpha}-bungarotoxin in mammalian brain. {alpha}-Bungarotoxin binding sites are known to be more abundant in the hippocampus of mouse strains that are particularly sensitive to nicotine-induced seizures. The {alpha}7 receptor is highly permeable to calcium, which could suggest a role in synaptic plasticity in the nervous system. Auditory gating deficiency, an abnormal response to a second auditory stimulus, is characteristic of schizophrenia. Mouse strains that exhibit a similar gating deficit have reduced hippocampal expression of the {alpha}7 subunit. We have cloned and sequenced the full length cDNA for the mouse {alpha}7 gene (Acra-7) and characterized its gene structure. The murine {alpha}7 shares amino acid identity of 99% and 93% with the rat and human {alpha}7 subunits, respectively. Using an interspecies ...
''Paraquat lung'' which is complicated with paraquat poisoning has been a lethal pulmonary pathology presenting intra-alveolar fibrosis, but an effective therapy has not been developed so far. We hypothesized that the type II alveolar cells producing surfactant were damaged by paraquat which was actively accumulated through out the blood by alveolar epithelial cells. To prove this hypothesis, we examined the effect of an intratracheal administration of an artificial lung surfactant (surfacten, Mitsubishi Tanabe Pharma Corporation, Osaka) on mortality in a model of murine paraquat poisoning. Paraquat was given intramuscularly 3 days after the intratracheal surfactant administration. The mice used were C57BL/6J strain and Balb/C strain. The lethal dose, 50% (LD50), of paraquat was about 28 mg/kg in the C57BL/6J strain and about 9 mg/kg in the Balb/C strain, respectively. Mortalities of paraquat poisoning in both strains of mice improved significantly when the mice ...
PNAS-4, a novel pro-apoptotic gene activated during the early response to DNA damage, can inhibit proliferation via apoptosis when overexpressed in some tumor cells. Recent studies have indicated that honokiol can induce apoptosis, inhibit angiogenesis, and suppress tumor growth. In the present study, we investigated whether mouse PNAS-4 (mPNAS-4) could augment the apoptosis of tumor cells induced by honokiol in vitro, and whether the antiangiogenic activity of honokiol and induction of apoptosis by mPNAS-4 could work cooperatively to improve the antitumor efficacy in vivo. In vitro, mPNAS-4 inhibited proliferation of murine colorectal carcinoma CT26 and Lewis lung carcinoma LL2 cells through induction of apoptosis, and significantly augmented the apoptosis of CT26 and LL2 cells induced by honokiol. Compared with treatment with mPNAS-4 or honokiol alone, in vivo systemic administration of an expression plasmid encoding mPNAS-4 and low-dose honokiol significantly ...
Glycosaminoglycan synthesis was studied in cell populations of ultraviolet light-induced murine cutaneous fibrosarcoma cells under conditions of varying growth rates in vitro. After labeling with the precursors, /sup 3/H-glucosamine and /sup 35/SO/sub 4/, sulfated glycosaminoglycans recoverable by direct proteolysis of the culture monolayers increased approximately 5-fold on a per cell basis from sparsely populated, exponential cell cultures (greater than 85% of cells in S, G2, or M phases) to stationary cultures inhibited by high cell density (greater than 50% of cells in G1). Within this cell surface-associated material, the relative ratio of heparan sulfate to the chondroitin sulfates was approximately 60/40% under conditions of exponential growth; in the growth-arrested cultures, the reverse ratio was found. The substratum attached material, obtained from the flask surface after ethyl glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid ...
A hyaluronic acid binding fraction was purified from the supernatant media of both 3T3 and murine sarcoma virus (MSV) transformed 3T3 cultures by hyaluronate and immunoaffinity chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis resolved the hyaluronate affinity-purified fraction into three major protein bands of estimated molecular weight (M/sub r,e/) 70K, 66K, and 56K which contained hyaluronate binding activity and which were termed hyaluronate binding proteins (HABP). Hyaluronate affinity chromatography combined with immunoaffinity chromatography, using antibody directed against the larger HABP, allowed a 20-fold purification of HABP. Fractions isolated from 3T3 supernatant medium also contained additional binding molecules in the molecular weight range of 20K. This material was present in vanishingly small amounts and was not detected with a silver stain or with (/sup 35/S)methionine label. The three protein species isolated by ...
Purpose: Antitumor activity of the dichloroplatinum(II)-histamine complexes labeled with I-125 or I-131 was investigated in a transplantable murine adenocarcinoma (MA) model. Methods: The tumor model was obtained in C3H/W female mice after subcutaneous inoculation of the tumor cells derived from the mice bearing a mammary tumor of spontaneous origin. Antitumor activities of the platinum-histamine complexes were investigated in three independent experiments, which differed in applied doses of preparations (PtCl{sub 2}Hist, PtCl{sub 2}[{sup 125}I]Hist, PtCl{sub 2}[{sup 131}I]Hist, PtCl{sub 2}Hist/PtCl{sub 2}[{sup 125}I]Hist and PtCl{sub 2}Hist/PtCl{sub 2}[{sup 131}I]Hist), treatment schedules as well as stages of the disease progress in the animals used. Experiment 1 included long-term, multidose treatment with low single doses (treatment duration 31-32 days; 8-10 doses of ca. 0.25{center_dot}MTD{sub Pt} each). Experiment 2 included short-term, multidose treatment ...
Platinum(II) complexes (1-4) with bidentate N,Nprime-ligands, O,Oprime-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), of (S,S)-ethylenediamine-N,Nprime-di-2-(4-methyl)pentanoic acid were synthesized and characterized by IR, 1H NMR and 13C NMR spectroscopy and elemental analysis. DFT calculations were performed for the complexes and it was found that only one diastereoisomer could be formed. Cytotoxic activity of complexes 1-4 was determined against chronic lymphocytic leukemia cells (CLL) and compared to the activity of ligand precursors L12HCl-L42HCl and corresponding palladium(II) complexes, [PdCl2L] (L = L1-L4). The complexes were found to exhibit significantly higher antitumor activities than cisplatin on CLL cells. Cytotoxic effect of platinum(II) complexes on CLL cel...
Maps transformed so as to have constant density of residential population were used to analyze the spatial distribution of disease in three specific areas. Each area had received recent attention because of suspected environmental pollution. The area adjacent to the Rocky Flats Facility (CO) was examined to identify any association between possible plutonium releases and increases in lung cancer or leukemia incidence. The industrial area of northern Contra Costa County (CA) was studied to explore a relationship between petrochemical industrial emissions and histologic-specific lung cancers. Finally, a suspected increase in the risk of congenital cardiac defects possibly related to pollution of the Santa Clara County (CA) water supply was investigated. No evidence of elevated risk of disease was found to be associated with either the Rocky Flats Facility or the polluted water of Santa Clara County. An increase in lung cancer, found by other investigators in earlier ...
The human smooth muscle myosin heavy chain locus (MYH11) was mapped by fluorescence in situ hybridization to the middle of the p arm of chromosome 16 using a genomic cosmid clone containing coding sequences of the gene as probe. Probe from coding sequence, when applied to Southern blots of a panel of hybrids containing different portions of human chromosome 16, localized the gene to 16p13.13-13.12. Coding sequence PCR primers, when used on the DNA from a CHO-mouse hybrid clone mapping panel informative for mouse chromosomes, showed that the gene was located on mouse chromosome 16. These results correct a recent assignment of MYH11 from 16q12.2 to the region of the 16p-arm inversion breakpoint seen in acute myelomonocytic leukemia (AMML) M4Eo and demonstrate that the conflicting data do not result from the presence of additional MYH genes on the q arm of the chromosome. Also, a new region of conserved synteny between human 16p and mouse 16 is established. 10 refs., ...
Lytic activity and recovery of natural killer (NK) cells was monitored in pediatric patients with leukemias (ALL, AML, CML, JMML) and myelodysplastic syndromes after transplantation of T cell depleted stem cells from matched unrelated (n = 18) and mismatched related (haploidentical, n = 29) donors. CD34 + selection with magnetic microbeads resulted in 8 x 10^3/kg residual T cells. No post-transplant immune suppression was given. NK cells recovered rapidly after transplantation (300 CD56+/@mL at day 30, median), whereas T cell recovery was delayed (median: 12 CD3+/@mL at day 90). NK activity was measured as specific lysis of K 562 targets several times (mean: 3 assays per patient). Four temporal patterns of lytic activity could be differentiated: consistently low, consistently high, decreas...
For the risk estimate of fatal malignancies, an effective dose was proposed on the basis of the assumption that the risk should be equal whether the whole body irradiated uniformly or whether there is non-uniform irradiation. The effective dose was defined by the product of organ or tissue doses and a weighting factor representing the proportion of risk factor for a fatal malignancy resulting from organ or tissue irradiation to the total malignant factor. The risk of malignancies can be derived by multiplying the malignant significant factor by the product of the risk factor and the effective dose. For the genetic risk, a significant factor was a relative child expectancy and organ or tissue doses were gonad doses. And, for the leukemogenic risk, a significant factor was the leukemia significant factor and organ or tissue dose was mean bone marrow dose. The present method makes it easy to estimate the risk for individuals and population from medical and ...
This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and published original articles are also given. (N.I.)
Population doses from diagnostic and therapeutic uses of radiopharmaceuticals have been estimated on the basis of a nation wide survey data on the number of investigations and treatments used radiopharmaceuticals in the nuclear medicine and the annual amount of their activities. The gonad and marrow doses were calculated from published biokinetics data from humans, employing the MIRD method. The resultant annual genetically significant dose from diagnostic and therapeutic uses of radiopharmaceuticals was 0.36 and 0.02 mrad (3.6 and 0.2 #mu#Gy) per person, respectively, with a total 0.38 mrad (3.8 #mu#Gy) per person. The annual per Caput mean bone marrow dose was 2.3 mrad (23 #mu#Gy) for diagnosis and 0.2 mrad (2 #mu#Gy), for therapy. The resultant annual leukemia significant dose was 1.8 mrad (18 #mu#Gy) per person for diagnostic uses and 0.2 mrad (2 #mu#Gy) per person for therapeutic use, with a total of 2.0 mrad (20 #mu#Gy) per person. These population doses by ...
Serum ferritin levels were measured in 72 normal subjects and in 214 cases with various diseases by an immunoradiometric assay. In normal subjects, the serum ferritin levels were 27-230 ng/ml. Elevated serum ferritins were observed in most cases with iron excess and acute hepatitis. Markedly elevated levels were found in the majority of cases with acute leukemia, malignant lymphoma, hepatoma, and pancreatic cancer. High ferritin levels were also found in other malignant diseases. However, the range overlapped broadly with that of nonmalignant diseases. The serum ferritin correlated significantly with serum iron in normals and in those with iron deficiency anemia. In most nonmalignant cases, the serum ferritin and iron levels distributed on a regression line obtained from levels in normals and those with iron deficiency anemia. However, 92% of the malignant cases showed a serum ferritin to iron ratio higher than that of normal subjects. The estimation of the serum ...
Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to stimulate bone resorption in vitro. We have now investigated whether these cytokines also cause a similar action when administered in vivo. This was made possible by the adaptation of a newly developed technique that enables the continual assessment of bone resorption in vivo in mice by measuring urinary excretion of {sup 3}H from ({sup 3}H)tetracycline-prelabeled animals. Experiments using maneuvers known to influence bone resorption, such as a change in dietary calcium or administration of parathyroid hormone or dichloromethylenebisphosphonate, indicate that the technique is reliable and sensitive in mice. Daily intravenous administration of either recombinant human or recombinant murine TNF-alpha, as well as subcutaneous administration of recombinant human IL-1 alpha, were found to stimulate bone resorption in a dose-dependent manner. The effect was maximal within 2 days. Thus, ...
Several series of pyrimidine nucleosides were evaluated as part of a larger program to develop non-invasive brain imaging agents. The interaction of these antitumor/antiviral nucleosides with an NBMPR-sensitive murine erythroctye nucleoside transporter was evaluated by determining their inhibitory effect (K_i) on zero-trans influx of thymidine. Within each series of compounds, which had F, Cl, Br or I as halogen substituents, an increase in size of the halogen atom or a decrease in electronegativity decreased affinity for the transporter. Partition coefficients (P) of these pyrimidine nucleosides were measured to determine their potential to diffuse across the blood-brain-barrier (BBB). Most of the pyrimidine nucleosides had lower P values (log P < 0.9), and were considered to be poor candidates for simple diffusion across the BBB, although an active BBB transport mechanism for some nucleosides could be operative. For a given series, it was found that log P ...
CBA/Ca mice were infected by either the intravenous or intraperitoneal route with Mycobacterium microti and the subsequent changes in local macrophage populations examined. Following infection, the number of macrophages increased and they showed greater expression of both MHC Class II molecules. This response was not dependent on viability of the mycobacteria, in contrast to reports with other microorganisms such as Listeria. Studies in sublethally irradiated mice indicated that persistent antigen could give rise to a response after a period of host recovery which was radiation dose dependent. This procedure also highlighted differences in the regulation of different murine class II antigens in vivo, as seen by delayed re-expression of I-E antigens. Macrophage accessory cell function, as assessed by an in vitro T cell proliferation assay, correlated with Ia expression after fixation, but not after indomethacin treatment; this highlights the diverse nature of ...
Skin sensitization is the most commonly reported occupational illness, causing much suffering to a wide range of people. Identification and labeling of environmental allergens is urgently required to protect people from skin sensitization. The guinea pig maximization test (GPMT) and murine local lymph node assay (LLNA) are the two most important in vivo models for identification of skin sensitizers. In order to reduce the number of animal tests, quantitative structure-activity relationships (QSARs) are strongly encouraged in the assessment of skin sensitization of chemicals. This paper has investigated the skin sensitization potential of 162 compounds with LLNA results and 92 compounds with GPMT results using a support vector machine. A particle swarm optimization algorithm was implemented for feature selection from a large number of molecular descriptors calculated by Dragon. For the LLNA data set, the classification accuracies are 95.37% and 88.89% for the ...
As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma-ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST-6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha-MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha-MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha-MSV-transformed KMST-6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma-ray-transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha-MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one ...
Radixin is a cytoskeletal protein that may be important in linking actin to the plasma membrane. Recent cloning of the murine and porcine radixin cDNAs revealed a protein highly homologous to ezrin and moesin. The authors have cloned and sequenced the human radixin cDNA and found the predicted amino acid sequence for the human protein to be nearly identical to those predicted for radixin in the two other species. By Southern analyses of Chinese hamster x human somatic cell hybrid DNA and of PCR products derived from hybrids, the coding gene (RDX) was mapped to 11q. Fluorescence chromosomal in situ hybridization with a cDNA plasmid further localized this gene to band 11q23. However, PCR amplification with [open quotes]radixin-specific[close quotes] primers on the hybrid DNA panel yielded an additional, very similar DNA sequence that was further characterized by direct sequencing of PCR products. This sequence represents a truncated version and the respective locus ...
Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Mutations in PTEN-induced kinase 1 (PINK1) are a frequent cause of recessive PD. Autophagy, a pathway for clearance of protein aggregates or impaired organelles, is a newly identified mechanism for PD development. However, it is still unclear what molecules regulate autophagy in PINK1-silenced cells. Here we report that autophagosome formation is promoted in the early phase in response to PINK1 gene silencing by lentivirus transfer vectors expressed in mouse striatum. Reduced PP2A activity and increased phosphorylation of PP2A at Y307 (inactive form of PP2A) were observed in PINK1-knockdown dopaminergic cells and striatum tissues. Treatment with C2-ceramide (an agonist of PP2A) reduced autophagy levels in PINK...
Bone morphogenetic protein (BMP)-4 has a crucial role on primordial germ cells (PGCs) development in vivo which can promote stem cell differentiation to PG-like cells. In this study, we investigated the expression of Mvh as one of the specific genes in primordial germ cells after treatment with different doses of BMP4 on bone mesenchymal stem cells (BMSCs)-derived PGCs. Following isolation of BMSCs from male mouse femur and tibia, cells were cultured in medium for 72?h. Passage 4 murine BMSCs were characterized by CD90, CD105, CD34, and CD45 markers and osteo-adipogenic differentiation. Different doses of BMP4 (0, 0.01, 0.1, 1, 5, 25, 50, and 100?ng/ml) were added to BMSCs for PGCs differentiation during 4-days culture. Viability percent, proliferation rates, and expression of Mvh gene wer...
Abstract TLR9 recognizes unmethylated CpG-containing DNA commonly found in bacteria. Synthetic oligonucleotides containing CpG-motifs (CpG ODNs) recapitulate the activation of TLR9 by microbial DNA, whereas inversion of the CG dinucleotide within the CpG motif to GC (GpC ODNs) renders such ODNs inactive. This difference cannot be attributed to binding of ODNs to the full-length TLR9 ectodomain, as both CpG and GpC ODNs bind comparably. Activation of murine TLR9 requires cleavage into an active C-terminal fragment, which binds CpG robustly. We therefore compared the ability of CpG and GpC ODNs to bind to full-length and C-terminal TLR9, and their impact on the cleavage of TLR9. We found that CpG binds better to C-terminal TLR9 when compared with GpC, despite comparably low binding of both O...
N-ethyl-N-nitrosourea (ENU) mutagenesis has led to the elucidation of several regulator genes for melanocyte and skin development. Here we characterized a mutant from ENU mutagenesis with similar phenotype as that of Splotch mutant, including exencephaly, spina bifida and abnormal limbs in homozygotes as well as white belly spotting and occasionally loop-tail in heterozygotes. This novel mutant was named as Sp(xG). Through genome-wide linkage analysis in backcross progenies with microsatellite markers, the Sp(xG) was confined to a region between D1MIT415 and D1MIT7 on chromosome 1, where notable Pax3 gene was located. Direct sequencing revealed that Sp(xG) carried a nucleotide A894G missense transition in exon 6 of Pax3 gene that resulted in Asn to Asp substitution at amino acid 269 within the highly-conserved homeodomain (HD) DNA recognition module, which was the first point mutation found in this domain in mice. This N269D mutation impaired the transactivation capacity of Pax3 ...
The role of intracellular Ca2+ (Ca2+i) on hematopoiesis was investigated in long term bone marrow cultures using cytokines and agonists of P2 receptors. Cytokines interleukin 3 and granulocyte/macrophage colony stimulator factor promoted a modest increase in Ca2+i concentration ([Ca2+]i) with activation of phospholipase Cgamma, MEK1/2, and Ca2+/calmodulin kinase II. Involvement of protein kinase C was restricted to stimulation with interleukin 3. In addition, these cytokines promoted proliferation (20 times) and an increase in the Gr-1(-)Mac-1+ population with participation of gap junctions (GJ). Nevertheless ATP, ADP, and UTP promoted a large increase in [Ca2+]i, moderate proliferation (6 times), a reduction in the primitive Gr-1(-)Mac-1(-)c-Kit+ population, and differentiation into macrophages without participation of GJ. It is likely that Ca2+i participates as a regulator of hematopoietic signaling: moderate increases in [Ca2+]i would be related to cytokine-dependent proliferation ...
Sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) has worse outcome because of multiresistance to a large group of antibiotics, which may lead to death from septic shock. In the present study, we firstly found that artesunate in combination with oxacillin was capable of protecting mice challenged with live MRSA WHO-2 (WHO-2) and the protection was related to the reduced TNF-a and IL-6 levels and decreased bacterial load. Based on above results, artesunate was further investigated from two aspects in vitro, anti-inflammation effect and antibacterial enhancement effect on antibiotics. Artesunate not only inhibited TNF-a and IL-6 release but also inhibited mRNA and protein expressions of TLR2 and Nod2, two important receptors, in murine peritoneal macrophages stimulated wit...
Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best ...
An exposure chamber is described for the quantifiable addition of fine and ultrafine aerosol particulate matter directly to cells and used to demonstrate the in vitro cytotoxicity of fine 1,4-naphthoquinone particles to murine lung epithelial cells. The electrostatic particulate dosage and exposure system (EPDExS) operates on the principle of electrostatic precipitation and is shown to deposit fine and ultrafine aerosol particles directly to cells with 100% efficiency for particle diameters in the range of 40-530nm. This range is not limited by the EPDExS, but rather by the aerosolization method used for this study. Numbers of particles deposited onto the cells are counted with a condensation particle counter, negating any need to calculate or estimate particle exposure. The process of particle introduction, assessed using Trypan blue dye exclusion, had no effect on cell viability. In combination with a differential mobility classifier, the EPDExS can deliver ...
Purpose: During recent years, more intensified systemic and local treatment regimens have increased the 5-year survival figures in localized Ewing's sarcoma to more than 60%. There is, however, concern about the risk of second malignancies (SM) in long-term survivors. We have analyzed the second malignancies in patients treated in the German Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and Methods: From January 1981 through June 1991, 674 patients were registered in the two sequential multicentric Ewing's sarcoma trials CESS 81 (recruitment period 1981-1985) and CESS 86 (1986-1991). The systemic treatment in both studies consisted of a four-drug-regimen (VACA = vincristine, actinomycin D, cyclophosphamide, and adriamycin; or VAIA = vincristine, actinomycin D, ifosfamide, and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy in curative patients was either complete surgery (n = 162), surgery plus ...
New platinum(II) complexes with asymmetrically substituted chiral diamine ligands A{sub 2}PtX{sub 2}, (A{sub 2}=NH{sub 2}CH(CH{sub 3})CH{sub 2}NH(c-C{sub 5}H{sub 9}) (apcpa), NH{sub 2}CH(CH{sub 3})CH{sub 2}NH(c-C{sub 6}H{sub 11}) (apcha); X{sub 2}=2Cl, isopropylidenmalonate (IPM), 1,1'-cyclobutandicarboxylate (CBDCA) have been synthesized and characterized by means of elemental analyses, infrared and NMR spectroscopies, and X-ray crystallography. The crystal structures of (S-apcha)Pt[CBDCA]{center_dot}3H{sub 2}O (orthorhombic, P2{sub 1}2{sub 1}2(No. 18), a=6.926(3), b=15.243(3), c=19.319(4) A, V=2039.5(10) A{sup 3}, Z=4, R=0.072) and (S-apcha)Pt[IPM]{center_dot}2.5H{sub 2}O (monoclinic, P2/c(No. 13), a=9.882(1), b=18.502(1), c=22.056(1) A, V=4032.8(5) A{sup 3}, Z=8, R=0.093) exhibit that the platinum atoms achieve a typical square planar arrangement with two nitrogen atoms in cis position and with the chiral center retained. The spectroscopic data disclose that these platinum ...
Two children with cutaneous lymphoma and leukemia who were treated with total skin electron beam therapy (TSEB) are described here. Patient 1. A 7-year-old boy was admitted because of a mass over the bilateral parotis and anemia. The white blood cell count on admission was 5,000/ul. Bone marrow examination revealed 70 per cent monoblasts (M5a type by FAB classification). Complete remission was obtained following the regimen of daunomycin, cytosine arabinoside, 6-mercaptopurine and prednisolone. He was again admitted because of a skin nodule on the left thigh 19 months after initial diagnosis. A biopsy of the skin nodule demonstrated monoblastic infiltration. He received 20 Grays (Gy) to the left thigh and this led to resolution of the skin nodule. At that time, other skin nodules appeared on the right upper and lower extremities. He was treated with TSEB. Daily doses of 1 Gy were given twice a week with a 4 MeV electron beam and a total dose of 10 Gy was ...
In this experiments, we established long-termed culture methods of bone marrow stromal cells for proliferation and differentiation of stem cells. And we selected some extracts which support maximal proliferation of stromal cells with this method. We conformed the synergic effects of herval mixture extracts for stromal cell growth. The proliferation of stromal cells was increased rather by the addition of mixture extracts than by addition of single strain extract. In the previous and cooperative experiments, we selected complex extracts which increased the number of nonadherent mononuclear cells. Different cytokine expression patterns were observed stromal cells cultured in the presence or absence of mixture extracts which support differentiation of nonadherent cells. Stimulation of macrophage cell line with herval extracts with the treatments of recombinant interferon-{gamma} resulted in increased nitric oxide synthesis in a dose-dependent manners. In addition, these extracts induced ...
A retrospective review was made of 2,659 autopsy patients obtained during the past 31 years and a half in Hiroshima Atomic Bomb Hospital. Of the patients, 1,328 (49.9%) were A-bomb survivors. Five hundred and six A-bomb survivors (38.1%) had been exposed at up to 2,000 m from the hypocenter. There was no correlation between the incidence of malignancy and the presence of exposure to A-bombing. The incidence of multiple malignancy was slightly higher in A-bomb survivors exposed at the place nearer the hypocenter. In the group of A-bomb survivors, cancer of the lung was the most common for men; and cancer of the stomach was the most common for women. The incidence of malignancy has been high in the exposed group during the early eras of examination; however, this figure has recently become high in the non-exposed group. Regarding the kinds of malignancy, there was no significant difference between the exposed and non-exposed groups. The incidence of leukemia was high ...
HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration into the Sfpi1 locus activates the myeloid ...
The population doses and risks of stochastic effects from occupational exposures in Japan in 1978 were estimated on the basis of a nation-wide survey. The survey was conducted on annual collective dose equivalents by sex, age group and type of radiation work for about 82,500 workers other than the workers in nuclear power stations. The data on the workers in nuclear power stations were obtained from the offitial publication of the Japan Nuclear Safety Commission. The total number of workers except for nuclear power stations was estimated to be about 170,000 persons. Radiation works were subdivided as follows: medical works including dental; nondestructive inspectional; non-atomic energy industrial; research and educational; atomic energy industrial and nuclear power industrial. The annual collective dose equivalents were estimated to be about 6,000 man rem for medical workers, 450 man rem for non-destructive inspectional, 450 man rem for non-atomic energy industrial and 13,300 man rem ...
In this experiments, we established long-termed culture methods of bone marrow stromal cells for proliferation and differentiation of stem cells. And we selected some extracts which support maximal proliferation of stromal cells with this method. We conformed the synergic effects of herbal mixture extracts for stromal cell growth. The proliferation of stromal cells was increased rather by the addition of mixture extracts than by addition of single strain extract. In the previous and cooperative experiments, we selected complex extracts (Him-I, Him-II) which increased the number of nonadherent mononuclear cells. Different cytokine expression patterns were observed stromal cells cultured in the presence or absence of mixture extracts which support differentiation of nonadherent cells. Some fractions of Him-I and Him-II increased the proliferation of bone marrow cells irradiated {gamma}-ray(4Gray). Stimulation of macrophage cell line with herval extracts with the treatments of recombinant ...
Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many species of mice and rats but not in humans and dog; substantial ...
Collective dose equivalent and population dose from occupational exposures in Japan, 1988 were estimated on the basis of a nationwide survey. The survey was conducted on annual collective dose equivalents by sex, age group and type of radiation work for about 0.21 million workers except for the workers in nuclear power stations. The data on the workers in nuclear power stations were obtained from the official report of the Japan Nuclear Safety Commission. The total number of workers including nuclear power stations was estimated to be about 0.26 million. Radiation works were subdivided as follows: medical works including dental; non-atomic energy industry; research and education; atomic energy industry and nuclear power station. For the determination of effective dose equivalent and population dose, organ or tissue doses were measured with a phantom experiment. The resultant doses were compared with the doses previously calculated using a chord length technique and with data from ICRP ...
Collective dose equivalent and population dose from occupational exposures in Japan, 1988 were estimated on the basis of a nationwide survey. The survey was conducted on annual collective dose equivalents by sex, age group and type of radiation work for about 0.21 million workers except for the workers in nuclear power stations. The data on the workers in nuclear power stations were obtained from the official report of the Japan Nuclear Safety Commission. The total number of workers including nuclear power stations was estimated to be about 0.26 million. Radiation works were subdivided as follows: medical works including dental; non-atomic energy industry; research and education; atomic energy industry and nuclear power station. For the determination of effective dose equivalent and population dose, organ or tissue doses were measured with a phantom experiment. The resultant doses were compared with the doses previously calculated using a chord length technique and with data from ICRP ...
As a central supervision authority the National Electrical Safety Board (Elsaekerhetsverket) has the main responsibility for the safety of high voltage power lines and other power electric equipment. It is therefore also responsible for questions concerning the effects of power frequency magnetic fields on the environment. According to the rules it is not allowed to draw overhead power lines with a voltage exceeding 1000 V above buildings. Their minimum distance to buildings must not be below 5 m. For regions comprised by rural development plans the directions prescribe a minimum distance of 10 m between buildings and high voltage transmission lines with a voltage of 55 kV or more. The publication of two large epidemiological studies about exposure to magnetic fields and cancer in Sweden in autumn 1992 has brought magnetic fields problems to general notice again. A statement on health risks form electromagnetic fields was issued by SSI in January 1993. SSI and Elsaekerhetsverket ...
The murine 3T3-L1 fibroblast under appropriate incubation conditions differentiates into an adipocyte phenotype. This 3T3-L1 adipocyte exhibits many of the morphologic, biochemical, and insulin-responsive features of the normal rodent adipocyte. Using quantitative electron microscopic (EM) autoradiography we find that, when /sup 125/I-insulin is incubated with 3T3-L1 adipocytes, the ligand at early times of incubation localizes to the plasma membrane of the cell preferentially to microvilli and coated pits. When the incubation is continued at 37 degrees C, /sup 125/I-insulin is internalized by the cells and preferential binding to the villous surface is lost. With the internalization of the ligand, two intracellular structures become labeled, as determined by the method of hypothetical grain analysis. These include large clear, presumably endocytotic, vesicles and multivesicular bodies. Over the first hour of incubation the labeling of these structures increases in ...
The influence of reconstituting a murine monoclonal IgG_1 antibody kit with pertechnetate Tc99m on antibody distribution in the liver, spleen and sternal bone marrow of patients was examined. The "9"9"mTc-labelled antibody used is directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen (CEA) and has been successfully applied for imaging tissue inflammation and bone marrow scanning. Radioactivity uptake was determined in the liver, spleen, bone marrow and a precordial background region in a consecutive series of 25 patients, examined with an antibody preparation, routinely radiolabelled according to the manufacturer's recommendations and in 14 patients, in whom the antibody was reconstituted with special care, avoiding bubble formation and dropping of buffer into the antibody-containing vial. Gentle compared with routine antibody reconstitution caused a highly significant reduction of the antibody uptake in the liver, as determined ...
Soluble epoxide hydrolase (sEH) plays an important role in the metabolism of endogenous chemical mediators involved in the regulation of blood pressure and inflammation. 1,3-Disubstituted ureas with a polar group located on the fifth atom from the carbonyl group of urea function are active inhibitors of sEH both in vitro and in vivo. However, their limited solubility in water and relatively high melting point lead to difficulties in formulating the compounds and poor in vivo efficacy. To improve these physical properties, the effect of structural modification of the urea pharmacophore on the inhibition potencies, water solubilities, octanol/water partition coefficients (log P), and melting points of a series of compounds was evaluated. For murine sEH, no loss of inhibition potency was observed when the urea pharmacophore was modified to an amide function, while for human sEH 2.5-fold decreased inhibition was obtained in the amide compounds. In addition, a NH group ...
Two plasmids which express either nearly intact or truncated filamentous hemagglutinin (FHA) from Bordetella pertussis and which are marked with a tetracycline resistance (Tcr) gene were transformed into Salmonella dublin SL1438, an aroA deletion mutant intended for use as an attenuated oral vaccine against salmonellosis. These S. dublin recombinants, when fed to mice, induced serum immunoglobulin, immunoglobulin M (IgM), and sometimes IgA antibody responses to FHA and S. dublin. In addition, IgA antibodies against FHA were found in gut wash fluids. S. dublin carrying pDB2300, a multicopy plasmid encoding truncated FHA protein, induced a better antibody response than did S. dublin carrying pDB2000, a low-copy-number plasmid encoding full-sized FHA. Administration of tetracycline to mice enhanced the stability of recombinant plasmids, and tetracycline-treated mice developed higher anti-FHA titers. Although neither strain examined is suitable for use in a human oral vaccine, these data ...
Over the past few years there has been a great deal of interest in reducing experimental systems to a lab-on-a-chip scale. There has been particular interest in conducting high-throughput screening studies using microscale devices, for example in stem cell research. Microwells have emerged as the structure of choice for such tests. Most manufacturing approaches for microwell fabrication are based on photolithography, soft lithography, and etching. However, some of these approaches require extensive equipment, lengthy fabrication process, and modifications to the existing microwell patterns are costly. Here we show a convenient, fast, and low-cost method for fabricating microwells for cell culture applications by laser ablation of a polyester film coated with silicone glue. Microwell diameter was controlled by adjusting the laser power and speed, and the well depth by stacking several layers of film. By using this setup, a device containing hundreds of microwells can be fabricated in a ...
The Chediak-Higashi syndrome (CHS) is a severe autosomal recessive condition, features of which are partial oculocutaneous albinism, increased susceptibility to infections, deficient natural killer cell activity, and the presence of large intracytoplasmic granulations in various cell types. Similar genetic disorders have been described in other species, including the beige mouse. On the basis of the hypothesis that the murine chromosome 13 region containing the beige locus was homologous to human chromosome 1, we have mapped the CHS locus to a 5-cM interval in chromosome segment 1q42.1-q42.2. The highest LOD score was obtained with the marker D1S235 (Z{sub max} = 5.38; {theta} = 0). Haplotype analysis enabled us to establish D1S2680 and D1S163, respectively, as the telomeric and the centromeric flanking markers. Multipoint linkage analysis confirms the localization of the CHS locus in this interval. Three YAC clones were found to cover the entire region in a contig ...
The transcriptional silencing of some cell cycle inhibitors and tumor suppressors, such as p16 and retinoic acid receptor beta(2), by DNA hypermethylation at CpG islands is commonly found in human oral squamous carcinoma cells. We examined the effects of the DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (5-Aza; 0.25 mg/kg body weight), all-trans retinoic acid (RA; given at 100 microg/kg body weight and 1 mg/kg body weight), and the combination of 5-Aza and the low-dose RA on murine oral cavity carcinogenesis induced by the carcinogen 4-nitroquinoline 1-oxide (4-NQO) in a mouse model. All the drug treatments were done for 15 weeks after a 10-week 4-NQO treatment. Mice in all drug treatment groups showed decreases in the average numbers of neoplastic tongue lesions. The combination of 5-Aza and RA effectively attenuated tongue lesion severity. Although all drug treatments limited the increase in the percentage of proliferating cell nuclear antigen-positive ...
Background: Some former retrospective studies have suggested that patients with Ewing's sarcoma might have a very high risk for developing secondary sarcomas if treated with radiotherapy. We have evaluated the risk of second malignancies (SM) in patients treated in the German Cooperative Ewing's Sarcoma Studies CESS 81 and CESS 86. Materials and methods: From January 1981 through June 1991, a total number of 674 patients was registered in the two multicentric Ewing's sarcoma trials CESS 81 (1981 through 1985) and CESS 86 (1986 through June 1991). The systemic treatment consisted in both studies of a four-drug-chemotherapy (VACA= vincristine, actinomycin D, cyclophosphamide and adriamycin; or VAIA= vincristine, actinomycin D, ifosfamide and adriamycin) and a total number of four courses, each lasting nine weeks, was recommended by the protocol. Local therapy was either complete surgery or surgery plus postoperative radiotherapy with 36-46Gy or definitive radiotherapy with 46 to 60Gy. ...
The herpes simplex virus type 1 thymidine kinase (HSV1-TK) reporter system is being used to directly and indirectly monitor therapeutic gene expression, immune cell trafficking and protein-protein interactions in various living animals. However, the issues of HSV1-TK enzyme stability in living cells and whether this reporter system is optimal for dynamic studies of gene expression events in genetic imaging have not be addressed. The purpose of the present study was to evaluate the application of this reporter system in dynamic studies of transcriptional gene regulation. To achieve this purpose, we established two tetracycline-inducible murine sarcoma cell lines, tetracycline-turn-off HSV1-tk-expressing cell line (NG4TL4/tet-off-HSV1-tk) and tetracycline-turn-off Luc-expressing cell line (NG4TL4/tet-off-Luc), to create an artificially regulated gene expression model in vitro. The dynamic transcriptional events mediating a series of doxycycline (Dox) inductions were ...