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1.
Nat Water ; 1(1): 60-73, 2023.
Article in English | MEDLINE | ID: mdl-38665803

ABSTRACT

Known locally as the water mountain, for millennia Japan's iconic Mt Fuji has provided safe drinking water to millions of people via a vast network of groundwater and freshwater springs. Groundwater, which is recharged at high elevations, flows down Fuji's flanks within three basaltic aquifers, ultimately forming countless pristine freshwater springs among Fuji's foothills. Here we challenge the current conceptual model of Fuji being a simple system of laminar groundwater flow with little to no vertical exchange between its three aquifers. This model contrasts strongly with Fuji's extreme tectonic instability due to its unique location on top of the only known continental trench-trench-trench triple junction, its complex geology and its unusual microbial spring water communities. On the basis of a unique combination of microbial environmental DNA, vanadium and helium tracers, we provide evidence for prevailing deep circulation and a previously unknown deep groundwater contribution to Fuji's freshwater springs. The most substantial deep groundwater upwelling has been found along Japan's most tectonically active region, the Fujikawa-kako Fault Zone. Our findings broaden the hydrogeological understanding of Fuji and demonstrate the vast potential of combining environmental DNA, on-site noble gas and trace element analyses for groundwater science.

3.
Ann Oncol ; 26(9): 1966-1973, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26133966

ABSTRACT

BACKGROUND: Information about the impact of cancer treatments on patients' quality of life (QoL) is of paramount importance to patients and treating oncologists. Cancer trials that do not specify QoL as an outcome or fail to report collected QoL data, omit crucial information for decision making. To estimate the magnitude of these problems, we investigated how frequently QoL outcomes were specified in protocols of cancer trials and subsequently reported. DESIGN: Retrospective cohort study of RCT protocols approved by six research ethics committees in Switzerland, Germany, and Canada between 2000 and 2003. We compared protocols to corresponding publications, which were identified through literature searches and investigator surveys. RESULTS: Of the 173 cancer trials, 90 (52%) specified QoL outcomes in their protocol, 2 (1%) as primary and 88 (51%) as secondary outcome. Of the 173 trials, 35 (20%) reported QoL outcomes in a corresponding publication (4 modified from the protocol), 18 (10%) were published but failed to report QoL outcomes in the primary or a secondary publication, and 37 (21%) were not published at all. Of the 83 (48%) trials that did not specify QoL outcomes in their protocol, none subsequently reported QoL outcomes. Failure to report pre-specified QoL outcomes was not associated with industry sponsorship (versus non-industry), sample size, and multicentre (versus single centre) status but possibly with trial discontinuation. CONCLUSIONS: About half of cancer trials specified QoL outcomes in their protocols. However, only 20% reported any QoL data in associated publications. Highly relevant information for decision making is often unavailable to patients, oncologists, and health policymakers.


Subject(s)
Quality of Life , Randomized Controlled Trials as Topic/methods , Research Design , Cohort Studies , Humans , Neoplasms/therapy , Retrospective Studies , Surveys and Questionnaires
4.
J Hum Hypertens ; 24(2): 117-23, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19536166

ABSTRACT

This analysis shows the economic benefit of antihypertensive treatment in patients 80 years of age or older from the perspective of the Swiss healthcare system. The cost-effectiveness analysis of antihypertensive treatment in the elderly was carried out applying the results of the Hypertension in the Very Elderly Trial study to the Swiss healthcare system. The analysis shows that hypertension treatment provides, compared with placebo, an additional life expectancy of 0.0457 years per patient, over a follow-up period of 2 years. The medication cost was covered by the reduction of costs related to the treatment of strokes, myocardial infarctions and heart failure: the total cost per patient in the active group resulted in a dominant strategy of savings compared with the placebo group. Sensitivity analysis yielded a stable estimate after varying the costs of medication, stroke, myocardial infarction, heart failure and life expectancy, confirming the robustness of these results. Moreover, considering that antihypertensive treatment also positively affects the incidence of dementia, those net benefits might even be underestimated.


Subject(s)
Antihypertensive Agents/economics , Antihypertensive Agents/therapeutic use , Drug Costs , Health Care Costs , Health Services for the Aged/economics , Hypertension/drug therapy , Hypertension/economics , National Health Programs/economics , Age Factors , Aged, 80 and over , Cost Savings , Cost-Benefit Analysis , Double-Blind Method , Female , Heart Failure/economics , Heart Failure/etiology , Heart Failure/prevention & control , Humans , Hypertension/complications , Life Expectancy , Male , Models, Economic , Multicenter Studies as Topic , Myocardial Infarction/economics , Myocardial Infarction/etiology , Myocardial Infarction/prevention & control , Randomized Controlled Trials as Topic , Retrospective Studies , Stroke/economics , Stroke/etiology , Stroke/prevention & control , Switzerland , Time Factors , Treatment Outcome
6.
Genes Chromosomes Cancer ; 26(1): 47-53, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10441005

ABSTRACT

Isolation of cell lines that display various degrees of transformed phenotypes may be very useful to clarify multistep mechanisms of oncogenesis, but malignant transformation of human diploid fibroblasts in culture is a very rare event. We attempted to isolate variously transformed cell lines from human diploid fibroblasts (RB) of a patient with hereditary retinoblastoma. The RB cells exhibited normal karyotypes with the exception of one copy of chromosome 13, which contained a large deletion at the q14-22 region, where the RB1 gene is located. By transfection with SV40 early genes and repeated passage, we succeeded in obtaining SV40-transfected mortal, immortalized, anchorage-independent, and tumorigenic RB cell lines. DNA fingerprinting showed that these cell lines were not contaminants, but derivatives of the original RB cells. The remaining RB1 allele may be wild-type even in the malignant cell lines, because the expression and the LT-binding ability were normal. Furthermore, we did not find any homozygous loss in 16 polymorphic markers located in the 13q14-22 region in the transformed cell lines. However, introduction of a copy of a normal chromosome 13 into the anchorage-independent cell line suppressed its anchorage-independent growth ability. All these data, together with the fact that the RB cells containing the deletion progressed to a tumorigenic state spontaneously, but normal fibroblasts did not, raise the possibility that a new tumor suppressor gene, located at 13q14-22, may play a critical role in neoplastic transformation. We conclude that these RB cell lines provide an excellent system for identification of genes involved in malignant transformation of human cells. Genes Chromosomes Cancer 26:47-53, 1999.


Subject(s)
Cell Movement/genetics , Cell Transformation, Neoplastic , Chromosomes, Human, Pair 13/genetics , Fibroblasts/metabolism , Cell Adhesion/genetics , Cell Transformation, Viral , Chromosome Banding , Chromosome Deletion , Clone Cells/cytology , Diploidy , Fibroblasts/cytology , Humans , Hybrid Cells/cytology , Karyotyping , Phenotype , Retinoblastoma/genetics , Retinoblastoma/pathology , Tumor Cells, Cultured
8.
Cancer ; 58(10): 2244-50, 1986 Nov 15.
Article in English | MEDLINE | ID: mdl-2875783

ABSTRACT

The chromosomes of leukemic blood cells in eight Japanese patients with acute adult T-cell leukemia (ATL) were examined by a direct method or short-term culture method without any mitogens. Six patients showed a chromosome 14 anomaly with a break at band q11-13: inv(14)(q11q32) in two patients, t(11;14)(p13;q13) in one patient, t(14;14)(q11;q32) in addition to del(14)(q11q13) in another, and only del(14)(q11q13) in two patients. Thus, a proximal 14q rearrangement exists in ATL as in other types of T-cell malignancies. Based on these facts, the pathogenesis of ATL is discussed in reference to the literature.


Subject(s)
Chromosome Aberrations/genetics , Chromosomes , Deltaretrovirus Infections/genetics , Chromosome Disorders , Humans , Japan , Karyotyping , Preleukemia/genetics
10.
Clin Immunol Immunopathol ; 36(3): 306-19, 1985 Sep.
Article in English | MEDLINE | ID: mdl-2990783

ABSTRACT

We report phenotypic and functional characterization of lymph node cells from 27 patients with T lymphoma from the Nagasaki district of Japan. Nagasaki is one of several areas where adult T-cell leukemia is endemic, and sera from 18 of 23 patients examined (78.3%) were positive for antibody to adult T-cell leukemia-associated antigen. The majority of cases (24 of 27) showed the Leu-2a-, 3a+, MASO36c- phenotype similar to adult T-cell leukemia, but seemed to be subdivided into four groups according to the presence or absence of Leu-1 antigen and the receptor for sheep erythrocytes (SRBC). Eleven cases had both Leu-1 antigen and the receptor for SRBC (E-RFC+, Leu-1+, 2a-, 3a+), but 6 cases lacked Leu-1 antigen (E-RFC+, Leu-1-, 2a-, 3a+), 4 cases lacked receptors for SRBC (E-RFC-, Leu-1+, 2a-, 3a+), and 3 cases lacked both of these markers (E-RFC-, Leu-1-, 2a-, 3a+). The effects of lymph node T cells on pokeweed mitogen (PWM)-induced normal B-cell differentiation was studied in 10 cases. Lymph node T cells of 5 cases showed helper activity without any suppressor activity, and 2 cases showed suppressor activity with almost no detectable helper activity, similar to adult T-cell leukemia cells. Two other cases lacked particular functional effects. These results suggest the possibility that Leu-3a+ T-cell lymphoma may be functionally subdivided into at least two types, a helper type and a suppressor (adult T-cell leukemia) type.


Subject(s)
Antigens, Surface/analysis , Leukemia/pathology , Lymphoma/pathology , Retroviridae Infections/pathology , T-Lymphocytes/classification , Adolescent , Adult , Antibodies, Viral/immunology , Antigens, Differentiation, T-Lymphocyte , B-Lymphocytes/immunology , Cell Differentiation , Deltaretrovirus/immunology , Humans , Immune Tolerance , Leukemia/immunology , Leukemia/microbiology , Lymph Nodes/immunology , Lymph Nodes/pathology , Lymphocyte Cooperation , Lymphoma/immunology , Lymphoma/microbiology , Middle Aged , Retroviridae Infections/immunology , Retroviridae Infections/microbiology , Rosette Formation , T-Lymphocytes/immunology , T-Lymphocytes, Helper-Inducer/immunology , T-Lymphocytes, Regulatory/immunology
11.
Blut ; 50(4): 209-11, 1985 Apr.
Article in English | MEDLINE | ID: mdl-3157413

ABSTRACT

A case of adult T-cell leukemia (ATL) with an unusual phenotype is presented. Leukemia cells of this patient reacted with anti-Leu-2a monoclonal antibody, although most of ATL cases are reported to show the phenotype of helper/inducer T-cell. It is indicated that the surface phenotype of ATL is rather heterogeneous.


Subject(s)
Leukemia/genetics , T-Lymphocytes , Antibodies, Monoclonal/immunology , Antigens, Surface/immunology , Female , Humans , Leukemia/classification , Middle Aged , Phenotype , Rosette Formation , T-Lymphocytes, Helper-Inducer
12.
Br J Haematol ; 58(1): 53-60, 1984 Sep.
Article in English | MEDLINE | ID: mdl-6590091

ABSTRACT

Serial haematopathological and cytogenetic studies disclosed three distinct clinical phase in a case of refractory anaemia (RA), a subtype of myelodysplastic syndrome (MDS; FAB group, 1982): first, chronic MDS phase (1 year 10 months) with karyotypic abnormality (45, XY, --7) (Clone I); second, hypo-aplastic phase concurrent with first clonal evolution (45, XY, --7, 12p--) (Clone II); third, acute myelomonocytic leukaemia phase (6 months) with second clonal evolution (45, XY, --7,t (1q --; Bq+), Bq --, 12p --) (Clone III). In the second phase the bone marrow became almost aplastic as Clone II expanded progressively, indicating simultaneous occurrence in Clone II stem cells of growth advantage for self-renewal function over Clone I and normal stem cells, and arrest of differentiation. These observations support the hypothesis that leukaemic change in MDS, at least in RA, occurs by stepwise clonal evolution(s), not by progressive arrest of differentiation in original MDS clone.


Subject(s)
Bone Marrow Diseases/pathology , Bone Marrow/pathology , Leukemia, Myeloid, Acute/pathology , Anemia, Aplastic/genetics , Anemia, Aplastic/pathology , Bone Marrow/ultrastructure , Bone Marrow Diseases/genetics , Cell Count , Chromosome Banding , Humans , Karyotyping , Leukemia, Myeloid, Acute/genetics , Male , Middle Aged
13.
Cancer Genet Cytogenet ; 12(3): 255-9, 1984 Jul.
Article in English | MEDLINE | ID: mdl-6722765

ABSTRACT

The gene for erythrocyte glutathione reductase (E-GR) activity has been assigned to chromosome #8. In the present series, we examined the E-GR activity in 14 cases with chronic myelodysplastic syndrome (CMS, preleukemia), atypical acute myelogenous leukemia (AML), or chronic myelogenous leukemia (CML), with and without acquired trisomy #8. No difference in the incidence of high levels of this enzyme was found between two groups, i.e., those with and without trisomy #8 suggesting the existence of a complex regulatory system in addition to chromosome #8.


Subject(s)
Chromosomes, Human, 6-12 and X , Glutathione Reductase/genetics , Hematologic Diseases/genetics , Trisomy , Glutathione Reductase/blood , Humans
14.
J Immunol Methods ; 61(2): 217-26, 1983 Jul 15.
Article in English | MEDLINE | ID: mdl-6345678

ABSTRACT

An enzyme immunoassay for polyamines is described which uses beta-galactosidase labeled spermine and antiserum raised in rabbits against spermine-bovine serum albumin synthesized by coupling spermine to mercaptosuccinylated bovine serum albumin with a bifunctional cross-linker, N-(gamma-maleimidobutyryloxy)-succinimide. The lower limit of detection by this assay, which involves a double antibody technique for the separation of antibody-bound and free antigen, was 1 ng of spermine per tube. The anti-spermine serum showed 88% cross-reaction with spermidine but only 0.13% with putrescine, 0.08% with 1,3-diaminopropane, and 0.04% with cadaverine. The method has been used to measure serum polyamine levels in healthy subjects and cancer patients, in whom mean concentrations of 58.1 ng/ml and 94.8 ng/ml (as spermine), were respectively noted. This enzyme immunoassay is specific, accurate and easy to perform, and appears suitable for routine clinical use.


Subject(s)
Galactosidases/metabolism , Spermidine/blood , Spermine/blood , Animals , Antibody Formation , Antibody Specificity , Humans , Immunoenzyme Techniques , Neoplasms/analysis , Rabbits , Spermine/immunology
19.
Acta Pathol Jpn ; 31(1): 135-42, 1981 Jan.
Article in English | MEDLINE | ID: mdl-7234417

ABSTRACT

Described here is an autopsy case of a 30-year-old woman with systemic hemangiomatosis accompanied by coagulopathy and microangiopathic hemolytic anemia. She had hepato-splenomegaly, anemia, thrombocytopenia, prolonged prothrombin time and partial thromboplastin time, and fibrinogenopenia. A splenectomy was performed and a diffuse angioma of the spleen was found. Postmortem examination revealed cavernous hemangiomas and hemangioendotheliomatous lesions in the liver, bone marrow, intestine, and lymph nodes. Coagulation studies suggested that exacerbation of coagulopathy occurred due to Liniac (10MV X-ray) irradiation. Our observation raised the possibility that the irradiation might lead to chronic localized consumption coagulopathy, which was confined to the hemangioma, to acute disseminated types of intravascular coagulation.


Subject(s)
Anemia, Hemolytic/etiology , Blood Coagulation Disorders/etiology , Hemangioma/pathology , Adult , Erythrocyte Count , Female , Hemangioma/complications , Hemangioma/radiotherapy , Humans , Radiotherapy/adverse effects
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