Search Results - (Author, Cooperation:S. Clifford)

2018-09-27

Nature Publishing Group (NPG)

2041-4889

Biology

Medicine

2015-08-01

American Association for the Advancement of Science (AAAS)

0036-8075

1095-9203

Biology

Chemistry and Pharmacology

Computer Science

Medicine

Natural Sciences in General

Physics

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary On the basis of response rates of up to 50%, BCNU [1,3-bis(2-chloroethyl)-1-nitrosourea] is the primary drug used in the chemotherapy of anaplastic gliomas. Preclinical data obtained in several experimental systems show that the cytotoxicity of chloroethylnitrosoureas can be increased by the concomitant use of thiopurines. In this phase I trial, patients with anaplastic gliomas received standard-dose BCNU (200 mg/m2×1) in combination with escalating doses of intravenous 6-mercaptopurine (200, 350, 500, and 750 mg/m2 daily×3), with BCNU being given on day 3 to maximize the effect of the drugs on cellular DNA. No increase in hematologic toxicity was demonstrated as the dose of 6-mercaptopurine was increased. Responses and stabilization of disease were observed in several patients. Due to the safety of and the evidence of activity found for this regimen in the present trial, 750 mg/m2 6-mercaptopurine has been incorporated into subsequent studies.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Abstract The activity of dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts derived from ependymomas (D528 EP, D612 EP), childhood high-grade gliomas (D-456 MG, D-212 MG), adult high-grade gliomas (D-245 MG, D-54 MG), and medulloblastomas (D425 Med) growing s.c. and i.c. (intracranially) in athymic nude mice. Topotecan was given at a dose of 1.9 mg/kg by i.p. injection in 0.9% saline using a volume of 90 ml/m2 on days 1–5 and 8–12, which represents the dose lethal to 10% of treated animals. Topotecan was active in the therapy of all s.c. xenografts tested, with growth delays ranging from 6.3 days in D-54 MG to 55.7 days in D528 EP. Topotecan produced statistically significant tumor regressions in D425 Med, D-456 MG, D-245 MG, D528 EP, and D612 EP. No tumor regression was seen in any control animal. Statistically significant increases in median survival were seen in the two i.c. xenografts — D-456 MG (28.6% increase) and D-54 MG (39% increase) —treated with topotecan. These studies suggest that topotecan may be an important new addition to the therapy of central nervous system tumors.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Summary We used human anaplastic glioma xenografts to evaluate the therapeutic efficacy of combinations of alkylating drugs, either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), 1-(2-chloroethyl)-3-(2,5-dioxo-3-piperidyl)-1-nitrosourea (PCNU), or procarbazine, and thiopurines, either 6-mercaptopurine (6MP) or 6-thioguanine (6TG). Using growth delay as the endpoint in subcutaneous (s.c.) tumors and increased life span as the endpoint in intracranial (i.c.) tumors, we found that combinations of chloroethylnitrosoureas (CENUs) and thiopurines were significantly more active than either type of agent alone. In contrast, combinations of procarbazine and thiopurines were not significantly more active than procarbazine alone. The therapeutic potentiation of the CENU was greater when the latter was given on the 4th day of the thiopurine treatment cycle than when it was given on the 1st day. Characterization of the interaction between CENUs and thiopurines also revealed a supraadditive therapeutic response at higher BCNU doses in combination with 6TG. Interaction between the nitrosoureas and the thiopurines probably occurs in the guanine base of tumor DNA and has important therapeutic implications.

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1432-0843

Key words Alkyltransferase ; 1 ; 3-Bis(2-chlorethyl)-1-nitrosourea ; Carmustine ; O6-Benzylguanine ; temozolomide

Springer Online Journal Archives 1860-2000

Medicine

Abstract  O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl adducts from DNA and may be important in tumor resistance to alkylation chemotherapy. MGMT was visualized in human cells and tumor tissues with monoclonal antibodies against MGMT and immunofluorescence microscopy, and fluorescent signals were quantified by digital image analysis. MGMT was found both in the cytoplasm and the nucleus, and in either locale the protein reacts with alkylated DNA bases and becomes inactivated and lost from the cell. Cell lines in culture and xenografts showed a broad normal distribution of nuclear MGMT levels, but human brain tumors often showed a skewed distribution, with a significant fraction of cells with high levels of MGMT. O6-Benzylguanine, a suicide substrate inactivator for MGMT activity, reduced MGMT in human cells and in a mouse xenograft to levels undetectable by antibody assay 1 h post-treatment. In melanoma specimens taken from a patient 3 h post-treatment with temozolomide, MGMT levels were reduced by 70%. This quantitative immunofluorescence assay can be used to monitor MGMT and its depletion in human tumors to improve the use of alkylating agents in cancer chemotherapy.

Electronic Resource

1432-0843

Springer Online Journal Archives 1860-2000

Medicine

Abstract. The activity of dimethylaminomethyl-10-hydroxycamptothecin (topotecan) was evaluated against a panel of xenografts derived from ependymomas (D528 EP, D612 EP), childhood high-grade gliomas (D-456 MG, D-212 MG), adult high-grade gliomas (D-245 MG, D-54 MG), and medulloblastomas (D425 Med) growing s.c. and i.c. (intracranially) in athymic nude mice. Topotecan was given at a dose of 1.9 mg/kg by i.p. injection in 0.9% saline using a volume of 90 ml/m2 on days 1–5 and 8–12, which represents the dose lethal to 10% of treated animals. Topotecan was active in the therapy of all s.c. xenografts tested, with growth delays ranging from 6.3 days in D-54 MG to 55.7 days in D528 EP. Topotecan produced statistically significant tumor regressions in D425 Med, D-456 MG, D-245 MG, D528 EP, and D612 EP. No tumor regression was seen in any control animal. Statistically significant increases in median survival were seen in the two i.c. xenografts – D-456 MG (28.6% increase) and D-54 MG (39% increase) – treated with topotecan. These studies suggest that topotecan may be an important new addition to the therapy of central nervous system tumors.

Electronic Resource

1573-7373

human gliomas ; athymic mice ; GFAP

Springer Online Journal Archives 1860-2000

Medicine

Abstract Sixteen of 17 anaplastic human gliomas (AHGs) transplanted into athymic mice produced progressively growing subcutaneous nodules at the site of implantation. Thirty-four of 68 animals (50%) receiving transplanted tissue developed 500 m3 tumors in 24 to 364 days. Fourteen AHG were passed to a second animal generation, and 11 showed continued growth. Eight of these were serially passed, with one reaching a sixth animal generation, four reaching a fifth, and a three third. Once growth occurred in a second animal generation, no AHGs were lost in subsequent passages because of failure to grow. Of 234 animals receiving tumors beyond the first animal generation, 189 (80.8%) developed tumors. Average doubling times of the exponentially growing tumors in serial passage ranged from 3.0 to 19.1 days. This growth rate tended to increase and stabilize in early animal passages. The tumors growing in animals contained cell types which were present in the original human tumors, including fibrillary and protoplasmic astrocytes, small anaplastic cells, gemistocytes, anaplastic spindle cells, and multinucleate giant cells. Glial fibrillary acidic protein (GFAP) was detected in 15 of 17 biopsy specimens and in 12 of 14 AHGs in animals. These data illustrate the value of the athymic mouse system for the investigation of human brain tumors by demonstrating a high rate of successful transplantation, quantitative growth data on serially passed tumors, and morphological and immunochemical resemblance of the tumors in mice to the original human tumors.

Electronic Resource

1573-7373

p53 ; ependymoma ; tumor suppressor genes ; gliomas ; SSCP

Springer Online Journal Archives 1860-2000

Medicine

Summary Ependymomas, which comprise 5% of central nervous system tumors, have not been extensively characterized genetically. The p53 tumor suppressor gene is frequently mutated in human cancer, and is important in the pathogenesis of other central nervous system (CNS) tumors. Chromosomal DNA corresponding to the p53 tumor suppressor gene was amplified by the polymerase chain reaction (PCR) from 31 archival ependymoma specimens. DNA was screened for the presence of p53 mutations by single strand conformational polymorphism (SSCP) analysis; samples with altered mobility were further tested for the presence of mutation by direct DNA sequence analysis. Of the 31 ependymomas tested, one contained a detectable DNA sequence change in the p53 gene. Sequencing revealed a silent mutation in exon 6, at codon 213, which represents a known p53 sequence polymorphism. These findings suggest that in contrast to many other human cancers, p53 mutation is not important in the pathogenesis or progression of ependymomas.

Electronic Resource

1573-1529

Rock slopes ; physical model ; base fiction

Springer Online Journal Archives 1860-2000

Geosciences

Electronic Resource

1573-0646

central nervous system tumors ; Didemnin B

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Abstract Didemnin B 6.3 mg/m2 was administered intravenously to 48 patients with recurrent or progressive central nervous system tumors. One patient of 39 (2.9%, 95% confidence limits 0.1 to 13.5) eligible patients had a confirmed partial response utilizing standard solid tumor criteria which lasted 14 months. Toxicity was significant. Nausea and vomiting and lethargy were the most frequent toxicities, but multiple severe toxicities were seen. Further investigation of Didemnin B at this dose is not warranted in patients with central nervous system malignancies.

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article

2024

Empirische Untersuchung ; Qualitative Forschung ; Diskriminierung ; Rassismus ; Studium ; Gemeinwesenarbeit ; Soziale Arbeit ; Asien ; USA

Social work, Bd. 69 (2024) H. 2, S. 117-124, 0037-8046

1545-6846

English

Literaturangaben

2018-04-19

Royal Society

2054-5703

Natural Sciences in General

environmental science

2018-03-14

Oxford University Press

0022-1899

1537-6613

Medicine

1526-100X

Blackwell Publishing Journal Backfiles 1879-2005

Biology

Flow regulation, which has largely eliminated flooding along the Rio Grande in central New Mexico, has substantially changed the riparian ecosystem. We investigated managed flooding as a means of restoring ecosystem function. After collecting baseline data during 1991 and 1992 in two riparian forest sites that had not flooded for about 50 years, we flooded an experimental site for 27–32 days during late spring of 1993, 1994, and 1995, leaving the reference site unflooded. During the final year of the study we compared these sites to two additional sites located within the riverside levee, one of which has been flooding naturally while the second remained largely unflooded. Three years of experimental flooding did not change the total biomass of either woody debris or forest-floor litter at the experimental flood site. Both woody debris and forest-floor litter, however, were significantly lower at the natural flood site than at the experimental flood site and two unflooded sites. Leaf and wood decomposition rates increased with flooding. The decay rate for cottonwood logs at the unflooded site (0.010 per year) predicted a half-life of 69.3 years, while the decay rate of 0.065 per year after 3 years of experimental flooding predicted a half-life of 10.6 years. This suggests that a decade of annual flooding may be used to restore the organic debris to pre-regulation levels. Flooding may also have caused an increase in litter production. These results suggest that experimental flooding has initiated a process of restoring ecosystem function within the riparian forest.

Electronic Resource

1471-4159

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Abstract: The metabolism of 2-deoxyglucose has been studied in 540 μm and 1,000 μm hypothalamic brain slices. Slice 2-deoxyglucose (2DG) and 2-deoxyglucose-6-phosphate (2DG6P) levels were measured after tissue homogenization and perchloric acid extraction. By analyzing the uptake and washout kinetics with nonlinear least-squares methods, we have determined the rate constants for three-, four-, or five-parameter kinetic models and obtained a value for the in vitro lumped constant (LC). The kinetic analysis reveals a small, slowly decaying, 2DG component that is not predicted by any of the models. If this component is treated as a separate, parallel compartment, then the four- and five-parameter models are essentially equivalent. To compare our data to prior in vivo data, we combined 2DG and 2DG6P to produce Ci*, the total slice radioactivity, and analyzed the first 45 min of uptake. These data were fit best by a three-parameter model and the slowly decaying pool was not identified. Calculation of glucose utilization from total tissue radioactivity, measured by whole slice homogenization and by image analysis of au-toradiograms, showed excellent correlation between the two methods. Image analysis of radioactivity in the suprachias-matic nucleus, which is present in these slices, revealed a spontaneous diurnal variation in in vitro glucose utilization in close quantitative agreement with prior in vivo measurements. The kinetic analysis of the 1,000 μm slice was qualitatively similar to that of the 540 μm slice but revealed an increase in the LC and a large decrease in k1 as well as the expected large increase in the hexokinase rate constant, k3. Overall, in vitro glucose utilization increased by about 60%. These results are consistent with our prior studies of the 1,000 μm slice and support our interpretation that the 1,000 μm slice is an excellent in vitro model for brain ischemia without infarction.

Electronic Resource

1468-2257

Blackwell Publishing Journal Backfiles 1879-2005

Geography

Economics

The Job Training Partnership Act of 1982 was developed to train the disadvantaged for work or better jobs. The Act that passed targeted the economically disadvantaged but stressed efficiency in the operation of the program. Program performance standards were established, and local Private Industry Councils (PICs) were developed to operate the program and to involve local business in JTPA training. Critics argued that this structure resulted in “creaming” of participants to the exclusion of the most disadvantaged workers. We test the “creaming” hypothesis using data on JTPA participants in Tennessee in 1987 and a sample of disadvantaged workers in Tennessee extracted from the Current Population Surveys. We find that racial and welfare targets are met but that the most able among those groups are chosen for help. We also find some evidence of “channeling.” The most disadvantaged groups are less likely to receive the most successful type of training — on-the-job training. Finally, we present alternative strategies to encourage PICs to do less “creaming,” and we make predictions about their likely success.

Electronic Resource

1467-9248

Blackwell Publishing Journal Backfiles 1879-2005

Political Science

The aim of this paper is to clarify the continuing debate about the theoretical characteristics of vote trading. It sets about this by first emphasizing existing distinctions among types of vote trading systems, most importantly, the distinction between trades on entire platforms characterizing social states (implicit vote trading) and trades on the individual issues making up the platforms (explicit vote trading). The subdivisions of the latter type are more carefully explored, with the key results being that: while all vote trading systems may lead to circularity in the attempt to choose; and while implicit vote trading inevitably involves such circularity; vote trading over individual, independent issues may be stable. The challenge to the social choice field is therefore to be more careful in specifying the conditions of foresight, renegotiability and the like, and to compare theoretical systems for explicit vote trading with actual legislative rules.

Electronic Resource

1399-3038

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

The diagnostic accuracy of the skin prick test (SPT) in food allergy is controversial. We have developed diagnostic cut-off levels for SPT in children with allergy to cow milk, egg and peanut. Based on 555 open food challenges in 467 children (median age 3.0 yr) we defined food-specific SPT weal diameters that were ‘100% diagnostic’ for allergy to cow milk (≥8 mm), egg (≥7 mm) and peanut (≥8 mm). In children 〈2 yr of age, the corresponding weal diameters were ≥6 mm, ≥5 mm and ≥4 mm, respectively. These SPT cut-off levels were prospectively validated in 90 consecutive children ≤2 yr with challenge-proven food allergy. In young infants under 6 months of age who have not previously been exposed to a particular food item, the SPT were often negative or below the diagnostic cut-off but reached the diagnostic cut-off at the time of challenge in the second year of life. We assessed the diagnostic agreement between food-specific immunoglobulin E (IgE) antibody levels and SPT in a cohort of 820 infants and children under 2 yr of age (median age 13.1 months) with suspected allergy to cow milk, egg or peanut. When applying published 95%-positive predictive CAP values, the diagnostic accuracy of SPT and IgE antibody levels was similar for cow milk, but SPT was more sensitive in diagnosing allergy to egg (p 〈 0.0001) and peanut (p 〈 0.0001). Further studies are required to define age-specific diagnostic IgE antibody and SPT cut-off levels use in infants under 2 yr of age with suspected food allergies.

Electronic Resource

1600-065X

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Summary: Studies in non-human primates to evaluate tolerance strategies in organ transplantation have led to innovation in human transplantation. The two strategies we have studied in detail in non-human primates are T-cell depletion by anti-CD3 immunotoxin and co-stimulation blockade. Each of these strategies has been extended into early human trials in renal transplantation. The results of these human and non-human primate studies are summarized. Continued progress in better and safer immunosuppressive methods remains closely linked to research using non-human primates. However, there has not been a one-to-one correspondence between efficacy in the primate and efficacy in humans. Rather, principles can be derived from non-human primate studies that can be extended into human trials with the knowledge that regimens will likely differ in humans compared to non-human primates.

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