Distribution and abundance of freshwater decapods in an Atlantic rainforest catchment with a dammed future / Distribuição e abundância de decápodes de água doce e sua associação com variáveis ambientais em uma bacia hidrográfica de Mata Atlântica que será represada

Abstract Variations in physical characteristics along the course of a river influence habitat availability which reflects in species distribution. Knowledge of ecology and diversity of lotic species is important for evaluating how river ecosystems will respond to environmental impacts. Freshwater decapods are a group of high ecological and economic importance, but the knowledge about factors influencing their distribution is scarce in Brazil. We performed a survey of decapods to describe their abundance and distribution as well as to study their relationships with stream physical variables and especially their association with different substrates types. We studied 23 sites located in 15 tributaries of Guapiaçú River, RJ, where we collected decapods in different substrates types and measured a set of physical variables. We found five decapods species, including amphidromous and non-amphidromous shrimps and crabs. Decapods were strongly associated with leaf-litter substrates and their abundance was related to a multivariate axis describing longitudinal changes in stream characteristics. We concluded that decapods occurring in the Guapiaçú catchment inhabit mainly small streams with preserved riparian forests where they find shelter and potential prey of invertebrates. The ongoing project to build a dam on the Guapiaçú River will have negative consequences to migrating shrimps and we strongly recommend that mitigating actions, such the construction of structures to allow the passage of migrating fauna, should be taken.

Resumo Variações nas características físicas de um rio ao longo do seu curso influenciam a disponibilidade de habitas e dessa forma a distribuição de espécies. O conhecimento sobre a ecologia e diversidade de espécies lóticas é importante para avaliar como esses ecossistemas responderão a impactos ambientais. Decápodes de água doce são um grupo de grande importância ecológica e econômica, contudo o conhecimento sobre fatores influenciando sua distribuição ainda é escasso no Brasil. Nós realizamos um levantamento de decápodes para descrever sua abundância e distribuição, bem como estudar sua relação com características físicas dos rios, especialmente sua associação com tipos diferentes de substrato. Nós estudamos 23 localidades distribuídas em 15 rios tributários do Rio Guapiaçú, RJ, onde coletamos decápodas em diferentes tipos de substratos e medimos um conjunto de variáveis físicas. Nós encontramos cinco espécies de decápodas incluindo camarões anfídromos e não anfídromos e caranguejos. Esses organismos foram fortemente associados a substratos de folhiço alóctone e sua abundância foi relacionada com um eixo PCA que descreve as mudanças nas características físicas longo do curso do rio. Nós concluímos que os decápodas que ocorrem na bacia do Rio Guapiaçú habitam principalmente pequenos córregos com mata ciliar preservada, onde podem encontrar abrigo e um potencial campo de caça onde predam invertebrados. O projeto atualmente em curso para a construção de uma represa no Rio Guapiaçú irá afetar negativamente a fauna de camarões anfídromos, assim nós recomendamos fortemente que ações mitigadoras, como a construção de estruturas para permitir a passagem da fauna migrante sejam tomadas.

Distribution and abundance of freshwater decapods in an Atlantic rainforest catchment with a dammed future.

Variations in physical characteristics along the course of a river influence habitat availability which reflects in species distribution. Knowledge of ecology and diversity of lotic species is important for evaluating how river ecosystems will respond to environmental impacts. Freshwater decapods are a group of high ecological and economic importance, but the knowledge about factors influencing their distribution is scarce in Brazil. We performed a survey of decapods to describe their abundance and distribution as well as to study their relationships with stream physical variables and especially their association with different substrates types. We studied 23 sites located in 15 tributaries of Guapiaçú River, RJ, where we collected decapods in different substrates types and measured a set of physical variables. We found five decapods species, including amphidromous and non-amphidromous shrimps and crabs. Decapods were strongly associated with leaf-litter substrates and their abundance was related to a multivariate axis describing longitudinal changes in stream characteristics. We concluded that decapods occurring in the Guapiaçú catchment inhabit mainly small streams with preserved riparian forests where they find shelter and potential prey of invertebrates. The ongoing project to build a dam on the Guapiaçú River will have negative consequences to migrating shrimps and we strongly recommend that mitigating actions, such the construction of structures to allow the passage of migrating fauna, should be taken.

Core Standards of the EUBIROD Project. Defining a European Diabetes Data Dictionary for Clinical Audit and Healthcare Delivery.

BACKGROUND: A set of core diabetes indicators were identified in a clinical review of current evidence for the EUBIROD project. In order to allow accurate comparisons of diabetes indicators, a standardised currency for data storage and aggregation was required. We aimed to define a robust European data dictionary with appropriate clinical definitions that can be used to analyse diabetes outcomes and provide the foundation for data collection from existing electronic health records for diabetes. METHODS: Existing clinical datasets used by 15 partner institutions across Europe were collated and common data items analysed for consistency in terms of recording, data definition and units of measurement. Where necessary, data mappings and algorithms were specified in order to allow partners to meet the standard definitions. A series of descriptive elements were created to document metadata for each data item, including recording, consistency, completeness and quality. RESULTS: While datasets varied in terms of consistency, it was possible to create a common standard that could be used by all. The minimum dataset defined 53 data items that were classified according to their feasibility and validity. Mappings and standardised definitions were used to create an electronic directory for diabetes care, providing the foundation for the EUBIROD data analysis repository, also used to implement the diabetes registry and model of care for Cyprus. CONCLUSIONS: The development of data dictionaries and standards can be used to improve the quality and comparability of health information. A data dictionary has been developed to be compatible with other existing data sources for diabetes, within and beyond Europe.

About rats and jackfruit trees: modeling the carrying capacity of a Brazilian Atlantic Forest spiny-rat Trinomys dimidiatus (Günther, 1877) - Rodentia, Echimyidae - population with varying jackfruit tree (Artocarpus heterophyllus L.) abundances.

We carried out a six-year study aimed at evaluating if and how a Brazilian Atlantic Forest small mammal community responded to the presence of the invasive exotic species Artocarpus heterophyllus, the jackfruit tree. In the surroundings of Vila Dois Rios, Ilha Grande, RJ, 18 grids were established, 10 where the jackfruit tree was present and eight were it was absent. Previous results indicated that the composition and abundance of this small mammal community were altered by the presence and density of A. heterophyllus. One observed effect was the increased population size of the spiny-rat Trinomys dimidiatus within the grids where the jackfruit trees were present. Therefore we decided to create a mathematical model for this species, based on the Verhulst-Pearl logistic equation. Our objectives were i) to calculate the carrying capacity K based on real data of the involved species and the environment; ii) propose and evaluate a mathematical model to estimate the population size of T. dimidiatus based on the monthly seed production of jackfruit tree, Artocarpus heterophyllus and iii) determinate the minimum jackfruit tree seed production to maintain at least two T. dimidiatus individuals in one study grid. Our results indicated that the predicted values by the model for the carrying capacity K were significantly correlated with real data. The best fit was found considering 20~35% energy transfer efficiency between trophic levels. Within the scope of assumed premises, our model showed itself to be an adequate simulator for Trinomys dimidiatus populations where the invasive jackfruit tree is present.

Ecological Niche Model used to examine the distribution of an invasive, non-indigenous coral.

All organisms have a set of ecological conditions (or niche) which they depend on to survive and establish in a given habitat. The ecological niche of a species limits its geographical distribution. In the particular case of non-indigenous species (NIS), the ecological requirements of the species impose boundaries on the potential distribution of the organism in the new receptor regions. This is a theoretical assumption implicit when Ecological Niche Models (ENMs) are used to assess the potential distribution of NIS. This assumption has been questioned, given that in some cases niche shift may occur during the process of invasion. We used ENMs to investigate whether the model fit with data from the native range of the coral Tubastraea coccinea Lesson, 1829 successfully predicts its invasion in the Atlantic. We also identified which factors best explain the distribution of this NIS. The broad native distributional range of T. coccinea predicted the invaded sites well, especially along the Brazilian coast, the Caribbean Sea and Gulf of Mexico. The occurrence of T. coccinea was positively related to calcite levels and negatively to eutrophy, but was rather unaffected to other variables that often limit other marine organisms, suggesting that this NIS has wide ecological limits, a trait typical of invasive species.

Responses of Chironomidae (Diptera; Insecta) to the exclusion of shrimps and Ephemeroptera in a coastal forest stream, Rio de Janeiro, Brazil.

In a benthic community on a continuous flat granite substrate in a third-order coastal forest stream, the dominant chironomid (Cricotopus) increased in number when shrimps (Macrobrachium olfersi and Potimirim glabra) and baetid ephemeropterans were excluded by electricity. The response appeared to be mediated by an increase in periphyton and sediments, rather than a reduction of direct predation or interference. Chironomids, periphyton and sediments decreased significantly compared to the control when shrimps only were excluded. Baetid ephemeropteran appeared to be the most important determinants of periphyton and sediment mass; the density of chironomids appeared to follow the quantity of periphyton and sediments.

Responses of Chironomidae (Diptera; Insecta) to the exclusion of shrimps and Ephemeroptera in a coastal forest stream, Rio de Janeiro, Brazil

In a benthic community on a continuous flat granite substrate in a third-order coastal forest stream, the dominant chironomid (Cricotopus) increased in number when shrimps (Macrobrachium olfersi and Potimirim glabra) and baetid ephemeropterans were excluded by electricity. The response appeared to be mediated by an increase in periphyton and sediments, rather than a reduction of direct predation or interference. Chironomids, periphyton and sediments decreased significantly compared to the control when shrimps only were excluded. Baetid ephemeropteran appeared to be the most important determinants of periphyton and sediment mass; the density of chironomids appeared to follow the quantity of periphyton and sediments.

Os quironomídeos dominantes (Cricotopus) de uma comunidade bentônica aumentaram em densidade quando camarões (Macrobrachium olfersi e Potimirim glabra) e efemerópteros betídeos foram excluídos por eletricidade de um substrato rochoso contínuo em um córrego de Mata Atlântica. Esta resposta parece ter sido mais influenciada por um aumento no perifíton do que pela redução da predação direta ou competição por interferência. Quando somente os camarões foram excluídos, os quironomídeos, perifíton e sedimentos sofreram redução significativa em comparação com os controles. Efemerópteros betídeos parecem ter sido os maiores determinantes da quantidade de sedimentos e perifíton; a densidade de quironomídeos parece seguir a quantidade de perifíton e sedimentos.

Responses of leaf processing to impacts in streams in Atlantic rain forest, Rio de Janeiro, Brazil--a test of the biodiversity-ecosystem functioning relationship?

The relationship between biodiversity and ecosystem functioning has been intensely debated and researched in recent times. It is generally agreed that there is redundancy of species in ecosystems such that loss of species does not necessarily result in change in the functioning of the ecosystem in which they occur. However the state of our knowledge does not allow prediction of sensitivity or specificity of this relationship for any particular ecosystem. A widely-held opinion is that ecosystem functioning is relatively stable to environmental impact, whereas biodiversity is more sensitive. We tested this in streams of the Atlantic forest using leaf decomposition as an aspect of ecosystem functioning and measuring the diversity of the associated fauna. In lightly impacted streams of the urban park Parque Estadual da Pedra Branca, RJ, leaf processing rate of a hard-leaf species, Myrcia rostrata (Myrtaceae) was more than 50% slower than in "intact" streams at the biological reserve of Ilha Grande, RJ. Taxon diversity of fauna of the leaves was not significantly lower in the impacted than the intact streams. We construe this as preliminary evidence contrary to the notion that ecosystem functioning is less sensitive than biodiversity to impacts in this system.

Responses of leaf processing to impacts in streams in Atlantic rain Forest, Rio de Janeiro, Brazil - a test of the biodiversity-ecosystem functioning relationship?

The relationship between biodiversity and ecosystem functioning has been intensely debated and researched in recent times. It is generally agreed that there is redundancy of species in ecosystems such that loss of species does not necessarily result in change in the functioning of the ecosystem in which they occur. However the state of our knowledge does not allow prediction of sensitivity or specificity of this relationship for any particular ecosystem. A widely-held opinion is that ecosystem functioning is relatively stable to environmental impact, whereas biodiversity is more sensitive. We tested this in streams of the Atlantic forest using leaf decomposition as an aspect of ecosystem functioning and measuring the diversity of the associated fauna. In lightly impacted streams of the urban park Parque Estadual da Pedra Branca, RJ, leaf processing rate of a hard-leaf species, Myrcia rostrata (Myrtaceae) was more than 50 percent slower than in "intact" streams at the biological reserve of Ilha Grande, RJ. Taxon diversity of fauna of the leaves was not significantly lower in the impacted than the intact streams. We construe this as preliminary evidence contrary to the notion that ecosystem functioning is less sensitive than biodiversity to impacts in this system

t(11;22)(q23;q11.2) In acute myeloid leukemia of infant twins fuses MLL with hCDCrel, a cell division cycle gene in the genomic region of deletion in DiGeorge and velocardiofacial syndromes.

We examined the MLL genomic translocation breakpoint in acute myeloid leukemia of infant twins. Southern blot analysis in both cases showed two identical MLL gene rearrangements indicating chromosomal translocation. The rearrangements were detectable in the second twin before signs of clinical disease and the intensity relative to the normal fragment indicated that the translocation was not constitutional. Fluorescence in situ hybridization with an MLL-specific probe and karyotype analyses suggested t(11;22)(q23;q11. 2) disrupting MLL. Known 5' sequence from MLL but unknown 3' sequence from chromosome band 22q11.2 formed the breakpoint junction on the der(11) chromosome. We used panhandle variant PCR to clone the translocation breakpoint. By ligating a single-stranded oligonucleotide that was homologous to known 5' MLL genomic sequence to the 5' ends of BamHI-digested DNA through a bridging oligonucleotide, we formed the stem-loop template for panhandle variant PCR which yielded products of 3.9 kb. The MLL genomic breakpoint was in intron 7. The sequence of the partner DNA from band 22q11.2 was identical to the hCDCrel (human cell division cycle related) gene that maps to the region commonly deleted in DiGeorge and velocardiofacial syndromes. Both MLL and hCDCrel contained homologous CT, TTTGTG, and GAA sequences within a few base pairs of their respective breakpoints, which may have been important in uniting these two genes by translocation. Reverse transcriptase-PCR amplified an in-frame fusion of MLL exon 7 to hCDCrel exon 3, indicating that an MLL-hCDCrel chimeric mRNA had been transcribed. Panhandle variant PCR is a powerful strategy for cloning translocation breakpoints where the partner gene is undetermined. This application of the method identified a region of chromosome band 22q11.2 involved in both leukemia and a constitutional disorder.

Genomic imprinting and Wilms' tumor.

The selective loss of maternal and reduplication of paternal chromosome 11p15.5 alleles in Wilms' tumors (WTs) points to the existence of a paternally imprinted tumor suppressor gene(s) and/or a maternally imprinted dose-dependent growth-promoting gene(s) in this chromosomal region. Two reciprocally imprinted chromosome 11p15.5 genes, H19, a candidate tumor suppressor gene, and IGF2, a candidate dominant oncogene, have been well-characterized in terms of their imprinting and expression status in WTs. Here we review and extend data indicating that a majority of WTs show a bipaternal epigenotype at these loci, with H19 inactive and IGF2 biallelically active. This can arise either through loss of heterozygosity (LOH) or by a non-LOH pathway involving localized biallelic hypermethylation of H19 DNA. Conversion to this bipaternal endpoint has recently been found to affect not only these two genes, but also at least one other imprinted 11p15.5 gene, KIP2. Since 11p15.5 LOH and biallelic H19 hypermethylation can occur both early and late in tumor progression and since early loss is not associated with bilaterality or multifocality of WTs, these types of lesions appear to be permissive rather than rate-limiting in Wilms' tumorigenesis.

Metabolism of meso-2,3-dimercaptosuccinic acid in lead-poisoned children and normal adults.

Meso-2,3-dimercaptosuccinic acid (DMSA, or succimer) is an oral chelating agent for heavy-metal poisoning. While studying the urinary elimination of unaltered DMSA, altered DMSA (i.e., its mixed disulfides), and lead in children with lead poisoning, we observed a pattern of urinary drug elimination after meals suggestive of enterohepatic circulation. The excretion of lead in urine patterned the elimination of altered DMSA rather than the parent molecule. In addition, the half-life of elimination of DMSA via the kidney was positively associated with blood lead concentration. Two additional crossover studies of DMSA kinetics were conducted in normal adults to confirm the presence of enterohepatic circulation of DMSA after meals. In one, increases in plasma total DMSA concentration were observed after meals in all six subjects; these increases were prevented by cholestyramine administration 4, 8, and 12 hr after DMSA. In the second, the administration of neomycin also prevented increases in DMSA after meals. These studies indicate that 1) a metabolite(s) of DMSA undergoes enterohepatic circulation and that microflora are required for DMSA reentry; 2) in children, moderate lead exposure impairs renal tubular drug elimination; and 3) a metabolite of DMSA appears to be an active chelator.

MTS1/p16/CDKN2 lesions in primary glioblastoma multiforme.

The multiple tumor suppressor 1 (MTS1) gene encoding the p16 inhibitor of cyclin-dependent kinase 4 is deleted or mutated in a wide variety of human tumor cell lines, but the importance of this gene as a tumor suppressor in vivo appears to be highly dependent on tumor type. Because MTS1/p16/CDKN2 and the homologous MTS2/p15 gene map to a region of chromosome 9p21, which is frequently deleted in malignant gliomas, we searched for lesions of these genes in primary biopsies of glioblastoma multiforme (GBM). Our analysis confirms a sizable frequency of homozygous deletion of MTS1/p16/CDKN2 (9/27 cases) and also reveals a low but detectable frequency of intragenic DNA lesions (one point mutation in exon 2 leading to premature termination) among GBMs that retain one or both copies of the gene. No mutations were found in exon 2 of MTS2/p15 (12 cases examined), and one GBM showed a DNA deletion breakpoint in the 30 kb between MTS1/p16/CDKN2 and MTS2/p15 resulting in deletion of MTS1/p16/CDKN2 with retention of MTS2/p15. In contrast to the high-grade tumors, none of 12 low-grade gliomas showed MTS1/p16/CDKN2 deletions. These data support a role for MTS1/p16/CDKN2 as a tumor suppressor gene in the in vivo evolution of GBMs. Given that two tumors with hemizygous MTS1/p16/CDKN2 deletions and loss of heterozygosity for chromosome 9p21 did not contain detectable intragenic mutations, there may be one or more additional relevant 9p21 tumor suppressor genes.

Epigenetic lesions at the H19 locus in Wilms' tumour patients.

To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms' tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20-fold from fetal kidney levels. Of the expression-negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non-neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms' tumorigenesis.

Cytosine arabinoside and mitoxantrone treatment of relapsed or refractory childhood leukemia: initial response and relationship to multidrug resistance gene 1.

The objective of this study was to determine the response rate and toxicity of high-dose cytosine arabinoside (AC) and mitoxantrone (M) in relapsed or refractory childhood acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) and to correlate response with the expression of the multidrug resistance gene 1 (mdr1). Twenty-nine patients were treated with AC 1.0 g/m2 infused over 2 h every 12 h for eight doses (days 1-4) and M 12 mg/m2 infused over 1 h (days 3-6). Mdr1 expression was determined by a polymerase chain reaction (pcr) assay. Ten of 15 patients (67%) with AML obtained a complete remission (CR) of 3 to 30+ months duration. Eight of 14 (57%) ALL patients obtained a CR of 1 to 23+ months duration. The major toxicities were hematopoietic and infectious. Seventy-nine per cent of patients developed a documented infection during induction. Mdr1 did not correlate with a lower induction rate. This AC/M regimen is active in childhood AML and ALL.

Tumour-suppressor activity of H19 RNA.

Loss of heterozygosity in certain human embryonal tumours implicates a tumour-suppressor gene at chromosome 11p15.5 and selective loss of maternal alleles suggests that this gene is paternally imprinted. The human H19 gene maps to 11p15.5, is expressed in differentiating fetal cells and is paternally imprinted. We report here that two embryonal tumour cell lines, RD and G401, showed growth retardation and morphological changes when transfected with an H19 expression construct. More importantly, clonogenicity in soft agar and tumorigenicity in nude mice were abrogated in the G401-H19 transfectants. In addition to demonstrating its tumour-suppressor potential, this transfection system should help structural and functional studies of the enigmatic H19 gene.

Imprinting of human H19: allele-specific CpG methylation, loss of the active allele in Wilms tumor, and potential for somatic allele switching.

Genomic imprinting and monoallelic gene expression appear to play a role in human genetic disease and tumorigenesis. The human H19 gene, at chromosome 11p15, has previously been shown to be monoallelically expressed. Since CpG methylation has been implicated in imprinting, we analyzed methylation of H19 DNA. In fetal and adult organs the transcriptionally silent H19 allele was extensively hypermethylated through the entire gene and its promoter, and, consistent with a functional role for DNA methylation, expression of an H19 promoter-reporter construct was inhibited by in vitro methylation. Gynogenetic ovarian teratomas were found to contain only hypomethylated H19 DNA, suggesting that the expressed H19 allele might be maternal. This was confirmed by analysis of 11p15 polymorphisms in a patient with Wilms tumor. The tumor had lost the maternal 11p15, and H19 expression in the normal kidney was exclusively from this allele. Imprinting of human H19 appears to be susceptible to tissue-specific modulation in somatic development; in one individual, cerebellar cells were found to express only the otherwise silent allele. Implications of these findings for the role of DNA methylation in imprinting and for H19 as a candidate imprinted tumor-suppressor gene are discussed.

Induction of growth suppression and modification of gene expression in multi-drug-resistant human glioblastoma multiforme cells by recombinant human fibroblast and immune interferon.

The combination of recombinant human fibroblast (IFN-beta) and immune (IFN-gamma) interferon induces enhanced growth suppression and modifies the antigenic phenotype in parental and multi-drug-resistant (MDR) human glioblastoma multiforme (GBM) cells. The present study was conducted to explore the mechanism underlying this cooperative interaction between interferons in inducing growth suppression in MDR-GBM cells. For this analysis we have utilized 2 MDR-GBM cell lines which display a differential sensitivity to growth suppression when exposed to IFN-beta or IFN-gamma. GBM-18-B3 (MDR) cells are more sensitive to growth inhibition by IFN-gamma than by IFN-beta, whereas GBM-18-A3 (MDR) cells are inhibited to a greater degree by IFN-beta than by IFN-gamma. In both cell types, however, growth is suppressed to a greater degree by the combination of interferons than by equivalent concentrations of either type of interferon used alone. Growth suppression induced by the interferons, alone or in combination, was not associated with comparable changes in the steady-state level of MDRI mRNA. In addition, the anti-proliferative effect of interferon was similar in GBM-18 (MDR) cells grown in the presence or absence of colchicine. GBM-18-A3 and GBM-18-B3 cells differed in their de novo and interferon-inducible expression levels of IFN-beta-responsive genes, isg-15 and isg-54. In contrast, both cell types responded in a similar manner with respect to expression of the IFN-gamma-responsive gene, HLA Class II (HLA-DR beta), and HLA Class I, fibronectin and ICAM-I. No further increase in expression of any of the genes was observed which was unique to the combination of interferons.

Controlled study of meso-2,3-dimercaptosuccinic acid for the management of childhood lead intoxication.

We examined the efficacy and safety of meso-2,3-dimercaptosuccinic acid (DMSA) in children with markedly elevated blood lead (BPb) concentrations. Among 19 children with BPb concentrations of 50 to 69 micrograms/dl (2.41 to 3.33 mumol/L) who received a 5-day inpatient oral course of DMSA (1050 mg/m2 per day), the mean BPb concentration decreased by 61%; in four who received calcium disodium ethylenediaminetetraacetic acid (CaNa2EDTA) (1000 mg/m2 per day intravenously), it decreased by 45% (p less than 0.0007). Urinary lead excretion was comparable in both groups. Treatment with DMSA was more effective than treatment with CaNa2EDTA in restoring metabolic activity to the heme pathway and was well tolerated even among nine patients who received concomitant iron supplementation and two who had homozygous deficiency of glucose-6-phosphate dehydrogenase. On discharge, these 19 children received either no chelation therapy or DMSA, 350 or 700 mg/m2 per day for 14 days on an outpatient basis. After 14 days the mean BPb values for the no-chelation, low-DMSA, and high-DMSA groups were 73%, 66%, and 50% of the pretreatment values, respectively. We conclude that a 5-day oral course of DMSA is effective in the treatment of children with severe lead poisoning. In addition, on an outpatient basis the administration of DMSA, 700 mg/m2 per day, is capable of delaying the typical rebound in BPb values and should ultimately reduce the need for repeated hospitalizations.

Effect of recombinant fibroblast interferon and recombinant immune interferon on growth and the antigenic phenotype of multidrug-resistant human glioblastoma multiforme cells.

To study the effect of drug resistance on the response of stage IV astrocytomas to interferon, a human glioblastoma multiforme cell line, GBM-18, was transfected with an expression-vector plasmid containing a human multidrug resistance (MDR) gene (pHaMDR1/A), and clones surviving in colchicine were isolated. GBM-18 multidrug-resistant subclones displayed cross-resistance to other chemotherapeutic agents, including vincristine, doxorubicin, and dactinomycin. The multidrug-resistant phenotype was reversible when GBM-18 multidrug-resistant cells were cultured in colchicine and the calcium-channel blocker verapamil. The level of the MDR1 gene (also known as PGY1) message was increased in GBM-18 multidrug-resistant cells selected for increased resistance to colchicine, and this effect was not correlated with an amplification of the MDR1 gene. In both parental GBM-18 and GBM-18 multidrug-resistant cells, growth was suppressed to a greater degree when cultures were treated with the combination of fibroblast interferon (IFN-beta) and immune interferon (IFN-gamma). Parental cells and multidrug-resistant subclones varied in their de novo and/or interferon-modulated expression of HLA class I and class II antigens, a high-molecular-weight melanoma-associated antigen, and intercellular adhesion molecule 1 (ICAM-1). Of the antigens tested, ICAM-1 and HLA class I antigens were the most sensitive to enhanced expression induced by IFN-beta and IFN-gamma when used alone or in combination. The results of the present study indicate that multidrug-resistant human glioblastoma multiforme cells retain their increased sensitivity to the antiproliferative activity of the combination of IFN-beta plus IFN-gamma, and differences in antigenic phenotype are apparent in independent multidrug-resistant glioblastoma multiforme clones.