Assessing the chronic toxicity of atrazine, permethrin, and chlorothalonil to the cladoceran Ceriodaphnia cf. dubia in laboratory and natural river water.

The majority of ecotoxicological data are generated from standard laboratory-based experiments with organisms exposed in nonflowing systems using highly purified water, which contains very low amounts of dissolved organic matter and suspended particulates. However, such experimental conditions are not ecologically relevant. Thus, there is a need to develop more realistic approaches to determining toxicity, including both lethal and sublethal effects. This research provides information on the effect of natural water constituents, such as suspended particulates and dissolved organic matter, in river water (RW) on the chronic toxicity (7-day reproductive impairment) of the pesticides atrazine, chlorothalonil, and permethrin to the freshwater cladoceran Ceriodaphnia cf. dubia. Standard bioassays were conducted under standard laboratory and more environmentally realistic conditions (using RW). The 7-day IC25 (reproduction impairment) values of atrazine, chlorothalonil, and permethrin to C. cf. dubia ranged from 862.4 to >1000, 51.3 to 66.4, and 0.19 to 0.23 µg/L, respectively. Using the Globally Harmonized System of Classification and Labelling of Chemicals, atrazine is classified as moderately to highly toxic, whereas permethrin and chlorothalonil were both highly toxic. The presence of dissolved organic matter and suspended particles in natural RW did not significantly (p > 0.05) change the toxicity of any of the pesticides to C. cf. dubia compared with that tested in laboratory water (LW). For the tested pesticides, toxicity testing in LW provided an adequate estimate of the hazard posed.

Dissecting prenatal, postnatal, and inherited effects: ART and design.

With the failure of common variants alone to explain the bulk of trait heritability, it becomes more important to understand the contribution of maternally inherited effects, prenatal effects, and postnatal environmental effects. These effects can be disentangled by studying families containing children conceived by assisted reproductive technologies (ART). We propose and develop a model that is an extension of the variance component model commonly used in pedigree analysis. Our model is flexible enough to allow any number of family members and degrees of relationship; thus, researchers can use both small and extended families simultaneously. Simulations demonstrate that our method has appropriate statistical properties and is robust to model misspecification and accurate in the presence of missing data. Most importantly, our method is able to disentangle maternally inherited effects from prenatal effects, which are confounded in traditional family studies. Our analyses also provide guidance to researchers designing studies that will use ART families to clarify genetic and environmental factors underlying traits.

Acetylcholinesterase activity in the freshwater shrimp Caridina nilotica as a biomarker of Roundup(®) herbicide pollution of freshwater systems in South Africa.

The use of Caridina nilotica whole-body acetylcholinesterase (AChE) activity as a potential biomarker of Roundup(®) pollution of aquatic ecosystems was investigated. Forty days post hatch (dph) shrimps were exposed to different concentrations of 0.0, 4.3, 6.7, 10.5, 16.4, 25.6 and 40.0 mg/L in a 96 h acute toxicity test; and 0.0, 2.2, 2.8, 3.4, 4.3 and 5.4 mg/L in a 21 d chronic toxicity test. Whole-body AChE activities were determined at the end of the exposure periods by spectrophotometric assay of sample extract; activities were then normalized against protein contents in the samples and expressed in nanomoles of substrate hydrolyzed. Results of both tests showed that AChE activity was concentration-dependent. Mean AChE activities and standard deviations (±SD) for 96 h acute toxicity were 3.6239 (± 0.4185), 3.4157 (± 1.1842), 2.537 (± 1.3989), 2.4253 (± 1.4202), 2.4127 (± 1.9097), 2.0017 (± 1.1080) and 2.316 (± 0.4001) nmol/min/mg protein; while activity levels for 21 d test were 3.6907(± 0.3401), 2.8473 (± 0.713), 2.9134 (± 0.9879), 2.6738 (± 0.7117), 2.3019 (± 0.4464) and 2.1478 (± 0.864) nmol/min/mg protein. Reference basal AChE activity for 40 dph C. nilotica based on the two control groups was estimated as 3.6907 (± 0.3401) nmol/min/mg proteins. The present work provides ecotoxicological basis for the possible use of AChE activity in C. nilotica as a biomarker for monitoring Roundup(®) pollution in freshwater systems.

Lipid peroxidation in the freshwater shrimp Caridina nilotica as a biomarker of Roundup(®) herbicide pollution of freshwater systems in South Africa.

Glyphosate-based herbicides used to control weeds and invading alien plant species in South Africa ultimately end up in freshwater ecosystems, but no South African environmental water quality guideline exists to regulate these bio-active chemicals. Ecotoxicological tests to assess the possibility of using lipid peroxidation (LPx) in Caridina nilotica as a potential biomarker of Roundup(®), a glyphosate-based herbicide, pollution were conducted. In two separate tests, 40 days post hatch shrimps were exposed to different concentrations of 4.3, 6.7, 10.5, 16.4, 25.6 and 40.0 mg/L in a 96 h acute toxicity test; and 2.2, 2.8, 3.4, 4.3 and 5.4 mg/L in a 21 d chronic toxicity test, using static-non renewal and static-renewal methods, respectively. Shrimp whole body LPx was estimated by thiobarbituric acid reactive species (TBARS) assay, performed by a malondialdehyde (MDA) reaction with 2-thiobarbituric acid (TBA) measured spectrophotometrically. Final MDA concentrations were expressed as nmol MDA produced/mg protein. Results showed that LPx was significantly lower in control animals than in animals exposed to different Roundup(®) concentrations, (p < 0.05). The present work provides an ecotoxicological basis for the possible use of LPx in Caridina nilotica as a biomarker for monitoring Roundup(®) pollution in freshwater ecosystems.

Cytogenetic analysis in relapsed childhood acute lymphoblastic leukemia.

The nature of the cytogenetic abnormalities present at relapse of childhood acute lymphoblastic leukemia (ALL) and their relationship to the disease and the karyotype at diagnosis have not been clearly defined. This report describes cytogenetic analyses of 50/51 consecutive relapsed childhood ALL patients. Evolution of the karyotype was common, with structural abnormalities particularly frequent. Rearrangements involving chromosome 1 occurred frequently, particularly in patients with greater than 50 chromosomes. In patients with less than or equal to 50 chromosomes, structural aberrations were often unbalanced, leading to loss of genetic material, but these did not show a predominance of chromosome 1 abnormalities. These differences among the cytogenetic groups of ALL are an indication that the chromosomal abnormalities occurring in ALL reflect different biological events underlying this disease, and that different biological processes are involved in the several cytogenetic groups of ALL patients not only at initiation, but also during the progression and evolution of the disease.

Wisconsin cystic fibrosis chest radiograph scoring system.

A new clinical scoring system for patients with cystic fibrosis is needed because of recent advances in diagnosis and treatment which have changed the course of this disease. Chest radiograph scoring is the best objective measure of pulmonary disease for longitudinal studies beginning with infants; however, based on pilot studies, previous scoring systems are not sensitive enough in discriminating between degrees of mild lung disease. Therefore, a new radiographic scoring system was developed with the goal of achieving both sensitivity and reproducibility. This objective was pursued by applying multiattribute utility theory, using a panel of interpreters with expertise in cystic fibrosis radiology, and employing mathematical modeling techniques to weight the various components. The system was developed and validated in three phases including comparison to the Brasfield method of quantitative radiology. The data demonstrate that the new system can be applied reliably and conveniently to generate reproducible scores of pulmonary disease severity. Evaluation of the scores by four independent raters using chest radiographs from 61 patients at an average age of 8.37 years revealed good agreement with a .714 Kendall coefficient of concordance. Assessment of serial changes over time was performed using a group of 176 chest radiographs from 25 patients ranging from 4 weeks to 6 years old; this showed that the Wisconsin system generates score differences that are greater in magnitude with disease progression compared with the Brasfield method. Therefore, the new method is more sensitive to progression of mild disease and should be superior to prior radiographic scoring systems for evaluating therapies designed to modify the early course of disease. The Wisconsin system is designed to be useful in longitudinal clinical studies involving young children with cystic fibrosis and is capable to detecting progression from normality to mild lung disease.

High-resolution chromosome analysis: I. Applications and limitations.

High-resolution chromosome preparations were examined in 55 couples experiencing multiple spontaneous abortions to determine if such studies might provide additional cytogenetic information. One translocation [46,XY,t(14;18) (q32; q22.2)] was detected that was not observed on routine metaphase preparations (GTG banding). In addition, an abnormality (not from the original sample) suspected on routine analysis was accurately identified as [46,XY, dir ins (12;21) (p12.3;q22.-1q22.2)] only after high-resolution studies. Metaphases with a total of 500-650 discernible bands per haploid set are most informative for high-resolution analysis of a complete karyotype. Chromosomes yielding this number of bands demonstrate 6.7-14.2% homolog discordance and usually require only three to five karyotypes to reach a diagnosis. GTG proved more effective than RBG banding in conjunction with high-resolution studies.

Molecular cytogenetic identification of four X chromosome duplications.

Four cases with previously unidentified X-chromosome abnormalities were studied by standard cytogenetic techniques and FISH in order to demonstrate the origin of the extra segment on the abnormal X chromosomes. All cases were identified as X-chromosome duplications by using a chromosome-specific painting probe. Application of appropriate locus-specific DNA probes as an adjunct to GTG- and RBG-banding proved useful in defining the breakpoints and the extent of the duplications. Although the duplicated X chromosome in female cases was selectively inactivated, as demonstrated by its late-replicating pattern, abnormal clinical findings were manifested in 3 female patients.

Deletions in chromosome 2 and fragile sites.

We report on 2 patients with de novo deletions of 2q and chromosome constitutions of 46,XY,del(2)(q32.3q33.3) and 46,XX,del(2) (q21q23.2), respectively. Comparisons of breakpoints of interstitial deletions show frequent correspondence to common fragile sites.

Familial translocation resulting in Wolf-Hirschhorn syndrome in two related unbalanced individuals: clinical evaluation of a 39-year-old man with Wolf-Hirschhorn syndrome.

A chromosomal translocation between chromosomes 4 and 8 resulting in Wolf-Hirschhorn syndrome in 2 individuals has been traced through 4 generations of a family. Ascertainment of the family was through a newborn infant with evident Wolf-Hirschhorn syndrome who had an unbalanced chromosomal translocation [46,XY,-4,+der(4),t(4;8) (p15.32;p22)]. Discussion with the family documented a paternal great-uncle who also had a similar phenotype and profound mental retardation. Subsequently this individual was found to have the same unbalanced chromosome constitution as the propositus. The 39-year-old great-uncle is the oldest reported individual with the Wolf-Hirschhorn syndrome. The importance of chromosome evaluation of older individuals with mental retardation syndromes is emphasized.

Clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome.

In a clinical and cytogenetic survey of 39 individuals with Prader-Labhart-Willi syndrome (PLWS) (23 males and 16 females ranging in age from 2 weeks to 39 years), an interstitial deletion of chromosome 15 (breakpoints q11 and q13) was identified in 21 cases and apparently normal chromosomes in the remainder. Studies of parental chromosome 15 variants showed that the del[15q] was paternal in origin, although chromosomes of both parents were normal. All chromosome deletions were de novo events. Possible causes for the chromosome deletion and the role of chromosome rearrangements in individuals with PLWS are discussed. Clinical characteristics of the deletion and nondeletion groups were recorded and compared with 124 individuals reported in the literature. Individuals with the chromosome deletion were found to have lighter hair, eye, and skin color, greater sun sensitivity, and higher intelligence scores than individuals with normal chromosomes. Correlation studies of metacarpophalangeal pattern profile variables and dermatoglyphic findings indicate apparent homogeneity of the deletion group and heterogeneity of individuals with PLWS and normal chromosomes.

Marker chromosome 21 identified by microdissection and FISH.

A child without Down syndrome but with developmental delay, short stature, and autistic behavior was found to be mosaic 46,XX/47,XX,+mar(21) de novo. The marker was a small ring or dot-like chromosome. Microdissection of the marker was performed. The dissected fragments were biotinylated with sequence-independent PCR as a probe pool for fluorescence in situ hybridization (FISH). FISH results suggested an acrocentric origin of the marker. Subsequent FISH with alpha-satellite DNA probes for acrocentric chromosomes, and chromosome-specific 21 and 22 painting probes confirmed its origin from chromosome 21.

A family with three recessive traits and homozygosity for a long 9qh+ chromosome segment.

We report a family in which a mentally retarded, proportionately dwarfed girl had a child from a presumably incestuous mating that had the Ellis van-Creveld syndrome, presumed autosomal recessive hydrocephalus (Dandy-Walker type), and homozygosity for an extremely long 9qh+ chromosomal marker. The mentally retarded mother had normal birth weight, unusual facial appearance, and virtual absence of secondary sexual hair; she developed severe hypoglycemia during pregnancy. Her parents were first cousins, and she may have a previously unreported autosomal recessive syndrome.

Partial deletion of chromosome 6p: delineation of the syndrome.

Here we summarize the clinical findings of five new patients and nine patients reported in the literature with deletions of the short arm of chromosome 6. The del(6p) syndrome appears to include the following clinical findings: mental retardation, microcephaly, abnormal sutures, broad nasal bridge, various eye and ear abnormalities, a short neck with excess skin folds, and a normal birth weight and length.

An apparently acentric marker chromosome originating from 9p with a functional centromere without detectable alpha and beta satellite sequences.

Recently, we studied a patient with minor abnormalities and an apparently acentric marker chromosome who carried a deleted chromosome 9 and a marker chromosome in addition to a normal chromosome 9. The marker was stable in mitosis but lacked a primary constriction. The origin of the marker was established by fluorescent in situ hybridization (FISH) using a chromosome 9 painting probe. Hybridization of unique sequence 9p probes localized the breakpoint proximal to 9p13. Additional FISH studies with all-human centromere alpha satellite, chromosome 9 classical satellite, and beta satellite probes showed no visible evidence of these sequences on the marker [Curtis et al.: Am J Hum Genet 57:A111, 1995]. Studies using centromere proteins (CENP-B, CENP-C, and CENP-E) were performed and demonstrated the presence of centromere proteins. These studies and the patient's clinical findings are reported here.

Brief clinical report: two children with de novo del(9p).

We describe two patients with characteristic manifestations of the del(9p) syndrome. Among the prominent manifestation are moderate mental retardation, trigonocephaly, flat nasal bridge, anteverted nostrils, long philtrum, square and hyperconvex nails, and apparently long digits. The metacarpophalangeal pattern profiles of the patients showed that the clinical impression of long fingers may be due to relative shortness of the metacarpals rather than to elongation of the phalanges.

PCR and FISH analysis of a ring Y chromosome.

A newborn male infant presented with midshaft hypospadias, chordee, and undescended left testis. Both gonads lacked the tunica albuginea and appeared to be adjacent to structures resembling fallopian tubes. On biopsy, there was marked dysgenesis of both gonads, with a paucity of testicular tubules and foci of ovarian-like stroma. Peripheral blood karyotype was 46,X,mar(Y) [39]/45,X [5]. Right gonadal biopsy material showed the same mosaicism but with a higher proportion of 45,X cells (46%). PCR and FISH analyses with primers/probes from different Yp, Yq, and Ycen loci defined the structure of the marker Y as a probable complex ring with breakpoints in Yq11.21 (very close to the centromere) and in Yp11.32 (the pseudoautosomal region). Based on the phenotype and the laboratory findings, the prognosis given to the patient was for short stature and azoospermia without an increased risk for gonadoblastomas.

Head circumference of children with Down syndrome (0-36 months)

This study provides statistically appropriate head circumference reference curves for males and females with Down syndrome (DS) from birth to 36 months of age. A total of 239 males and 182 females from five study populations, yielding a combination of cross-sectional and longitudinal data, were used for the analysis. The method of least squares was used to test the fit of the growth model y = a+bx+c[log(x + 1)], where x is age in months. These standardized curves should provide information of value in the medical, physical, and developmental management of children with DS.