Neuropsychological correlates of learning disabilities: Subtype identification by the tryon clustering method

Since Samuel Orton's (1937) assertion that dyslexia reflects abnormal brain organization, the relationship of learning disabilities to brain dysfunction has been the topic of considerable debate. Recently, learning-disabled individuals have been studied in conjunction with those known to have neurological dysfunction, in a search for common subtypes. In the present study, a population of 177 children, ages 9-0 to 14-0, were assessed on an augmented version of the Children's Halstead-Reitan Battery. One hundred twenty-nine Ss were learning-disabled, 37 of whom also had verified brain damage. The remaining 48 children had neither learning disabilities nor evidence of brain damage. Patterns of neuropsychological performance were determined using Tryon's clustering methods. The procedure yielded six subject clusters: (A) and (B)—children with low general intellectual ability; (C) children who are clumsy and lethargic; (D) children with language dysfunction; (E) children with faulty spatial orientation; and (F) children with no detectable neuropsychological deficits. These clusters were similar to those identified by investigators who have used other subject-clustering methods. Brain-damaged individuals were more prevalent in some clusters (e.g., A and B) than in others (e.g., E and F), and substantial numbers of learning disabled subjects were also found in clusters where brain-damaged individuals tended to cluster, indicating similar neuropsychological profiles. The cluster structure was validated by comparison with subtypes identified by other investigators, as well as by tests of association between clusters with exogenous factors (e.g., history of prematurity; seizures).     

A sensitive method for assay of a novel tricyclic compound using coulometric electrochemical detection

A reversed-phase high-performance liquid chromatographic method using coulometric electrochemical detection in the oxidative mode has been developed for the analysis of 3-(9-chloro-5,6-dihydro-11-H-pyrrolo[2,1-b][3]benzazepine-11-ylidene- N,N-dimethyl-1-propanamine(E)-Z-butenedioate hydrogen maleate (1) in plasma of patients dosed with 2-8 mg/kg/d of the drug. Concentrations as little as 0.1 ng/mL of 1 in plasma can be estimated with a mean coefficient of variation of 7.4 +/- 1.08%. The utility of the procedure was demonstrated by the analysis of 500 patient samples from a rising multiple-dose study.     

Functional properties of recombinant GABAA receptors composed of single or multiple β subunit subtypes

GABA_A receptor (GABAR) isoforms in the central nervous system are composed of combinations of α(1–6), β(1–4), γ(1–4), δ(1) and (1) subunit subtypes arranged in a pentamer. Many regions of the brain express high levels of mRNA encoding several different subunits and even multiple subunit subtypes. The stoichiometry of GABAR isoforms is unclear, and the number and identity of individual subunit subtypes that are coassembled remain uncertain. To examine the role of β subunit subtypes in the functional properties of GABARS and to determine whether multiple β subtypes can be coassembled in functional GABARs, plasmids containing cDNAs encoding rat β1 and/or β3, α5 and γ2L subtypes were cotransfected into L929 fibroblasts. The properties of the expressed receptor populations were determined using whole-cell and single-channel recording techniques. The α5β1γ2L isoform was less sensitive to GABA than the α5β3γ2L isoform. α5β1γ2L isoform currents were also insensitive to the allosteric modulator loreclezole, while α5β3γ2L isoform currents were strongly potentiated by loreclezole. Fibroblasts transfected with plasmids containing cDNAs for both β1 and β3 subtypes along with α5 and γ2L subtypes produced a receptor population with an intermediate sensitivity to GABA which was insensitive to loreclezole. These results suggest that functional GABARs can be formed that contain two different β subunit subtypes with properties different from receptors that contain only a single β subtype and that the β subunit subtypes influence the response of GABARs to GABA and to the allosteric modulator loreclezole.     

Low-Calcium Diets Enhance Phytate-Phosphorus Availability

This study showed that, in chickens, the negative effects of phytate-phosphorus in a low inorganic phosphorus diet could be completely reversed through the additive effects of reduced dietary calcium and increased cholecalciferol. In the future, perhaps greater reliance on more readily available plant phosphorus sources may be instituted in developing countries, where cheap sources of inorganic phosphorus are difficult to obtain.     

Lack of involvement of reactive oxygen in the cytotoxicity of mitoxantrone,CI941 and ametantrone in MCF-7 cells: comparison with doxorubicin

Summary The MCF-7 cell S9 fraction and whole MCF-7 cells can mediate one-electron-redox cycling of doxorubicin, giving rise to concomitant oxidation of reduced nicotinamide adenine dinucleotide phosphate (NADPH), formation of a drug semiquinone free radical, consumption of molecular oxygen and formation of superoxide anions and hydroxyl radicals. Doxorubicin redox cycling was consistent with DNA strand breakage and cell kill in MCF-7 cells. In contrast, no evidence for redox cycling was found for mitoxantrone (MIT), CI941 or ametantrone (AMET) in MCF-7 cells. Despite the absence of redox cycling, the CI941, MIT, and AMET concentrations resulting in 50% mortality (LC₅₀; 1.5×10^–10, 5.2×10^–9 and 1.2×10^–6 m, respectively) of MCF-7 cells were lower than that of DOX (3.0×10^–6 m). Furthermore, the higher cytotoxicity of MIT and CI941 as compared with AMET or DOX was associated with greater efficiency in inducing DNA strand breakage in MCF-7 cells as determined by alkaline elution. Sine MIT and CI941 proved to be the most potent DNA-damaging and cytotoxic agents in this study, the ability of DOX to undergo redox cycling does not appear to confer increased cytotoxic potential on this agent. The present study revealed several important aspects with regards to the structural modification of anthraquinone antitumour agents. Firstly, the C1 and C4 postitioning of the hydroxyethylamino side chains on MIT, CI941 and AMET is associated with a lack of flavin reductase-mediated activation of these agents. Secondly, the possession of a C5 or C8 aromatic hydroxyl group appears to be intimately involved in the enhanced DNA strand breakage and cytotoxic potency of MIT and CI941, since AMET does not possess these groups. These findings indicate that future development of quinone antitumour agents should concentrate on compounds that do not undergo redox cycling but do possess aromatic hydroxyl groups, since the latter appear to be responsible for the enhanced cytotoxicity of MIT and CI941.Abbreviations DOX doxorubicin - MIT mitoxantrone - AMET ametantrone - SOD superoxide dismutase - DMPO 5,5-dimethyl-1-pyrroline-N-oxide - ESR electron spin resonance - SSF strand scission factor This work was funded by the Cancer Research Campaign (UK)     

Vein of Galen aneurysm presenting with recurrent aseptic meningitis and subsequent spontaneous thrombosis

Clinical and laboratory findings are described in the case of a patient with a vein of Galen aneurysm who presented with recurrent aseptic meningitis for which no etiology could be identified. The patient subsequently developed thalamic and intraventricular hemorrhage associated with partial thrombosis of the dilated vein of Galen. Review of the literature revealed no previously reported association of these conditions. Recurrent cerebral venous thrombosis involving the fistula is hypothesized as the cause of repeated inflammatory reactions near the subarachnoid space. More extensive thrombosis may then have precipitated the hemorrhage.