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S Darling

Publications and source records attributed to S Darling.

At least 19 recordsLinked to original sources
PubMed2005

Neuropsychological evidence for separating components of visuo-spatial working memory.

There is increasing evidence to support the idea that visuo-spatial working memory can be segregated into separate cognitive subsystems. However, the nature of these systems remains unclear. In this paper we report data from two brain injured patients suggesting that information about visual appearance is retained in a different subsystem from information about spatial location, and that this differential processing can be observed when the style of presentation (sequential or simultaneous) is controlled.

Adolescent↗
PubMed2001

Altered responsiveness to stress and NMDA following prenatal exposure to cocaine.

Pregnant Sprague--Dawley rats were treated once daily with 40-mg/kg cocaine or saline from gestation days (GD) 12 to 21. A third group of pregnant dams was used as a pairfed control. Male and female offspring were examined for stress endurance response as determined by the cold-water swim test on postnatal days (PND) 21, 30, 40, and 60. Male and female offspring exposed to cocaine in utero were found to have diminished tolerance and altered hormonal response to stress. Moreover, prenatal cocaine exposure has been associated with significant increases in severity of N-methyl-D-aspartate (NMDA; 35 mg/kg) behavioral responses (tail twitches, wetdog shaking, and convulsion) as compared to control. Examining the experimental groups for pain sensitivity using the tail-flick and the hot-plate methods indicated that prenatal cocaine exposure altered pain sensitivity. NMDA receptor binding studies showed an increase in receptor density in the hippocampus and hypothalamus of the cocaine-treated group. These results indicate that gestational cocaine exposure is associated with long-term alterations in response to stress, NMDA receptor, and pain sensitivity in the rat offspring.

Aging↗
PubMed2001

Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells.

The neuropathology associated with Parkinson's disease within and around the substantia nigra is thought to involve excessive production of free radicals, dopamine autoxidation, defects in the expression of glutathione peroxidase, attenuated levels of reduced glutathione, altered calcium homeostasis, excitotoxicity and genetic defects in mitochondrial complex I activity. While the neurotoxic mechanisms are vastly different for excitotoxins and N-methyl-4-phenylpyridinium ion (MPP+), both are thought to involve free radical production, compromised mitochondrial activity and excessive lipid peroxidation. In the present study, several dietary antioxidant compounds, monoamine oxidase inhibitors and ergogenic compounds were examined for protective action against neurotoxicity induced by L-glutamate (15 mM) or MPP+-HCl (5 mM) in a plastic adhering variant of murine pheochromocytoma cells. The results show no significant protective effects exhibited by azulene, (+)-catechin, curcrumin, (-)-epigallocatechin gallate, green tea, morin, pygnogenol, silymarin, clove oil, garlic oil or rosemary, extract. Compounds, which were effective in providing protection against L-glutamate-induced cell death, were coenzyme Q-0, coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. Compounds, which provided protection against MPP+-HCl toxicity, were allopurinol, coenzyme Q-10, L-deprenyl, N-acetyl-L-cysteine and sesame oil. In both models, significant protection was achieved in the presence of coenzyme Q-10, L-deprenyl and N-acetyl-L-cysteine. These results indicate that the mechanism of cell death in both of these toxicity models is most likely not related to the destructive effects of free radicals.

1-Methyl-4-phenylpyridinium↗
PubMed1999

Gender differences in knee cartilage volume as measured by magnetic resonance imaging.

OBJECTIVE: The aim of this study was to analyze sex differences in knee cartilage volume. METHODS: Articulate cartilage volumes were determined by processing images acquired in the sagittal plane using T1-weighted fat saturation magnetic resonance on an independent work station. The knees of 28 subjects (17 male, 11 female) who underwent MRI for clinical indications (pain <3 months) but who had a normal X-ray and structurally normal MRI were examined. RESULTS: Males had significantly larger cartilage volumes than females, with difference in cartilage volume remaining statistically significant after adjusting for age, height, weight and bone volume. The differences for males relative to females were: femoral cartilage volume [4.1 ml 95% CI (2.0, 6.1)]; and patella cartilage volume [1.4 ml (0.2, 2.7)]. Although not statistically significant, the tibial cartilage volume also showed these sex differences. Exploratory analysis indicated an increasing gender difference with increasing age for patellar cartilage volume. CONCLUSION: Men have significantly larger knee cartilage volume than women, independent of body and bone size. The mechanisms for this will need to be determined.

Adult↗
PubMed1996

Functional activity of new C-terminal cyclic-neurotensin fragment analogs.

Neurotensin (NT, pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu) is a tridecapeptide that displays a wide spectrum of biological actions. Cyclic derivatives of a hexapeptide NT [(8-13)] (N alpha MeArg-Lys-Pro-Trp-Tle-Leu, Tle = tert-leucine) were designed and prepared by a combination of solution and solid-phase peptide synthetic methodologies. As reported previously, several analogs possessed nanomolar binding affinities for NT receptors in newborn (10-day-old) mouse brain membrane preparations. In this study, we determined the functional ability of these analogs to mobilize intracellular free calcium, [Ca2+]i, in HT-29 cells (human colonic adenocarcinoma). Of greatest interest were the cyclic compounds 2, 6 and 9 that had Ki values of 0.19, 3.50 and 4.18 microM for [3H]NT labeled receptors in the HT-29 cell membrane assay, respectively. In the functional assay, compounds 2 and 6 mobilized [Ca2+] with EC50 values of 0.13 and 20 microM, respectively. In comparison, Compound 9 blocked the NT-induced mobilization of [Ca2+]i, with an IC50 of 1.70 microM. The present findings indicate that small molecule cyclic analogs, that possess functional activity, can be designed and may have therapeutic utility in the treatment of schizophrenia and possibly other neurological disorders.

Amino Acid Sequence↗
PubMed1996

Mice as models of human developmental disorders: natural and artificial mutants.

Over the past year, the mouse has been used as a model to make significant contributions towards our understanding of human developmental disorders. The existence of both natural and artificial mouse mutants has not only facilitated the identification of mutations and provided candidate genes for human disorders but has also increased our knowledge regarding the cellular and molecular processes involved in normal mammalian embryogenesis.

Animals↗
PubMed1993

Proliferation and migration of primordial germ cells in We/We mouse embryos.

We have examined the numbers and distribution of primordial germ cells in We/We, We/+, and +/+ mouse embryos using Southern blotting to determine embryo genotypes. At early somite stages (5-7 somites: approximately 8 1/2 days post coitum [dpc]) there are 50 to 100 germ cells in embryos of all genotypes. The number of germ cells in We/+ and +/+ embryos then begins to increase: at later somite stages (17-19 somites: approximately 9 1/2 dpc) they number about 200, and by 10 1/2 dpc there are approximately 725 We/+ and 850 +/+ germ cells. During this time, however, the number of germ cells in We/We embryos remains less than 100. At 8 1/2 dpc, the distribution of germ cells in the hindgut endoderm is the same in all genotypes. By 9 1/2 dpc, 30% of We/We germ cells are found in ectopic sites (allantois and vitelline artery); germ cell distribution along the length of the hindgut appears normal, but germ cells remain confined to the floor of the gut in We/We embryos, rather than being distributed around its circumference as in the other two genotypes. By 10 1/2 days, the migration of We/We germ cells through the dorsal mesentery lags behind that of the other genotypes, and a larger proportion remains in the gut wall.

Alleles↗
PubMed1989

Inducible expression of an hsp68-lacZ hybrid gene in transgenic mice.

Transgenic mice have been generated that express the E. coli beta-galactosidase gene under the control of the promoter from the mouse heat-shock gene, hsp68. Sequences from -664 to +113 relative to the start of transcription of the hsp68 gene were sufficient to direct stress-induced expression of the beta-galactosidase gene in adult tail tissue and various tissues of fetal stages of development. Expression was detected in situ by staining with the chromogenic substrate, X-gal. The hybrid gene was refractory to induction in preimplantation embryos until the blastocyst stage of development, as reported for the endogenous hsp68 gene. No constitutive expression was observed by in situ staining or Northern analysis at any stage of development, even in tissues that constitutively express the endogenous hsp68 gene. We conclude that the hsp68 promoter region included in the construct contains sufficient sequence information for heat and arsenite inducibility, but it does not contain sequences controlling tissue-specific expression during development. This tightly regulated inducible promoter may provide a useful tool for short-term inducible gene expression in transgenic mice.

Animals↗
PubMed1987

Pseudoautosomal genes in man.

MIC2, which encodes the 12E7 antigen, is the only well-defined pseudoautosomal gene in man. We have isolated cDNA and genomic sequences corresponding to MIC2 and have produced monoclonal antibodies reacting with the 12E7 antigen. These molecular tools have been used to investigate the genetics and biochemistry of the MIC2 system. Recent results suggest that MIC2 is the most proximal of the currently defined pseudoautosomal markers and that the escape of MIC2 from X-inactivation may be intrinsic to an associated HTF island found at the 5' end of the gene. Investigation of the inter-relationship between MIC2 and the XG locus has led us to postulate the existence of a second pseudoautosomal gene in man.

Antibodies, Monoclonal↗
PubMed1985

The human Y chromosome.

Despite its central role in sex determination, genetic analysis of the Y chromosome has been slow. This poor progress has been due to the paucity of available genetic markers. Whereas the X chromosome is known to include at least 100 functional genetic loci, only three or four loci have been ascribed to the Y chromosome and even the existence of several of these loci is controversial. Other factors limiting genetic analysis are the small size of the Y chromosome, which makes cytogenetic definition difficult, and the absence of extensive recombination. Based on cytogenetic observation and speculation, a working model of the Y chromosome has been proposed. In this classical model the Y chromosome is defined into subregions; an X-Y homologous meiotic pairing region encompassing most of the Y chromosome short arm and, perhaps, including a pseudoautosomal region of sex chromosome exchange; a pericentric region containing the sex determining gene or genes; and a long arm heterochromatic genetically inert region. The classical model has been supported by studies on the MIC2 loci, which encode a cell surface antigen defined by the monoclonal antibody 12E7. The X linked locus MIC2X, which escapes X inactivation, maps to the tip of the X chromosome short arm and the homologous locus MIC2Y maps to the Y chromosome short arm; in both cases, these loci are within the proposed meiotic pairing region. MIC2Y is the first biochemically defined, expressed locus to be found on the human Y chromosome. The proposed simplicity of the classical model has been challenged by recent molecular analysis of the Y chromosome. Using cloned probes, several groups have shown that a major part of the Y chromosome short arm is unlikely to be homologous to the X chromosome short arm. A substantial block of sequences of the short arm are homologous to sequences of the X chromosome long arm but well outside the pairing region. In addition, the short arm contains sequences shared with the Y chromosome long arm and sequences shared with autosomes. About two-thirds of XX males contain detectable Y derived sequences. As the amount of Y sequences present varies in different XX males, DNA from these subjects can be used to construct a map of the region around the sex determining gene. Assuming that XX males are usually caused by simple translocation, the sex determining genes cannot be located in the pericentric region. Although conventional genetic analysis of the Y chromosome is difficult, this chromosome is particularly suited to molecular analysis. Paradoxically, the Y chromosome may soon become the best defined human chromosome at the molecular level and may become the model for other chromosomes.

Antibodies, Monoclonal↗
PubMed1980

Model for antenatal diagnosis of beta-thalassaemia and other monogenic disorders by molecular analysis of linked DNA polymorphisms.

Polymorphisms of DNA restriction sites within the human fetal globin genes have been used to identify chromosomes that carry beta-thalassaemia genes in individuals heterozygous for this disease. This has allowed an antenatal diagnosis for beta-thalassaemia to be carried out by observation of the pattern of the inherited polymorphism of a linked DNA sequence not involved in the genetic pathogenesis of the disease. In the populations we have investigated there is no constant pattern of polymorphism that segregates with the beta-thalassaemia gene. The use of linked polymorphisms should, therefore, be applicable to antenatal diagnosis both of beta-thalassaemia and of any other single-gene defect for which there is a DNA probe specific for a sequence linked to the affected locus.

DNA↗
PubMed1978

Urinary excretion of albumin beta2-microglobulin and free light chains during lithium treatment.

Albumin, beta2-microglobulin and free light chains were determined in urine in nine manic-depressive patients before and at intervals during three months of lithium treatment (longitudinal study). The same determinations were carried out in twenty-seven manic-depressive patients who had been treated with lithium for 3 months to 20 years and also in a control group (transversal study). There were no statistically significant changes in urinary excretions of albumin, beta2-microglobulin and free light chains during the longitudinal study. In one patient albumin excretion gradually increased during the study and remained elevated on reexamination 1 year later. No significant differences were found between the lithium treated patients and control subjects in the transversal study in either albumin, beta2-microglobulin or free light chain excretion. It is not clear whether the increased and sustained albumin excretion in one of the patients was due to lithium or was conincidental. The study shows that in most patients lithium treatment does not affect renal protein excretion.

Adult↗
PubMed1978

Plasma renin concentration during lithium therapy.

Plasma renin concentration was determined in patients given lithium treatment. In longitudinal study plasma renin concentration was determined in nine patients before the start of lithium treatment and at intervals during 3 months of treatment. In a transversal study, 18 patients given lithium treatment for 2--20 years were compared with 11 control persons. In the longitudinal study, plasma renin concentrations did not, during lithium treatment, deviate significantly from pre-treatment values. In the transversal study, values in the lithium treated patients did not differ significantly from values in the control group. There were no correlations, in the transversal study, between serum lithium concentrations and plasma renin concentrations. Our study indicates that the plasma renin concentration remains unaffected by lithium administered in nontoxic doses.

Adult↗
PubMed1977

Reduced renal calcium excretion during lithium therapy.

The renal excretion of calcium was determined in ten subjects before and at intervals during 3 months of lithium treatment. The calcium excretion fell by more than 40% within the first week of treatment and remained low throughout the treatment period. The reduction in urinary calcium excretion could be accounted for by an increase in fractional tubular reabsorption of calcium. There were no changes in serum calcium or inorganic phosphate, nor in urinary inorganic phosphate. The results indicate that lithium interferes with the regulation of calcium metabolism.

Adult↗
PubMed1977

Plasma prolactin during lithium treatment.

Plasma prolactin was determined in a longitudinal study, where -9 manic-depressive patients were examined before lithium treatment and at various times during the treatment with the aim of unravelling a possible association between initial changes in water and sodium balance during lithium treatment and changes in plasma prolactin level. No significant changes were found, nor could any correlation between serum lithium and plasma prolactin be established. Some reports have indicated association between breast cancer and prolonged elevated plasma prolactin, such as is seen during treatment with phenothiazines and reserpine. In a transversal study, determination of plasma prolactin during long-term lithium treatment in 26 patients did not reveal any elevation compared with 16 controls. Lithium is accordingly not among the drugs which produce prolonged elevation of plasma prolactin.

Adult↗