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A Stanford

Publications and source records attributed to A Stanford.

11 recordsLinked to original sources

The clock drawing test is a poor screen for very mild dementia.

OBJECTIVE: To determine whether performance on the clock drawing test varies as a function of dementia severity and particularly whether it differentiates cognitively normal older adults from those with very mild dementia. METHODS: Clock drawings were obtained during the initial clinical assessments of 75 participants in a longitudinal study of healthy aging and dementia of the Alzheimer type (15 cognitively normal, 25 with very mild dementia, 21 with mild dementia, and 14 with moderate to severe dementia, as staged by the Clinical Dementia Rating). Each clock drawing later was judged blindly and independently by two raters according to six commonly used sets of scoring criteria. RESULTS: The same pattern of results was obtained for all six scoring methods. Inter-rater reliability was consistently high. Spearman correlations indicated that as dementia severity increased, clock drawing performance decreased. Analyses of variance revealed that although those with mild or moderate/severe dementia performed significantly worse on the clock drawing test than did individuals who had very mild dementia or who were cognitively normal, the latter two groups did not differ significantly. Sensitivity and specificity analyses revealed that all methods could distinguish between normal aging and dementia of at least mild severity. However, sensitivity for detecting very mild dementia was poor. CONCLUSION: Although the clock drawing test can be scored reliably and can differentiate cognitively normal older adults from those with at least mild dementia of the Alzheimer type, it does not appear to be a useful screening instrument for detecting very mild dementia.

Aged↗

Nitric oxide protects thymocytes from gamma-irradiation-induced apoptosis in correlation with inhibition of p53 upregulation and mitochondrial damage.

Apoptosis plays a crucial role in clonal deletion in the thymus, and NO has been shown to prevent apoptosis in some cell types. Therefore, we examined the effect of NO on gamma-irradiation-induced thymocyte apoptosis. Treatment of 5 Gy gamma-irradiated thymocytes with 1 mM SNAP reduced cell death from 78 to 49% after 8 h incubation (spontaneous cell death in medium control cells was 26%). Coincubation with ZVAD blocked both the spontaneous cell death and the cell death induced by SNAP or gamma-irradiation. The gamma-irradiation-induced increase in caspase 3 and 6 activities was inhibited in the presence of SNAP. The increase in cytosolic cytochrome c as well as the decrease in mitochondrial membrane potential after gamma-irradiation was inhibited in the presence of SNAP. SNAP treatment also decreased the p53 upregulation in gamma-irradiated cells. In summary, we found that NO exerts a protective effect on mouse thymocyte apoptosis induced by gamma-irradiation. The mechanism of this protective effect may involve inhibition of p53 upregulation and reduction in mitochondrial damage, with subsequent inhibition of downstream caspase activation.

Animals↗

Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: interleukin-11 mRNA expression inversely correlates with extent of disease.

BACKGROUND/PURPOSE: The authors have shown previously that surgical specimens from infants with acute necrotizing enterocolitis (NEC) show upregulation of inducible nitric oxide (NO) synthase (iNOS) and interferon-gamma mRNA. However, the contribution of other inflammatory cytokines such as interleukin-8 (IL-8), IL-11, and IL-12 has not been defined. Likewise, the role of GTP-cyclohydrolase, the rate-limiting enzyme in tetrahydrobiopterin synthesis, and thus NO production by iNOS is unclear. In this study, the authors sought to further define the pattern of cytokine expression seen in infants with acute NEC. METHODS: The authors measured intestinal cytokine mRNA expression by semiquantitative reverse transcriptase polymerase chain reaction in 21 infants with histologically confirmed NEC, 18 with other inflammatory conditions, and in 9 patients without intestinal inflammation. Guanosine triphosphate-cyclohydrolase (GTP-CH) activity was measured by specific enzyme assay. Univariate exact logistic regression analysis was performed to identify predictors of outcome. RESULTS: IL-8 and IL-11 mRNA were upregulated in patients with acute NEC compared with those with other inflammatory conditions or those without disease; these levels returned to baseline at the time of stoma closure. Increased IL-11 mRNA decreased the likelihood of pan-necrosis (odds ratio, 0.93; P =.002). Increased IL-12 levels (but not IL-8) seemed to protect against pan-necrosis (odds ratio, 0.70; P =.06). CONCLUSIONS: Local upregulation of IL-11 may represent an adaptive response designed to limit the extent of intestinal damage in NEC. Decreased IL-12 levels may contribute to the pathogenesis of NEC by allowing bacteria to escape host defenses.

Acute Disease↗

Nitric oxide mediates dendritic cell apoptosis by downregulating inhibitors of apoptosis proteins and upregulating effector caspase activity.

BACKGROUND: Dendritic cells (DCs) play a crucial role in the amplification of the immune response by promoting antigen presentation, T-lymphocyte proliferation, and proinflammatory cytokine and nitric oxide (NO) production. We have previously shown that the exogenous NO donor, s-nitroso-N-acetyl-penicillamine, promotes DC apoptosis by disrupting the mitochondrial membrane potential, which induces cytochrome-C release and activates caspase 3. To further elucidate the signaling pathway, we examined the expression of cellular inhibitors of apoptosis proteins (cIAPs) and poly (ADP-ribose) polymerase cleavage (PARP), a terminal event in the apoptotic cascade. METHODS: DC2.4 were exposed to 250 micromol/L s-nitroso-N-acetyl-penicillamine for various intervals. Apoptosis and necrosis were measured by terminal deoxynucleotidyl transferase nick-end labeling assay or flow cytometry with Annexin V and propidium iodide. DC2.4 were cultured with the pan-caspase inhibitor, ZVAD (100 micromol/L). cIAP, pro-caspases, and PARP expression or activation was measured by Western blot. Caspase enzyme activity was confirmed with the use of specific substrates. RESULTS: NO-induced DC apoptosis correlated with the downregulation of cIAP expression. Caspase 3 and 6 were upregulated by SNAP and significantly inhibited by ZVAD. Maximal PARP cleavage occurred at 8 hours and coincided with the downregulation of cIAP and peak caspase 3 and near maximal caspase 6 activity. CONCLUSIONS: NO-induced DC apoptosis is associated with the downregulation of cIAP expression, which facilitates caspase cascade activation and subsequent PARP cleavage.

Amino Acid Chloromethyl Ketones↗

Differential expression within a family of novel wound-induced genes in potato.

Wounding in higher plants leads to an increased synthesis of specific messenger RNAs. A cDNA clone complementary to a wound-induced message from potato tubers was used to isolate a lambda clone from a genomic library of Solanum tuberosum var. Maris Piper. DNA sequence analysis has shown that this single genomic clone contains two novel wound-induced genes, called win1 and win2, organised in close tandem array. The coding sequences of these two genes are highly homologous and are interrupted by a single intron. However, the sequences of the introns and flanking regions have diverged widely. Win1 and win2 encode cysteine-rich proteins of 200 and 211 amino-acids, respectively, which show striking homologies to several chitin-binding proteins. Southern analysis of genomic DNA has shown that win1 and win2 are members of a small multi-gene family which is estimated to have a minimum of five members per haploid genome of Maris Piper and appears to be conserved within the Solanaceae. We have shown by Northern analysis and S1 mapping that the two genes exhibit differential organ-specific expression after the wounding of a potato plant.

Amino Acid Sequence↗

Dorsal diverticulum of the distal male urethra.

The lacuna magna is a congenital diverticulum embryologically arising from the dorsal aspect of the fossa navicularis. During a 1 year period, lacuna magna was diagnosed in five boys. Another 57 voiding cystourethrograms obtained in boys were reviewed retrospectively. Lacuna magna is demonstrable on properly performed voiding cystourethrography, but can be mimicked by pseudolesions created by improper radiographic technique. Clinical information, urographic evaluation, and methods of treatment are discussed.

Adolescent↗