Maternal self-administration of oral analgesia after Caesarean section.
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Analgesia, Patient-Controlled↗
Biomedical subjects
S Scott
Publications and source records attributed to S Scott.
The evolution of A beta peptide burden in the APP23 transgenic mice: implications for A beta deposition in Alzheimer disease.
BACKGROUND: High levels of A beta in the cerebral cortex distinguish demented Alzheimer's disease (AD) from nondemented elderly individuals, suggesting that decreased amyloid-beta (A beta) peptide clearance from the brain is a key precipitating factor in AD. MATERIALS AND METHODS: The levels of A beta in brain and plasma as well as apolipoprotein E (ApoE) in brain were investigated by enzyme-linked immunosorbent assay (ELISA) and Western blotting at various times during the life span of the APP23 transgenic (Tg) and control mice. Histochemistry and immunocytochemistry were used to assess the morphologic characteristics of the brain parenchymal and cerebrovascular amyloid deposits and the intracellular amyloid precursor protein (APP) deposits in the APP23 Tg mice. RESULTS: No significant differences were found in the plasma levels of A beta between the APP23 Tg and control mice from 2-20 months of age. In contrast, soluble A beta levels in the brain were continually elevated, increasing 4-fold at 2 months and 33-fold in the APP23 Tg mice at 20 months of age when compared to the control mice. Soluble A beta42 was about 60% higher than A beta40. In the APP23 Tg mice, insoluble A beta40 remained at basal levels in the brain until 9 months and then rose to 680 microg/g cortex by 20 months. Insoluble A beta40 was negligible in non-Tg mice at all ages. Insoluble A beta42 in APP23 Tg mice rose to 60 microg/g cortex at 20 months, representing 24 times the control A beta42 levels. Elevated levels of ApoE in the brain were observed in the APP23 Tg mice at 2 months of age, becoming substantially higher by 20 months. ApoE colocalized with A beta in the plaques. Beta-amyloid precursor protein (betaAPP) deposits were detected within the neuronal cytoplasm from 4 months of age onward. Amyloid angiopathy in the APP23 Tg mice increased markedly with age, being by far more severe than in the Tg2576 mice. CONCLUSIONS: We suggest that the APP23 Tg mouse may develop an earlier blockage in A beta clearance than the Tg2576 mice, resulting in a more severe accumulation of A beta in the perivascular drainage pathways and in the brain. Both Tg mice reflect decreased A beta elimination and as models for the amyloid cascade they are useful to study AD pathophysiology and therapy.
Aging↗
kappa-opioid receptor-mediated analgesia: hotplate temperature and sex differences.
The present experiment was designed to investigate the dose-effect and time-effect functions of the kappa-opioid receptor agonist [5alpha,7alpha, 8beta)-(-)-N-Methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro(4, 5)dec-8-yl]benzeneacetamide] (U69,593) in intact and gonadectomized male and female rats as a function of hotplate temperature (45 degrees C or 51 degrees C). At 45 degrees C baseline lick latencies were longer in female rats than in male rats. Lick latencies increased dose-dependently in all subjects except intact female rats. U69,593 increased lick latencies as a function of time since its administration in all subjects. At 51 degrees C baseline lick latencies did not differ between groups and they increased dose-dependently in all subjects. The effectiveness of U69,593 decreased as a function of time since its administration, but not in castrated male rats. These observations suggest that gonadal hormones could play a role in modulating the behavioral effects of U69,593 when subjects are tested at different hotplate temperatures.
Analgesics↗
Roles of the Dal82p domains in allophanate/oxalurate-dependent gene expression in Saccharomyces cerevisiae.
Allophanate/oxalurate-induced gene expression in Saccharomyces cerevisiae requires at least five transcription factors, four of which act positively (Gln3p, Gat1p, Dal81p, and Dal82p) and one negatively (Dal80p). Gln3p binds to and Gat1p is proposed to bind to single GATA sequences; Dal80p binds to pairs of specifically oriented and spaced GATA sequences, and Dal82p binds to a pathway-specific element, UIS(ALL). Dal82p consists of at least three domains as follows: (i) UIS(ALL) DNA-binding, (ii) transcriptional activation, and (iii) coiled-coil(DAL82). Here we show that the coiled-coil(DAL82) domain possesses two demonstrable functions. (i) It prevents Dal82p-mediated transcription when inducer is absent. (ii) It is a major, although not exclusive, domain through which the inducer signal is received. Supporting the latter conclusion, a 38-amino acid fragment, containing little more than the coiled-coil(DAL82) domain, supports oxalurate-inducible, Dal81p-dependent, reporter gene transcription. Dal81p is required for inducer responsiveness of LexAp-Dal82p and LexAp coiled-coil(DAL82)-mediated transcription but isn't needed for inducer-dependent activation mediated by a Dal82p containing deletions in both the coiled-coil(DAL82), UIS(ALL)-binding domains. There may be an interaction between Dal81p and the coiled-coil(DAL82) domain since (i) Dal81p is required for transcription mediated by LexA-coiled-coil(DAL82)p and (ii) a Dal81p-Dal82p complex is detected by two-hybrid assay.
Bacterial Proteins↗
Sensitivity to Fas-mediated apoptosis is determined below receptor level in human vascular smooth muscle cells.
Despite Fas expression, many cells resist Fas-induced apoptosis. Although differences in surface Fas expression can explain Fas resistance, multiple proteins below receptor level also inhibit Fas-induced apoptosis. To examine the mechanism of Fas resistance, we studied Fas-induced apoptosis in human medial vascular smooth muscle cells (VSMCs) from healthy coronary arteries. VSMCs showed marked heterogeneity to Fas-induced apoptosis, exhibiting both Fas-resistant (98.1+/-2.3% viable, n = 4, P = NS) and Fas-sensitive (31.3+/-2.6% viable, n = 3, P<0.01) cells. Fas-resistant VSMCs expressed surface Fas and could recruit RIP, indicating that functional receptor complexes were formed. However, Fas-resistant cells showed reduced expression of FADD, Fas ligand, and caspases 3, 7, and 8 and increased expression of FLIP and c-IAP-1. Fas-induced apoptosis was associated with cleavage of caspase 3 and blocked by inhibitors of caspase 3 or 8 but not caspase 1, 6, or 7. Selective inhibition of caspase 3 or 8 by antisense transfection inhibited Fas-induced apoptosis, but their reexpression could not rescue the Fas-resistant phenotype. In vivo, medial VSMCs showed marked heterogeneity of expression of caspase 3. We conclude that Fas sensitivity is determined not only by expression of surface Fas but by differential expression of Fas-signaling proteins below receptor level. Subpopulations of cells within the same tissue have different sensitivities to apoptosis, determined by expression of specific death-signaling proteins.
Adaptor Proteins, Signal Transducing↗
Extent of regretted sexual intercourse among young teenagers in Scotland: a cross sectional survey.
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Adolescent↗
Cholinergic deafferentation of the rabbit cortex: a new animal model of Abeta deposition.
Brain deposition of the amyloid beta-peptide (Abeta) is a critical step in the pathogenesis of Alzheimer's disease (AD) and human cerebral amyloid angiopathy (CAA). A small fraction of AD and CAA cases are caused by gene mutations leading to increased production and deposition of Abeta, but for the majority, there is no known direct genetic cause. We have hypothesized that Abeta deposition in these sporadic cases occurs as a result of cortical cholinergic deafferentation. Here we show that cortical cholinergic deafferentation, induced in rabbits by a selective immunotoxin, leads to Abeta deposition in cerebral blood vessels and perivascular neuropil. Biochemical measurements confirmed that lesioned animals had 2.5- and 8-fold elevations of cortical Abeta40 and Abeta42, respectively. Cholinergic deafferentation may be one factor that can contribute to Abeta deposition.
Alzheimer Disease↗
Functional domain mapping and subcellular distribution of Dal82p in Saccharomyces cerevisiae.
Previous studies have shown that (i) Dal81p and Dal82p are required for allophanate-induced gene expression in Saccharomyces cerevisiae; (ii) the cis-acting element mediating the induced transcriptional response to allophanate is a dodecanucleotide, UIS(ALL); and (iii) Dal82p binds specifically to UIS(ALL). Here we show that Dal82p is localized to the nucleus and parallels movement of the DNA through the cell cycle. Deletion analysis of DAL82 identified and localized three functional domains. Electrophoretic mobility shift assays identified a peptide (consisting of Dal82p amino acids 1-85) that is sufficient to bind a DNA fragment containing UIS(ALL). LexA-tethering experiments demonstrated that Dal82p is capable of mediating transcriptional activation. The activation domain consists of two parts: (i) an absolutely required core region (amino acids 66-99) and (ii) less well defined regions flanking residues 66-99 that are required for full wild-type levels of activation. The Dal82p C terminus contains a predicted coiled-coil motif that down-regulates Dal82p-mediated transcriptional activation.
Base Sequence↗
MSH2-deficient murine lymphomas harbor insertion/deletion mutations in the transforming growth factor beta receptor type 2 gene and display low not high frequency microsatellite instability.
High-frequency microsatellite instability (MSI), defined as more than 20% unstable loci, is an inconsistent finding in hematologic malignancies; consequently, the significance of deficient DNA mismatch repair (MMR) to their pathogenesis has been questioned. To further investigate the relationship between MMR deficiency and genomic instability in hematologic malignancies, this study evaluated MSH2-/- murine lymphomas for insertion/deletion (ID) mutations within the transforming growth factor (TGF)-beta receptor type II (TbetaR-II) gene and MSI at 10 neutral microsatellites. The lymphomas displayed ID mutations within short mononucleotide runs of TbetaR-II at a high frequency, whereas nonmalignant tissue from corresponding animals lacked mutations. Loss of TbetaR-II transcripts and protein was seen in 6 of 7 murine lymphomas harboring acquired TbetaR-II mutations. In the analysis of paired nonmalignant and tumor DNA samples, low-frequency but not high-frequency MSI was found. Low-frequency MSI occurred in 8 of 20 lymphomas and 12 displayed microsatellite stability. MSI was even less frequent in nonmalignant tissue as only 3 of 20 samples displayed low-frequency MSI and 17 displayed stability. Evaluation of 20 single cell clones from the MSH2-/- lymphoma cell lines R25 and L15 identified high-frequency MSI in 4 and 2 clones, respectively. The remaining clones showed low-frequency MSI or stability. These findings suggest that acquired TbetaR-II mutations represent important inactivating events in tumor pathogenesis following MSH2 deficiency. Furthermore, for some hematolymphoid malignancies, the evaluation of cancer-associated genes for ID mutations may represent a more sensitive marker of MMR deficiency than evaluation of neutral microsatellites for high-frequency MSI. (Blood. 2000;95:1767-1772)
Animals↗
Novel inhibitors of advanced glycation endproducts (part II).
Enhanced formation and accumulation of advanced glycation endproducts (AGEs), have been implicated as a major pathogenesis process leading to diabetic complications, normal aging, atherosclerosis, and Alzheimer's Disease. Several potential drug candidates as AGE inhibitors have been reported recently. The aim of this study was to develop classes of novel inhibitors of glycation, AGE formation, and AGE-crosslinking and to investigate their effects through in vitro chemical and immunochemical assays. A total of 92 compounds were designed and synthesized. The first 63 compounds were reported before. Nearly half of the 29 novel inhibitors reported here are benzoic acid derivatives and related molecules, and found to be potent inhibitors of multistage glycation, AGE formation, and AGE-protein crosslinking. All 29 compounds show some degrees of inhibitory activities as detected by the four assay methods, 9 compounds demonstrated high percent inhibition (PI) in all tests, 30 to 40 times stronger than aminoguanidine.
Animals↗
Evidence that pioglitazone, metformin and pentoxifylline are inhibitors of glycation.
Enhanced formation and accumulation of advanced glycation end products (AGEs) have been proposed to play a major role in the pathogenesis of diabetic complications, and atherosclerosis, leading to the development of a range of diabetic complications including nephropathy, retinopathy and neuropathy. Several potential drug candidates as AGE inhibitors have been reported recently. Aminoguanidine is the first drug extensively studied. However, there are no currently available medications known to block AGE formation. We have previously reported a number of novel and structurally diverse compounds as potent inhibitors of glycation and AGE formation. We have now studied several of the existing drugs, which are in therapeutic practice for lowering blood sugar or the treatment of peripheral vascular disease in diabetic patients, for possible inhibitory effects on glycation. We show that that three compounds; pioglitazone, metformin and pentoxifylline are also inhibitors of glycation.
Enzyme-Linked Immunosorbent Assay↗
Fracture blisters and sodium valproate: two case reports.
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Adult↗
Late review of the use of silver sulphadiazine dressings for the treatment of fingertip injuries.
The management of finger tip injuries is controversial. We sent out to review the long term outcome on conservative treatment with Silver Sulphadiazine dressings. 21 patients were reviewed at between 2 and 8 years after injury. All patients were satisfied with the treatment and the cosmetic results were good. We recommend this method of treatment.
Accidents, Occupational↗
Evidence by spectral karyotyping that 8q11.2 is nonrandomly involved in lipoblastoma.
We report two cases of lipoblastoma with chromosome 8-related aberrations, ie, a 92,XXYY,t(7;8Xp22;q11.2)x2 [8]/46,XY[16] in Case 1 and a 46,XY,-8,-13,add(16) (q22),+mar, +r [cp13]/46,XY[7] in Case 2. Using spectral karyotyping and fluorescence in situ hybridization techniques, the karyotype of Case 2 was redesignated as 46,XY, r(8), del(13)(q12), der(16)ins(16;8)(q22; q24q11.2)[cp13]/46,XY[7]. This report delineates a new chromosome rearrangement, ie, der(16)ins(16;8)(q22; q24q11.2) in lipoblastoma, and also confirms the t(7; 8)(p22;q11.2), reported only once previously, as a recurrent translocation involved in such a tumor. These findings provide valuable information for clinical molecular cytogenetic diagnosis of lipoblastoma. Furthermore, this report highlights the value of cytogenetic and molecular cytogenetic analysis in differential diagnosis of childhood adipose tissue tumors and adds to the number of lipoblastomas reported with chromosomal abnormalities at 8q11.2.
Chromosome Aberrations↗
Modelling the dynamics of scarlet fever epidemics in the 19th century.
Annual deaths from scarlet fever in Liverpool, UK during 1848-1900 have been used as a model system for studying the historical dynamics of the epidemics. Mathematical models are developed which include the growth of the population and the death rate from scarlet fever. Time-series analysis of the results shows that there were two distinct phases to the disease (i) 1848-1880: regular epidemics (wavelength = 3.7 years) consistent with the system being driven by an oscillation in the transmission coefficient (deltabeta) at its resonant frequency, probably associated with dry conditions in winter (ii) 1880-1900: an undriven SEIR system with a falling endemic level and decaying epidemics. This period was associated with improved nutritive levels. There is also evidence from time-series analysis that raised wheat prices in pregnancy caused increased susceptibility in the subsequent children. The pattern of epidemics and the demographic characteristics of the population can be replicated in the modelling which provides insights into the detailed epidemiology of scarlet fever in this community in the 19th century.
Adult↗
Salvage of the ruptured spleen in an infant with very low birth weight.
Hemorrhage from the traumatized spleen needs surgical intervention if the patient's cardiovascular status is unstable and not stabilizing with medical support. It is well recognized that salvage of the injured spleen is preferable to splenectomy because of risks of overwhelming postsplenectomy infection (OPSI). The authors report the case of a 746-g newborn with splenic hemorrhage that required surgical intervention to control bleeding. A 2-component fibrin tissue adhesive and a cellulose fabric were used.
Female↗
Interacting effects of nutrition and social class differentials on fertility and infant mortality in the pre-industrial population.
Inadequate nutrition of both the mother and her offspring at each stage of its development - before pregnancy, in the womb, in infancy and during early childhod - played an important role in the patterns of subfertility and infant mortality in a saturated, marginal, preindustrial community. It is suggested that the three social classes had different diets but all were deficient in some essential constituents. Differences in nursing practices in the social groups contributed to differential exogenous mortality and to malnourishment and maternal depletion in the subsistence and (paradoxically) in the elite classes, producing an interacting web of effects and generating a vicious circle from which they could not escape for 150 years. Although the population apparently preferred daughters, the persistent generation effect of low birthweight girls bearing low birthweight daughters probably contributed to the steady-state conditions in this compromised community.
England↗
Information gained from linking SEER Cancer Registry Data to state-level hospital discharge abstracts. Surveillance, Epidemiology, and End Results.
OBJECTIVES: Our goal was to link patients from the Iowa Surveillance, Epidemiology, and End Results (SEER) Registry to their respective inpatient discharge abstracts from an Iowa Health Care Cost and Utilization Project (HCUP)-formatted database and evaluate whether this linkage provides information related to cancer treatment variation. METHODS: Computer algorithms linked patients from the Iowa SEER Registry to discharge abstracts using 5 variables consistently defined between the databases (hospital identification, date of birth, admission date, discharge date, and zip code). Abstracts were reviewed for validity, and links not passing face validity were excluded. SUBJECTS: Our sample contained 7,296 patients with early-stage breast cancer (I, IIa, IIb) with surgery from the Iowa SEER Registry from 1989 through 1994 with contacts only with Iowa hospitals. RESULTS: Inpatient discharges abstracts were linked to 86.4% of the patients in our sample. More than 96% of the linked discharges for Medicare patients had a corresponding Medicare claim. Over 45% of the linked patients were not covered by Medicare. Comorbidity indexes were comparable to other published sources. Significant differences in diagnosis, comorbidities, and treatment were found across third-party payers. CONCLUSIONS: This linkage provides a valuable source of comorbidity and insurance data and perhaps the only source of secondary clinical information for the uninsured. This linkage is best suited for cancers requiring inpatient stays for treatment and for those states where border crossing for treatment is low.
Abstracting and Indexing↗