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Biomedical subjects

C Lewis

Publications and source records attributed to C Lewis.

At least 145 records · Page 8Linked to original sources
PubMed1996

Social influences on false belief access: specific sibling influences or general apprenticeship?

Some recent studies have found a relation between the number of siblings 3-4-year-old children have and their performance on false belief tasks. 2 experiments reported here examine a variety of factors in children's social environments, including daily contact with peers and adults as well as the numbers of their siblings, on a battery of false belief tests. In Experiment 1, 82 preschoolers were studied in Rethymnon, Crete, in order to obtain a range of extended kin available as a resource for the child. In Experiment 2, 75 Cypriot preschoolers were studied in Nicosia in order to examine the influences of each child's daily social contacts, as measured by maternal questionnaire. Logistic regression revealed that the factors which account for most of the predicted variance on the theory of mind tests were (a) the number of adult kin available (Experiment 1) or adults interacted with daily (Experiment 2), (b) the child's age, (c) the number of older siblings a child has, and (d) the number of older children interacted with daily. The results suggested that theory of mind is not simply passed from one sibling to another in a process of social influence. It seems more likely that a variety of knowledgeable members of her or his culture influence the apprentice theoretician of mind.

Age Factors↗
PubMed1995

Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons.

Cation-selective P2X receptor channels were first described in sensory neurons where they are important for primary afferent neurotransmission and nociception. Here we report the cloning of a complementary DNA (P2X3) from rat dorsal root ganglia that had properties dissimilar to those of sensory neurons. We also found RNA for (P2X1)(ref. 7), (P2X2)(ref. 8) and P2X4 (ref. 9) in sensory neurons; channels expressed from individual cDNAs did not reproduce those of sensory ganglia. Coexpression of P2X3 with P2X2, but not other combinations, yielded ATP-activated currents that closely resembled those in sensory neurons. These properties could not be accounted for by addition of the two sets of channels, indicating that a new channel had formed by subunit heteropolymerization. Although in some tissues responses to ATP can be accounted for by homomeric channels, our results indicate that ATP-gated channels of sensory neurons may form by a specific heteropolymerization of P2X receptor subunits.

Adenosine Triphosphate↗
PubMed1995

The phosphorylation state of the microtubule-associated protein tau as affected by glutamate, colchicine and beta-amyloid in primary rat cortical neuronal cultures.

The effects of the excitatory amino acid glutamate, the microtubule destabilizing agent colchicine, and beta 25-35-amyloid peptide on the phosphorylation state of tau were studied in rat cortical neurons in primary culture. Using immunocytochemistry and Western-blot analysis, we demonstrated that a proportion of tau in these cultures is normally highly phosphorylated, but most of this tau fraction is dephosphorylated after treatment of the cultures with glutamate or colchicine, but not with beta-amyloid; the glutamate- and colchicine-induced changes in tau phosphorylation commenced before cell death, as assessed by release of lactate dehydrogenase. Dephosphorylation of tau was readily revealed by using the monoclonal antibodies Tau.1 and AT8, which have phosphate-sensitive epitopes that both centre around serine-199 and -202 (numbering of the largest tau isoform). On Western blots and by immunocytochemistry, AT8 labelling strongly decreased after glutamate and colchicine treatments, whereas Tau.1 staining was more intense. Neurofilament monoclonal antibodies, including RT97, 8D8, SMI31 and SMI310, all additionally known to recognize tau in a phosphorylation-dependent manner, also demonstrated that glutamate and colchicine treatments of the cultures induced a dephosphorylation of tau. We also showed immunocytochemically that there is an increase in tau immunoreactivity in neuronal perikarya in response to glutamate and colchicine treatment, and this occurs concomitantly with the dephosphorylation of tau. Treatment of the primary rat cortical neuronal cultures with beta 25-35-amyloid peptide, under conditions which induce neuronal degeneration, did not induce a change in tau phosphorylation, and failed to act synergistically with glutamate to produce an increase in dephosphorylation of tau over that produced by glutamate treatment alone. These findings demonstrate that glutamate and colchicine induce tau dephosphorylation, as opposed to increased tau phosphorylation, which would be more indicative of Alzheimer-type neurodegeneration.

Amyloid beta-Peptides↗
PubMed1995

Estrogen-induction of dendritic spines in ventromedial hypothalamus and hippocampus: effects of neonatal aromatase blockade and adult GDX.

Treatment of male rats at birth with an aromatase inhibitor (Letrazole), followed by adult gonadectomy GDX, led to an increase in dendritic spine density on ventromedial hypothalamic neurons (VMN) when treated with estrogen as compared to a decrease when vehicle animals were given estrogen. In contrast, estrogen-treatment increased dendritic spine density on CA1 pyramidal neurons regardless of neonatal treatment. In addition, in CA1 there was a significant difference between the two estrogen groups. These results suggest that estrogen induction of dendritic spines in the VMN and CA1 is dependent on organizational effects of gonadal steroids.

Animals↗
PubMed1995

Role of mycotoxins in human and animal nutrition and health.

The impact of mycotoxins on human and animal health is now increasingly recognised. Mycotoxin entry to the human and animal dietary systems is mainly by ingestion but increasing evidence also points at entry by inhalation. Mycotoxins exhibit a wide array of biological effects and individual mycotoxins can be mutagenic, carcinogenic, embryotoxic, teratogenic, or oestrogenic. Average levels of ingestion of currently known mycotoxins in most EEC countries are rather low. Little is known about the consequences to humans of such mycotoxin intakes. Establishing a causal relationship between mycotoxin exposure and human disease is complicated by uncertainties associated with human epidemiological studies. Analysis of mycotoxin adducts in human populations can act as a surrogate for human genotoxicity. Mycotoxins can also be immunosuppressive and appear to involve cellular immune phenomena and non-specific humoral factors associated with immunity.

Animals↗
PubMed1995

Laparoscopic abdominoperineal excision of the rectum.

In laparoscopic abdominoperineal resection of the rectum (LAP-AP) an abdominal incision is completely avoided as the tumor is delivered through the perineal incision. It is our belief that the view provided in the pelvis by laparoscopy is significantly better than at laparotomy and allows excellent anatomical definition and meticulous dissection. In this study we compared the adequacy of excision of the first 12 patients undergoing LAP-AP to the last 16 patients undergoing open abdominoperineal resection (OP-AP). In all patients the procedure was carried with curative intent for adenocarcinoma and the Dukes staging and Jass score's were similar in both groups. [table: see text] The data demonstrate similar nodal harvest in both groups as well as extent of radial excision. However, two patients in the open group had microscopic radial margin involvement despite being microscopically clear at surgery. We conclude that although long-term follow-up is required to address the issue of local cancer recurrence, laparoscopic rectal dissection appears as good as open surgery and may allow a more precise assessment of excision margins.

Adult↗
PubMed1995

"Is this man your daddy?" suggestibility in children's eyewitness identification of a family member.

Studies of natural language development suggest that overextension of family memberships terms, such as daddy or papa, occurs in children in the second year of life, but rarely persists thereafter. However, in British Courts it is common for the testimony of 3- and even 4-year-olds to be dismissed on the grounds that these children may not be reliably identifying their father or stepfather when they claim that daddy was the perpetrator of abuse. This study examined whether 3-year-olds could be persuaded to confirm that a stranger who was labelled as daddy was their own father. A mock interview with experienced disclosure interviewers was conducted. Five of the 17 children--all from blue-collar families--misidentified a photograph of their own father when an identification question was repeated. Rather than undermining the validity of all preschoolers testimony, it is suggested that the responses of some children to apparently mundane questions of fact are influenced by contextual factors, including repetition of the question and the perceived omniscience of the interviewer.

Child Abuse↗
PubMed1995

Is a community-based mastoid microsuction service feasible: the audit of a pilot project.

Patients who have had a mastoidectomy form a considerable long-term follow-up commitment to their local ENT Department. A community-based mastoid aural toilet pilot project run by a GP is described using an operating microscope and suction apparatus in his surgery. To obtain the necessary information about community treatment, an audit was performed of all mastoidectomy patients from a large general practice in Portsmouth: 57 mastoidectomy patients were reviewed. During the project it was possible to transfer to the community microsuction project the long-term care of most of their mastoidectomy patients who were attending the hospital ENT outpatient clinic.

Adult↗
PubMed1995

Potential adverse effects of phytoestrogens.

Evaluation of the potential benefits and risks offered by naturally occurring plant estrogens requires investigation of their potency and sites of action when consumed at natural dietary concentrations. Our investigations have examined the effects of a range of natural dietary concentrations of the most potent plant isoflavonoid, coumestrol, using a rat model and a variety of estrogen-dependent tissues and endpoints. Treatments of immature females demonstrated agonistic action in the reproductive tract, brain, and pituitary at natural dietary concentrations. Experiments designed to test for estrogen antagonism demonstrated that coumestrol did not conform to the picture of a classic antiestrogen. However, coumestrol did suppress estrous cycles in adult females. Developmental actions were examined by neonatal exposure of pups through milk of rat dams fed a coumestrol, control, or commercial soy-based diet during the critical period of the first 10 postnatal days or throughout the 21 days of lactation. The 10-day treatment did not significantly alter adult estrous cyclicity, but the 21-day treatment produced in a persistent estrus state in coumestrol-treated females by 132 days of age. In contrast, the 10-day coumestrol treatments produced significant deficits in the sexual behavior of male offspring. These findings illustrate the broad range of actions of these natural estrogens and the variability in potency across endpoints. This variability argues for the importance of fully characterizing each phytoestrogen in terms of its sites of action, balance of agonistic and antagonistic properties, natural potency, and short-term and long-term effects.

Animals↗
PubMed1995

Sibling interaction of children with learning disabilities: a comparison of autism and Down's syndrome.

Two potentially contrasting hypotheses can be generated about sibling interactions involving a child with Down's syndrome or autism. Research on siblings would predict that learning disabled children adopt responsive roles. Studies of children with autism would predict impoverished interactions. Home observations were conducted on 30 sibling pairs involving children with autism or Down's syndrome. Both hypotheses were partially supported. All learning disabled children engaged in frequent bouts of interaction, usually directed by their sibling. While children with autism engaged in fewer bouts and imitated less, they did reciprocate their siblings' initiations. Sibling encounters provide a unique opportunity for such children to learn about social relationships.

Autistic Disorder↗
PubMed1995

Phytoestrogen influences on the development of behavior and gonadotropin function.

The effect of phytoestrogens on the sexual differentiation of gonadotropin function was examined by neonatal exposure of pups through milk of rat dams fed a coumestrol (100 micrograms/g), control, or chow diet during the "critical period" of the first 10 postnatal days or throughout the 21 days of lactation. In females, exposure to coumestrol throughout the period of lactation produced growth suppression and an acyclic condition in early adulthood resembling the premature anovulatory syndrome. When the period of treatment was restricted to the first 10 postnatal days, however, no effects on vaginal cyclicity were seen. The 10-day exposure period produced more marked effects in males, resulting in transitory reductions in body weight in weanling males and reductions in mount and ejaculation frequency and a prolongation of the latencies to mount and ejaculate. Testicular weights and plasma testosterone levels did not differ among treatment groups, suggesting that the deficits in male sexual behavior were not due to deficits in adult gonadal function. Few effects of chow treatment were observed. However, significant differences from controls were apparent for weight at vaginal opening in females, and mount rate for chow-treated males was intermediate between that of controls and that of the coumestrol-treated group. These data provide evidence that lactational exposure to phytoestrogen diets can alter neuroendocrine development in both female and male rats.

Animal Feed↗
PubMed1995

Pharmacological characterization of heterologously expressed ATP-gated cation channels (P2x purinoceptors).

cDNAs encoding P2x purinoceptors from human bladder smooth muscle and from rat PC-12 cells were expressed in oocytes and human embryonic kidney 293 cells. Agonist potencies of 2-methylthio-ATP = 2-chloro-ATP = ATP > = 2'- and 3'-O-(4-benzoylbenzoyl)-ATP > or = adenosine-5'-O-(3-thio)-triphosphate > or = P1,P5-di(adenosine-5') pentaphosphate >> ADP prevailed for both P2x purinoceptors. There were two main differences in agonist sensitivity between the two receptors. First, ATP was 10 times more potent at the receptor from bladder (EC50, 0.8 microM) than at the receptor from PC-12 cells (EC50, 8.2 microM). Second, alpha,beta-methylene-ATP and L- and D-beta,gamma-methylene-ATP were agonists in cells expressing the bladder smooth muscle receptor (EC50, 1-3 microM) but were ineffective in cells expressing the PC-12 receptor. The P2 purinoceptor antagonists suramin, pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid, and pyridoxal-5-phosphate acted similarly at both receptor forms, producing noncompetitive inhibition, with IC50 values of 1-5 microM for suramin and pyridoxal phosphate 6-azophenyl-2',4'-disulfonic acid and 10-20 microM for pyridoxal-5-phosphate. 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acid distinguished receptor subtypes, producing potent inhibition of the bladder smooth muscle P2x-mediated response, with an IC50 value of 3 microM; it inhibited the PC-12 form by < 40% at 100 or 300 microM. This study thus defines the pharmacological properties of homo-oligomeric forms of these two types of cloned P2x receptor channels.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Regulation of arcuate nucleus synaptology by estrogen.

Estrogen modulates the synaptology of the hypothalamic arcuate nucleus during sexual differentiation of the rat brain in both males and females. In males, testosterone of gonadal origin is converted to estrogen in the brain by an enzyme, aromatase, which is also present in females. The exposure of the male's hypothalamus to relatively high levels of estrogen (following a perinatal testosterone surge) leads to the development of a pattern of synaptogenesis which does not support an estrogen-induced gonadotrophin surge in the adult. In female rats, hypothalamic development occurs with permissively low levels of estrogen, enabling a midcycle estrogen-induced gonadotrophin surge and ovulation in adulthood. During adult reproductive life in female rats, circulating estrogen modulates the synaptology of the arcuate nucleus. The most physiological example of this is the 30-50% loss of axosomatic synapses following the preovulatory estrogen surge on diestrus-proestrus. Studies on post-synaptic membranes of the arcuate nucleus reveal sex differences in membrane organization and protein content which are estrogen-dependent. Estrogen apparently stimulates endocytosis of areas of post-synaptic membrane that are dense with small intramembranous protein particles, resulting in a reduction in the number of small intramembranous particles. This also appears to be the physiologic mechanism of neuronal changes in females during the estrus cycle. Repeated exposure to preovulatory levels of estrogen may lead to an age-related decline in reproductive capacity in female rats. Aging females lose the estrogen-induced gonadotrophin surge responsible for ovulation. This loss of function may result from a cumulative estrogen effect during the repeated ovarian cycles which results in a reorganization of the synaptology on which regulates the estrogen-induced gonadotrophin surge. The membrane organization of the senescent constant estrus aged female appears indistinguishable from the males. The hypothalamic circuits modulated by estrogen have yet to be delineated. However, recent research has shown that GABA, the monoamines, and several neuropeptides are participants in the estrogen-sensitive network which regulates GNRH secretion. In this regard, present work shows estrogen-induced changes in GABA and dopamine synapses in the arcuate nucleus.

Aging↗
PubMed1994

Audit of infection in continuous ambulatory peritoneal dialysis.

The major cause of failure of continuous ambulatory peritoneal dialysis is peritoneal or exit site infection with Staphylococcus aureus. From 1989-1992, eradication of nasal and perineal carriage, continued use of an occlusive dressing to the exit site, improved aseptic technique for dressing changes by the patient and avoidance of wetting of the dressing were used in an attempt to reduce staphylococcal infections. By comparison with the 3-year period prior to intervention, a significant increase in the life of the catheters was achieved (removed at 1 year, 13 vs. 28%, P < 0.001) with a reduction in episodes of peritonitis due to S. aureus. The study was not prospectively controlled but there did not appear to be any other factor to account for the sudden and consistent improvement observed.

Catheterization↗