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S Conroy

Publications and source records attributed to S Conroy.

29 records · Page 2Linked to original sources
PubMed1998

Elevation of IL-6 in transgenic mice results in increased levels of the 90 kDa heat shock protein (hsp90) and the production of anti-hsp90 antibodies.

Treatment of human peripheral blood lymphocytes (PBL) in vitro with the cytokine interleukin-6 (IL-6) induces increased levels of the 90 kDa heat shock protein (hsp90). Hsp90 levels are also elevated in PBLs of human patients with systemic lupus erythematosus (SLE) and in MRL/lpr mice with autoimmune disease. Although IL-6 is elevated in both these situations it has not been shown that it is involved in stimulating elevation of hsp90 levels in vivo. Here we show directly that the elevation of IL-6 in vivo either in mice transgenic for the IL-6 gene or in knock-out mice lacking a functional gene for the transcription factor C/EBP beta (NF-IL-6) does indeed result in elevated hsp90 levels. This overexpression is associated with the specific production of autoantibodies to hsp90 in these mice which is also observed in SLE patients and MRL/1pr mice. Hence IL-6 is likely to play a critical role in the regulation of hsp90 levels both in autoimmune disease states and potentially in normal cells in vivo. In turn the elevated levels of hsp90 produced in autoimmune diseases are likely to be responsible for the observed production of anti-hsp90 autoantibodies.

Animals↗
PubMed1998

Links between maternal care and persistent infant crying in the early months.

A community sample was screened to select three groups of infants and their mothers according to how much the babies cried at 6 weeks of age, the peak age for infant crying. The three groups--of moderate (n = 55), evening (n = 38) and persistent criers (n = 67) and their mothers--were assessed by diary, observation and questionnaire measures of mother and infant characteristics and interactions at 6 weeks and 5 months of infant age. At 6 weeks, mothers of persistent criers spent more time interacting with and physically stimulating their babies. Below-optimum maternal sensitivity/affection was linked to moderately increased crying in the infants overall. However, most mothers of persistent criers showed optimum sensitivity and affection, while no significant links between maternal sensitivity/affection and infant crying were found in the persistent crying group. By 5 months, when infant crying declined, the range and size of differences between mothers of persistent criers and other mothers declined. Home observations and a standard play measure failed to show group differences in maternal sensitivity, affection and intrusiveness at this age. The findings show that persistent infant crying in the early months often occurs in spite of high quality maternal care, so that in most cases the crying is probably not due to inadequate parenting. The need to distinguish general community cases from those at social or medical risk is emphasized and the findings' implications for professionals are discussed.

Adult↗
PubMed1997

Links between infant crying and sleep-waking at six weeks of age.

Infant crying, and parental concern about unexplained crying, peak when infants are around 6 weeks of age. Diary measures of amounts of time infants spent crying, sleeping, waking-settled and feeding at 6 weeks were obtained in three samples: a group of moderate criers (N = 45), a group with an evening crying peak (N = 33) and a group whose fuss/crying exceeded 3 h per day (persistent criers, N = 54). Substantial negative correlations between amounts of fuss/crying and sleeping, but few associations between fuss/crying and waking or feeding, were found. The persistent criers slept an average of 77 min per 24 h less than the moderate criers. The clearest group differences were in the daytime and all three groups showed evidence of a diurnal organisation in their behaviour. Persistent crying at 6 weeks is associated with a sleeping deficit.

Circadian Rhythm↗
PubMed1996

Bases for maternal perceptions of infant crying and colic behaviour.

According to the commonest definition, infant colic is distinguished by crying which is 'paroxysmal'-that is, intense and different in type from normal fussing and crying. To test this, maternal reports of the distress type of 67 infants whose fuss/crying usually exceeded three hours a day ('persistent criers') were scrutinised using 24 hour audiorecordings of the infants' distressed vocalisation. 'Moderate criers' (n = 55) and 'evening criers' (n = 38) were also assessed. Most of the distress in all three groups was fussing. In the audiorecordings the persistent criers showed a higher crying: fussing ratio than the moderate criers, but intense crying was rare. A third of the persistent criers were reported by their mothers to have occasional, distinct colic bouts of 'intense, unsoothable crying and other behaviour, perhaps due to stomach or bowel pain.' In the audiorecordings these periods were longer, but not paroxysmal in onset or more intense than the crying of persistent criers not judged to have colic. The audible features of the crying may be less important than its unpredictable, prolonged, hard to soothe, and unexplained nature.

Circadian Rhythm↗
PubMed1995

Increased levels of antibodies to heat shock proteins with increasing age in Mrl/Mp-lpr/lpr mice.

Approximately 30% of human patients with systemic lupus erythematosus (SLE) develop IgG autoantibodies to the highly conserved 90 kDa heat shock protein (hsp90). The development of anti-hsp90 antibodies is shown here to be paralleled in the Mrl/lpr mouse, which is an acknowledged model for SLE, but not in control BALB/c mice (P = 0.005). The generation of these antibodies appears to be closely linked to the onset of disease and titres of these antibodies increase with age, but there is no correlation with well-established clinical parameters of disease. Antibodies to hsp70 and hsp65 are also observed in the Mrl/lpr model; these antibodies appear to be unrelated to the pathogenesis of the disease.

Aging↗
PubMed1985

Subcellular localization of a membrane-associated transglutaminase activity in rat liver.

Fractionation of rat liver by homogenization and differential centrifugation revealed that only about 83% of the transglutaminase activity in the tissue is in a soluble form, and that the remainder is associated with the particulate fraction. This latter activity remained with the membranes even after they were extensively washed to remove 99% of such soluble enzymes as lactate dehydrogenase and aldolase. Subsequent fractionation of the membranes by isopycnic density gradient centrifugation in sucrose resulted in a single band of transglutaminase activity at a density of 1.194 g/cm3. This activity was coincident with the major band of plasma membranes, which was identified by its content of 5'-nucleotidase, alkaline phosphodiesterase I, alkaline phosphatase and leucine aminopeptidase activities. After treatment with digitonin and fractionation on sucrose gradients, the transglutaminase activity and the plasma membrane marker enzyme activities were found at a new density of 1.210 g/cm3, while the enzyme markers for the other membrane fractions remained unchanged. From these data, we conclude that approximately 17% of the transglutaminase activity in rat liver is specifically associated with the plasma membranes.

Acyltransferases↗
PubMedDate not supplied

Evidence that nerve growth factor plays a role in long-term potentiation in the rat dentate gyrus.

An inbred strain of Wistar rat (GH), which is deficient in nerve growth factor (NGF), was used to assess the possible role of NGF in the generation of long-term potentiation in perforant path-granule cell synapses. The data show that NGF was significantly decreased in the dentate gyrus of GH rats, that this deficit was accompanied by an impairment in long-term potentiation (LTP) and that intraventricular injection of NGF substantially reversed this impairment. Analysis of depolarization-induced glutamate release in synaptosomes prepared from dentate gyrus of control rats revealed that NGF alone was without effect, but in combination with the metabotropic glutamate receptor agonist, aminocyclopentane-1,3-dicarboxylic acid (ACPD), NGF induced a significant increase in release. This effect was occluded by prior induction of LTP, suggesting that the interaction between these agents may be required to enhance transmitter release which accompanies LTP in dentate gyrus. In contrast to the effect of NGF and ACPD on glutamate release in control rats, the combination of these agents had no effect on release in synaptosomes prepared from GH rats, which might be explained by the marked decrease in trk receptors in dentate gyrus of GH rats. It was concluded that the impaired ability of GH rats to sustain LTP is associated with a reduction in NGF concentration, a reduction in stimulated release of NGF and a decrease in trk receptors in dentate gyrus. It is proposed that these data indicate a role for NGF in the generation of long-term potentiation in perforant path-granule cell synapses.

Animals↗
PubMedDate not supplied

Prevalence of sedative drug use in geriatric in-patients: a multi-centre study.

OBJECTIVE: This cross-sectional study registered the prevalence of sedative drug use and withdrawal strategies in geriatric in-patients from 30 centres in nine European countries. METHODS: We conducted a survey among young geriatricians using a standardised questionnaire on sedative drug use for more than three weeks. The study population consisted of 1972 in-patients aged 75 years or older. Acute care (620), intermediate care/rehabilitation (359), long-term care (261), terminal care (47) and nursing home (685) settings were represented. The pre-specified outcomes included the prevalence of sedative drug use; the identification of main prescribers and main reasons for prescribing and, the assessment of withdrawal policy, including psychological counselling and involvement of general practitioners. RESULTS: Prevalence of sedative use was highest in long-term care (72%), followed by nursing homes (70%) and terminal care (59%). Geriatricians started prescribing sedatives after admission on 52% of all occasions. The main reasons for prescribing were continuation of medication taken at home (37%), sleep problems emerging after admission (26%) and post-admission worsening of existing sleep problems (20%). Most prescribers (70%) applied an active withdrawal policy. Short-term withdrawal programmes were mostly applied (57%). Most patients (60%) were psychologically counselled during withdrawal from sedatives. General practitioners were often (60%) involved in withdrawal policy. CONCLUSION: The prevalence of prescription of sedative drugs in geriatric in-patients is high. Appropriate setting specific guidelines are needed to control use of sedatives in geriatric in-patients and to ensure withdrawal from these drugs whenever possible.

Aged↗