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A Palmer

Publications and source records attributed to A Palmer.

At least 37 records · Page 2Linked to original sources
PubMed2000

Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment.

To examine neuronal activation associated with incentive motivation for cocaine, cocaine-seeking behavior (operant responding without cocaine reinforcement) and Fos expression were examined in rats exposed to saline and cocaine priming injections and/or a self-administration environment. Rats were first trained to self-administer cocaine or received yoked saline administration ("control"). They then received 21 daily exposures to either the self-administration environment ("extinction") or a different environment ("no extinction") without cocaine available. Extinction training, used to decrease incentive motivation for cocaine elicited by the self-administration environment, decreased cocaine-seeking behavior elicited by both the environment and the cocaine priming injection. Exposure to the self-administration environment enhanced Fos expression in the no extinction group relative to control and extinction groups in the anterior cingulate, basolateral amygdala, hippocampal CA1 region, dentate gyrus, nucleus accumbens shell and core, and central gray area, regardless of whether or not priming injections were given. The priming injections enhanced Fos expression in the ventral tegmental area, caudate putamen, substantia nigra pars reticulata, entorhinal cortex, central amygdala, lateral amygdala, arcuate nucleus, and central gray area, regardless of group. Thus, these changes likely reflect an unconditioned effect from either cocaine or injection stress. The priming injections also enhanced Fos expression in the anterior cingulate, but only in cocaine-experienced groups, suggesting that this enhancement reflects an experience-dependent motivational effect of the priming injections. The results suggest that different neural circuits may be involved in the incentive motivational effects of cocaine-paired environmental stimuli versus priming injections and that the anterior cingulate may be part of a common pathway for both.

Animals↗
PubMed2000

The activation of MAP kinase and p34cdc2/cyclin B during the meiotic maturation of Xenopus oocytes.

G2-arrested Xenopus oocytes are induced to enter M-phase of meiosis by progesterone stimulation. This process, known as meiotic maturation, requires the activation of p34cdc2/cyclin B complexes (pre-MPF) which is brought about by the prior translation of specific maternal mRNAs stored in the oocyte. One of these mRNAs encodes for the protein kinase Mos which has an essential role in oocyte maturation, most likely due to its ability to activate MAP kinase (MAPK). Here we review our current knowledge on the Mos/MAPK signalling pathway and a recently found connection between MAPK-activated p90rsk and the p34cdc2 inhibitory kinase Myt1. We also discuss a pathway that involves the protein kinase Plx1 and leads to the activation of the phosphatase Cdc25, as well as other regulators of p34cdc2/cyclin B activity which may have a role in oocyte maturation.

Animals↗
PubMed2000

Acoustically elicited behaviours in Lister hooded and Wistar rats.

It has been reported previously that experimenter-presented 20-kHz tones at low intensities produce bursts of locomotor running in Lister hooded rats, but reduced locomotion (freezing) in Wistar rats. Because rats emit 20-kHz tones when stressed, it was proposed that this ultrasound-elicited running and freezing behaviour in Lister hooded and Wistar rats, respectively, represents a model for qualitative strain differences in fear behaviour. The present studies examined the acoustic specificity of acoustically elicited locomotor behaviours in Lister hooded and Wistar rats. In Experiment 1, it was found that brief exposure (i.e., 15 s) of Lister hooded rats to tones at frequencies of 7, 12, or 20 kHz and intensities of 85-95 dB SPL, elicited running behaviour characterised by brief bursts of locomotion followed by periods of quiescence. Somewhat surprisingly, the 7- and 12-kHz tones elicited running behaviour at lower intensities than did the 20-kHz tones. In Experiment 2, it was found that exposure of Lister hooded rats to the 20-kHz acoustic stimulus (91-101 dB, SPL) for a much longer duration, up to 9 min, resulted in episodic bursts of locomotion and convulsions in a significant proportion of subjects. Both the maximal velocity of locomotion and the likelihood of occurrence of convulsions was related to the intensity of the acoustic stimulus. Exposure of Lister hooded rats to white noise for up to 9 min also elicited episodic bursts of locomotion and convulsions in an intensity-dependent manner. The white noise stimulus was found to be a more effective stimulus than the 20-kHz stimulus in this regard. In Experiment 3, it was found that Lister hooded rats exhibited reduced locomotion when they were exposed to a low-intensity 20-kHz acoustic stimulus (e.g., 81 dB, SPL). In Experiment 4, it was found that Wistar rats did not exhibit locomotor bursts or convulsions when presented with 20-kHz tones using stimulus parameters equal to and even greater than those that had been shown to be effective in producing locomotor bursts in Lister hooded rats. Rather, Wistar rats exhibited only reduced locomotion. The present data indicate that (1) running behaviour in Lister hooded rats is not specific for the 20-kHz stimulus. Moreover, (2) when compared to Lister hooded rats, Wistar rats are relatively insensitive to the running and convulsions elicited by acoustic stimuli. Finally, (3) both Lister hooded and Wistar rats exhibited reduced locomotion when presented with the 20-kHz tones, although the range of stimulus intensities that produces freezing behaviour is much more limited in Lister hooded rats because of their propensity to exhibit locomotor bursting and convulsions. Thus, it appears that the difference between the two strains with respect to their unconditioned locomotor responses to novel acoustic stimuli relates to the fact that Lister hooded rats are uniquely susceptible to acoustically elicited locomotor bursts and/or convulsions.

Acoustic Stimulation↗
PubMed2000

Graded expression of EphA3 in the retina and ephrin-A2 in the superior colliculus during initial development of coarse topography in the wallaby retinocollicular projection.

We describe the expression of EphA3 and EphA7 receptors and ephrin-A2 ligand in the retina and the superior colliculus during the development of the retinocollicular projection in the marsupial wallaby (Macropus eugenii), using immunoblotting and immunohistochemistry. EphA3 in the retina was in a striking, low central to high peripheral gradient, superimposed on which was a high temporal to low nasal level of expression. This distribution was evident from postnatal day 30, when axons are growing into the colliculus and forming a coarsely organized topographic projection, to postnatal day 65, when axons have arborized in their correct retinotopic positions. EphA7 showed a shallow centroperipheral gradient with no nasotemporal differences in expression. In the superior colliculus no rostrocaudal differences in distribution were detected for either of these receptors. Ephrin-A2 was distributed in a gradient increasing from the rostral to the caudal pole in the superficial layers of the superior colliculus only up to postnatal day 30. Ephrin-A2 was evenly distributed in the retina throughout development of the projection. Expression of EphA3 in the retina increased, while the expression of ephrin-A2 in the colliculus was downregulated over time. The graded expression of EphA3 and ephrin-A2 early in the development of the projection suggests that they play a role in establishment of coarse topography of retinal axons along the rostrocaudal axis of the superior colliculus. However, the gradients were not complementary, meaning that EphA3 alone cannot mediate the repulsive interactions with ephrin-A2 that have been postulated to underlie formation of the topographic map.

Animals↗
PubMed1999

A novel p34(cdc2)-binding and activating protein that is necessary and sufficient to trigger G(2)/M progression in Xenopus oocytes.

The activation of maturation-promoting factor (MPF) is required for G(2)/M progression in eukaryotic cells. Xenopus oocytes are arrested in G(2) and are induced to enter M phase of meiosis by progesterone stimulation. This process is known as meiotic maturation and requires the translation of specific maternal mRNAs stored in the oocytes. We have used an expression cloning strategy to functionally identify proteins involved in G(2)/M progression in Xenopus oocytes. Here we report the cloning of two novel cDNAs that when expressed in oocytes induce meiotic maturation efficiently. The two cDNAs encode proteins of 33 kD that are 88% identical and have no significant homologies to other sequences in databases. These proteins, which we refer to as p33(ringo) (rapid inducer of G(2)/M progression in oocytes), induce very rapid MPF activation in cycloheximide-treated oocytes. Conversely, ablation of endogenous p33(ringo) mRNAs using antisense oligonucleotides inhibits progesterone-induced maturation, suggesting that synthesis of p33(ringo) is required for this process. We also show that p33(ringo) binds to and activates the kinase activity of p34(cdc2) but does not associate with p34(cdc2)/cyclin B complexes. Our results identify a novel p34(cdc2) binding and activating protein that regulates the G(2)/M transition during oocyte maturation.

Amino Acid Sequence↗
PubMed1999

Diffusing wave spectroscopy microrheology of actin filament networks.

Filamentous actin (F-actin), one of the constituents of the cytoskeleton, is believed to be the most important participant in the motion and mechanical integrity of eukaryotic cells. Traditionally, the viscoelastic moduli of F-actin networks have been measured by imposing a small mechanical strain and quantifying the resulting stress. The magnitude of the viscoelastic moduli, their concentration dependence and strain dependence, as well as the viscoelastic nature (solid-like or liquid-like) of networks of uncross-linked F-actin, have been the subjects of debate. Although this paper helps to resolve the debate and establishes the extent of the linear regime of F-actin networks' rheology, we report novel measurements of the high-frequency behavior of networks of F-actin, using a noninvasive light-scattering based technique, diffusing wave spectroscopy (DWS). Because no external strain is applied, our optical assay generates measurements of the mechanical properties of F-actin networks that avoid many ambiguities inherent in mechanical measurements. We observe that the elastic modulus has a small magnitude, no strain dependence, and a weak concentration dependence. Therefore, F-actin alone is not sufficient to generate the elastic modulus necessary to sustain the structural rigidity of most cells or support new cellular protrusions. Unlike previous studies, our measurements show that the mechanical properties of F-actin are highly dependent on the frequency content of the deformation. We show that the loss modulus unexpectedly dominates the elastic modulus at high frequencies, which are key for fast transitions. Finally, the measured mean square displacement of the optical probes, which is also generated by DWS measurements, offers new insight into the local bending fluctuations of the individual actin filaments and shows how they generate enhanced dissipation at short time scales.

Actin Cytoskeleton↗
PubMed1999

Renal involvement in Gambian children with cerebral or mild malaria.

Kidney function was studied in 80 Gambian children with cerebral malaria, 73 children with mild malaria, and in 19 children with other febrile illnesses. Serum creatinine was measured, and the excretion in urine of immunoglobulin G, transferrin, albumin and alpha 1 microglobulin was determined. Twenty-five percent of children with cerebral malaria, and 4% of children with mild malaria had an elevated serum creatinine above 62 mumol/l. Increased urinary protein excretion was frequent: 53% of children with cerebral malaria had a glomerulo-tubular pattern of protein excretion, and 46% a tubular pattern. Median albuminuria was 68 mg/l in children with cerebral malaria, 18 mg/l in children with mild malaria, and 9 mg/l in febrile children with other diseases (P < 0.0001). There was no significant association between the proteinuria and height of fever or the degree of parasitaemia, and there was no significant association between death and signs of renal impairment. Renal involvement is common in children with malaria in The Gambia, with prerenal, glomerular, and tubulo-interstitial factors contributing. It is more pronounced in children with cerebral malaria than in those with mild malaria. However, renal dysfunction is relatively mild and does not indicate a worse prognosis.

Alpha-Globulins↗
PubMed1999

Biochemical and haematological variables in Gambian children with cerebral malaria.

Biochemical and haematological measurements were made in Gambian children who satisfied the criteria for the diagnosis of cerebral malaria over a 3-year period. Biochemical and haematological values were available for 388 and 624 children, respectively. Biochemical signs of renal and hepatic dysfunction were found and these may have contributed in a cumulative way to the high mortality seen in the study children. Cerebral involvement in children with cerebral malaria is only one, though the most important, manifestation of a multi-organ disease.

Blood Cell Count↗
PubMed1999

Chloramine-induced haemolysis presenting as erythropoietin resistance.

BACKGROUND: In December 1996 we identified an outbreak of erythropoietin (rHuEpo) resistance requiring a substantial increase in rHuEpo dosage in one of our four haemodialysis (HD) units. The dialysate chloramine levels in this unit had risen from <0.1 p.p.m. in 1996 to 0.25-0.3 p.p.m. in 1997. In the other three HD units levels remained <0.1 p.p.m. Other parameters of water quality were within accepted standards. METHODS: Monthly records of haemoglobin level and rHuEpo dose were available for 148 patients between January 1996 and May 1998. Seventy-two patients, with no recognized cause of rHuEpo resistance, were analysed in detail (August 1997 to April 1998). A subgroup of 15 patients was examined for evidence of haemolysis during HD (methaemoglobin and haptoglobin levels, reticulocyte counts and Heinz bodies). Larger carbon columns were installed in December 1997 to effect chloramine removal. RESULTS: There was an increase in mean methaemoglobinaemia of 23% (P<0.01) and a 21% fall in mean haptoglobin (P<0.01) across HD, although no patient had a reticulocytosis and only one patient with G6PD deficiency had Heinz bodies. Following installation of larger carbon columns there was an 18.6% rise (P<0.001) in mean haemoglobin level and a subsequent 25.0% reduction (P<0.001) in mean rHuEpo dose. Intradialytic changes in methaemoglobin and haptoglobin were abolished. The dialysate chloramine levels fell to < 0.1 p.p.m. Water company records subsequently revealed a sustained twofold increase in mains water chloramine from November 1996. CONCLUSIONS: This is the first report linking chloramine exposure and rHuEpo resistance, with only subtle signs of haemolysis. Unheralded changes in mains water constituents can directly affect dialysate water quality and clinical outcomes.

Adult↗
PubMed1999

Acute bacterial meningitis in The Gambia: a four-year review of paediatric hospital admissions.

Over a 4 year period, 1991 to 1994, 420 patients with acute bacterial meningitis were admitted to a tertiary urban hospital in The Gambia. Organisms were isolated from the cerebrospinal fluid in 64 per cent of cases. In the neonatal period Streptococcus pneumoniae was the single most common organism isolated. Amongst infants and children the two major pathogens were Haemophilus influenzae and S. pneumoniae. In the first year of life, children with S. pneumoniae meningitis were younger than those with H. influenzae infection (median age 3 months versus 6 months, p < 0.00003) and they had a higher case fatality rate (37 per cent versus 17 per cent, p = 0.002). In view of the high case fatality rate, there is a need to review overall case management. This will include a review of more effective antibiotics, the possible role of dexamethasone, and the inclusion of efficacious vaccines against H. influenzae and S. pneumoniae disease.

Acute Disease↗
PubMed1999

Etiology of serious infections in young Gambian infants.

BACKGROUND: Despite improvements in infant mortality rates in many developing countries including The Gambia, neonatal mortality remains high and many neonatal deaths are caused by infection. The study described in this paper was conducted to determine the bacterial and viral etiology of serious infections in Gambian infants younger than 91 days old. METHODS: At a first level health facility 497 infants with symptoms that could indicate serious infection were enrolled, of whom 239 with 1 or more signs of serious infection and 55 with no signs were investigated, yielding 17 cases with positive bacterial cultures of blood and/or cerebrospinal fluid. At a nearby pediatric referral hospital 198 infants were seen and 182 were investigated, yielding 35 positive bacterial cultures. RESULTS: There were 15 culture positive cases of meningitis caused by Streptococcus pneumoniae (7), Streptococcus pyogenes (2), Enterobacter cloacae (2), Escherichia coli (1), Haemophilus influenzae type b (1), Streptococcus agalactiae (1) and Salmonella spp. (1). Six of these children died. Thirty-three infants without meningitis had positive blood cultures for Staphylococcus aureus (17), S. pneumoniae (3), Salmonella spp. (5), E. coli (3), other enterobacteria (4) and S. agalactiae (1), of whom 14 died. Nasopharyngeal aspirates from 438 children were investigated for common respiratory viruses. Respiratory syncytial virus was found in 51, influenza A in 46, influenza B in 22, parainfluenza in 26 and adenovirus in 16. Respiratory syncytial virus and influenza A isolates were found most frequently toward the end of the wet season. Nasopharyngeal carriage of S. pneumoniae and H. influenzae was studied in 320 infants recruited during the first year. Of these 184 (58%) were positive for S. pneumoniae and 141 (44%) were positive for H. influenzae, 18 of which were type b. Infants with a bacterial isolate from blood or cerebrospinal fluid were more likely than the rest to die, whereas those with a viral isolate were less likely to die. CONCLUSIONS: The most important causes of serious infections in young Gambian infants are Staphylococcus aureus, S. pneumoniae and Salmonella spp.

Bacteria↗
PubMed1999

Improved outcome of clindamycin compared with beta-lactam antibiotic treatment for invasive Streptococcus pyogenes infection.

CONTEXT: Animal model studies have demonstrated the failure of penicillin to cure Streptococcus pyogenes myositis and have suggested that clindamycin is a more effective treatment. OBJECTIVE: To determine the most effective antibiotic treatment for invasive S. pyogenes infection in humans. DESIGN AND SETTING: We conducted a retrospective review of the outcomes of all inpatients from 1983 to 1997 treated for invasive S. pyogenes infection at Children's Hospital. PATIENTS: Fifty-six children were included, 37 with initially superficial disease and 19 with deep or multiple tissue infections. MAIN OUTCOME MEASURE: Lack of progression of disease (or improvement) after at least 24 h of treatment. RESULTS: The median number of antibiotic exposures was 3 per patient (range 1 to 6) with clindamycin predominating in 39 of 45 courses of protein synthesis-inhibiting antibiotics and beta-lactams predominating amongst the cell wall-inhibiting antibiotics in 123 of 126 of the remainder. Clindamycin was often used in combination with a beta-lactam antibiotic. Overall there was a 68% failure rate of cell wall-inhibiting antibiotics when used alone. Patients with deep infection were more likely to have a favorable outcome if initial treatment included a protein synthesis-inhibiting antibiotic as compared with exclusive treatment with cell wall-inhibiting antibiotics (83% vs. 14%, P = 0.006) with a similar trend in those with superficial disease (83% vs. 48%, P = 0.07). For those children initially treated with cell wall-inhibiting antibiotics alone, surgical drainage or debridement increased the probability of favorable outcome in patients with superficial disease (100% vs. 41%, P = 0.04) with a similar trend in a smaller number of deep infections (100% vs. 0%, P = 0.14). CONCLUSIONS: This retrospective study suggests that clindamycin in combination with a beta-lactam antibiotic (with surgery if indicated) might be the most effective treatment for invasive S. pyogenes infection.

Adolescent↗
PubMed1999

Risperidone use at a state hospital: a clinical audit 2 years after the first wave of risperidone prescriptions.

BACKGROUND: In spite of some inherent limitations, naturalistic data can provide information on populations that have greater heterogeneity than can controlled clinical trials and on functional outcomes that may be especially important in clinical practice. In the present retrospective naturalistic study, we evaluated key clinical outcomes among the first wave of risperidone-treated patients at a state psychiatric hospital. METHOD: Outcome data were extracted from the charts of 142 patients 2 years after initiation of treatment with risperidone. Their diagnoses included DSM-III-R schizophrenia (57%), schizoaffective disorder (22%), dementia and other organic conditions (7%), bipolar disorder (5%), and other psychiatric disorders (9%). RESULTS: During the 2-year period, 92 of 142 patients were discharged from the hospital: 61 (43%) were discharged on risperidone treatment and 31 (22%) were discharged on treatment with other drugs. At the time of the study, 50 of 142 patients were still in the hospital: of these, 18 (13%) were still receiving risperidone. The modal maximum daily dose of risperidone was 4.1 mg in patients discharged on risperidone treatment and 7.5 mg in patients still in the hospital. All groups were granted more ward privileges after starting risperidone, the most being granted to patients discharged from the hospital on risperidone treatment (p<.05 versus patients discharged on treatment with other drugs) and those still receiving risperidone in the hospital. Significantly fewer patients discharged on risperidone treatment than on treatment with other drugs were readmitted to the hospital within 2 years after discharge (p<.01). CONCLUSION: Improved privilege levels and a reduced readmission rate indicate that risperidone was an effective antipsychotic agent among a heterogeneous patient population in a state hospital. These factors may be especially important to justify use of this agent in the current fiscal climate.

Adult↗
PubMed1998

A link between MAP kinase and p34(cdc2)/cyclin B during oocyte maturation: p90(rsk) phosphorylates and inactivates the p34(cdc2) inhibitory kinase Myt1.

M-phase entry in eukaryotic cells is driven by activation of MPF, a regulatory factor composed of cyclin B and the protein kinase p34(cdc2). In G2-arrested Xenopus oocytes, there is a stock of p34(cdc2)/cyclin B complexes (pre-MPF) which is maintained in an inactive state by p34(cdc2) phosphorylation on Thr14 and Tyr15. This suggests an important role for the p34(cdc2) inhibitory kinase(s) such as Wee1 and Myt1 in regulating the G2-->M transition during oocyte maturation. MAP kinase (MAPK) activation is required for M-phase entry in Xenopus oocytes, but its precise contribution to the activation of pre-MPF is unknown. Here we show that the C-terminal regulatory domain of Myt1 specifically binds to p90(rsk), a protein kinase that can be phosphorylated and activated by MAPK. p90(rsk) in turn phosphorylates the C-terminus of Myt1 and down-regulates its inhibitory activity on p34(cdc2)/cyclin B in vitro. Consistent with these results, Myt1 becomes phosphorylated during oocyte maturation, and activation of the MAPK-p90(rsk) cascade can trigger some Myt1 phosphorylation prior to pre-MPF activation. We found that Myt1 preferentially associates with hyperphosphorylated p90(rsk), and complexes can be detected in immunoprecipitates from mature oocytes. Our results suggest that during oocyte maturation MAPK activates p90(rsk) and that p90(rsk) in turn down-regulates Myt1, leading to the activation of p34(cdc2)/cyclin B.

Animals↗
PubMed1998

A comparison of the early outcome of acute myocardial infarction in women and men. The Third International Study of Infarct Survival Collaborative Group.

BACKGROUND: In previous studies, unadjusted comparisons of mortality and major morbidity after acute myocardial infarction have generally indicated that women have a poorer outcome than men. Much larger studies are needed, with more complete adjustment for coexisting conditions, to determine whether this difference is explained by the older age of the women studied or by the presence of other unfavorable prognostic factors, or both. METHODS: As part of the Third International Study of Infarct Survival (ISIS-3), information was collected on deaths during days 0 to 35 and on major clinical events during hospitalization up to day 35 for 9600 women and 26,480 men with suspected acute myocardial infarction who were considered to have a clear indication for fibrinolytic therapy. We compared the outcome among women and men, first without adjustment, then with adjustment for age, and finally with adjustment for other recorded baseline characteristics by means of multiple logistic regression. RESULTS: The unadjusted odds ratio for death among women as compared with men was 1.73 (95 percent confidence interval, 1.61 to 1.86). The women were significantly older than the men, and after adjustment for age the odds ratio was reduced markedly to 1.20 (95 percent confidence interval, 1.11 to 1.29). Adjustment for other differences in base-line clinical features further reduced the odds ratio to 1.14 (95 percent confidence interval, 1.05 to 1.23). Excesses in other major clinical events among women were generally reduced to a similar extent by adjustment. CONCLUSIONS: It seems likely that there is at most only a small independent association between female sex and early mortality and morbidity after suspected acute myocardial infarction.

Adult↗
PubMed1998

A comparison of bone scintigraphy and MRI in the early diagnosis of the occult scaphoid waist fracture.

OBJECTIVE: To determine the accuracy of MRI in the assessment of the radiographically occult scaphoid fracture. DESIGN: This prospective study compared the sensitivity and specificity of MRI for detection of radiographically occult scaphoid fractures with bone scintigraphy (BS), the currently accepted imaging modality of choice. Consecutive patients with clinical signs of a scaphoid injury but no evidence of fracture on plain radiographs at presentation and after 7-10 days were evaluated by MRI and BS. All images were reported in masked fashion and the sensitivities and specificities of the imaging modalities determined. All patients with a scaphoid fracture demonstrated by MRI or BS were followed for at least a year after injury. PATIENTS: Forty-three subjects (aged 12-74 years) had both MRI and BS carried out on average 19 days from the injury date. RESULTS AND CONCLUSIONS: Six patients (14%) had scaphoid waist fractures. There were other bony injuries in a further six. In 40 patients there was agreement between the BS and MRI findings. In three cases there was discrepancy between the imaging modalities; in all three MRI was found to be the more sensitive and specific. MRI could become the investigation of choice for this injury.

Adolescent↗