Biomedical subjects

P Lawlor

Publications and source records attributed to P Lawlor.

47 records · Page 3Linked to original sources

PubMed1993

Brain-derived neurotrophic factor expression after long-term potentiation.

Long-term potentiation (LTP) of perforant-path dentate granule cell synapses, in awake rats, was followed by a time-dependent expression of brain-derived neurotrophic factor (BDNF) mRNA in dentate granule cells. This BDNF expression was blocked by the N-methyl-D-aspartate (NMDA) antagonist dizocilpine maleate (MK-801), which also blocked LTP induction, and by sodium pentobarbital, which shortens LTP persistence. These results suggest that BDNF may participate in the NMDA-receptor mediated cascade of events that result in LTP stabilization.

Animals↗

PubMed1993

Cholecystectomy and oesophageal reflux: a prospective evaluation.

The effect of cholecystectomy on oesophageal function was examined prospectively. Of 37 patients studied, 17 (46 per cent) were still symptomatic 3-4 months after surgery. Thirteen patients (35 per cent) had abnormal oesophageal pH profiles before cholecystectomy, increasing to 27 (73 per cent) afterwards (P < 0.002). The mean (s.e.m.) DeMeester acid reflux score increased from 15.2(2.1) to 34.2(5.2) (P < 0.001) after operation. Lower oesophageal sphincter function, as measured by the sphincter function index, was significantly reduced in the patients with abnormal pH profiles after operation (P < 0.01). Mean(s.e.m.) supine gastric alkaline shift (proportion of time at pH > 4) increased from 9.2(2.0) to 17.7(3.7) per cent (P < 0.02) and the incidence of gastritis from eight patients (22 per cent) to 23 (62 per cent) (P < 0.001). These data suggest that cholecystectomy results in gastro-oesophageal reflux that appears to be related to compromised sphincter competence.

Adult↗

PubMed1993

A new technique for measuring lower oesophageal sphincter competence in patients.

Oesophageal sphincter measurements were carried out on 80 patients using the stationary pull through technique; Normals (n = 21), Nutcracker (n = 12), Refluxers (n = 21), and Barrett's (n = 26). Sphincter pressure (LOSP), abdominal length of sphincter, and overall sphincter length were measured. The Sphincter Function Index (SFI) was calculated as the product of sphincter pressure and percentage sphincter length (AL) exposed to abdominal pressure. Patients also had routine endoscopy and 24 hour pHmetry. SFI values discriminated between all four groups. LOSP was significantly different for Barrett's (p < 0.01) and Nutcracker (p < 0.01) compared to normals. AL was significant for Refluxers (p < 0.001) and Barrett's (p < 0.001) compared to normals. SFI gives better discrimination than LOSP or AL alone and may be useful in evaluating the response to treatment.

Adult↗

PubMed1993

Is c-Jun involved in nerve cell death following status epilepticus and hypoxic-ischaemic brain injury?

Neurons undergoing delayed neuronal death produced by hypoxia-ischaemia (HI) or status epilepticus (SE) showed a massive expression of c-Jun in their nuclei 24 h after the insult. With SE there was also a weaker induction of c-Fos and Jun B in dying neurons. SE induced in the presence of the NMDA antagonist MK-801 produced no delayed c-Jun expression in the hippocampus and nerve cell death did not occur in this region, although there was a delayed c-jun expression in the amygdala/piriform region, and cell death occurred in this area. Activation of central muscarinic receptors with pilocarpine, or block of D2 dopamine receptors with haloperidol, treatments which do not cause neuronal damage, strongly induced Fos and Jun B in hippocampal and striatal neurons, but only induced c-Jun very weakly. Thus, c-Jun may participate in the genetic cascade of events that produce programmed cell death in neurons.

Animals↗

PubMed1993

MK801 induces immediate-early gene proteins and BDNF mRNA in rat cerebrocortical neurones.

Recent studies have shown that MK801, a potent phencyclidine receptor ligand, causes pathomorphological changes in rat cerebrocortical neurones. Here we report that doses of MK801 (1 and 5 mg kg-1) which have been shown to produce pathomorphological changes, induce the expression of immediate-early gene proteins (IEGPs) and brain-derived neurotrophic factor (BDNF) mRNA in rat cerebrocortical neurones. Blockade of central muscarinic receptors which has been shown to prevent MK801-induced pathomorphological changes in cerebrocortical neurones, also prevented MK801-induced expression of IEGPs and BDNF mRNA. The transiently increased expression of BDNF mRNA may be an acute compensatory response of these neurones to MK801-induced injury.

Animals↗

PubMed1992

Meal area index: a new technique for quantitative assessment in achalasia by ambulatory manometry during eating.

Ambulatory non-perfused oesophageal manometry was used to study oesophageal body function during consumption of a full meal in patients with achalasia. A measure of oesophageal body activity (the meal area index) was developed by calculating the total area under the pressure curve during eating, above the preprandial baseline oesophageal pressure, per meal minute. Untreated patients with achalasia (n = 13) were compared with normal subjects (n = 42), patients with benign stricture (n = 9) and patients with achalasia who had undergone Heller's myotomy (n = 17). The results showed a high meal area index in achalasia, due to a rise in baseline oesophageal pressure and frequent high-amplitude contractions during eating. This was not seen in normal subjects or patients with stricture. The high meal area index was abolished by successful Heller's myotomy but remained in two patients with persisting dysphagia. Sustained high intraoesophageal pressure is generated during consumption of a solid meal in untreated achalasia, resulting in a unique manometric profile. Manometry during eating using the meal area index permits quantitative assessment of oesophageal body function in achalasia and may aid in the assessment of response to treatment.

Ambulatory Care↗

PubMed1992

Induction of immediate-early gene proteins in dentate granule cells and somatostatin interneurons after hippocampal seizures.

The expression of the protein products of the immediate-early genes c-fos, Fos B, Fos-related proteins (FRAs), c-jun, jun B, jun D and krox-24 was investigated in the rat hippocampus at various times after electrically-induced hippocampal seizures. Hippocampal seizures induced all the immediate-early gene proteins in dentate granule cells with differing time-courses. In addition, Krox-24, Fos and Jun D were also induced in somatostatin-containing interneurons throughout the hippocampus and also in a small percentage of parvalbumin-containing interneurons. Thus, hippocampal seizures induce waves of immediate-early gene protein expression in dentate granule cells and a selective expression of krox-24, Fos and Jun D in hippocampal somatostatin interneurons. These results suggest that biochemical and/or morphological changes occurring in dentate granule cells and somatostatin interneurons after seizures may be regulated by immediate-early gene expression, and that these immediate-early gene proteins may be involved in seizure development in the nervous system.

Animals↗

PubMed1992

Basal expression of Fos, Fos-related, Jun, and Krox 24 proteins in rat hippocampus.

The basal expression of the protein products of the inducible immediate early genes (IEGs), Fos, Jun, and Krox 24, was investigated in rat hippocampus using immunocytochemical visualization methods with antisera specific for Fos only, Fos and the Fos-related antigens (FRAs), the Jun family, and Krox 24 (previously described as TIS 8, egr-1, NGF-IA or zif 268). In the normal adult rat brain basal levels of Jun, Krox 24 and Fos-related antigens but not Fos were seen within the hippocampus. More specifically very high basal levels of Jun were seen in the dentate granule cells with high basal Krox 24 levels seen in the CA1-subiculum region of the rat hippocampus. Basal FRAs but not Fos-positive cells were seen at low levels in the dentate granule cells. The implications of these results to the functioning of IEG proteins in hippocampal neurons is discussed.

Animals↗

PubMed1990

The role of CD44, CD45, CD45RO, CD46 and CD55 as potential anti-adhesion molecules involved in the binding of human tonsillar T cells to phorbol 12-myristate 13-acetate-differentiated U-937 cells.

In this study, we have shown that human tonsillar T cells adhere to phorbol 12-myristate 13-acetate(PMA)-differentiated U-937 cells. To examine the molecular mechanisms involved, the effect of a panel of monoclonal antibodies upon this adhesion was assessed in a quantitative binding assay. Antibodies against LFA-1 and ICAM-1 inhibited binding, directly implicated these molecules in T cell-PMA-induced U-937 adhesion. Furthermore, the adhesion was magnesium but not calcium dependent. Of the remaining antibodies that were tested, none of those against CD2, LFA-3, Mac-1, p150,95, CD43, CD45RA or CD56 affected binding. However, antibodies against CD44, CD45, CD45RO, CD46 and CD55 enhanced binding suggesting an anti-adhesive role for these molecules during U-937-T cell interaction.

Antigen-Presenting Cells↗

PubMedDate not supplied

Oesophageal motility and digestion of cream liqueurs in combination with common alcohol mixers.

When acidic mixers are added to cream liqueur curdling occurs. Oesophageal motility was studied in normal volunteers during ingestion of this mixture and the effect of combining with gastric juice was assessed in a simulated physiological environment. Twenty-four h ambulatory manometry and pH (n = 22) and gastric studies (n = 7) were carried out. There was no detrimental effect on oesophageal motility. The precipitation is rapidly broken down by the digestive process in the stomach.

Adult↗

PubMedDate not supplied

Apoptosis, neurotrophic factors and neurodegeneration.

Apoptosis is an active process of cell death characterized by distinct morphological features, and is often the end result of a genetic programme of events, i.e. programmed cell death (PCD). There is growing evidence supporting a role for apoptosis in some neurodegenerative diseases. This conclusion is based on DNA fragmentation studies and findings of increased levels of pro-apoptotic genes in human brain and in in vivo and in vitro model systems. Additionally, there is some evidence for a loss of neurotrophin support in neurodegenerative diseases. In Alzheimer's disease, in particular, there is strong evidence from human brain studies, transgenic models and in vitro models to suggest that the mode of nerve cell death is apoptotic. In this review we describe the evidence implicating apoptosis in neurodegenerative diseases with a particular emphasis on Alzheimer's disease.

Alzheimer Disease↗