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J Francis

Publications and source records attributed to J Francis.

At least 19 recordsLinked to original sources
PubMed1999

Decreased hippocampal expression, but not functionality, of GABA(B) receptors after transient cerebral ischemia in rats.

We have examined the effects of transient global ischemia on both the gene expression levels and the functionality of GABA(B) receptors in rat brain, using antisense in situ hybridization and electrophysiological evaluations. At the level of gene expression, no significant change in GABA(B) receptor expression was observed in any hippocampal subfield at either 6 or 12 h after challenge. At 24 h postchallenge, however, a significant decrease in GABA(B) receptor expression was observed in both the CA1 and CA3 subfields, whereas no change was observed in the dentate granule cell layer. Although expression in both the vulnerable CA1 and less vulnerable CA3 subfields was diminished at this time postchallenge, there was no significant difference in the degree of the diminished expression between these subfields. At the functional level, the dose-dependent ability of baclofen (1-100 microM) to inhibit an evoked excitatory postsynaptic potential (f-EPSP) in the CA1 subfield was evaluated at 24 h postischemia, in comparison with the dose-response observed in sham-operated subjects. No significant differences were observed in the efficacy of GABA(B) receptor-mediated inhibition of the elicited f-EPSP at any of the baclofen concentrations examined. These data demonstrate that although the mRNA expression levels for the GABA(B) receptor are diminished in both vulnerable and less vulnerable neurons of Ammon's horn at 24 h following transient global ischemia, the functionality of the GABA(B) receptor system is maintained at this time postchallenge.

Animals↗
PubMed1998

Effects of intragastric infusions of fat and carbohydrate on appetite ratings and food intake from a test meal.

Previous studies using meal preloads have indicated that carbohydrate has a greater satiating power than fat. To investigate the effects of macronutrients on ingestion and satiety, without the influence of meal design and orosensory factors, two groups of ten healthy, fasted male volunteers took part in two separate experiments involving rapid direct intragastric infusions of macronutrients. In the first experiment volunteers received isocaloric infusions of either Intralipid, or 1:1 Intralipid and glucose mixture or saline over 15 min on three separate occasions. In a second experiment volunteers received isocaloric infusions of either Intralipid or glucose. For both studies, appetite ratings were recorded for the first two hours of the study and energy and macronutrient intakes were evaluated from a test meal given 1.5 h after the infusion. Food diaries were used to monitor food intake for the remainder of the study day. In the first experiment, both Intralipid and the Intralipid/glucose mixture suppressed appetite ratings and reduced energy intake at lunch compared with saline but had no effect on energy intake during the remainder of the study day. No differences were found between nutrient conditions in suppressing appetite ratings or energy intake. In the second experiment there were no differences between the effects of Intralipid and glucose on hunger, fullness or on energy intake from the test meal or intake over the remainder of the day. Taken together, these results suggest that intragastric infusions of either Intralipid, glucose or a mixture of the two, reduced hunger and increased fullness, but they failed to confirm the hypothesis that different macronutrients have different satiating capacities.

Adolescent↗
PubMed1998

Relative contributions of intestinal, gastric, oro-sensory influences and information to changes in appetite induced by the same liquid meal.

To investigate the contribution of oral, gastric and intestinal factors in the control of appetitc, 425 ml (400 kcal) tomato soup was administered either orally, intragastrically (covertly and overtly) or intraduodenally (overtly) to nine healthy, fasted, male volunteers. Ratings of fullness, hunger and desire to eat were recorded over a period of 2 h and gastric emptying was measured after soup fed orally and intragastrically. Infusion of the soup into the small intestine at a rate commensurate with normal gastric emptying exerted no significant suppression of ratings of hunger and desire to eat and no significant production of fullness. Covert, intragastric infusion of the same soup suppressed appetite and this suppression was increased when the subjects were informed of the nature of the infusion, but there were no differences in gastric emptying profiles between covert and overt intragastric infusions of soup. Oral administration of the soup produced the greatest suppression of appetite compared with other conditions and also generated a slower rate of gastric emptying compared with both intragastric soup infusions. Strong correlations were observed between appetite ratings and both gastric and intestinal contents following intragastric infusions of the soup meal and these were enhanced following oral administration of soup. These results indicate how information, orosensory, gastric and intestinal factors can interact to elicit optimal expression of fullness and suppression of hunger. Specifically, the data not only demonstrate how the influence of gastric distension appears to overwhelm any direct influence of intestinal chemostimulation on appetite and how information modulates this effect, but the data also support an important role in appetite suppression for psychophysiological mechanisms stimulated by orosensory mechanisms.

Adolescent↗
PubMed1998

A nondenaturing purification scheme for the DNA-binding domain of poly(ADP-ribose) polymerase, a structure-specific DNA-binding protein.

Poly(ADP-ribose) polymerase (PARP) is thought to be involved in DNA repair given its ability to recognize and bind to DNA strand breaks. During apoptosis, PARP is proteolytically cleaved into two stable fragments, the N-terminal 25-kDa DNA-binding domain (DBD) and the 85-kDa fragment containing the automodification and catalytic domains. To understand the DNA-binding properties of PARP, we expressed a recombinant hexahistidine tagged protein (His-DBD) in Escherichia coli. We modified expression to facilitate protein folding by including zinc and reducing the induction temperature. Properly folded, the DNA-binding domain of PARP binds to single- and double-stranded DNA in a structure-specific manner. To eliminate contamination with bacterial DNA that occurred during the purification process, a purification procedure was developed to produce DNA-free protein. In addition, to remove the hexahistidine tag from the recombinant protein, thrombin cleavage was carried out while the recombinant protein was bound to a DNA column. This procedure stabilized the recombinant protein and resulted in nearly 100% cleavage with no appreciable loss to unwanted proteolytic degradation. This nondenaturing purification scheme results in high-quality, native PARP-DBD for use in structural and biochemical studies.

Amino Acid Sequence↗
PubMed1998

A comparison of adenosine and arbutamine for myocardial perfusion imaging.

We have compared our standard stress protocol (adenosine combined with exercise) with the new stress agent arbutamine, for thallium-201 myocardial perfusion imaging (MPI) in order to assess the comparative value of arbutamine. We studied 23 patients referred for MPI, and each patient had two studies (18 males, median age 66 years, five with previous myocardial infarction). Uptake scores were assigned to each of nine segments, and the extent and severity of defects were measured using a polar plot. Haemodynamic changes were greater with arbutamine (rate-pressure product increase 78% vs 51%, P = 0.003). Symptoms were experienced by 21 patients with arbutamine and 16 with adenosine (P = 0.07). Agreement between the techniques for classification of patients as normal or as having reversible, fixed or mixed defects was good (19 of 23 studies, 83%, kappa = 0.76). Agreement for similar classification of segments was also good (82%, kappa = 0.71). Segmental agreement for stress scores was good (86%, kappa = 0.77). However, mean size of stress defect was larger with adenosine (83+/-52 pixels vs 65+/-48 pixels, P<0.05), though severity and reversibility were similar (P = NS). We conclude that arbutamine provides comparable results to those obtained with adenosine and exercise and that the observed differences are not clinically significant.

Adenosine↗
PubMed1998

Simultaneous biplane first-pass radionuclide ventriculography using 99Tcm-tetrofosmin: a comparison with magnetic resonance imaging.

First-pass radionuclide ventriculography (FPRNV) using 99Tcm-labelled myocardial perfusion agents allows the assessment of myocardial function and perfusion simultaneously. We have assessed the feasibility of biplane FPRNV using 99Tcm-tetrofosmin, and have validated global and regional functional measurements by comparison with magnetic resonance imaging (MRI). FPRNV was performed at rest in 18 patients referred for assessment of known or suspected coronary artery disease (5 with previous myocardial infarction). A dual-headed camera was used to acquire RAO and LAO projections simultaneously. Left ventricular ejection fraction (LVEF) was calculated using standard methods and regional wall motion was evaluated visually in five myocardial segments using a 4-point scale and also by Fourier analysis. Cine MRI was performed in four oblique planes, LVEF was calculated using a biplane area-length method and regional motion was assessed visually in a similar fashion to FPRNV. Agreement between the techniques for LVEF was good using RAO FPRNV (mean +/- S.D. difference = 0.7 +/- 4.7%), but less good in the LAO projection (difference = 10.5 +/- 7.1%). Wall motion was normal by both FPRNV and MRI in 5 patients without CAD and 3 of the 13 patients with CAD. In the remaining 10 patients, wall motion by MRI was abnormal in 20 segments; FPRNV with visual analysis was abnormal in 8 patients (80%) and 16 (80%) segments. Fourier analysis showed regional abnormalities in 7 patients (70%) and 13 (65%) segments. There was good agreement (kappa = 0.68) between FPRNV (visual analysis) and MRI for wall motion scores, but moderate agreement (kappa = 0.55) between Fourier analysis and MRI. Thus, LVEF measured by FPRNV in the RAO projection agrees well with MRI. Normal regional wall motion is accurately identified, but regional abnormalities are better assessed with MRI.

Adult↗
PubMed1998

Alterations in differentiation and apoptosis induced by bufalin in cJun overexpressing U-937 cells.

Recent evidence suggests that c-jun plays a pivotal role in macrophage differentiation induced by multiple agents and that cJun overexpression induces partial macrophage differentiation in the leukemic cell line U-937. The novel differentiating agent bufalin, a Na+/K+ ATPase inhibitor, has also been shown to induce macrophage differentiation in U-937. In order to further define the role of c-jun in macrophage differentiation, we examined the function of c-jun/AP-1 during bufalin induced differentiation in both c-jun transfected and parental U-937 cells. In contrast to phorbol esters, bufalin does not significantly stimulate c-jun or c-fos mRNA expression or AP-1 transactivation. However, bufalin treatment leads to markedly greater morphologic and functional changes indicative of more extensive differentiation in the cJun overexpressing cells compared to the non-transfected controls. Furthermore, cJun overexpressing cells maintain greater viability in the presence of bufalin and arrest in a different phase of the cell cycle than do control cell lines (G0/G1 versus S/G2M, respectively), although some apoptosis occurs in all cell lines treated with bufalin. These data suggest that while bufalin can induce some degree of differentiation in U-937 cells independent of c-jun/AP-1 controlled pathways, the involvement of these pathways by enforced cJun expression enhances the extent of differentiation and shifts the balance between differentiation and apoptosis.

Antineoplastic Agents↗
PubMed1997

Kainic acid-induced generalized seizures alter the regional hippocampal expression of the rat Kv4.2 potassium channel gene.

Potassium channels play a key role in the regulation of membrane excitability. We investigated the gene expression response of the Kv4.2 subtype of potassium channel, in the rat hippocampus, to a brief (5 min) episode of kainic acid-induced seizures. Our results demonstrate that Kv4.2 expression is reduced in the granule cell layer of the dentate gyrus at 3 h post-seizure, while no significant changes in expression are observed in other hippocampal subfields. At 6 h post-challenge, expression in both dentate hilar cells and granule cells is reduced, while no other significant changes are observed. At 24 h post-challenge, expression levels for Kv4.2 in the dentate granule cells have rebounded to levels greater than control, while expression levels are significantly reduced in the CA3 and CA4 subfields. No significant changes in Kv4.2 expression are observed in kainic acid-administered animals that fail to seize, indicating that the changes in gene expression result from seizure activity and not from the direct actions of the administered kainic acid. These results demonstrate that brief kainic acid-induced epileptiform activity promotes alterations in the expression levels for the Kv4.2 subtype of potassium channel gene.

Animals↗
PubMed1997

A flickery block of a K+ channel mediated by extracellular Ca2+ and other agonists of the Ca2+-sensing receptors in dispersed bovine parathyroid cells.

Single K+ channel activities in parathyroid cells were studied using the patch-clamp technique. A K+ channel modulated by external Ca2+ (Ca2+o) was identified. This channel had a unitary conductance of 109pS at 150 mM K+o in the pipette solution. An increase in Ca2+o from 0.5-0.75 to 2-3 mM induced a flickery partial block of the channel over a wide voltage range. The mechanism of channel blockade included a significant increase in the number of closings per burst and a reduction of the mean open times. Addition of other divalent and polyvalent agonists of the Ca2+-sensing receptor (CaR) induced a similar channel blockade. With its typical characteristics and flickery block by CaR agonists, this channel differs from previously described types of K+ channels. It is probably strongly coupled to the CaR and may contribute to the depolarization of parathyroid cells which is known to occur at elevated levels of Ca2+o.

Animals↗
PubMed1997

Devazepide attenuates dl-fenfluramine-induced suppression of gastric emptying but not food intake in the 17 h food-deprived rat.

Recently a number of studies have provided evidence which suggests that CCK and 5-HT interact in the control of food intake. The present experiments further examine this mechanism and the possibility that CCK and 5-HT interact in the control of gastric emptying. The selective CCK-A receptor antagonist, devazepide, (0.03-3.0 mg/kg) administered alone had no intrinsic effect on gastric emptying. Devazepide (0.1 and 0.3 mg/kg) blocked dl-fenfluramine-induced (3.0 mg/kg) suppression of gastric emptying. However, devazepide (0.03-3.0 mg/kg) failed to attenuate the anorectic effect of the same dose of dl-fenfluramine. These results suggest that under the present experimental conditions CCK and 5-HT interact in the regulation of gastric emptying but not food intake. Thus the interaction between CCK and 5-HT in the regulation of gastric emptying appears not to affect the control of ingestive behaviour.

Animals↗
PubMed1997

Early onset of diabetic nephropathy.

A 12 year old Asian girl with a four year history of poorly controlled insulin dependent diabetes mellitus developed overt diabetic nephropathy. There were no clinical features of Rabson-Mendenhall syndrome. Screening for microalbuminuria would have identified incipient diabetic nephropathy and highlighted the importance of good glycaemic control. Although screening for microalbuminuria is recommended after five years from diagnosis, it may be appropriate to undertake this annually in those with poor glycaemic control.

Albuminuria↗
PubMed1996

Alleviation of behavioral deficits in aged rodents following implantation of encapsulated GDNF-producing fibroblasts.

The present study examined the effects of encapsulated cells which were genetically modified to secrete human glail-derived neurotrophic factor (hGDNF) on the motor deficits in aged rodents. Prior to implantation, animals were tested on a battery of motor tasks. Spontaneous locomotion and motor coordination was evaluated in young (5 month) and aged (20 months) rats. Aged animals tested for spontaneous locomotor activity were found to be hypoactive relative to young animals. Compared to the young animals the aged animals also: (1) were impaired on a bar pressing task, (2) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (3) fell more rapidly from a rotating rod and (4) were unable to maintain their balance on a series of wooden beams of varying widths. Following baseline testing, aged animals received either no implant, encapsulated baby hamster kidney fibroblast cells that were modified to produce hGDNF (BHK-hGDNF) or encapsulated BHK cells which were not modified to produce hGDNF (BHK-Control) implanted bilaterally into the striatum. Following surgery, a significant increase in locomotor activity and bar pressing was observed in those aged animals receiving BHK-hGDNF implants. Bar pressing in aged animals receiving BHK-Control cells was improved to a lesser extent and reached the level of performance seen in young rats. No recovery was observed in the animals receiving BHK-Control cell-loaded capsules on any of the other motor tasks. Histological analysis revealed that implants of hGDNF-producing cells produced a marked increase in the density of tyrosine hydroxylase staining in the striatum adjacent to the implant site. This increased staining was not seen in animals receiving BHK-Control cells. Histological analysis also revealed the presence of viable BHK-hGDNF cells within the capsules that continued to produce hGDNF as measured by ELISA. These results indicate that polymer-encapsulated hGDNF-secreting cells survive following implantation into aged rats and may be useful for treating some of the behavioral consequences of aging or disorders characterized by dopaminergic hypofunction.

Aging↗
PubMed1996

Pressure ulcers.

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Aged↗
PubMed1996

Performance of draught cattle in communal farming areas in Zimbabwe after dry season supplementation.

Sixty-four pairs of oxen owned by smallholders were randomly allocated to one of 3 supplementary treatments offered at one kg per head per day from July to October or to a control where no supplement was offered. The supplements were maize stover plus silverleaf hay (2:1 w/w), urea-treated maize stover (50 g urea/kg stover) and plain maize stover. Animals fed plain maize stover or no supplement lost weight (6 to 7% of initial weight), whilst those fed the other 2 supplements maintained their liveweights. Supplementation reduced time spent on feeding activities by 10 per cent. Animals fed on urea-treated maize stover or maize stover plus silverleaf hay ploughed at speeds that were 29% faster than oxen on the other treatments and covered 45% more area. Blood parameters indicated a general deficiency of nitrogen intake throughout the dry season. It was concluded that supplements of good quality have the potential to improve the working ability of communal area oxen.

3-Hydroxybutyric Acid↗