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J Francis

Publications and source records attributed to J Francis.

At least 19 recordsLinked to original sources

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

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

Pressure ulcers.

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Aged

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

Lack of interaction between devazepide and 8-OH-DPAT-induced hyperphagia in the rat.

Recently, a number of studies have provided evidence suggesting that CCK and 5-HT interact in the control of food intake. However, the majority of these studies have relied on the administration of exogenous CCK to investigate potential interactions. The aim of the present study was to focus on the potential role of endogenous CCK in 5-HT-CCK interactions. Our prediction was that the CCKA antagonist, devazepide, alone would potentiate the hyperphagic effect of the 5-HT1A agonist, 8-OH-DPAT, in free-feeding rats. The results showed that devazepide, at a dose that had no intrinsic effect (1.0 mg/kg), did not enhance the hyperphagic effect of 8-OH-DPAT (100 and 300 micrograms/kg). This suggests that when serotonergic inhibitory activity is reduced by 5-HT1A-receptor stimulation, there is no compensatory increase of endogenous CCK activity to excite 5-HT neurons and thereby inhibit food intake.

8-Hydroxy-2-(di-n-propylamino)tetralin

Cografting with polymer-encapsulated human nerve growth factor-secreting cells and chromaffin cell survival and behavioral recovery in hemiparkinsonian rats.

Encapsulated cell grafting is one approach for the delivery of neurotransmitters and/or neurotrophic factors to the brain. Baby hamster kidney (BHK) cells were genetically modified to secrete high levels of human nerve growth factor (hNGF). Following polymer encapsulation, these cells were implanted into the left lateral ventricle or the left striatum 1.5 mm away from striatally cografted unencapsulated adrenal medullary chromaffin cells in hemiparkinsonian rats. Although the animals receiving adrenal medulla alone or adrenal medulla with intraventricular hNGF-secreting cell grafting did not show recovery of apomorphine-induced rotational behavior, the animals receiving adrenal medulla with intrastriatal hNGF-secreting cell implants showed a significant recovery of rotational behavior 2 and 4 weeks after transplantation. Histological analysis revealed that in animals receiving adrenal medulla with intraventricular hNGF-secreting cell grafting, the number of tyrosine hydroxylase-immunoreactive (TH-IR) surviving chromaffin cells tended to be higher (approximately five to six times) than in animals receiving adrenal medulla alone; however, this increase did not reach statistical significance. In contrast, in animals receiving adrenal medullary cells together with intrastriatal hNGF-secreting cells, the number of TH-IR surviving chromaffin cells was more than 20 times higher than that in animals receiving adrenal medullary cells alone. Analysis of retrieved capsules revealed that hNGF continued to be released by encapsulated BHK-hNGF cells after 4 weeks in vivo. Moreover, histological analysis confirmed the presence of numerous viable encapsulated BHK-hNGF cells. These results indicate the potential use of intrastriatal implantation of encapsulated hNGF-secreting cells for augmenting the survival of cografted chromaffin cells as well as promoting the functional recovery of hemiparkinsonian rats. These data indicate that this approach may have potential application for treating Parkinson's disease.

Animals

Somatosensory evoked potentials in acute neurological decompression illness.

Somatosensory evoked potentials (SSEPs) were recorded on posterior tibial nerve stimulation during compression in 21 episodes of acute neurological decompression illness (DCI) involving 20 patients. A further two cases were monitored immediately after treatment only. The results were compared with previously published normal data from this laboratory and with recordings obtained during the compression of four normal volunteers. Compression had no effect on SSEPs in normal subjects: SSEP latency abnormalities were found in 17 of the episodes of DCI. An SSEP improvement at final recording was noted in 7 of the 11 episodes which were monitored during treatment and classified initially as neurophysiologically abnormal. SSEPs may assist in the diagnosis of DCI.

Adult

Improving feeding management and work performance of Mashona oxen through strategic supplementation with cobsheath-groundnut stover.

Six pairs of Mashona oxen ploughed dry, red clay soils in August (winter) and in mid-November (spring). Between September and November the oxen were randomly assigned to 3 feeding groups: no supplement (control), 400 g/head per day of cobsheath-groundnut stover for 70 days and 800 g/head per day of the same supplement for 35 days. Cobsheath-groundnut stover was fed in order to determine its potential as supplementary feed for draught oxen during the dry season. The liveweight (LW) lost by heavy oxen during winter ploughing was lower (P < 0.001) than that of light oxen. During spring ploughing heavy oxen again lost less (P < 0.001) LW than light ones. In addition, non-supplemented oxen lost more LW than those supplemented. Therefore feeding strategies for Mashona draught oxen should aim at providing adequate nutrients to at least maintain LW during the dry season. Heavy oxen outperformed (P < 0.001) light ones during winter ploughing. Work output of supplemented oxen in spring was also significantly greater (P < 0.05) than that of non-supplemented ones. This result demonstrated the benefits of supplementary feed during the dry season. Concentrations of lactate and free fatty acids in plasma, heart rates and rectal temperatures increased (P < 0.05) markedly during work. The increases were higher (P < 0.05) for light oxen, particularly those not fed supplement.

Animal Feed

The "dangerous multipara": fact or fiction?

OBJECTIVE: Our purpose was to compare the intrapartum complication incidence among grand multiparous women with that of age-matched control multiparous women. STUDY DESIGN: A total of 382 grand multiparous women (para > or = 5) were compared with 382 age-matched control subjects (para 2 to 4), all delivering between July 1989 and September 1991. Intrapartum complications classically associated with grand multiparity (abruptio placentae, dysfunctional labor, fetal malpresentation, postpartum hemorrhage, and shoulder dystocia) were compared. RESULT: Both groups had comparable antepartum complications and gestational ages at delivery. The overall intrapartum complication incidence for grand multiparous women was 33% (127/382 patients), not significantly different from that of the control multiparous women, 27% (103/382). Grand multiparity was associated with an increased incidence of macrosomia (16% vs 11%) and a decreased incidence of operative delivery (14% vs 21%). Macrosomia increased the incidence of intrapartum complications from 31% to 46% (p < 0.03) in the grand multiparous patients, and a trend was observed in the multiparous patients, from 26% to 37%. However, when properly controlled, this was noted to be a confounding variable and was not related to parity. CONCLUSIONS: In a largely Hispanic population grand multiparous patients do not have an increased incidence of intrapartum complications.

Adult

Comparisons between the effects of 5-HT and DL-fenfluramine on food intake and gastric emptying in the rat.

5-Hydroxytryptamine (5-HT) dose-dependently increased gastric emptying in rats, whereas DL-fenfluramine produced a biphasic dose response curve for gastric emptying. Thus, fenfluramine increased gastric emptying at a dose of 0.1 mg/kg but decreased it at doses of 1 and 3 mg/kg. Both 5-HT and DL-fenfluramine produced significant decreases in food intake. As 5-HT produced opposing effects on gastric emptying and food intake, it appears that the anorectic effect of 5-HT may not depend on changes in the rate of gastric emptying. In contrast, doses of DL-fenfluramine that decreased feeding also decreased gastric emptying, which suggests that reduced food intake may at least partly result from decreased gastric emptying. Taken together, these results suggest that the effects of 5-HT and DL-fenfluramine on feeding and gastric emptying may be mediated by different mechanisms.

Animals

The effect of anticonvulsant drugs on GABA-stimulated chloride uptake.

Eight anticonvulsant drugs-including clonazepam, diazepam and phenobarbital-were tested for their effects on GABA-stimulated chloride uptake in rat cerebral cortical microsacs (unfiltered synaptoneurosomes). "Mid" and "high" therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response tests were done. In the initial screens, enhancement of GABA-stimulated uptake was found only with phenobarbital, clonazepam and diazepam. In subsequent concentration-response tests, the effects of phenobarbital were found to occur throughout the range of normal, anticonvulsant concentrations, whereas the effects of clonazepam and diazepam were observed only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's anticonvulsant effects are mediated via the GABAA receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism.

Animals

Rat C-reactive protein causes a charge modification of LDL and stimulates its degradation by macrophages.

We have previously shown the binding of low-density lipoprotein (LDL) to immobilized rat C-reactive protein (CRP) and the formation of a fluid-phase complex between these two proteins. In this report we used immunoelectrophoresis and agarose gel electrophoresis to show increased anodic migration of the LDL particle as a result of the modification of LDL by rat CRP. The degradation of the modified 125I-LDL by rat peritoneal macrophages was increased more than twofold in the presence of rat CRP. The increase in rat CRP-mediated 125I-LDL degradation by macrophages was dependent on the concentrations of 125I-LDL and rat CRP. This increased 125I-LDL degradation was inhibited by phosphorylcholine. In contrast, the degradation of 125I-acetyl-LDL by macrophages was not affected by rat CRP, although acetylated LDL inhibited the rat CRP-stimulated degradation of 125I-LDL. Increasing concentrations of LDL did not affect the degradation of rat 125I-CRP by the macrophages, which suggested that the rat CRP and the modified LDL did not enter the cell as a complex. Our results suggested that the increased degradation of 125I-LDL was caused by the charge modification of 125I-LDL by rat CRP, due to a fluid-phase complex formation between 125I-LDL and rat CRP, and that the degradation involved the scavenger receptor present on the macrophages.

Animals

Selective dopamine D-1 receptor agonists, SK&F 38393 and CY 208-243 reduce sucrose sham-feeding in the rat.

Gastric-fistulated rats were trained to sham-feed a 10% sucrose solution in a 60 min test. The selective dopamine D-1 receptor agonists, SK&F 38393 (3 and 10 mg/kg, s.c.) and CY 208-243 (1 and 3 mg/kg, s.c.) both produced dose-related reductions in sham-feeding. These effects were present in the first 5 min of the test period, and persisted throughout the remainder of the test. The data confirm and extend results for an anorectic effect of SK&F 38393 and demonstrate, for the first time, a similar anorectic effect of CY 208-243.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben

A microstructural analysis of the effects of presatiation on feeding behavior in the rat.

Rats were familiarized with eating a sweetened mash, and were divided into three groups. Before a test meal, the animals were allowed to eat the mash for 0, 2.5, or 5 min, respectively, to vary the degree of their satiation. Their subsequent consumption of the meal and their behavior over the course of a 30-min period was observed, to provide a microstructural description of the behavioral changes that are characteristic of increasing satiation. Presatiation, as expected, reduced the size of the test meal, and did so predominantly by reducing the duration of feeding, especially during the first 5 min of the test period. There was a slight reduction in the rate of eating as a function of presatiation, and a tendency for the latency to initiate feeding to increase. When other responses were considered separately, there was little effect of presatiation on their microstructural parameters. However, the duration of a composite category (comprising rearing, grooming, and stationary) did increase significantly as a function of presatiation. These data provide a behavioral template for satiation, against which to compare treatments that purport to manipulate feeding satiation.

Animals

Vitamin K coagulation status in surgical newborns and the risk of bleeding.

The vitamin K coagulation status in surgical newborns, who may be at increased risk of developing hypocoagulability and hemorrhage, has not previously been studied. Therefore, we measured the combined activity of the plasma vitamin K-dependent coagulation factors (Thrombotest), total prothrombin, PIVKA II, plasma vitamin K1, fibrinogen, D-Dimer, and platelets in 49 newborns admitted to a neonatal surgical intensive care unit. All infants had significant pathology, and treatment involved surgery in all but two. Twenty-three infants (47%) underwent surgery on two or more occasions. Intravenous or oral antibiotics were used in all patients and many received more than one course. All infants had vitamin K1 prophylaxis at birth. At day 0 (date of birth), the mean Thrombotest and total prothrombin levels were 51% (range, 20% to 100%) and 40% (range, 24% to 59%), respectively. Coagulation activity decreased on day 1 (P > .1) and was followed by a graduate increase in clotting activity, reaching normal adult levels (> 60%) at day 5 for Thrombotest and day 24 for total prothrombin. Only three infants had a Thrombotest less than 20%. PIVKA II was detected in 20 cases (41%). However, levels were within normal limits (< 0.9%) in 17 of these, and between 1.0 and 4.8% in the remaining three infants. There was no relationship between elevated PIVKA levels and coagulation activity in these patients. Plasma vitamin K1 was very high, particularly in the first days of life.(ABSTRACT TRUNCATED AT 250 WORDS)

Birth Weight