Biomedical subjects

C B Lawrence

Publications and source records attributed to C B Lawrence.

At least 19 recordsLinked to original sources

PubMed2002

Centrally administered galanin-like peptide modifies food intake in the rat: a comparison with galanin.

Galanin-like peptide (GALP) is a recently identified neuropeptide that shares sequence homology with the orexigenic neuropeptide, galanin. In contrast to galanin, GALP is reported to bind preferentially to the galanin receptor 2 subtype (GalR2) compared to GalR1. The aim of this study was to determine the effect of GALP on feeding, body weight and core body temperature after central administration in rats compared to the effects of galanin. Intracerebroventricular (i.c.v.) injection of GALP (1 micro g-10 micro g) significantly stimulated feeding at 1 h in both satiated and fasted Sprague-Dawley rats. However, 24 h after GALP injection, body weight gain was significantly reduced and food intake was also usually decreased. In addition, i.c.v. GALP caused a dose-related increase in core body temperature, which lasted until 6-8 h after injection, and was reduced by peripheral administration of the cyclooxygenase inhibitor, flurbiprofen (1 mg/kg). Similar to GALP, i.c.v. injection of galanin (5 micro g) significantly increased feeding at 1 h in satiated rats. However, there was no difference in food intake and body weight at 24 h, and galanin only caused a transient rise in body temperature. Thus, similar to galanin, GALP has an acute orexigenic effect on feeding. However, GALP also has an anorectic action, which is apparent at a later time. Therefore, GALP has complex opposing actions on energy homeostasis.

Animals↗

PubMed2001

Enhanced disease resistance conferred by expression of an antimicrobial magainin analog in transgenic tobacco.

Magainins are a group of short peptides originally isolated from frog skin and thought to function as a natural defense mechanism against infection due to their antimicrobial properties. The engineered magainin analog peptide Myp30 was found to inhibit spore germination of the oomycete, Peronospora tabacina (Adam) in vitro, and the growth of a bacterial pathogen Erwinia carotovora subsp. carotovora (Jones). Transgenic tobacco (Nicotiana tabacum L.) plants expressing Myp30 were evaluated for resistance to these pathogens. The expression of the peptide only to an extracellular location resulted in significant reduction in sporulation and lesion size due to P. tabacina infection. A significant increase in resistance to the bacterial pathogen was also observed regardless of the targeting location of the peptide.

Antimicrobial Cationic Peptides↗

PubMed2001

Anorexic but not pyrogenic actions of interleukin-1 are modulated by central melanocortin-3/4 receptors in the rat.

The cytokine interleukin-1 (IL-1), which mediates many responses to infection and injury, induces anorexia and fever through direct actions in the central nervous system. The melanocortin neuropeptides, such as alpha melanocyte-stimulating hormone (alpha-MSH), reportedly antagonize many actions of IL-1, including fever and anorexia. However, it is unknown whether endogenous melanocortins modulate anorexia induced by IL-1. The objective of the present study was to establish the effect of endogenous melanocortins on IL-1-induced anorexia and fever in the rat. Intracerebroventricular (i.c.v.) injection of IL-1beta caused a significant reduction in food intake and body weight gain, and a rise in core body temperature in conscious rats. Coadministration of the melanocortin-3/4 receptor (MC3/4-R) antagonist, SHU9119, reversed IL-1beta-induced reductions in food intake and body weight, but did not affect the febrile response to IL-1beta. These data suggest IL-1beta may elicit its effects on food intake through the melanocortin system, predominantly via the MC3-R or MC4-R. In contrast, IL-1beta-induced fever does not appear to be mediated or modulated by MC3-R or MC4-R activity.

Animals↗

PubMed2000

The yeast polyadenylate-binding protein (PAB1) gene acts as a disease lesion mimic gene when expressed in plants.

We have expressed the gene (PAB1) encoding the yeast polyadenylate-binding protein (Pab1p) in tobacco. Plants that accumulate the Pab1p display a range of abnormalities, ranging from a characteristic chlorosis in leaves to a necrosis and large inhibition of growth. The severity of these abnormalities reflects the levels of yeast Pab1p expression in the transgenic plants. In contrast, no obvious differences could be seen in callus cultures between the transgene and vector control. Plants that display PAB-associated abnormalities were resistant to a range of plant pathogens, and had elevated levels of expression of a pathogenesis-related gene. These two properties--impairment of growth and induction of defense responses--indicate that the yeast PAB1 gene can act as a disease lesion mimic gene in plants.

Cell Division↗

PubMed2000

Alternative role for prolactin-releasing peptide in the regulation of food intake.

Prolactin-releasing peptide (PrRP) is a peptide ligand for the human orphan G-protein-coupled receptor hGR3/GPR10 and causes the secretion of prolactin from anterior pituitary cells. However, the lack of immunoreactive staining for PrRP in the external layer of the median eminence seems to rule out this peptide as a classical hypophysiotropic hormone and, furthermore, PrRP is less effective than another inducer of prolactin secretion, thyrotropin-releasing hormone, both in vitro and in vivo. Here we show a reduction in the expression of PrRP mRNA during lactation and fasting and an acute effect of PrRP on food intake and body weight, supporting the hypothesis of an alternative role for the peptide.

Animals↗

PubMed1999

Hypothalamic control of feeding.

Our understanding of the hypothalamic control of energy homeostasis has increased greatly since the discovery of leptin, the adipose cell derived protein. Recent studies have identified several new hypothalamic neuropeptides that affect food intake and energy balance. By studying these molecules and their neuronal systems, receptors and interactions, we are beginning to unravel the circuitry between peripheral adipogenic signals and hypothalamic effector pathways.

Animals↗

PubMed1998

Genes from mycoparasitic fungi as a source for improving plant resistance to fungal pathogens.

Disease resistance in transgenic plants has been improved, for the first time, by the insertion of a gene from a biocontrol fungus. The gene encoding a strongly antifungal endochitinase from the mycoparasitic fungus Trichoderma harzianum was transferred to tobacco and potato. High expression levels of the fungal gene were obtained in different plant tissues, which had no visible effect on plant growth and development. Substantial differences in endochitinase activity were detected among transformants. Selected transgenic lines were highly tolerant or completely resistant to the foliar pathogens Alternaria alternata, A. solani, Botrytis cinerea, and the soilborne pathogen Rhizoctonia solani. The high level and the broad spectrum of resistance obtained with a single chitinase gene from Trichoderma overcome the limited efficacy of transgenic expression in plants of chitinase genes from plants and bacteria. These results demonstrate a rich source of genes from biocontrol fungi that can be used to control diseases in plants.

Base Sequence↗

PubMed1998

Interleukin-1 beta and interleukin-1 receptor antagonist do not affect glutamate release or calcium entry in rat striatal synaptosomes.

The cytokine interleukin-1 beta (IL-1 beta) has been implicated in various forms of neurodegeneration, and several lines of evidence indicate that it also modulates synaptic transmission in the central nervous system. Excessive release of the excitatory neurotransmitter L-glutamate results in cell death and probably mediates many neurodegenerative conditions. We set out to test the hypothesis that involvement of IL-1 beta in neurodegeneration results in some interaction with excitatory amino acid-mediated synaptic transmission in the rat striatum, either by modifying glutamate release or actions. Presynaptic effects of IL-1 beta and the IL-1 receptor antagonist (IL-1ra) on glutamate release and calcium entry were investigated in isolated nerve terminals (synaptosomes) prepared from the striatum. In order to evaluate the involvement of IL-1 in neuronal damage caused by glutamate receptor over-activation, the effect of IL-1ra was studied on N-methyl-D-aspartate (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor-mediated brain damage in the rat striatum and cortex in vivo. Neither rat recombinant IL-1 beta (rrIL-1 beta: 0.01-2 nM) or human recombinant IL-1ra (hrIL-1ra: 0.2 microM) had any significant effect on the KCl-evoked glutamate efflux or calcium entry in striatal synaptosomes, indicating that their actions are unlikely to be presynaptic. In contrast, intrastriatal infusion of hrIL-1ra markedly inhibited (by 43-46%, P < 0.05) neuronal damage caused by striatal NMDA or AMPA receptor activation in the rat in vivo, whereas no effect was seen on damage induced in the cortex. Thus, our data suggest that IL-1 beta and IL-1ra influence neuronal damage in the striatum by acting to modify events that occur after excitatory amino acid receptor activation.

Animals↗

PubMed1998

Interleukin-1beta and the interleukin-1 receptor antagonist act in the striatum to modify excitotoxic brain damage in the rat.

The cytokine interleukin-1 (IL-1) has been implicated in ischaemic, traumatic and excitotoxic brain damage. The results presented here reveal novel actions of IL-1 in the striatum which markedly exacerbate cortical neuronal damage elicited by local excitotoxins in the striatum or cortex. Intrastriatal infusion of IL-1 receptor antagonist, IL-1ra, markedly inhibited striatal neuronal damage caused by N-methyl-D-aspartate (NMDA) or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor activation in the rat. In contrast, intracortical infusion of IL-1ra failed to inhibit NMDA or AMPA receptor-induced damage in the cortex. Intrastriatal co-infusion of IL-1 with the NMDA or AMPA receptor agonist did not affect local striatal damage induced by activation of either glutamate receptor subtype, but caused extensive cortical damage when administered into the striatum with AMPA. This secondary damage was significantly reduced by pretreatment with the NMDA receptor antagonist (MK-801), which did not affect local (striatal) damage caused by AMPA. Infusion of IL-1beta into the striatum (but not the cortex) markedly enhanced cortical damage caused by infusion of an NMDA or AMPA receptor agonist into the cortex. These data reveal selective actions of IL-1 and IL-1ra in the striatum, which influence cortical neuronal loss and suggest that IL-1 selectively enhances damage caused by AMPA receptor activation.

Animals↗

PubMed1997

Short-day weight loss and effect of food deprivation on hypothalamic NPY and CRF mRNA in Djungarian hamsters.

The effect of food deprivation on hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) gene expression in the Djungarian hamster was quantified by in situ hybridization. Hamsters housed in short days (SD) for 18 wk decreased body weight by 40% and exhibited 200% increases in both NPY and CRF mRNA when deprived of food for 24 h. Prior gonadectomy in long days (LD) affected neither basal gene expression nor the induction of gene expression by food deprivation. Gene expression in juvenile LD hamsters similar in body weight to SD animals was relatively insensitive to food deprivation of either 24- or 48-h duration or to subsequent refeeding. In juvenile hamsters, food deprivation for 24 but not 48 h decreased ob (obese) gene expression in inguinal but not epididymal white adipose tissue; ob mRNA levels were restored by refeeding. All food-deprived hamsters had reduced plasma insulin concentrations, but plasma cortisol was only elevated in SD food-deprived animals. NPY gene expression was also increased after daily dexamethasone injections in adult LD hamsters. These results suggest that the neuroendocrine consequences of food deprivation in SD Djungarian hamsters are determined by some factor other than absolute body mass such as the size of adipose tissue reserves.

Animal Feed↗

PubMed1996

Regulation of galanin gene expression in the hypothalamic paraventricular nucleus of the obese Zucker rat by manipulation of dietary macronutrients.

Lean and obese male Zucker rats were fed high fat (72% of energy as fat), high carbohydrate (66% of energy as carbohydrate) or intermediate diets for 4 weeks commencing 1 week after weaning. We examined the effects of these diets on growth rates, plasma insulin and corticosterone titres, and hypothalamic gene expression of 3 appetite-related neuropeptides. Messenger RNA levels for neuropeptide Y (NPY), galanin (GAL) and corticotropin-releasing factor (CRF) in critical hypothalamic locations were measured by in situ hybridization in each brain. Obese rats grew more rapidly and had elevated plasma insulin and corticosterone concentrations relative to their lean littermates. The obese phenotype was also associated with elevated NPY gene expression in the arcuate nucleus of the hypothalamus and increased GAL gene expression in the hypothalamic paraventricular nucleus. There was no effect of diet on NPY or CRF gene expression in either lean or obese rats. However, maintenance on the high fat diet had a significant effect on GAL gene expression in obese but not lean rats: high fat diet significantly reduced mRNA levels in the obese rats. This reduction in GAL mRNA was accompanied by attenuation of the hyperinsulinemia that is characteristic of this genetic obesity.

Animals↗

PubMed1996

Localization of leptin receptor mRNA and the long form splice variant (Ob-Rb) in mouse hypothalamus and adjacent brain regions by in situ hybridization.

Expression of the leptin receptor gene has been examined in mouse hypothalamus and other brain regions by in situ hybridization. With a probe recognizing all the known splice variants, receptor mRNA was evident in several brain regions (cortex, hippocampus, thalamus), with strong expression in the hypothalamus (arcuate, ventromedial, paraventricular and ventral premammillary nuclei), choroid plexus and leptomeninges. A probe specific to the long splice variant of the leptin receptor (Ob-Rb), containing the putative intracellular signaling domain, again revealed strong expression in the hypothalamus; there was, however, minimal hybridization to choroid plexus and leptomeninges. These results indicate that the hypothalamus is a key site of leptin action, although other brain regions are also targeted.

Alternative Splicing↗

PubMed1996

A graph conceptual model for developing Human Genome Center databases.

We have developed a representation of genome data which has proven itself useful for describing data at a Human Genome Center. Genomic data have a graph-like structure and representing the concepts and relationships of genetics as a graph simplifies the development of databases for genome laboratories. Graphs are a comfortable communication medium for biologists and computer scientists and graph diagrams assist in the development of databases by facilitating the exchange of expertise. We have tailored a graph language for modeling genomic data and describe our process of using graphs to develop genome databases.

Computer Graphics↗

PubMed1996

Hypothalamic NPY and CRF gene expression in the food-deprived Syrian hamster.

Because the Syrian hamster, Mesocricetus auratus, does not increase food intake in response to food deprivation, we investigated whether hypothalamic NPY gene expression in this species was sensitive to this imposed state of negative energy balance. In the rat, food deprivation for 48 h resulted in a 150% increase in total preproNPY gene expression in the arcuate nucleus of the hypothalamus (ARC). NPY gene expression in food-deprived Syrian hamsters did not differ significantly from that of ad lib-fed controls, although there was a trend towards increased mRNA levels in the fasted animals. However, food deprivation for 48 h was associated with a rise in preproCRF mRNA in the paraventricular nucleus of the hypothalamus (PVN) of 80-g, but not 150-g, hamsters. The expected reductions in plasma insulin accompanied food deprivation in the Syrian hamster, but cortisol titre was only elevated in the lower body weight group. NPY gene expression in the Syrian hamster appeared, however, to be sensitive to glucocorticoids; daily administration for 28 days of the synthetic glucocorticoid, dexamethasone, increased ARC NPY mRNA levels by 43%. The response of NPYergic and other hypothalamic neuropeptide systems to food deprivation, and the involvement of neuroendocrine substrates in energy homeostasis, may vary between species.

Animals↗

PubMed1996

Coexpression of leptin receptor and preproneuropeptide Y mRNA in arcuate nucleus of mouse hypothalamus.

Leptin, the protein product of the adipose tissue-specific ob (obese) gene (1), reduces the body weight, adiposity and food intake of obese ob/ob mice on peripheral or central injection (2, 3, 4). [125I]leptin binding has been detected in mouse choroid plexus (5), from which a leptin receptor gene was expression cloned (5). The gene has at least 6 splice variants (6, 7). Leptin receptor mRNA was localized in the hypothalamus by in situ hybridization being particularly abundantly expressed in the arcuate nucleus (8). There is evidence linking the physiological effects of injected leptin with hypothalamic neuropeptide Y (9, 10) (NPY), which has potent central effects on food intake and energy balance (11), and is also expressed in the arcuate nucleus. Here we report dual in situ hybridization studies for leptin receptor and NPY gene expression in the mouse arcuate nucleus, where the majority of cells examined expressed both genes. This provides the first direct evidence that leptin acts on cells that express NPY mRNA.

Animals↗

PubMed1995

Fat mobilisation in short days is not associated with altered noradrenergic sensitivity of adipocytes in Djungarian hamsters.

One of the primary physiological responses of the Djungarian hamster to short photoperiods is a reduction in body weight with fat mobilisation. The depletion of fat to a minimum level may be regulated either in the periphery, through the sensitivity of adipocytes to hormonal stimulation, or centrally, via adjustments in efferent activity. To investigate this, we examined the lipolytic pathway in fat cells from animals at various stages of entrainment to long or short photoperiod. Short photoperiod exposure of up to a 10-week duration was without effect on basal glycerol release by unstimulated cells or on the ability of norepinephrine or an adenosine analogue to stimulate or inhibit lipolysis, respectively. Prolonged exposure to short photoperiod reduced basal glycerol release, but adipocytes retained their sensitivity to hormonal stimulation. Short photoperiod had no effect on the density or affinity of membrane-bound beta-adrenergic or adenosine receptors, or upon the ability of isoproterenol or forskolin to stimulate adenylate cyclase in adipocyte membranes. This suggests that the regulation of fat depletion in short photoperiod is determined centrally and does not involve alterations in adipocyte sensitivity and, in particular, the desensitisation of the adipocyte beta-adrenergic receptor-linked adenylate cyclase pathway.

Adenylyl Cyclase Inhibitors↗

PubMed1995

Hypothalamic NPY and prepro-NPY mRNA in Djungarian hamsters: effects of food deprivation and photoperiod.

Two catabolic states leading to loss of body weight were compared in the Djungarian hamster (Phodopus sungorus campbelli). Hypothalamic neuropeptide Y (NPY) and gene expression for NPY and corticotropin-releasing factor (CRF) were examined after withdrawal of food for 48 h or exposure to short photoperiod for 10 or 20 wk. Food deprivation was accompanied by increases in both NPY and prepro-NPY mRNA in the hypothalamic arcuate nucleus (ARC). Increases in gene expression were limited compared with published data from the rat and were inversely related to predeprivation body weight. Exposure to short photoperiod for 20 wk reduced body weight by 39%, but the activity of the NPY-ergic system was not affected; peptide concentration and gene expression were similar in short photoperiod hamsters and long photoperiod controls. The hypothalamic NPY-ergic system of the Djungarian hamster is sensitive to weight loss due to imposed manipulations of energy balance, but the catabolism observed in short photoperiod gives rise to a body weight that is appropriate to the season encoded by the photoperiod. CRF gene expression was not affected by food deprivation or short photoperiod.

Animals↗

PubMed1995

Identification of human gene structure using linear discriminant functions and dynamic programming.

Development of advanced technique to identify gene structure is one of the main challenges of the Human Genome Project. Discriminant analysis was applied to the construction of recognition functions for various components of gene structure. Linear discriminant functions for splice sites, 5'-coding, internal exon, and 3'-coding region recognition have been developed. A gene structure prediction system FGENE has been developed based on the exon recognition functions. We compute a graph of mutual compatibility of different exons and present a gene structure models as paths of this directed acyclic graph. For an optimal model selection we apply a variant of dynamic programming algorithm to search for the path in the graph with the maximal value of the corresponding discriminant functions. Prediction by FGENE for 185 complete human gene sequences has 81% exact exon recognition accuracy and 91% accuracy at the level of individual exon nucleotides with the correlation coefficient (C) equals 0.90. Testing FGENE on 35 genes not used in the development of discriminant functions shows 71% accuracy of exact exon prediction and 89% at the nucleotide level (C = 0.86). FGENE compares very favorably with the other programs currently used to predict protein-coding regions. Analysis of uncharacterized human sequences based on our methods for splice site (HSPL, RNASPL), internal exons (HEXON), all type of exons (FEXH) and human (FGENEH) and bacterial (CDSB) gene structure prediction and recognition of human and bacterial sequences (HBR) (to test a library for E. coli contamination) is available through the University of Houston, Weizmann Institute of Science network server and a WWW page of the Human Genome Center at Baylor College of Medicine.

Algorithms↗