PubMed Health⌕ Search

Biomedical subjects

M Sleeman

Publications and source records attributed to M Sleeman.

8 recordsLinked to original sources
PubMed2001

Identification of a new fibroblast growth factor receptor, FGFR5.

A novel fibroblast growth factor receptor (FGFR), designated FGFR5, was identified from an EST database of a murine lymph node stromal cell cDNA library. The EST has approximately 32% identity to the extracellular domain of FGFR1-4. Library screening with this EST identified two full-length alternative transcripts which we designated as FGFR5 beta and FGFR5 gamma. The main difference between these transcripts is that FGFR5 beta contains three extracellular Ig domains whereas FGFR5 gamma contains only two. A unique feature of FGFR5 is that it does not contain an intracellular tyrosine kinase domain. Predictive structural modelling of the extracellular domain of FGFR5 gamma suggested that it was a member of the I-set subgroup of the Ig-superfamily, consistent with the known FGFRs. Northern analysis of mouse and human FGFR5 showed detectable mRNA in a broad range of tissues, including kidney, brain and lung. Genomic sequencing identified four introns but identified no alternative transcripts containing a tyrosine kinase domain. Extracellular regions of FGFR5 beta and 5 gamma were cloned in-frame with the Fc fragment of human IgG(1) to generate recombinant non-membrane bound protein. Recombinant FGFR5 beta Fc and R5 gamma Fc demonstrated specific binding to the ligand FGF-2, but not FGF-7 or EGF. However, biological data suggest that FGF-2 binding to these proteins is with lower affinity than its cognate receptor FGFR2C. The above data indicate that this receptor should be considered as the fifth member of the FGFR family.

3T3 Cells↗
PubMed1993

Growth, nitrogen metabolism, and cardiac responses to clenbuterol and ketoclenbuterol in rats and underfed cattle.

Two beta-adrenoceptor agonists, clenbuterol and ketoclenbuterol, were examined for their effects on growth and cardiac tissue. In female rats, clenbuterol caused a 48% increase in weight gain (P < .05), with improved feed efficiency (26%; P < .1) and increased muscle mass (9%; P < .1). Ketoclenbuterol had less effect on weight gain (30%) and feed efficiency (16%) and did not increase muscle mass. Next we studied the adverse cardiovascular effects of these compounds. Neither drug increased the force of contraction of isolated rat ventricular papillary muscle. Clenbuterol was potent at causing an increase in the rate of contraction of isolated rat atria, and when fed to cattle over 2 d, the drug caused heart rate to increase by 92 to 117%. In contrast, ketoclenbuterol was not a potent stimulator of atrial rate in the rat, and in cattle it caused a smaller increase in heart rate than clenbuterol (12 to 27%). Finally, cattle that were underfed to simulate dry-season tropical pasture conditions were treated with clenbuterol or ketoclenbuterol for 35 d. Ketoclenbuterol caused no beneficial changes in N metabolism. The results obtained with clenbuterol were equivocal, and might have been confounded partly by the refusal of some treated animals to eat all the feed offered. Although clenbuterol did not cause a reduction in total urinary N output relative to control animals, marked reductions in plasma urea concentrations and in urea synthesis were observed (23 to 53%; P < .001). We conclude that ketoclenbuterol is not effective for attenuation of dry-season protein loss in cattle. Clenbuterol seems to be less effective in underfed cattle than in well-fed cattle, and further evidence is required to judge whether compounds of this nature are likely to benefit tropical cattle under harsh grazing conditions.

Adrenergic beta-Agonists↗
PubMed1989

Changes in food intake and stomach contents of tumor-bearing rats after treatment with dopamine antagonists.

The appetite-stimulating (orexigenic) potential of the peripheral dopamine (DA) receptor antagonist domperidone was compared with that of the central DA antagonist pimozide in anorexic, tumor-bearing rats. DA antagonists were administered via the intraperitoneal route on Days 7-15 after the subcutaneous implantation of the Walker 256 carcinosarcoma. The doses of domperidone injected were 0.05 and 0.1 mg/kg once daily and 0.1 mg/kg twice daily. The dose of pimozide given was 0.1 mg/kg daily. While all doses of DA antagonists caused an initial drop in body weight and food intake, the body weight of pimozide-injected animals was not reduced significantly (in the early stages of drug treatment) as it was with the various doses of domperidone. There was significantly more food in the stomachs of domperidone- and pimozide-treated animals compared with those of the vehicle-treated, tumor-bearing animals at the time of sacrifice. These results indicate that short- and long-term satiety factors, in addition to gastric motility, should be considered when assessing the orexigenic potential of various drugs.

Animals↗
PubMed1988

Observations on dopamine receptor antagonists and gastric ulceration associated with experimental anorexia cachexia.

Gastric ulceration is frequently reported to occur in tumour-bearing animals and man, even when such tumours are not associated with organs of digestion. That central and peripheral dopamine (DA) containing neurones may be relevant to this phenomenon, is supported by the fact that the DA receptor antagonists domperidone (0.1 and 0.05 mg/kg) and pimozide (0.1 mg/kg) were observed to prevent gastric ulceration commonly reported in rats bearing the Walker 256 carcinosarcoma. Daily administration of these drugs prevented the formation of ulcers similar to those observed in vehicle-treated animals. These results demonstrate that DA neurone function is important in the formation of gastric ulcers in tumour-bearing animals and suggest that such compounds may be useful in cancer management.

Animals↗
PubMed1988

Facilitation of cancer-associated anorexia by cholecystokinin.

Cholecystokinin octapeptide (CCK-8, 5 micrograms/kg) was injected i.p. into male Sprague-Dawley rats bearing the Walker 256-carcinosarcoma, or into non-tumour bearing controls, on a 20-h food deprivation schedule. Food and water intake and body weight maintenance were monitored for 15 days after tumour implantation and compared to that of tumour-bearing animals not injected with CCK-8. Food intake was significantly reduced for the duration of the two 4-day periods of CCK-8 injection, indicating that behavioural tolerance to this peptide did not occur. The severity of anorexia and body weight loss in tumour-bearing animals was significantly greater than that observed in non-tumour bearing controls, for the first 13 days of observation. These results indicate that endogenous peptides, such as CCK, may function in tumour-bearing animals to enhance the anorexia and wasting which typifies the anorexia cachexia syndrome.

Animals↗
PubMed1987

Further studies on the neurochemical specificity of 6-hydroxydopamine as compared to radiofrequency lesions.

Despite the large volume of literature during the past 15 years addressing the problem concerning the neurochemical specificity of 6-hydroxydopamine (6-OHDA), there is still disagreement over this issue. While some claim that the catecholamine-specific effects of this drug can be maximized by controlling the dose injected, others claim that all doses of 6-OHDA produce non-specific damage (NSD), thereby contraindicating its use in experimental paradigms. In the present study, we examined the degree of neurochemical specificity of 6-OHDA by comparing the volume of proximal accumulation to that of NSD, produced by 6-OHDA (2 microliter of 8 micrograms/microliter) or radiofrequency (RF) lesions (60 degrees C for 50 s and 45 degrees C for 30 s), placed in the medial forebrain bundle. The volume of NSD and accumulation produced by 6-OHDA was significantly less than that produced by large RF lesions which had a similar effect on the gross behaviour of albino rats. Smaller RF lesions produced similar volumes of NSD but less amine accumulation than did 6-OHDA, and did so without affecting normal behaviour. The ratio of NSD to accumulation in 6-OHDA treated rats was 3/1, while large and small RF lesions produced a NSD/accumulation ratio of 15/1. The present study introduces a novel method of determining the degree of neurochemical specificity which can be achieved with 6-OHDA and reveals that it is several magnitudes more neurochemically specific than RF lesions.

Animals↗
PubMedDate not supplied

Cholecystokinin, behavioral tolerance and tumor-induced anorexia.

Cholecystokinin octapeptide (CCK-8, 5 micrograms/kg, IP) was injected daily, for two 4-day periods, into rats bearing the Walker 256 carcinosarcoma (TB) and non-tumor bearing (NTB) control animals. All animals were on a 20 hr food and water deprivation schedule and monitored for food and water intake and bodyweight for 4 hr daily. Food intake was significantly reduced by the daily administration of CCK. Behavioral tolerance to CCK was not observed in either the NTB or TB rats. These results indicate that the parameters describing the phenomenon of behavioral tolerance to CCK are yet to be clearly defined and that peptides other than CCK may underlie the mechanism primarily responsible for producing anorexia associated with cancer.

Animals↗