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Biomedical subjects

C Bishop

Publications and source records attributed to C Bishop.

At least 19 recordsLinked to original sources
PubMed2005

Inhibition of in-stent restenosis in rabbit iliac arteries with photodynamic therapy.

OBJECTIVES: Photodynamic therapy (PDT, the combination of light with a photosensitising drug in the presence of oxygen) inhibits restenosis after angioplasty without stenting. This study assesses the potential of PDT for prevention of in-stent re-stenosis. DESIGN AND METHODS: Normal rabbits were given the photosensitising agent 5-aminolaevulinic acid (ALA) 60 mg/kg, 3 h prior to endovascular illumination of the iliac artery (635 nm at 50 J/cm(2)) either immediately before or after deployment of an oversized (3 mm diameter) stent. PDT treated arteries were retrieved 3 or 28 days later and assessed for cell counts and vascular morphometry. Control arteries (stent but no PDT) were examined at 28 days. RESULTS: There were no adverse events and all vessels were patent at the end of the study. At 3 days there was almost complete medial cell ablation when light was delivered before stent deployment (17+/-1 cells/hpf), with little effect when illumination followed stent deployment (184+/-17 cells/hpf, p<0.0001). Twenty-eight days after PDT, the neointimal areas were 1.41+/-0.52 mm(2) (stent with no PDT), 1.24+/-0.54 mm(2) (light after stent) and 0.60+/-0.21 mm(2) (light before stent) (p=0.004). CONCLUSIONS: PDT before stent deployment caused almost complete medial cell ablation at 3 days with inhibition of in-stent restenosis at 28 days. PDT is worthy of further study as an adjuvant to percutaneous intervention in patients with vascular disease.

Aminolevulinic Acid↗
PubMed2003

Combined intrastriatal dopamine D1 and serotonin 5-HT2 receptor stimulation reveals a mechanism for hyperlocomotion in 6-hydroxydopamine-lesioned rats.

Loss of dopaminergic innervation to the striatum increases the sensitivity of dopamine (DA) D1 and serotonin (5-HT) 5-HT2 receptor signaling. Previous work from our laboratory has shown that systemic co-administration of D1 and 5-HT2 receptor agonists leads to the synergistic overexpression of striatal preprotachykinin mRNA levels in the DA-depleted, but not intact animals. In the present study, we examined this mechanism as related to locomotor behavior. Adult male Sprague-Dawley rats were subject to bilateral i.c.v. 6-hydroxydopamine (6-OHDA; 200 microg in 10 microl/side) or vehicle (0.9% saline and 0.1% ascorbic acid). After 3 weeks, rats were tested for locomotor responses to bilateral intrastriatal infusions of vehicle (0.9% NaCl), the D1 agonist SKF82958 [(+/-)6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetra-hydro-(1H)-3-benzazepine hydrobromide; 0.1, 1.0 or 10.0 microg/side], the 5-HT2 agonist DOI [(+/-)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane; 0.1, 1.0 or 10.0 microg/side] or subthreshold doses of DOI and SKF82958 (0.1 microg+0.1 microg in 0.8 microl/side). Rats with DA loss demonstrated supersensitive locomotor responses to SKF82958, but not DOI. Combined administration of subthreshold SKF82958 and DOI doses (0.1 microg+0.1 microg) synergistically increased locomotor behavior only in 6-OHDA-lesioned rats. These effects were blocked by either the D1 antagonist SCH23390 3-methyl-1-phenyl-2,3,4,5-tetrahydro-7-chloro-8-hydroxy-(1H)-3-benzazepine or the 5-HT2 antagonist ritanserin (each 1.0 microg in 0.8 microl/side). The results of this study suggest that the behavioral synergy induced by local co-stimulation of D1 and 5-HT2 receptors within the 6-OHDA-lesioned striatum may lead to hyperkinesias that can occur with continued pharmacological treatment of Parkinson's disease.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Hypothalamic paraventricular nucleus injections of urocortin alter food intake and respiratory quotient.

Corticotropin releasing hormone (CRH) acts on the central nervous system to alter energy balance and influence both food intake and sympathetically-mediated thermogenesis. CRH is also reported to inhibit food intake in several models of hyperphagia including neuropeptide Y (NPY)-induced eating. The recently identified CRH-related peptide, urocortin (UCN), also binds with high affinity to CRH receptor subtypes and decreases food intake in food-deprived and non-deprived rats. The present experiment characterized further the feeding and metabolic effects of UCN by examining its impact after direct injections into the paraventricular nucleus (PVN) of the hypothalamus. In feeding tests (n=8), UCN (50-200 pmol) was injected into the PVN at the onset of the dark cycle and food intake was measured 1, 2 and 4 h postinjection. In separate rats (n=8), the metabolic effects of UCN were monitored using an open circuit calorimeter which measured oxygen consumption (V(O2)) and carbon dioxide production (V(CO2)). Respiratory quotient (RQ) was calculated as V(CO2)/V(O2). UCN suppressed feeding at all times studied and reliably decreased RQ within 30 min of infusion. Additional work examined the effect of UCN (50-100 pmol) pretreatment on the feeding and metabolic effects of NPY. NPY, injected at the start of the dark period, reliably increased 2 h food intake. This effect was blocked by PVN UCN administration. Similarly, UCN blocked the increase in RQ elicited by NPY alone. These results suggest that UCN-sensitive mechanisms within the PVN may modulate food intake and energy substrate utilization, possibly through an interaction with hypothalamic NPY.

Animals↗
PubMed2001

Whole-body metabolism varies across the estrous cycle in Sprague-Dawley rats.

Food intake in rats and other mammals is lowest at estrus and highest at diestrus. While much is known about the effects of different estrous phases on energy intake, as well as some of the metabolic effects the associated hormones exert, little has been reported about changes in whole-body metabolism that accompany those phases. This study investigates how energy expenditure (EE) and respiratory quotient (RQ) vary in intact female Sprague-Dawley rats (n=12) tested mid-light cycle over 2 h on days associated with estrus vs. diestrus. Rats showed small but reliable decreases in body weight on days associated with estrus, but not diestrus. EE was significantly increased by approximately 21% on the day associated with estrus compared to diestrus. At the same time, RQ was significantly decreased by approximately 7% on the day associated with estrus, indicating a relative shift to fat over carbohydrate as the energy substrate to support energetic needs. Future investigations of ingestive processes can integrate the present findings to investigate how gender differences in feeding and metabolism contribute to regulatory behaviors.

Animals↗
PubMed2001

A Y-encoded subunit of the translation initiation factor Eif2 is essential for mouse spermatogenesis.

In mouse and man, deletions of specific regions of the Y chromosome have been linked to early failure of spermatogenesis and consequent sterility; the Y chromosomal gene(s) with this essential early role in spermatogenesis have not been identified. The partial deletion of the mouse Y short arm (the Sxrb deletion) that occurred when Tp(Y)1CtSxr-b (hereafter Sxrb) arose from Tp(Y)1CTSxr-b (hereafter Sxra) defines Spy, a Y chromosomal factor essential for normal spermatogonial proliferation. Molecular analysis has identified six genes that lie within the deletion: Ube1y1 (refs. 4,5), Smcy, Uty, Usp9y (also known as Dffry), Eif2s3y (also known as Eif-2gammay) and Dby10; all have closely similar X-encoded homologs. Of the Y-encoded genes, Ube1y1 and Dby have been considered strong candidates for mouse Spy function, whereas Smcy has been effectively ruled out as a candidate. There is no Ube1y1 homolog in man, and DBY, either alone or in conjunction with USP9Y, is the favored candidate for an early spermatogenic role. Here we show that introduction of Ube1y1 and Dby as transgenes into Sxrb-deletion mice fails to overcome the spermatogenic block. However, the introduction of Eif2s3y restores normal spermatogonial proliferation and progression through meiotic prophase. Therefore, Eif2s3y, which encodes a subunit of the eukaryotic translation initiation factor Eif2, is Spy.

Animals↗
PubMed2001

Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene.

Proteins encoded by the human CYP3A genes metabolize every second drug currently in use. The activity of CYP3A gene products in the general population is highly variable and may affect the efficacy and safety of drugs metabolized by these enzymes. The mechanisms underlying this variability are poorly understood, but they include gene induction, protein inhibition and unknown genetic polymorphisms. To better understand the regulation of CYP3A expression and to provide a basis for a screen of genetic polymorphisms, we determined and analysed the sequence of the human CYP3A locus. The 231 kb locus sequence contains the three CYP3A genes described previously (CYP3A4, CYP3A5 and CYP3A7), three pseudogenes as well as a novel CYP3A gene termed CYP3A43. The gene encodes a putative protein with between 71.5% and 75.8% identity to the other CYP3A proteins. The highest expression level of CYP3A43 mRNA is observed in the prostate, an organ with extensive steroid metabolism. CYP3A43 is also expressed in several other tissues including liver, where it can be induced by rifampicin. CYP3A43 transcripts undergo extensive splicing. The identification of a new member of the CYP3A family and the characterization of the full CYP3A locus will aid efforts to identify the genetic variants underlying its variable expression. This, in turn, will lead to a better optimization of therapies involving the numerous substrates of CYP3A proteins.

Amino Acid Sequence↗
PubMed2000

Posterodorsal amygdala lesions reduce feeding stimulated by 8-OH-DPAT.

Injections of the serotonin (5-HT)(1A) agonist, 8-hydroxy-2(di-n-propylamino)tetralin, (8-OH-DPAT), either systemically or into the midbrain raphe nuclei, elicit food intake in otherwise satiated rats. Lesions of the paraventricular nucleus of the hypothalamus are well known for producing long-term overeating, but past research has excluded this site as a potential locus for short-term 8-OH-DPAT feeding effects. More recent work shows that small lesions of the posterodorsal amygdala (PDA) elicit overeating in their own right. Since this and related regions of the amygdala receive 5-HT innervations from the dorsal raphe nucleus (DRN), we determined if PDA lesions might alter feeding after injecting 8-OH-DPAT into this midbrain region. Adult female rats received either bilateral electrolytic lesions of the PDA or sham lesions. After recording weight gains for over 1 month, all rats were implanted with DRN cannulae, then randomly tested every 3-4 days for 1 h intake of standard lab chow after 0, 0.4, 0.8 or 1.6 nmol injections of 8-OH-DPAT. Additional 90 min measures of intake were also made after 0 vs. 250 microg (760 nmol) 8-OH-DPAT s.c. At the two highest DRN doses tested, lesioned rats showed 50% less intake compared to shams. A similar profile emerged after the single s.c. dose. These results suggest that the PDA may be an important locus at which reduced release of endogenous 5-HT stimulates feeding. Alternatively, the PDA may represent part of a larger brain circuit whose integrity is necessary for eliciting intake in response to a variety of feeding stimuli.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2000

Comparison of the relative effects of 1,24-dihydroxyvitamin D(2) [1, 24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1,24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] on selected vitamin D-regulated events in the rat.

The present experiments were conducted to compare the relative hypercalciuric and hypercalcemic activities of 1,24-dihydroxyvitamin D(2) [1,24-(OH)(2)D(2)], 1,24-dihydroxyvitamin D(3) [1, 24-(OH)(2)D(3)], and 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)] in 7-week-old rats. The rats were dosed orally with each sterol for 7 days at a rate of 1 ng/g body weight/day. We also monitored the effect of the three compounds on the induction of mRNA for CaATPase and for 25-hydroxyvitamin D-24-hydroxylase in the kidney and intestine, on plasma vitamin D metabolite levels, and on the capacity to evoke modification in the vitamin D receptor/retinoic acid X receptor (VDR/RXR) heterodimer conformation. Plasma calcium was elevated in the rats treated with 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3), but not in the 1,24-(OH)(2)D(2)-dosed rats. Urinary calcium was elevated significantly (relative to controls) in all groups. The order of hypercalciuric activity was 1,25-(OH)(2)D(3) >/= 1,24-(OH)(2)D(3) >/= 1,24-(OH)(2)D(2) > control. Duodenal plasma membrane calcium ATPase (PMCA) mRNA was elevated to a similar extent in all groups relative to controls. Duodenal 24-hydroxylase mRNA was elevated in all groups relative to controls; however, the elevations were significantly higher in the 1,24-(OH)(2)D(3) and 1, 25-(OH)(2)D(3) groups compared with the 1,24-(OH)(2)D(2) group. Kidney 24-hydroxylase also was elevated significantly in the 1, 24-(OH)(2)D(3)- and 1,25-(OH)(2)D(3)-treated rats but not in the 1, 24-(OH)(2)D(2)-treated rats. Recombinant human vitamin D receptor (hVDR) extracts were incubated with saturating concentrations of 1, 24-(OH)(2)D(2), 1,24-(OH)(2)D(3), and 1,25-(OH)(2)D(3) and subsequently analyzed by electrophoretic mobility shift assay (EMSA). Overall binding was comparable for all metabolites; however, the 1, 24-(OH)(2)D(2) complex exhibited distinctly altered mobility relative to 1,24-(OH)(2)D(3) and 1,25-(OH)(2)D(3), suggestive of an effect on hVDR/hRXR conformation. These data suggest that 1, 24-(OH)(2)D(2) is not as potent as either of the vitamin D(3) sterols at affecting hypercalcemia or hypercalciuria in young growing rats; however, 1,24-(OH)(2)D(2) can evoke other biological responses similar to the vitamin D(3) sterols. These different responses may be related to the alterations in conformation state of the hVDR/hRXR heterodimer.

Analysis of Variance↗
PubMed2000

Effects of three neurochemical stimuli on delayed feeding and energy metabolism.

Infusions of norepinephrine (NE), the gamma-aminobutyric acid agonist, muscimol (MUS), or neuropeptide Y (NPY) into the paraventricular nucleus (PVN) of the hypothalamus all increase food intake. Such feeding may be due to direct activation of behavioral processes driving ingestion and/or to alterations in nutrient metabolism that feeding serves to normalize. To examine these possibilities, male Sprague-Dawley rats received PVN infusions of vehicle, 20 nmol NE, 1 nmol MUS or 100 pmol NPY at dark onset, then food intake was measured under three feeding conditions: (1) 1 and 2 h immediately after injections, (2) 1 h after a 1 h delay between injections and access to food, and (3) 1 h after a 1 h feeding delay, but with injections occurring just before presenting food. Measures of energy expenditure (EE) and respiratory quotients (RQs) in the absence of food were made over 2 h in parallel experiments. Results confirmed that NE, MUS and NPY all increased dark-onset feeding, but only NPY increased intake above control levels after a 1 h feeding delay. No neurochemically-induced changes in EE were observed, nor were there changes in RQs after NE or MUS. However, NPY reliably enhanced RQs from 30 to 120 min of testing. Our findings imply that NE and MUS initiate relatively immediate, short-term feeding that is not associated with changes in nutrient metabolism and does not summate with cues stimulated by delayed access to food. NPY initiates more protracted feeding temporally linked to enhanced carbohydrate metabolism. This may indicate that part of NPY's feeding stimulatory effects are secondary to physiological processes driving ingestion.

Animals↗
PubMed2000

Imposed vibration influences perceived tactile smoothness.

According to the duplex theory of tactile texture perception, detection of cutaneous vibrations produced when the exploring finger moves across a surface contributes importantly to the perception of fine textures. If this is true, a vibrating surface should feel different from a stationary one. To test this prediction, experiments were conducted in which subjects examined two identical surfaces, one of which was surreptitiously made to vibrate, and judged which of the two was smoother. In experiment 1, the vibrating surface was less and less often judged smoother as the amplitude of (150 Hz) vibration increased. The effect was comparable in subjects who realized the surface was vibrating and those who did not. Experiment 2 showed that different frequencies (150-400 Hz) were equally effective in eliciting the effect when equated in sensation level (dB SL). The results suggest that vibrotaction contributes to texture perception, and that, at least within the Pacinian channel, it does so by means of an intensity code.

Adolescent↗
PubMed1999

Lay health advisor activity levels: definitions from the field.

One type of lay health advisor model assumes that an effective mechanism for reaching the underserved is through informal advice-givers called natural helpers. Despite the growing use of this approach, few programs have defined what an active lay health advisor does within the natural helping process. To explore perceptions and definitions of lay health advisors' activity, we conducted semistructured, in-person interviews with four field staff who coordinate the advisors' activities in a breast cancer screening program. These staff viewed lay health advisor activity as fluctuating over the course of a year, occurring along a continuum of participation (inactive, moderately active, active, and superactive), and reflecting varying degrees of proactivity and participation in multiple activities. These results suggest an empirical process for refining the definition of an active lay health advisor, improving advisors' productivity in achieving outreach objectives, and managing and monitoring their ongoing activities.

Breast Neoplasms↗
PubMed1999

Inter-observer variation. An alternative method of assessing the role of ultrasonic imaging in clinical decision-making in lower limb arterial disease.

BACKGROUND: The aim of the study is to determine the role of duplex scanning in deciding on the final treatment for patients with lower limb arterial disease compared to intra-arterial digital subtraction arteriography (IA DSA). METHODS: Eighty-two patients (55 males, 27 females, mean age 68 years) with lower limb arterial disease had both duplex and arteriography performed. The findings of both modalities were reported by sonographer and radiologist in 164 anonymous reports. Five vascular surgeons (consultant grade) were asked to plan their treatment on the data provided in these reports. For the purposes of statistical analysis, the actual treatment the patient received was used as the reference standard. Both reports and treatment decisions were coded (double blinded). RESULTS: The overall accuracy of duplex scanning to assess arterial disease of the lower limbs showed a sensitivity of 92%, and specificity of 99%. The accuracy of the decisions based on duplex was 84% and kappa with k of 0.62 (95% CI+0.14) compared to the reference standard, while the accuracy of the decision based on arteriography was 85% and kappa 0.63 (95% CI+0.14). The accuracy of decisions based on duplex compared to those based on arteriography (arteriography used as reference standard) was 91% and a kappa of 0.77 (95% CI+0.14). CONCLUSIONS: Duplex scanning is an accurate diagnostic modality, and clinical decisions can be safely based on its findings.

Aged↗
PubMed1997

Gene sequence, localization, and evolutionary conservation of DAZLA, a candidate male sterility gene.

We have isolated the human homologue of the mouse germ cell-specific transcript Tpx2, which we had previously mapped to mouse chromosome 17. Sequence analysis shows that the human gene is part of the DAZ (Deleted in Azoospermia) family, represents the human homologue of the mouse Dazla and Drosophila boule genes, and is termed DAZLA. Like Dazla and boule, DAZLA is single copy and maps to 3p25. This defines a new region of synteny between mouse chromosome 17 and human chromosome 3. Unlike DAZ, which has multiple DAZ repeats, DAZLA encodes a putative RNA-binding protein with a single RNA-binding motif and a single DAZ repeat. DAZLA is more closely related to Dazla in the mouse than to the Y-linked homologue DAZ (88% identity overall with mouse Dazla compared to 76% identity with the human DAZ protein sequence). Southern blot analysis showed that DAZLA is autosomal in all mammals tested and that DAZ has been recently translocated to the Y chromosome, sometime after the divergence of Old World and New World primates. To investigate the evolutionary relatedness of DAZLA and DAZ further, their partial genomic structures were obtained and compared. This revealed that the genomic organization of both genes in the 5' region is highly conserved. DAZLA is a new member of the DAZ family of genes, which is associated with spermatogenesis and male sterility. Familial cases of male infertility in humans show an autosomal recessive mode of inheritance. It is possible that some of these families may carry mutations in the DAZLA gene.

Amino Acid Sequence↗
PubMed1997

Alerting effects of methylphenidate under basal and sleep-deprived conditions.

Six men and 3 women on each of 4 days received 10 mg of methylphenidate or placebo (2 times a day) at 0800 and 1200 after 8 hr or 0 hr of sleep. Sleep latency was measured by the Multiple Sleep Latency Test (MSLT) at 0930, 1130, 1330, 1530, and 1730. Participants also completed divided-attention and auditory vigilance tasks at 1000 and 1400 and the Profile of Mood States (POMS) and the Addiction Research Center Inventory (ARCI) after the 0930 and 1330 latency tests. The drug increased mean latency on the MSLT in both sleep conditions. Performance only showed drug effects after prior sleep deprivation. On the POMS, the drug increased Vigor and reduced Fatigue and Depression scale scores, primarily after sleep deprivation. The drug increased the ARCI Amphetamine and Morphine-Benzedrine scores only in the basal state. The ARCI Pentobarbital score was increased by sleep deprivation and decreased by the drug.

Adult↗