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H Chapman

Publications and source records attributed to H Chapman.

36 records · Page 2Linked to original sources
PubMed1999

Eggshell sampling: quantitative or qualitative data?

This research evaluated the use of qualitative presence/absence data compared with quantitative real number counts of Aedes vigilax eggshell data to obtain information on the spatial distribution of eggshells in several salt marsh vegetation types. Eggshells were extracted by subsampling and flotation, a method that does not recover all eggshells. The results of the analysis of presence/absence data were compared with those of real numbers. The general conclusions were similar by either method, suggesting that presence/absence data may be sufficient to rapidly determine eggshell distribution patterns.

Aedes↗
PubMed1998

Antagonism of the IL-6 cytokine subfamily--a potential strategy for more effective therapy in rheumatoid arthritis.

Pro-inflammatory cytokines, some of which have the capacity to modulate cartilage and bone metabolism, are important mediators of the frequently sustained and destructive inflammation that characterises rheumatoid arthritis (RA). Tumour necrosis factor alpha (TNF alpha) and interleukin-1 (IL-1) have been studied extensively in this regard. That these proteins are important is no longer in doubt following the demonstration that the IL-1 receptor antagonist and neutralising antibodies directed against TNF alpha are clinically effective. Recent studies suggest that interleukin-6 (IL-6) and other members of the IL-6 cytokine subfamily are also potentially important cytokines in the pathogenesis of RA. The recognition of shared molecular subunits in the receptors for these cytokines raises the possibility that components of these receptors or their derivatives, either alone or in combination, may be useful for antagonising members of the IL-6 cytokine subfamily. Effective antagonism could be therapeutically beneficial in respect to attenuating inflammation and protecting critically important chondral and skeletal tissue. In this review the rationale and possible strategies for such antagonism are discussed.

Animals↗
PubMed1998

Identification of high-affinity binding sites for the insulin sensitizer rosiglitazone (BRL-49653) in rodent and human adipocytes using a radioiodinated ligand for peroxisomal proliferator-activated receptor gamma.

A radioiodinated ligand, [125I]SB-236636 [(S)-(-)3-[4-[2-[N-(2-benzoxazolyl)-N-methylamino]ethoxy]3-[125I]i odo phenyl]2-ethoxy propanoic acid], which is specific for the gamma isoform of the peroxisomal proliferator activated receptor (PPARgamma), was developed. [125I]SB-236636 binds with high affinity to full-length human recombinant PPARgamma1 and to a GST (glutathione S-transferase) fusion protein containing the ligand binding domain of human PPARgamma1 (KD = 70 nM). Using this ligand, we characterized binding sites in adipose-derived cells from rat, mouse and humans. In competition experiments, rosiglitazone (BRL-49653), a potent antihyperglycemic agent, binds with high affinity to sites in intact adipocytes (IC50 = 12, 4 and 9 nM for rat, 3T3-L1 and human adipocytes, respectively). Binding affinities (IC50) of other thiazolidinediones for the ligand binding domain of PPARgamma1 were comparable with those determined in adipocytes and reflected the rank order of potencies of these agents as stimulants of glucose transport in 3T3-L1 adipocytes and antihyperglycemic agents in vivo: rosiglitazone > pioglitazone > troglitazone. Competition of [125I]SB-236636 binding was stereoselective in that the IC50 value of SB-219994, the (S)-enantiomer of an alpha-trifluoroethoxy propanoic acid insulin sensitizer, was 770-fold lower than that of SB-219993 [(R)-enantiomer] at recombinant human PPARgamma1. The higher binding affinity of SB-219994 also was evident in intact adipocytes and reflected its 100-fold greater potency as an antidiabetic agent. The results strongly suggest that the high-affinity binding site for [125I]SB-236636 in intact adipocytes is PPARgamma and that the pharmacology of insulin-sensitizer binding in rodent and human adipocytes is very similar and, moreover, predictive of antihyperglycemic activity in vivo.

3T3 Cells↗
PubMed1998

The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities.

The role of beta3- and other putative atypical beta-adrenoceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine beta3-adrenoceptor (beta3AR) agonists with varying intrinsic activities and selectivities for human cloned betaAR subtypes. The ability to demonstrate beta1/2AR antagonist-insensitive (beta3 or other atypical betaAR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective beta3AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited beta1/2AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full beta3AR agonist elicited full lipolytic and inotropic responses that were sensitive to beta1/2AR antagonism, despite it having very low efficacies at cloned beta1- and beta2ARs. A component of the response to another phenylethanolamine selective beta3AR agonist (SB-215691) was insensitive to beta1/2AR antagonism in some experiments. Because no [corrected] novel aryloxypropanolamine had a beta1/2AR antagonist-insensitive inotropic effect, these results establish more firmly that beta3ARs mediate lipolysis in human white adipocytes, and suggest that putative 'beta4ARs' mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned betaARs which betaARs will mediate responses to agonists in tissues that have a high number of beta1- and beta2ARs or a low number of beta3ARs.

Adipose Tissue↗
PubMed1997

Leukemia inhibitory factor (LIF) binding protein attenuates the phlogistic and abolishes the chondral effects of LIF in goat joints.

OBJECTIVE: To investigate the ability of murine leukemia inhibitory factor (LIF) binding protein (mLBP) to attenuate the effects of recombinant human LIF (rhLIF) in goat radiocarpal joints in vivo. METHODS: Endotoxin-free saline (1 ml) containing either 0.5 or 1 microg of rhLIF was injected into the left and right radiocarpal joints of male angora goats. One hour later the right radiocarpal joints were injected with either 1 or 5 microg of naturally occurring mLBP in 1 ml saline, while the left radiocarpal joints (controls) received 1 ml saline vehicle alone. Goat joints were examined for clinical features of inflammation and synovial fluid (SF) was aspirated on Day 0 (before injection) and Days 2 and 6 postinjection. Leukocyte counts and concentrations of keratan sulfate were determined in the SF. Proteoglycan synthesis and proteoglycan content of cartilage was determined ex vivo in cartilage explants obtained at Day 6. RESULTS: Preliminary time course studies in vitro showed that mLBP had to be added to cartilage explant cultures within 1 h of rhLIF for effective antagonism to occur. In joints injected with either 0.5 or 1 microg rhLIF significant increases in swelling, effusion volume, leukocyte counts, and SF keratan sulfate concentrations were observed relative to controls. Statistically significant depressions of ex vivo proteoglycan synthesis and in proteoglycan content of articular cartilage were also observed relative to controls. In joints injected with 1 microg rhLIF followed by 1 microg mLBP, statistically significant improvement was only observed in the rate of ex vivo cartilage proteoglycan synthesis. The observed rate did not differ significantly from that obtained in joints treated with vehicle alone. In contrast, in joints injected with 0.5 microg rhLIF followed by 5 microg mLBP, statistically significant improvement was observed in all variables. Treatment with 5 microg mLBP effectively negated the effects of rhLIF on joint swelling, effusion volume, leukocyte infiltration, and cartilage proteoglycan catabolism. CONCLUSION: Murine LBP has the ability to attenuate the phlogistic effects of rhLIF in radiocarpal joints of goats and also abolishes the stimulatory effect of rhLIF on cartilage proteoglycan catabolism and depression of ex vivo proteoglycan synthesis. These antiinflammatory and chondral effects suggest that a humanized derivative of mLBP could be a clinically useful antagonist for LIF in inflammatory diseases.

Animals↗
PubMed1997

Self-help groups, family carers and mental health.

Deinstitutionalization has changed both the setting and delivery of mental health care. Mental health nurses are now providing complex and diverse services in contexts that are often far removed from the traditional realms of health care provision. If they are to meet the challenge of contemporary and future mental health-care needs, it is essential that mental health nurses be aware and understand the changing mental health environment. One specific change that has received limited attention in the literature is the increase in socio-political awareness of family carers of people with mental illness, and the concomitant increase in their collective voice and influence through self-help groups.

Adaptation, Psychological↗
PubMed1996

Regulation of intracellular Ca2+ in response to muscarinic and glutamate receptor agonists during the differentiation of NTERA2 human embryonal carcinoma cells into neurons.

Single cell microfluorimetry was used to study intracellular calcium ion signals ([Ca(2+)](i)) evoked by acetylcholine (ACh), glutamate receptor agonists and by KCI-induced membrane depolarization, during neuronal differentiation of the human embryonal carcinoma (EC) cell line, NTERA2. In undifferentiated NTERA2 EC cells, [Ca(2+)](i) was elevated in response to ACh, but not to the glutamate receptor agonists NMDA, kainate or AMPA. The ACh-induced rise in [Ca(2+)](i) was dependent upon both Ca(2+) influx and Ca(2+) mobilization from cytoplasmic calcium stores. Three other human EC cell lines responded similarly to ACh but not to glutamate or KCI-induced depolarization. In neurons derived from NTERA2 cells by retinoic acid induction, [Ca(2+)](i) signals were evoked by ACh, NMDA, kainate and by an elevation of the extracellular KCI concentration. As in undifferentiated EC cells, the ACh-mediated increases in [Ca(2+)](i) were governed by both Ca(2+) influx and Ca(2+) mobilization. In contrast, the effects of NMDA, kainate and KCI did not involve intracellular Ca(2+) mobilization. The appearance of glutamate and KCI responsiveness was not detected in non-neuronal differentiated derivatives of NTERA2 cells. Using a number of pharmacologically defined muscarinic receptor antagonists we found that NTERA2 EC cells express M(1), M(3), M(4) and possibly M(5) receptor subtypes linked to changes in [Ca(2+)](i), whilst only M(3) and M(5) are present in NTERA2-derived neurons. The results were supported by PCR analysis of the muscarinic mRNA species expressed in the cells. The data demonstrate that differentiation of NTERA2 EC cells into neurons involves the induction of functional glutamate receptors coupled to rises in [Ca(2+)](i), and changes in the expression of muscarinic ACh receptor subtypes.

Calcium↗
PubMed1996

The selectivity in vitro of the stereoisomers of the beta-3 adrenoceptor agonist BRL 37344.

The stimulation by BRL 37344 of lipolysis in rat adipose tissues, and of relaxation of the rat distal colon, is mediated by the beta-3 adrenoceptor. The stereochemical requirements of the beta-3 adrenoceptor are poorly understood. The activities of the four stereoisomers of BRL 37344 (i.e., two pairs of diastereoisomers) on three beta-3 adrenoceptor-mediated responses (brown and white adipose tissue lipolysis and relaxation of distal colon) have been determined and compared with those responses mediated by beta-1 adrenoceptors (increase in atrial rate) and beta-2 adrenoceptors (uterine relaxation). The potency order for the stereoisomers (RR>RS=SR>>SS) was the same for all tissues, regardless of whether the response was mediated by beta-1, beta-2 or beta-3 adrenoceptors. These results indicate that both chiral centers are determinants of agonist potency at all three subtypes of the beta adrenoceptor. Furthermore, agonist activity at beta-1, beta-2 and beta-3 adrenoceptors resides predominantly with the RR enantiomer. Finally, the RR enantiomer of BRL 37344 was a more potent agonist in brown adipocytes (EC50 = 3.3 +/- 0.8 nM) than in white adipocytes (EC50 = 5.7 +/- 0.9 nM) or colon (EC50 = 27.5 +/- 7.7 nM).

Adrenergic beta-Agonists↗
PubMed1991

Additional evidence for functional subclassification of alpha-2 adrenoceptors based on a new selective antagonist, SK&F 104856.

SK&F 104856 (2-vinyl-7-chloro-3,4,5,6-tetrahydro-4-methyl-thieno[4,3,2ef][3] benzazepine) shows a similar selectivity profile to the previously reported alpha adrenoceptor antagonist, SK&F 104078 (6-chloro-9-[(3-methyl-2-butenyl)oxy]-3-methyl-1H-2,3,4,5-tetrahydro-3- benzazepine), having the ability to block alpha-1 and postjunctional alpha-2 adrenoceptors, although having little or no activity at most prejunctional alpha-2 adrenoceptors. SK&F 104856 is more potent than SK&F 104078, and lacks the 5-hydroxytryptamine receptor antagonist activity associated with the earlier compound. The postjunctional vs. prejunctional selectivity of SK&F 104856 at alpha-2 adrenoceptors in the same tissue preparation was demonstrated in both canine and human saphenous vein. Concentrations substantially higher than those required to block postjunctional alpha-2 adrenoceptor-agonist induced vasoconstriction had no effect on the ability of norepinephrine, acting on prejunctional alpha-2 adrenoceptors, to inhibit stimulation evoked transmitter overflow in the human tissue, and only a small effect in the canine vein. As observed with SK&F 104078, SK&F 104856 has some prejunctional alpha-2 adrenoceptor antagonist activity in the rat vas deferens, although the receptor dissociation constant is nearly 50-fold higher than that at the postjunctional alpha-2 adrenoceptor in the canine saphenous vein. The results obtained with SK&F 104856 provide additional evidence to support the premise that alpha-2 adrenoceptors can be functionally differentiated. Because SK&F 104856 can selectively antagonize certain alpha-2 adrenoceptor-mediated responses, this agent may be a useful tool to evaluate the functional roles of the multiple alpha-2 adrenoceptor subtypes that have been identified in biochemical and molecular studies.

Adrenergic alpha-Agonists↗
PubMed1989

Novel alpha 2-adrenoceptor antagonists show selectivity for alpha 2A- and alpha 2B-adrenoceptor subtypes.

Pharmacological characterization of mammalian alpha 2-adrenoceptors in various tissues and species has provided evidence for the existence of two alpha 2-adrenoceptor subtypes. These subtypes can be defined in rat and human tissues by prazosin which is alpha 2B selective and oxymetazoline which is alpha 2A selective. In addition to these agents, two types of alpha 2-adrenoceptor antagonists are described which show high affinity and selectivity for the alpha 2A-adrenoceptor and the alpha 2B-adrenoceptor respectively.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Practical synthesis, separation, and stereochemical assignment of the PMPA pro-drug GS-7340.

The practical synthesis of a mixed phenoxy-amidate derivative of PMPA with high oral bioavailability and favorable pharmacokinetics is described. The non-stereoselective synthetic route produces a 1:1 mixture of two diastereomers at phosphorous. Simulated moving bed chromatography using Chiralpak AS enabled kilo-scale isolation of the more potent diastereomer (GS-7340). The GS-7340 phosphorous chiral center was found to be (S) by X-ray crystallography.

Adenine↗
PubMedDate not supplied

Purification of PMPA amidate prodrugs by SMB chromatography and x-ray crystallography of the diastereomerically pure GS-7340.

The diastereomers of GS-7171, aryl phosphoramidate derivatives of the anti-HIV nucleotide analog 9-[2-R-(phosphonomethoxy)propyl]adenine (tenofovir, PMPA), were isolated by batch elution chromatography and continuous simulated moving bed chromatography. The absolute configuration of the more pharmacologically active diastereomer, GS-7340, was determined to be (R,S,S) by single crystal x-ray crystallography.

Adenine↗
PubMedDate not supplied

An efficient process for the synthesis of cyclic HPMPC.

1-[((S)-2-Hydroxy-2-oxo-1,4,2-dioxaphosphorinan-5-yl)methyl] cytosine (cyclic HPMPC) was readily synthesized in gram to multi-kilogram quantities by treating a DMF suspension of HPMPC with four molar equivalents of ethyl chloroformate. This dehydrative intramolecular cyclization process typically afforded cHPMPC in 94% isolated yield and high purity. Benign by-products and solvents were easily removed.

Antiviral Agents↗
PubMedDate not supplied

Why do nurses not make use of a solid research base?

Although research-based practice was advocated in 1972 in the Briggs report, it is suggested that nursing has failed to rise to the challenge. This paper examines some of the explanations why nurses have difficulty in combining research-based theory and practice.

Clinical Nursing Research↗
PubMedDate not supplied

Functional bracing of tibial shaft fractures.

This paper examines the reduced risk of non-union in tibial fractures by allowing controlled motion at the fracture site. It argues that this can also stimulate healing and can be achieved by using functional bracing, which holds the position of the limb, allows weight-bearing and mobilisation of neighbouring joints. It also describes how to apply such a brace.

Casts, Surgical↗