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Biomedical subjects

J Carlton

Publications and source records attributed to J Carlton.

At least 19 recordsLinked to original sources
PubMed2006

Determinants of health related quality of life and health state utility in patients with age related macular degeneration: the association of contrast sensitivity and visual acuity.

BACKGROUND: There has been increasing interest in the use of measures of health related quality of life (HRQoL) and health state utility values in Age Related Macular Degeneration (ARMD). Visual acuity has been found to be an important determinant of such measures in previous studies. More recently, another measure of visual impairment, contrast sensitivity has received considerable attention. We designed a study to examine whether the contribution of contrast sensitivity in explaining HRQoL and health utilities over and above that of visual acuity. METHODS: 209 patients with unilateral or bilateral ARMD were recruited into a cross-sectional study of patients from a large teaching hospital. Patients underwent visual tests (near and distant visual acuity, contrast sensitivity) and completed a vision function questionnaire, the VF-14, HUI3, and time trade-off. RESULTS: Using multivariate regression analysis, the study revealed that contrast sensitivity remained a statistically significant predictor of all outcome measures even when visual acuity was included. This result was supported by the correlation coefficients between measures. CONCLUSIONS: The measurement of contrast sensitivity appears to be better related to a person's HRQoL and health utility. Future studies should consider incorporating contrast sensitivity in addition to visual acuity. Studies, in particular economic evaluations, may underestimate the effect of treatment unless contrast sensitivity is considered.

Adult↗
PubMed2004

Membrane targeting by pleckstrin homology domains.

Pleckstrin homology (PH) domains are small modular domains that occur once, or occasionally several times, in a large variety of signalling proteins. In a number of instances, PH domains act to target their host protein to the cytosolic face of cellular membranes through an ability to associate with phosphoinositides. In this review, we discuss recent advances in our understanding of PH domain function. In particular we describe the structural aspects of how PH domains have evolved to bind various phosphoinositides, how PH domains regulate phosphoinositide-mediated association to plasma and internals membranes, and finally raise the issue of PH domains in protein:protein interactions and the allosteric regulation of their host protein.

Allosteric Regulation↗
PubMed2000

There's no place like home : an evaluation of early supported discharge for stroke.

BACKGROUND AND PURPOSE: Because stroke management is aimed at facilitating community reintegration, it would be logical that the sooner the patient can be discharged home, the sooner reintegration can commence. The purpose of this study was to determine the effectiveness of prompt discharge combined with home rehabilitation on function, community reintegration, and health-related quality of life during the first 3 months after stroke. METHODS: A randomized trial was carried out involving patients who required rehabilitation services and who had a caregiver at home. When medically ready for discharge, persons with stroke were randomized to either the home intervention group (n=58) or the usual care group (n=56). The home group received a 4-week, tailor-made home program of rehabilitation and nursing services; persons randomized to the usual care group received services provided through a variety of mechanisms, depending on institutional, care provider, and personal preference. The main outcome measure was the Physical Health component of the Measuring Outcomes Study Short-Form-36 (SF-36). Associated outcomes measures included the Timed Up & Go (TUG), Barthel Index (BI), the Older Americans Resource Scale for instrumental activities of daily living (OARS-IADL), Reintegration to Normal Living (RNL), and the SF-36 Mental Health component. RESULTS: The total length of stay for the home group was, on average, 10 days, 6 days shorter than that for the usual care group. There were no differences between the 2 groups on the BI or on the TUG at either 1 or 3 months after stroke; however, there was a significantly beneficial impact of the home intervention on IADL and reintegration (RNL). By 3 months after stroke, the home intervention group showed a significantly higher score on the SF-36 Physical Health component than the usual care group. The total number of services received by the home group was actually lower than that received by the usual care group. CONCLUSIONS: Prompt discharge combined with home rehabilitation appeared to translate motor and functional gains that occur through natural recovery and rehabilitation into a greater degree of higher-level function and satisfaction with community reintegration, and these in turn were translated into a better physical health.

Aged↗
PubMed1998

The Plasmodium falciparum translationally controlled tumor protein homolog and its reaction with the antimalarial drug artemisinin.

Artemisinin and its derivatives are important new antimalarial drugs. When Plasmodium falciparum-infected erythrocytes are incubated with [10-3H]dihydroartemisinin, several malaria-specific proteins become labeled. One of these proteins is the P. falciparum translationally controlled tumor protein (TCTP) homolog. In vitro, dihydroartemisinin reacts covalently with recombinant TCTP in the presence of hemin. The association between drug and protein increases with increasing drug concentration, plateauing at approximately 1 drug/TCTP molecule. By Scatchard analysis, there appear to be 2 hemin binding sites on TCTP with dissociation constants of approximately 18 microM. When the single cysteine moiety is blocked by pretreatment with iodoacetamide, hemin binding is not affected, whereas drug binding is reduced by two-thirds. Thus, TCTP reacts with artemisinin in situ and in vitro in the presence of hemin and appears to bind to hemin. The function of the malarial TCTP and the role of this reaction in the mechanism of action of artemisinin await elucidation.

Amino Acid Sequence↗
PubMed1998

A chloroquine resistance locus in the rodent malaria parasite Plasmodium chabaudi.

We have located a possible chloroquine resistance locus in the genome of the rodent malaria parasite Plasmodium chabaudi. Two genetically distinct clones of the parasite were grown in vivo and allowed to undergo genetic crossing. The clones differed from each other in their susceptibility to chloroquine; AS(3CQ) had been selected for a low level of resistance to the drug whereas AJ is chloroquine-sensitive. Independent recombinant progeny (20) were cloned from the products of two crosses, phenotyped for their susceptibility to chloroquine, and genotyped for their inheritance of 46 chromosome-specific markers. No association was found between chloroquine susceptibility and the inheritance of pcmdr1, the P. chabaudi homologue of the pfmdr1 multi-drug resistance gene of P. falciparum. Also, there was no association between chloroquine susceptibility and the inheritance of a marker linked to a putative chloroquine resistance locus in a P. falciparum cross. However, 16 of the progeny clones showed co-segregation of four linked markers on chromosome 11 with their resistance phenotype. This result suggests that a locus for chloroquine resistance exists on this chromosome in P. chabaudi.

Animals↗
PubMed1995

Attenuation of alcohol-induced hypothermia by cyclo (His-Pro) and its analogs.

Acute administration of cyclo (His-Pro) to rats cause a dose-dependent decrease in ethanol-induced hypothermia. Bromination of the imidazole moiety of histidine in cyclo (His-Pro) resulted in a significant increase in its potency to attenuate ethanol hypothermia. In contrast, benzylation of the imidazole moiety of histidine or the substitution of one or both of the amino acids in cyclo(His-Pro) led to a total loss of its thermomodulatory activity. In conclusion, it appears from these preliminary data that it may be possible to design analogs of CHP that may be effective antagonists for ethanol hypothermia.

Animals↗
PubMed1995

Pfcrk-1, a developmentally regulated cdc2-related protein kinase of Plasmodium falciparum.

A gene encoding a novel cdc2-related protein kinase has been identified in Plasmodium falciparum, using degenerate oligonucleotides designed to hybridise to regions that are conserved in members of the cdc2 gene family. This gene, called Pfcrk-1, is located on chromosome 4. It is most closely related to the p58GTA gene family, members of which are negative regulators of cell growth in vertebrates. Pfcrk-1 is developmentally regulated, as indicated by stage-specific accumulation of mRNA in gametocytes.

Amino Acid Sequence↗
PubMed1994

Maternal inheritance of extrachromosomal DNA in malaria parasites.

Plasmodium falciparum has two extrachromosomal genomes, the mitochondrial 6-kb DNA element and the 35-kb circular DNA. The mitochondrial gene cytochrome b on the 6-kb element has been shown to be inherited uniparentally. In order to ascertain whether the route is maternal or paternal we have examined preparations of male and female gametes of the closely related Plasmodium gallinaceum for the presence of extrachromosomal DNA. DNA from purified preparations of gametes was hybridised to probes for both the 6-kb and 35-kb extrachromosomal genomes. Both probes hybridised to the preparation of Plasmodium gallinaceum female gametes but not to that of the males. We conclude that the extrachromosomal DNAs of malaria parasites are transmitted maternally.

Animals↗
PubMed1992

Preparative peptide purification by cation-exchange and reversed-phase perfusion chromatography.

Cation exchange was compared to reversed-phase chromatography for the preparative purification of a 28-residue peptide (vasoactive intestinal polypeptide) on the 100-mg scale. Optimized high-speed, high-resolution methods were developed for both chromatographic modes on POROS Perfusion Chromatography flow-through particle chromatography columns. While both methods appeared to provide similar purity, the cation exchange column had approximately ten times the loading capacity per unit column volume as the reversed-phase column. Five-minute methods for desalting the cation exchange-purified peptide and analysis of fractions were developed using small reversed-phase columns. The cation-exchange method was scaled up to process 95 mg of crude peptide in a 12-min run.

Amino Acid Sequence↗
PubMed1991

Isolation, ultrastructure, and partial characterization of collagen from the perineurium of the Florida lobster, Panulirus argus.

Highly concentrated extracellular filaments in the perineurium of the Florida spiny lobster, Panulirus argus, were isolated using ultracentrifugation and linear sucrose gradients. The pellet obtained was highly enriched for the filaments as observed by transmission electron microscopy. Fibril diameter and axial periodicity measurements were obtained from filaments positively and negatively stained with uranyl acetate. A period between 14.0 and 25.0 nm and an average fibril diameter of 15.0 nm were observed. The filaments proved resistant to solubilization by most conventional agents and by several collagenases. NaOH (0.1 M at 100 degrees C) safely dissolved the filaments for measurements of protein content by the Lowry method and carbohydrate content with anthrone reagent. These tests revealed a protein content of approximately 84% and a high carbohydrate content of approximately 15%. Polyacrylamide electrophoresis of an acid-pepsin filament extract revealed a highly concentrated band (approximately 100,000) corresponding to the alpha-1 and alpha-2 bands of vertebrate type I collagen. Wide angle X-ray diffraction yielded meridional reflections that confirmed the filaments as collagen when compared with mammalian collagen X-ray diffraction. The amino acid composition was determined with a computer-assisted Beckman amino acid analyzer, which showed a glycine content of 279 residues/1000. Hydroxylysine and hydroxyproline were present in lower concentrations than expected.

Amino Acids↗
PubMed1991

Reduction of complications associated with total parenteral nutrition by introduction of a clinical monitoring team. The Total Parenteral Nutrition Committee.

The introduction of Total Parenteral Nutrition (TPN) in the treatment of malnourished patients with unusable gastrointestinal tracts has become commonplace throughout the world. However there are significant metabolic (4.2 to 7.7%) and septic (7 to 27%) complications associated with this therapy. In 1984 a TPN committee was formed at Royal Newcastle Hospital and a TPN nurse was appointed. This series documents the use of TPN at Royal Newcastle Hospital from August 1984 to July 1989. There were 251 patients who received TPN, representing 3422 days of TPN. The primary catheter sepsis rate was 10.4% at the commencement of the series and decreased appreciably to 3.2%. The formation of the TPN committee and the appointment of a TPN nurse have represented a considerable cost in time and money but this action has been justified by the drop in the sepsis rate resulting in a decrease in morbidity and mortality associated with TPN.

Adolescent↗
PubMed1990

Long-term actions of d-fenfluramine in two rat models of obesity. II. Responses to stress.

In the previous study (part I), we reported that a 28-day regimen of d-fenfluramine administered via osmotic pump sustained weight reductions in normal weight and obese rats without depleting brain 5-HT. Peripheral actions of d-fenfluramine were also examined. Here we extend those findings to night-time observations and to stressful conditions. This treatment regimen had no effects on night-time concentrations of insulin, triglycerides or corticosterone or on the stress-induced rise in triglycerides and corticosterone. The thermic response to cold was unaltered. Glucose tolerance was enhanced in lean, but not obese rats.

Animals↗
PubMed1989

Selection of optimal axon ratio for nerve regeneration.

The traditional teaching that "nerve fibers are lost at the suture line" after a nerve repair was investigated by asking the question, "Can the number of nerve fibers distal to a nerve repair site be increased by increasing the number of nerve fibers proximally?" Ratios of proximal to distal nerve fibers were increased from 1:1 to 2.5:1 to 3.5:1 by suturing peroneal or posterior tibial or sciatic nerve proximally to peroneal nerve distally. At one year following the repair, distal nerve fiber numbers increased to twice normal as the ratio increased to 2.5:1, and then nerve fiber numbers plateaued. Nerve function, as judged by walking track analysis, was best in the peroneal:peroneal group (1:1 ratio), suggesting that appropriateness rather than number of proximal fibers was more critical in this nerve repair model.

Animals↗
PubMed1989

Long term actions of d-fenfluramine in two rat models of obesity. I Sustained reductions in body weight and adiposity without depletion of brain serotonin.

In a treatment regimen designed to simulate clinical situations, d-fenfluramine was administered chronically (28 days) via osmotic minipumps to lean and obese female rats. Drug effects were assessed in dietary obese, ovariectomized obese, estradiol-treated ovariectomized and unoperated Chow-fed rats. Various central and peripheral effects of d-fenfluramine were measured and compared to effects of dietary restriction as well as posttreatment changes. d-Fenfluramine suppressed food intake and body weight in all but estradiol-treated rats and was especially effective in obese ovariectomized rats. This method of administration did not deplete brain 5-HT within 28 days. The measured drug actions that may be important in: appetite suppression and weight loss include chronic stimulation of brain 5-HT activity without depletion; stimulation of (Na+- K+)ATPase activity; reduction in lipoprotein lipase activity and effects on carbohydrate metabolism.

Adipose Tissue↗
PubMed1988

Dexfenfluramine: effects on food intake in various animal models.

The effects of dexfenfluramine on food intake of rats are compared and contrasted among several paradigms. Paradigms that involve overfeeding rather than deprivation, show a greater effect of the agent. Furthermore, both stress-induced eating as well as a food-motivated response (running) are particularly sensitive to inhibition by dexfenfluramine. The results of chronic administration of dexfenfluramine on both behavior and neurochemistry are reviewed, with particular reference to brain 5-HT. The effects of dexfenfluramine on diet selection and conditioned preferences are discussed. Finally, we suggest that species differences may exist in either the neurochemical and/or behavioral responses to dexfenfluramine.

Animals↗