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Biomedical subjects

A L Green

Publications and source records attributed to A L Green.

At least 19 recordsLinked to original sources

Deep brain stimulation for neuropathic cephalalgia.

The aim of this study was to determine the efficacy of deep brain stimulation (DBS) in the treatment of various types of intractable head and facial pains. Seven patients underwent the insertion of DBS electrodes into the periventricular/periaqueductal grey region and/or the ventroposteromedial nucleus of the thalamus. We have shown statistically significant improvement in pain scores (visual analogue and McGill's) as well as health-related quality of life (SF-36v2) following surgery. There is wide variability in patient outcomes but, overall, DBS can be an effective treatment. Our results are compared with the published literature and electrode position for effective analgesia is discussed.

Adult↗

Immature teratoma arising from a benign cortical abnormality.

CASE REPORT: The authors report the case of an immature teratoma of the left parieto-occipital region in a 13-year-old girl. The patient had a computed tomographic (CT) scan of the brain aged 10 months old, following a minor head injury. This demonstrated an abnormality in the same region, which had been reported as 'a cortical malformation'. DIAGNOSIS: We propose that the lesion on the original imaging is a mature teratoma or other silent dystopic germ cell element that subsequently transformed into the immature teratoma. DISCUSSION: The potential triggers for such a transformation and the management of patients with similar incidental radiological findings are discussed.

Adolescent↗

Cost analysis of unilateral and bilateral pallidotomy for Parkinson's disease.

With the rapid increase in provision of deep brain stimulation for Parkinson's disease, the efficacy of pallidotomy in symptom alleviation appears to be increasingly ignored. We demonstrate that lesional surgery is effective with benefit over a significant period of time with very significant societal cost savings. Such studies are essential for future planning of services so that maximum numbers of patients can benefit from surgery, both lesional and neuromodulation, as deemed appropriate.

Adult↗

Post-herpetic trigeminal neuralgia treated with deep brain stimulation.

Post-herpetic neuralgic affects up to 20% of patients after an attack of trigeminal Herpes Zoster infection. Past medical and surgical treatments have been unrewarding. We report the successful treatment of such a case with deep brain stimulation into the region of the contralateral periventricular grey area (PVG) and ventral posterior lateral thalamic nucleus (VPL).

Adult↗

The current management of tibial fractures: are clinical guidelines effective?

BACKGROUND: The production of clinical guidelines is increasing and will continue to do so with the introduction of clinical governance. In 1997, the British Orthopaedic Association (BOA) and the British Association of Plastic Surgeons (BAPS) published joint guidelines on the management of open tibial fractures. It is not known whether these guidelines reached their target audience, or indeed influenced clinical practice. METHODS: We determined the effectiveness of these guidelines by sending a postal questionnaire survey to 172 orthopaedic surgeons. RESULTS: Only 57% of consultants were aware of the guidelines, 70% of registrars and 25% of staff grades. Less than 29% of orthopaedic consultants would choose to consult the plastic surgical team pre-operatively in the management of an open tibial fracture and only 43% would seek plastic surgical involvement at all. The primary aim of increasing multidisciplinary communication has not been achieved. CONCLUSIONS: The awareness of, and adherence to, these guidelines is sub-optimal. This clearly has implications for both the future management of open tibial fractures and the further production of guidelines.

Compartment Syndromes↗

A face on transmembrane segment 8 of the lactose permease is important for transport activity.

Previous work on the lactose permease of Escherichia coli has shown that mutations along a face of predicted transmembrane segment 2 (TMS-2) play a critical role in conformational changes associated with lactose transport [Green, A. L., Anderson, E. J., and Brooker, R. J. (2000) J. Biol. Chem. 275, 23240-23246]. In the current study, mutagenesis was conducted along the side of predicted TMS-8 that contains the first amino acid in the conserved loop 8/9 motif. Several substitutions at positions 261, 265, 272, and 276 were markedly defective for downhill lactose transport although these mutants were well expressed. Substitutions along the entire side of TMS-8 containing the first amino acid in the loop 8/9 motif displayed defects in uphill lactose transport. Again, substitutions at positions 261, 265, 268, 272, and 276 were the most defective, with several of these mutants showing no lactose accumulation against a gradient. According to helical wheel plots, Phe-261, Thr-265, Gly-268, Asn-272, and Met-276 form a continuous stripe along one face of TMS-8. These results are discussed according to our hypothetical model, in which the two halves of the protein form a rotationally symmetrical dimer. In support of this model, alignment of predicted TMS-2 and TMS-8 shows an agreement between the amino acid residues in these transmembrane segments that are critical for lactose transport activities.

Amino Acid Sequence↗

Networking senescence-regulating pathways by using Arabidopsis enhancer trap lines.

The last phase of leaf development, generally referred to as leaf senescence, is an integral part of plant development that involves massive programmed cell death. Due to a sharp decline of photosynthetic capacity in a leaf, senescence limits crop yield and forest plant biomass production. However, the biochemical components and regulatory mechanisms underlying leaf senescence are poorly characterized. Although several approaches such as differential cDNA screening, differential display, and cDNA subtraction have been employed to isolate senescence-associated genes (SAGs), only a limited number of SAGs have been identified, and information regarding the regulation of these genes is fragmentary. Here we report on the utilization of enhancer trap approach toward the identification and analysis of SAGs. We have developed a sensitive large-scale screening method and have screened 1,300 Arabidopsis enhancer trap lines and have identified 147 lines in which the reporter gene GUS (beta-glucuronidase) is expressed in senescing leaves but not in non-senescing ones. We have systematically analyzed the regulation of beta-glucuronidase expression in 125 lines (genetically, each contains single T-DNA insertion) by six senescence-promoting factors, namely abscisic acid, ethylene, jasmonic acid, brassinosteroid, darkness, and dehydration. This analysis not only reveals the complexity of the regulatory circuitry but also allows us to postulate the existence of a network of senescence-promoting pathways. We have also cloned three SAGs from randomly selected enhancer trap lines, demonstrating that reporter expression pattern reflects the expression pattern of the endogenous gene.

Arabidopsis↗

A revised model for the structure and function of the lactose permease. Evidence that a face on transmembrane segment 2 is important for conformational changes.

The lactose permease is an integral membrane protein that cotransports H(+) and lactose into the bacterial cytoplasm. Previous work has shown that bulky substitutions at glycine 64, which is found on the cytoplasmic edge of transmembrane segment 2 (TMS-2), cause a substantial decrease in the maximal velocity of lactose uptake without significantly affecting the K(m) values (Jessen-Marshall, A. E., Parker, N. J., and Brooker, R. J. (1997) J. Bacteriol. 179, 2616-2622). In the current study, mutagenesis was conducted along the face of TMS-2 that contains glycine-64. Single amino acid substitutions that substantially changed side-chain volume at codons 52, 57, 59, 63, and 66 had little or no effect on transport activity, whereas substitutions at codons 49, 53, 56, and 60 were markedly defective and/or had lower levels of expression. According to helical wheel plots, Phe-49, Ser-53, Ser-56, Gln-60, and Gly-64 form a continuous stripe along one face of TMS-2. Several of the TMS-2 mutants (S56Y, S56L, S56Q, Q60A, and Q60V) were used as parental strains to isolate mutants that restore transport activity. These mutations were either first-site mutations or second-site suppressors in TMS-1, TMS-2, TMS-7 or TMS-11. A kinetic analysis showed that the suppressors had a higher rate of lactose transport compared with the corresponding parental strains. Overall, the results of this study are consistent with the notion that a face on TMS-2, containing Phe-49, Ser-53, Ser-56, Gln-60, and Gly-64, plays a critical role in conformational changes associated with lactose transport. We hypothesize that TMS-2 slides across TMS-7 and TMS-11 when the lactose permease interconverts between the C1 and C2 conformations. This idea is discussed within the context of a revised model for the structure of the lactose permease.

Biological Transport↗

Polymerase chain reaction techniques for differentiating cytotoxic and noncytotoxic Pasteurella trehalosi from Rocky Mountain bighorn sheep.

OBJECTIVE: To evaluate 2 polymerase chain reaction (PCR)-based methods for differentiating cytotoxic and noncytotoxic Pasteurella trehalosi from Rocky Mountain bighorn sheep (Ovis canadensis canadensis). SAMPLE POPULATION: 23 isolates of P. trehalosi from bighorn sheep in Colorado, including 18 from free-ranging herds and 5 from a captive herd. PROCEDURE: Using a sequence of the leukotoxin gene region of P. haemolytica serotype 1, 7 PCR primers were designed. A PCR amplification was performed on a sample of bacterial cell suspensions from pure cultures of P. trehalosi with known in vitro cytotoxic effects. The 2 most promising primer pairs were used in a study of 23 P. trehalosi isolates. Results were analyzed for association with cytotoxicity and 3 distinct ribotypes (Eco, Aco, and Bco). RESULTS: Significant associations were observed between in vitro cytotoxicity and PCR results for coding region, between ribotype Eco classification and PCR results for coding region, and between ribotype Eco classification and PCR results for promoter region. There was a negative association between ribotype Aco classification and PCR results for coding and promoter regions. CONCLUSIONS AND CLINICAL RELEVANCE: The PCR for the leukotoxin A coding region may be useful in differentiating cytotoxic from noncytotoxic P. trehalosi isolates recovered from bighorn sheep. It may be useful for studying epidemiologic features of pasteurellosis in bighorn sheep and for designing vaccines to protect wild sheep against pneumonia caused by P. trehalosi and P. haemolytica.

Animals↗

Carbohydrate ingestion augments creatine retention during creatine feeding in humans.

Blood and urine samples were obtained from four groups of healthy male subjects (A-D, total n = 22) before, during and after ingesting the following: group A, 5 g of creatine in solution; groups B and C, 5 g of creatine and 93 g of simple carbohydrate in solution: group D, a creatine- and carbohydrate-free solution. Subjects ingested the above preparations every 4 h for the remainder of the day and throughout the next day (total daily creatine dose = 20 g), and reported back to the laboratory on day 3 to undergo the same procedures as on day 1. Throughout this time, subjects weighed and recorded all dietary intake, and those in groups B and C ingested a prescribed isoenergetic high carbohydrate diet. Subjects in group C also performed 1 h of cycling exercise at 70% of their maximal oxygen consumption on the morning of each day. On both days 1 and 3, peak plasma creatine concentration, the area under the plasma creatine concentration/time curve and urinary creatine concentration were lower in groups B and C than in group A. Conversely, serum insulin concentration was higher in groups B and C than in A. No differences were evident when comparing groups B and C. These data suggest carbohydrate ingestion augmented creatine retention during creatine feeding and that creatine retention was not further increased when exercise was performed prior to ingestion.

Adult↗

Carbohydrate ingestion augments skeletal muscle creatine accumulation during creatine supplementation in humans.

This study investigated the effect of carbohydrate (CHO) ingestion on skeletal muscle creatine (Cr) accumulation during Cr supplementation in humans. Muscle biopsy, urine, and plasma samples were obtained from 24 males before and after ingesting 5 g Cr in solution (group A) or 5 g Cr followed, 30 min later, by 93 g simple CHO in solution (group B) four times each day for 5 days. Supplementation resulted in an increase in muscle phosphocreatine (PCr), Cr, and total creatine (TCr; sum of PCr and Cr) concentration in groups A and B, but the increase in TCr in group B was 60% greater than in group A (P < 0.01). There was also a corresponding decrease in urinary Cr excretion in group B (P < 0.001). Creatine supplementation had no effect on serum insulin concentration, but Cr and CHO ingestion dramatically elevated insulin concentration (P < 0.001). These findings demonstrate that CHO ingestion substantially augments muscle Cr accumulation during Cr feeding in humans, which appears to be insulin mediated.

Adenosine Diphosphate↗

Effect of oral creatine supplementation on respiratory gas exchange and blood lactate accumulation during steady-state incremental treadmill exercise and recovery in man.

1. Oral creatine supplementation has been shown to increase muscle creatine and phosphocreatine concentrations with consequent benefits on performance during short-term maximal exercise. However, recently there have been anecdotal reports that creatine supplementation can also influence the pattern of substrate utilization and improve performance during more prolonged, submaximal exercise, which, based on recent experimental evidence, may have some scientific justification. 2. Eight men performed a continuous incremental exercise test running at 10 km/h on a motorized treadmill at predetermined workloads from 50% to 90% of maximal oxygen uptake, before and after 5 days of creatine supplementation (4 x 5 g daily). Exercise was performed for 6 min at each workload to achieve a steady state, and respiratory gas exchange and blood lactate concentrations were measured during the last 30 s at each workload. Measurements were also made at 5-min intervals for the first 15 min of recovery. 3. The results showed no measurable effect of creatine supplementation on respiratory gas exchange and blood lactate concentrations during either incremental submaximal exercise or recovery. This suggests that creatine supplementation does not influence substrate utilization during and after this type of exercise.

Adult↗

Antifibrillatory effects of clofilium in the rabbit isolated heart.

1. This study was designed to determine whether clofilium exhibits antifibrillatory activity in a pinacidil + hypoxia-induced model of ventricular fibrillation (VF) in Langendorff-perfused hearts. 2. Ten minutes after exposure to vehicle or clofilium (0.1, 1.0 and 10.0 microM), hearts were exposed to pinacidil (1.25 microM), then subjected to 12 min of hypoxia and reoxygenated. Onset to VF was recorded. Additional groups of hearts were pretreated with UK-68,798 (1.0, 3.0 and 10.0 microM), a delayed rectifier channel blocker, and 5-hydroxydecanoate (10 microM), a known ATP-dependent K+ channel blocker, and subjected to an identical protocol. 3. Clofilium decreased the incidence of VF in a concentration-dependent manner; 7/9 control hearts developed VF vs 1/9 hearts (P = 0.007, Fisher's Exact) treated with 10.0 microM clofilium. In addition, 5-hydroxydecanoate protected hearts from VF, while UK-68,798 pretreatment did not. 4. In a separate group of hearts, electrically-induced VF was converted to sinus rhythm in 10/11 hearts after clofilium was introduced as a bolus. 5. Clofilium is capable of preventing VF in the rabbit isolated heart in a concentration-dependent manner. We have data to suggest that the ability of clofilium to attenuate the effects of pinacidil+hypoxia in our model may include blockade of metabolically active K+ channels, i.e., KATP (glibenclamide-sensitive) channel.

Action Potentials↗

Effect of Ado A1- and A2-receptor activation on ventricular fibrillation during hypoxia-reoxygenation.

We examined the hypothesis that adenosine (Ado)-induced alterations in ventricular electrophysiology may contribute to arrhythmogenesis in a setting of myocardial hypoxia through activation of Ado A1 and A2 receptors in the rabbit isolated perfused heart. There was a 20% incidence of ventricular fibrillation (VF) in control hearts subjected to perfusion conditions of hypoxia and reoxygenation. The incidence of VF was increased to 50% in the presence of 1 microM Ado when hearts were exposed to hypoxia-reoxygenation. The incidence of VF was 20% when Ado was increased to 10 microM. Inhibition of the Ado A2 receptor with 3,7-dimethyl-l-propargylxanthine (DMPX; 10 microM) increased the incidence of VF to 100% when 10 microM Ado was added to the perfusion medium. The A1 antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 1 microM), attenuated (from 100% to 20%) VF induced by Ado + DMPX (10 microM each). The ventricular refractory period and monophasic action potential duration were determined in a separate group of hearts. Our findings indicate that 1) Ado A1-receptor stimulation facilitates VF by decreasing action potential duration and refractoriness in hearts subjected to hypoxia and reoxygenation and 2) the arrhythmogenic potential of Ado A1-receptor stimulation is modulated by simultaneous activation of the ventricular A2 Ado receptor.

Action Potentials↗

The effect of some tricyclic antidepressants on the inhibition of mouse brain monoamine oxidase in-vivo by phenelzine.

Four tricyclic antidepressants, amitriptyline, imipramine, desipramine and iprindole have been shown to partially protect mouse brain monoamine oxidase in-vivo from the irreversible enzyme inhibition produced by subsequent injection of phenelzine. Levels of protection were similar when the enzyme was assayed with selective substrates (5-hydroxytryptamine and phenethylamine) for both the A and B forms of the enzyme. Although other explanations cannot at this stage be ruled out, these observations are consistent with the tricyclic antidepressants acting as reversible inhibitors of brain monoamine oxidase in-vivo.

Animals↗