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Biomedical subjects

J Wood

Publications and source records attributed to J Wood.

At least 199 records · Page 11Linked to original sources

Estimation of agonist affinity and efficacy by direct, operational model-fitting.

A few years ago Black and Leff (1983) presented a theoretical model for agonist action that can be fitted directly to experimental agonist concentration-effect data in order to estimate affinities and relative efficacies of agonists. The model has been successfully applied to data obtained using experimental designs commonly employed in pharmacologic experiments. This article describes the methodology used to fit the model equations to data for full and partial agonists, shows how affinity and efficacy estimates are calculated for these values, and shows how experimental design influences these calculations.

Models, Biological↗

Clock mutations alter developmental timing in Drosophila.

The developmental time of period mutants in Drosophila melanogaster was monitored under different environmental conditions. We observed that the pers mutants, which have short 19 h circadian cycles, develop faster from eggs to adult than the wild-type: perL mutants, which have long 28 h circadian rhythms, complete development more slowly than the wild-type. These results suggest that endogenous timers may be involved in regulating the development time of D. melanogaster.

Analysis of Variance↗

Activity of herpes simplex virus type 1 latency-associated transcript (LAT) promoter in neuron-derived cells: evidence for neuron specificity and for a large LAT transcript.

By using chloramphenicol acetyltransferase (CAT) assays in neuron-derived cell lines, we show here that promoter activity associated with the herpes simplex virus type 1 latency-associated transcript (LAT) had neuronal specificity. Promoter activity in these transient CAT assays coincided with a DNA region containing excellent RNA polymerase II promoter consensus sequences. Primer extension analysis in a LAT promoter-CAT plasmid construct placed the start of transcription about 28 nucleotides from the first T in the consensus TATA box sequence. Neuronal specificity of this promoter was suggested by examining the effect of sequences upstream of the promoter on CAT activity in neuronal versus nonneuronal cells. In nonneuronal cells, promoter activity was decreased 3- to 12-fold with the addition of upstream sequences. In contrast, in neuron-derived cells, the addition of upstream sequences did not decrease promoter activity. The LAT promoter predicted by our transient CAT assays was located over 660 nucleotides upstream from the 5' end of the previously mapped 2-kilobase (kb) LAT. This unusual location was explained by in situ and Northern (RNA) blot hybridization analyses that suggested that LAT transcription began near the promoter detected in our CAT assays, rather than near the 5' end of the 2-kb LAT. In situ hybridization with neurons from latently infected rabbits detected small amounts of LAT RNA within 30 nucleotides of the consensus TATA box sequence. This suggested that LAT transcription began near this TATA box. Northern blot hybridization of RNA from ganglia of latently infected rabbits revealed a faint 8.3-kb band of the same sense as LAT. We conclude that (i) the LAT promoter has neuronal specificity, (ii) the LAT promoter is located over 660 nucleotides upstream of the 5' end of the previously characterized stable 2-kb LAT, (iii) LAT transcription begins about 28 nucleotides from the first T of the consensus TATA box sequence and extends to near the first available polyadenylation site approximately 8.3 kb away, and (iv) this 8.3-kb RNA may be an unstable precursor of the more stable 2- and 1.3-kb LATs.

Animals↗

A review of diabetes care initiatives in primary care settings.

This paper describes a variety of initiatives by general practitioners who assumed varying degrees of responsibility for diabetic patients. The initiatives differ in size, the way they were launched, the support given to general practitioners and the groups of people with diabetes. Evaluation of two projects demonstrate that general practitioners in selected practices, when compared to hospital colleagues, achieve as good or even better outcomes in terms of metabolic control and thoroughness of review. The outcomes of other initiatives are less encouraging, although the evidence is exteremely sparse and somewhat dated. A full quality assessment of all kinds of initiatives is urgently required.

Diabetes Mellitus↗

Needle aspiration of nonfunctioning parathyroid cysts.

Until recently, nonfunctioning parathyroid cysts were usually identified at operation for a presumed thyroid mass. Thyroid needle biopsy now allows their preoperative diagnosis and potential definitive treatment. This study reviews four patients with nonfunctioning parathyroid cysts treated during a two-year period. Three women and one man range in age from 28 to 70 years. Each presented with an asymptomatic thyroid mass ranging from 3 to 5 cm in length. None had symptoms of primary hyperparathyroidism. Serum calciums were from 9.2 to 10.7 mg/dl and serum phosphoruses were 3.2 to 4.4 mg/dl. Needle aspiration revealed 5 to 85 cc of water-clear fluid. C-terminal parathyroid hormone in three patients was 12,600, 6,500 and 61,200 pg/ml and N-terminal PTH was 1,700 pg/ml in one. All four had normal serum calcium and phosphorus on follow-up ranging from six months to two years. Two patients had resolution of their cysts with a single aspiration. One patient had recurrence but has no evidence of recurrence six months after injection with tetracycline. Another patient had a recurrence but remains well one year following reaspiration. Nonfunctioning parathyroid cysts present as a thyroid mass. Needle aspiration of water-clear fluid high in parathormone is diagnostic and, in most patients, is the therapeutic modality of choice.

Adult↗

The antagonism by BW A868C of PGD2 and BW245C activation of human platelet adenylate cyclase.

1. In glycerol-lysed human platelets, prostaglandin D2 (PGD2) and the hydantoin BW245C both activate adenylate cyclase in a biphasic manner. These activations are qualitatively different from those of carbacyclin, iloprost and prostaglandin E2 (PGE2) whose E/[A] curves can be adequately described by rectangular hyperbolae. 2. Prostaglandin E1 (PGE1) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbolae. 2. Prostaglandin E1 (PGE1) had E/[A] curves of slope significantly lower than that expected for a rectangular hyperbola. 3. The selective PGD2 antagonist BW A868C shifts the first phase of the PGD2 and BW245C E/[A] curves but has no effect on the second phase. 4. Applying a two-receptor model enables a pKB to be derived for BW A868C of 9.11. 5. BW A868C has no effect on carbacyclin, iloprost, prostacyclin, PGE1 and PGE2 at a concentration 1,000 fold that of its KB against PGD2 and BW245C. 6. These results indicate that PGD2 and BW245C are capable of activating adenylate cyclase in human platelets through the DP-receptor and by another mechanism as yet uncharacterized.

Adenylyl Cyclases↗

Rostral ventrolateral medulla muscarinic receptor involvement in central ventilatory chemosensitivity.

The muscarinic receptor antagonist atropine (105 mM) dramatically decreased the response to increased CO2 when applied by cotton pledgets to the rostral ventrolateral medulla ventilatory chemosensitive area in anesthetized, paralyzed, vagotomized, glomectomized, and servoventilated cats with integrated phrenic nerve activity used as respiratory center output. Lower dose atropine (4.4 mM) and the M1-muscarinic receptor subtype antagonist pirenzepine (10 mM) also significantly decreased the mean CO2 response slope 48.3 +/- 6.2 and 40.7 +/- 6.0% (SE), respectively, and significantly decreased the maximum response value 26.3 +/- 8.1 and 19.2 +/- 3.2%, respectively, without significant effects on blood pressure or on the phrenic response to carotid sinus nerve stimulation. The M2-muscarinic receptor subtype antagonist AF-DX 116 (10 mM) had no significant effect on phrenic output or blood pressure. Application of carbachol (10 mM) at the rostral area augmented eucapnic phrenic output and the maximum value of the CO2 response but decreased the initial slope, effects blocked by atropine. Carbachol also decreased the response to carotid sinus nerve stimulation, suggesting that the system was saturated by carbachol stimulation. Muscarinic cholinergic receptors accessible to surface application at the rostral ventrolateral medulla antagonized by pirenzepine but not AF-DX 116 appear to be involved in the central chemoreceptor process.

Animals↗

Penetrating neck injuries: recommendations for selective management.

There were 225 patients with penetrating neck wounds admitted over a 4-year period. Mechanism of injury included stab wounds in 59%, gunshot wounds in 32%, and shotgun wounds in 9%. Location of injury was Zone 1, 16%, Zone 2, 42%, Zone 3, 18%, posterior triangle, 12%, and multiple, 12%. The patients were divided into five groups based upon clinical presentation, location of injury and method of management: Group 1 (n = 31) had serious blood loss or respiratory distress and were immediately explored; Group 2 (n = 76) had anterior wounds and equivocal physical findings either without (n = 60) or with negative (n = 16) contrast studies and these had "mandatory explorations"; Group 3 (n = 17) and Group 4 (n = 80) presented the same as Group 2 but Group 3 patients had positive contrast studies and were explored, while contrast studies were negative in Group 4 patients who were observed; Group 5 (n = 21) had posterior injuries and/or presented late with minimal physical findings and they were observed. Positive exploration occurred in 90% of Group 1, 28% of Group 2, and 82% of Group 3. There were no missed injuries in Groups 4 or 5. Two missed esophageal injuries occurred in Group 2, and a missed carotid injury occurred in Group 3. The following guidelines for management have resulted. 1) Unstable patients require immediate exploration. 2) Stable patients with equivocal physical findings can be managed according to results of esophageal examination and angiography. 3) Patients with low probability of injury due to location and clinical presentation can be observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Pulmonary edema following retrobulbar block.

We report a patient requiring keratoplasty who developed acute pulmonary edema following the administration of a retrobulbar block for anesthesia. A variety of factors that may have been implicated in the genesis of this complication are discussed.

Anesthesia, Local↗

Continuing education in general practice in the UK: a review.

This paper reviews developments in continuing education in general practice in the UK in the 1980s. It highlights the growing awareness at national level of the need to develop performance review as a form of continuing education in general practice and the steps that have been taken to restructure the postgraduate medical education system. It also draws attention to the lack of change in the general pattern of continuing education, despite some uncoordinated growth of activity outside postgraduate centres and the emergence of some educational innovations. The paper concludes by putting forward proposals for a programme of action and for the appointment of properly trained general practitioner tutors in each district to support, coordinate and extend educational initiatives.

Education, Medical, Continuing↗

Immature tendon adaptation to strenuous exercise.

White Leghorn roosters (3 wk old) were randomly assigned to runner or control groups. Runners were subjected to a progressive treadmill running program for 8 wk, 5 days/wk at 70-80% maximal O2 consumption (VO2 max). After 8 wk, runners showed a significant elevation in gastrocnemius fumarase activity (51%) and a 21% increase in VO2max compared with controls. The exercise program induced a significant increase in tendon collagen deposition (46%) without any changes in DNA, proteoglycan, and collagen concentrations or tendon dry weight. Also, tendon collagen from runners contained fewer (50%) pyridinoline cross-links. These results suggest that high-intensity exercise causes greater matrix-collagen turnover in growing chickens, resulting in reduced maturation of tendon collagen.

Adaptation, Physiological↗

Morbidity and mortality of craniotomy for excision of supratentorial gliomas.

Extensive surgical resection of supratentorial gliomas increases survival. However, some reports suggest that the perioperative morbidity and mortality outweigh the potential benefit of the procedure. We examined prospectively morbidity and mortality in 104 consecutive patients who underwent surgery for supratentorial glioma, as well as other factors that might affect the short-term outcome. To determine if our experience was unusual, we compared these results with those obtained from another academic neurosurgical center by a review of the records of 109 patients also treated surgically for supratentorial glioma. Mortality was 3.3% and the medical plus neurologic morbidity was 31.7%. Functionally significant neurologic worsening occurred in 42 (19.7%) patients. Complications were more frequent in patients with moderate or severe preoperative disabilities than those with mild or no preoperative disability. Patients with complete resection had fewer acute neurologic complications, and no greater risk of being neurologically impaired at 1 week, than patients with biopsy or less extensive procedures. Morbidity and mortality correlated with location: deep-midline lesions had a higher overall rate of perioperative complications (p = 0.032) and mortality (p = 0.019) and bilateral lesions a higher rate of hemorrhage (p = 0.017) and hydrocephalus (p = 0.010). Older patients (greater than 55 years) and those receiving high daily dose of preoperative dexamethasone (greater than or equal to 24 mg) had a significantly higher risk of surgical mortality. Reoperation for recurrent tumor carried no greater risk of mortality, neurologic deterioration, and infection than a first operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗