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G Jones

Publications and source records attributed to G Jones.

At least 289 records · Page 16Linked to original sources
PubMed1994

Structure, expression and gene sequence of a juvenile hormone esterase-related protein from metamorphosing larvae of Trichoplusia ni.

A carboxylesterase with an encoded molecular size of 61 kDa and a high sequence similarity to juvenile hormone esterase (JHE) has been cloned from cDNA prepared from final instar larvae of Trichoplusia ni. The absence of a recognizable encoded signal peptide suggests that the enzyme, JHER (for JHE-related) may not be secreted, in contrast to JHE. When the amino acid sequence of JHE, JHER and other esterases were mapped onto the secondary and tertiary structure determined crystallographically for acetylcholinesterase, certain structural features for the substrate binding/catalytic site were identified as common only to JHE and JHER. However, several differences between JHE and JHER were identified in residues at the binding/catalytic site, suggesting that although the two enzymes prefer similar natural substrates, these substrates are not identical. JHER is present as a single-copy gene, transcribed during the feeding stage of the final stage of the final larval stadium, but not after metamorphic commitment to the pupal developmental programme. The gene transcribes a single-size message of 2.0 kb. The genes for JHER and JHE appear to be physically juxtaposed in the T. ni genome. The 5' flanking sequence to the JHER gene possesses some sequences in common with the JHE gene, but is also missing some regulatory elements previously identified in the JHE gene. Sequences conserved between the promoters for the two genes were identified that were different from previously reported regulatory elements of eukaryotic transcription factors.

Acetylcholinesterase↗
PubMed1994

Increased biological activity of 20-epi-1,25-dihydroxyvitamin D3 is due to reduced catabolism and altered protein binding.

The 20-epi series of vitamin D3 analogs has been shown to be made up of more potent inducers of cell differentiation than calcitriol in vitro. Using 20-epi-1 alpha,25-dihydroxyvitamin D3 (MC 1288), we attempted to rationalize this increased biological activity by examining several parameters including the binding affinity of the analog for the plasma binding globulin (DBP) and the target cell vitamin D receptor (VDR), as well as attempting to measure the rate at which MC 1288 is metabolized. MC 1288 was found to be metabolized 36 times more slowly than its epimer 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3), forming several metabolites which were analogous to metabolites of 1,25-(OH)2D3 formed in the side chain oxidation pathway. Bovine thymus VDR bound MC 1288 with five times greater affinity than calcitriol, while rat plasma DBP did not bind MC 1288 even at a concentration of 50 microM, 5000 times the B50 of 25-OH-D3, the ligand used in the assay. Using a vitamin D-inducible growth hormone gene reporter system we were able to demonstrate that MC 1288 induces human growth hormone (hGH) activity 30-fold more efficiently than 1,25-(OH)2D3 in the presence of fetal calf serum (FCS), while the analog is only 10 times more efficient than 1,25-(OH)2D3 in the absence of FCS. We therefore conclude that MC 1288 is more biologically active than calcitriol in vitro due to a combination of factors: the increased VDR binding affinity, the decreased DBP binding affinity, and the decreased rate of metabolism. As with other analogs of vitamin D, the altered protein binding and decreased catabolism of MC 1288 may be important in pharmaceutical applications such as a topical treatment for psoriasis or skin cancer.

Animals↗
PubMed1994

In vitro metabolism of the anti-psoriatic vitamin D analog, calcipotriol, in two cultured human keratinocyte models.

Calcipotriol (MC903) is a side chain analog of the vitamin D hormone calcitriol, containing a 22-23 double bond, a 24(S)-hydroxyl function, and carbons 25, 26, and 27 incorporated into a cyclopropane ring which has been developed for treating psoriasis. The in vitro metabolism of calcipotriol was studied in two keratinocyte cell models, HPK1A and HPK1A-ras. Calcipotriol was initially converted into the 24-ketone (MC1046) and its 22,23-hydrogenated derivative (MC1080), metabolites observed in osteosarcoma, kidney, and hepatoma cell lines. We also observed the formation of further metabolites, identified as the two 23-hydroxylated derivatives of MC1080 (MC1439 and MC1441), the two 23,24-dihydroxylated compounds (MC1575 and 1577), and the side chain-cleaved compounds, tetranor-1,23-(OH)2D3 and calcitroic acid, the end products of catabolism of calcitriol. These findings suggest that calcitriol and calcipotriol may share catabolic enzymes. The biological activity of each of the principal metabolites of calcipotriol, assessed using a growth hormone reporter gene transcriptional activation system and a vitamin D receptor assay, was found to be lower than that of calcipotriol. If the extensive in vitro metabolism of calcipotriol is also found in normal and psoriatic keratinocytes in vivo, then this may explain the lack of systemic calcemic activity of topically applied drug.

Animals↗
PubMed1994

Phospholipase C-gamma 1 binding to intracellular receptors for activated protein kinase C.

Phospholipase C-gamma 1 (PLC-gamma 1; EC 3.1.4.11) hydrolyzes phosphatidylinositol 4,5-bisphosphate to generate diacylglycerol and inositol 1,4,5-trisphosphate and is activated in response to growth factor stimulation and tyrosine phosphorylation. Concomitantly, the enzyme translocates from the cytosol to the particulate cell fraction. A similar process of activation-induced translocation from the cytosol to the cell particulate fraction has also been described for protein kinase C (PKC). We have previously shown that activated PKC binds to specific receptor proteins, receptors for activated C kinase, or RACKs, of approximately 30 kDa. Here, we show that PLC-gamma 1 bound to these RACKs and inhibited subsequent PKC binding to RACKs. However, unlike PKC, the binding of PLC-gamma 1 to RACKs did not require phospholipids and calcium. After epidermal growth factor treatment of intact A-431 cells, the binding of PLC-gamma 1 to RACKs increased as compared with PLC-gamma 1 from control cells. This increase in PLC-gamma 1 binding to RACKs was due to the phosphorylation of PLC-gamma 1. Additional data indicated that PLC-gamma 1 binds to RACKs in solution; epidermal growth factor receptor-dependent PLC-gamma 1 phosphorylation and activation decreased in the presence of RACKs. It is possible that, in vivo, PLC-gamma 1 associates with RACKs or with other PLC-gamma 1-specific anchoring proteins in the particulate cell fraction. Since a PKC C2 homologous region is present in PLC-gamma 1, the C2 region may mediate the activation-induced translocation of the enzyme to the cell particulate fraction and the anchoring protein-PLC-gamma 1 complex may be the active translocated form of PLC-gamma 1.

Amino Acid Sequence↗
PubMed1994

Regulation of juvenile hormone esterase gene transcription by juvenile hormone.

Juvenile hormone (JH) is a major hormone regulating insect development. We have obtained a cDNA and a genomic clone for juvenile hormone esterase (JHE), the enzyme that is involved in the degradation of juvenile hormone and which is critical for insect development. Analysis of the regulation of JHE during the final larval stadium in the cabbage looper, Trichoplusia ni, showed that the JHE mRNA levels are maximal on days 2 and 4 of the final stadium. Nuclear run-on analyses demonstrated that changes in JHE mRNA levels are primarily due to changes in the transcription rate of the gene, which may be a single copy in the genome. Treatment with a JH analog resulted in induction of JHE gene transcription, which could be detected within three hours after treatment. Salient features present in the 5' flanking region of this JH-sensitive gene are presented, including the presence of sequences closely resembling binding sites for members of the family of nuclear receptors. This report is the first direct demonstration, by nuclear run-on analysis, of JH induction of gene transcription.

Amino Acid Sequence↗
PubMed1994

Fibrin structures during tissue-type plasminogen activator-mediated fibrinolysis studied by laser light scattering: relation to fibrin enhancement of plasminogen activation.

The aim was to relate fibrin structure and the stimulatory effect of fibrin on plasminogen activation during t-PA-mediated fibrinolysis using Lys78-plasminogen as activator substrate. Structural studies were undertaken by static and dynamic laser light scattering, cryo transmission electron microscopy and by the measurement of conversion of fibrin to X-, Y- and D-fragments. The kinetics of plasmin formation were monitored by measurement of the rate of pNA-release from Val-Leu-Lys-pNA. The process of fibrin formation and degradation comprised three phases. In the first phase, protofibrils with an average length of about 10 times that of fibrinogen were formed. The duration of this phase decreased with increasing t-PA concentration. The second phase was characterized by a sudden elongation and lateral aggregation of fibrin fibers, most pronounced at low levels of t-PA, and by formation of fragment X-polymer. The third phase was dominated by fragmentation of fibers and by formation of Y- and D-fragments. Plasmin degraded the fibers from within, resulting in the formation of long loose bundles, which subsequently disintegrated into thin filaments with a length of less than 10 and a mass per length close to one relative to fibrinogen. Plasmin generation at high t-PA concentrations sets in just prior to (and at low t-PA concentrations shortly after) the onset of the rapid second phase of elongation and lateral aggregation of fibrin fibers. The maximal rate of plasmin formation per mol t-PA was the same at all concentrations of activator and was achieved close to the time of the peak level of fragment X-polymer. Plasmin formation ceased after formation of substantial amounts of Y- and D-fragments. At this stage the length was between 300 and 3 and the mass per length close to 1, both relative to fibrinogen. In conclusion our results indicate that (1) formation of short fibrin protofibrils is the minimal requirement for the onset of the stimulatory effect of fibrin on plasminogen activation by t-PA, (2) formation of fragment X protofibrils is sufficient to induce optimal stimulation of plasminogen activation, and (3) plasmin degrades laterally aggregated fibrin fibers from within, resulting in the conversion of the fibers into long loose bundles, which later disintegrate into thin filaments.

Amino Acid Sequence↗
PubMed1994

Symptomatic fracture incidence in elderly men and women: the Dubbo Osteoporosis Epidemiology Study (DOES).

This longitudinal population-based study documents the incidence of all symptomatic fractures from 1989 to 1992 in an elderly, predominantly Caucasian population of males and females (> or = 60 years as at 1 January 1989) living in the geographically isolated region of the city of Dubbo, NSW, Australia. Fractures were ascertained by reviewing reports from all radiology services in the region. There were 306 fractures in 271 patients during the study period representing 11,401 person-years of observation. In the 60-80 year age group only 10% of fractures involved the hip, while in the over-80 age group this proportion rose to 41%. Incidence of distal forearm, hip and total fractures increased exponentially in both sexes with increasing age. Rib fractures were relatively common, with incidence rates for rib fractures similar to those for humeral fractures. Overall fracture incidence was 2685 per 100,000 person-years (males 1940 per 100,000 and females 3250 per 100,000). Residual lifetime fracture risk in a person aged 60 years with average life expectancy was 29% for males and 56% for females. Symptomatic fracture rates with the improved methodology in this study were higher than previously reported in both elderly males and females, with a marked preponderance of non-hip fractures in the 60-80 year age group. These symptomatic fractures have previously been underestimated, if not largely ignored, in public health approaches including cost-benefit analyses of osteoporosis prevention and treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Hematological and lipid changes in newborn piglets fed milk replacer diets containing vegetable oils with different levels of n-3 fatty acids.

To test if linolenic acid (18:3n-3) from vegetable oils would affect bleeding times and platelet counts in newborns, piglets were used as a model fed milk replacer diets containing 25% (by wt) vegetable oils or oil mixtures for 28 d and compared to sow-reared piglets. The oils tested included soybean, canola, olive, high oleic sunflower (HOAS), a canola/coconut mixture and a mixture of oils mimicking canola in fatty acid composition. All piglets fed the milk replacer diets showed normal growth. Bleeding times increased after birth from 4-6 min to 7-10 min by week 4 (P < 0.001), and were higher in pigs fed diets containing 18:3n-3, as well as in sow-reared piglets receiving n-3 polyunsaturated fatty acids (PUFA) in the milk, as compared to diets low in 18:3n-3. Platelet numbers increased within the first week in newborn piglets from 300 to 550 x 10(9)/L, and remained high thereafter. Milk replacer diets, containing vegetable oils, generally showed a transient delay in the rise of platelet numbers, which was partially associated with an increased platelet volume. The oils showed differences in the length of delay, but by the third week of age, all platelet counts were > 500 x 10(9)/L. The delay in rise in platelet counts appeared to be related to the fatty acid composition of the oil, as the effect was reproduced by a mixture of oils with a certain fatty acid profile, and disappeared upon the addition of saturated fatty acids to the vegetable oil. There were no alterations in the coagulation factors due to the dietary oils. Blood plasma, platelets and red blood cell membranes showed increased levels of 18:3n-3 and long-chain n-3 PUFA in response to dietary 18:3n-3. The level of saturated fatty acids in blood lipids was generally lower in canola and HOAS oil-fed piglets as compared to piglets fed soybean oil or reared with the sow. The results suggest that consumption of milk replacer diets containing vegetable oils rich in 18:3n-3 does not represent a bleeding risk, and that the transient lower platelet count can be counterbalanced by the addition of saturated fatty acids to the vegetable oils.

Animals↗
PubMed1994

Patient preference for high or low dose rate brachytherapy in carcinoma of the cervix.

High and low dose rate are two competing methods of brachytherapy. Existing data do not support choosing one method over the other for treating carcinoma of the uterine cervix. Arguments include clinical efficacy, monetary cost, radiation safety, and patient preference. There are no published data on patient preference. We developed a questionnaire to elicit patient preference and to measure its strength. Subjects received descriptions of both treatment options and their probable outcomes. We elicited preference for one low or three high dose rate fractions, and for two low or five high dose rate fractions, assuming both methods to be isoeffective. Strength of initial preference was measured by asking subjects how much of a change, in either the changes for cure or the chances for toxicity, would make them change preference. The questionnaire was completed by female staff at our centre (n = 90), by a group of previously treated patients (n = 18), and by a group of newly diagnosed patients (n = 20). When both methods were assumed to be isoeffective, only 34% of the 38 patients preferred three fractions of high dose rate to one fraction of low dose rate. However, when high dose rate was assumed to be 2% more curative, or 6% less toxic, a simple majority of 50% then said they would prefer high dose rate. Both preference and strength of preference for low dose rate were significantly associated with a greater travelling distance for treatments. Age, marital status, family structure, education, employment, and family income were not associated. In summary, a majority of our patients preferred low dose rate brachytherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Current issues and future directions for performance-related research in sport psychology.

Thirty-seven British and international sport psychologists were asked to nominate performance-related issues that they considered to be priorities for research over the next 5-10 years. Their responses were subjectively categorized into seven different domains of sport psychology: motivational issues in performance; aspects of skill acquisition and motor control that might influence the attainment of excellence; stress and performance; interpersonal issues and group dynamics; the implications for well-being of the pursuit of excellence; psychological skills training; and the role of the sport psychologist. Each of these domains was then reviewed in order to confirm the research issues that had been nominated and identify any other outstanding issues that had not been nominated. Although it was not possible to provide detailed literature reviews because of page restrictions, every attempt was made to offer sufficient evidence to provide a clear rationale for each research issue, and enable the interested reader to trace all the necessary research literature.

Forecasting↗
PubMed1994

Endoscopic transaxillary subpectoral breast augmentation.

The transaxillary approach to breast augmentation is an established technique that offers the advantage of a remote incision in an aesthetically acceptable area. The main disadvantage to this approach is the lack of visualization of the implant pocket, necessitating blind, blunt dissection of the pectoral muscle origins. Occasionally, this limitation may result in improper implant placement and poor aesthetic results. In order to address this shortcoming, we have explored the use of minimally invasive endoscopic techniques in transaxillary augmentation to allow division of the pectoral muscle origin under direct visualization, effectively lowering the inframammary crease. Initial dissections and instrument development were performed in five unpreserved female cadavers. Subsequently, 103 implants have been placed in 53 patients utilizing the endoscopic transaxillary approach. Follow-up ranges from 2 weeks to 20 months. There have been no hematomas, infections, capsular contractures, or other complications. Aesthetic results have been good, and patient acceptance is high. By providing predictable and reproducible control of the inframammary crease, endoscopic dissection has allowed us to expand our indications for the transaxillary approach to breast augmentation. Surgical technique and brief clinical experience are described.

Adult↗
PubMed1994

Primary hyperparathyroidism masked by antituberculous therapy-induced vitamin D deficiency.

Antituberculous chemotherapy agents, particularly rifampicin and isoniazid, affect vitamin D metabolism and can create biochemical evidence of vitamin D deficiency. Vitamin D deficiency induces a state of resistance to parathyroid hormone. This study sought to explain the temporary resolution of hypercalcaemia and hypercalciuria, during antituberculous chemotherapy with rifampicin and isoniazid, in a subject with a surgically proven parathyroid adenoma and coincidental spinal tuberculosis. Serum ionized calcium, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, plasma parathyroid hormone, and 24-hour urine excretions of calcium, inorganic phosphorus and hydroxyproline were sequentially measured over a 3-year interval that included 18 months of antituberculous chemotherapy. Initial serum ionized calcium was 1.52 mmol/l (normal 1.20-1.35 mmol/l), 24-hour urine calcium excretion was 9.40 mmol/day (normal 1.25 to 7.50 mmol/day) and plasma intact PTH was 9.2 pmol/l (normal 0.0-4.5 pmol/l). During antituberculous chemotherapy the serum ionized calcium and 24-hour urine calcium excretion were normal but the plasma PTH rose to higher levels. Following completion of the chemotherapy, hypercalcaemia and hypercalciuria returned with levels similar to those observed pretreatment. Serum 25-hydroxyvitamin D was low at 6.25 nmol/l (normal 20 to 90 nmol/l) during antituberculous chemotherapy, but was normal before and after. Serum 1,25-dihydroxyvitamin D was normal throughout the 3-year interval. We conclude that the antituberculous chemotherapy induced relative vitamin D deficiency and resistance to parathyroid hormone action, thereby masking the hyperparathyroidism and hypercalcaemia until the chemotherapy was completed.

Adenoma↗
PubMed1994

In vivo dihydrotachysterol2 metabolism in normal man: 1 alpha- and 1 beta-hydroxylation of 25-hydroxydihydrotachysterol2 and effects on plasma parathyroid hormone and 1 alpha,25-dihydroxyvitamin D3 concentrations.

It has recently been shown that in the rat, dihydrotachysterol (DHT) is extensively metabolized in the side-chain in vivo along pathways similar to those of vitamin D. In addition 25-hydroxy-DHT2 [25OHDHT2] is hydroxylated at C1, producing both 1 alpha- and 1 beta- hydroxy compounds. An in vivo study in 1988 demonstrated that in normal adult subjects receiving oral DHT2, plasma 1 alpha,25-dihydroxyvitamin D [1,25-(OH)2D] concentrations fell, but with unchanged plasma PTH levels. Down-regulation of 1,25-(OH)2D3 production by 25-(OH)DHT2 or some other unknown metabolite was also suggested as an explanation for these observations. To investigate whether either of the newly characterized 1 alpha,25- or 1 beta,25-(OH)2DHT2 was formed in vivo in normal man, DHT2 (approximately 1 mg/day, orally) was administered to healthy volunteers (three males and one female). Plasma was analyzed by high performance liquid chromatography and gas chromatography-mass spectrometry, demonstrating the formation of both 1 alpha,25- and 1 beta,25-(OH)2DHT2 in vivo in normal human subjects. Plasma levels of 1,25-(OH)2D3, PTH, ionized and total calcium, inorganic phosphate, and alkaline phosphatase were monitored. The plasma concentrations of DHT2, 25OHDHT2, and 1 alpha,25- and 1 beta,25-(OH)2DHT2 were measured by gas chromatography-mass spectrometry. In all volunteers, plasma ionized calcium increased slightly during DHT2 administration; 1,25-(OH)2D3 and PTH concentrations fell. Plasma levels of DHT2 and its metabolites rose over the same period. The average fall in the level of plasma 1,25-(OH)2D (60-70 pmol/L) was mirrored by a rise in the concentration of 1 alpha,25-(OH)2DHT2 (550 pmol/L). This ratio is appropriate, because it has previously been shown that in a reconstituted COS cell, 1 alpha,25-(OH)2DHT3 has roughly one tenth the potency of 1,25-(OH)2D3. At maximum concentration, the ratios of DHT2/25OHDHT2/1 beta,25-(OH)2DHT2/1 alpha,25-(OH)2DHT2 were approximately 10:1:2:0.1. The concentration of 1 beta,25-(OH)2DHT2 was greater than that of 25OHDHT2, and the ratio of 1 alpha,25- to 1 beta,25-(OH)2DHT2 (1:20) was substantially lower than that in rat plasma (3:10). The data presented here suggest that the active DHT2 metabolite in man is 1 alpha,25-(OH)2DHT2 and that the fall in plasma 1,25-(OH)2D seen during DHT therapy may be partly the result of suppressed PTH secretion.

Administration, Oral↗
PubMed1994

High dose rate versus low dose rate brachytherapy for squamous cell carcinoma of the cervix: an economic analysis.

Brachytherapy is an established and important part of the management of invasive carcinoma of the cervix. Available evidence suggests that low dose rate (LDR) and high dose rate (HDR) are equivalent in terms of tumour control, adverse effects and survival. Proponents of outpatient HDR argue that it is less costly than LDR, but no economic evaluation has been published. We compared the costs of HDR and LDR (capital, operating, maintenance, source and operating costs) for Nucletron intracavitary equipment under alternative assumptions about the number of patients treated per year, the number of insertions per patient and discount rate. For example, for 3 HDR fractionations compared with 1 LDR fractionation, the LDR-3 (Nucletron) is the most cost-effective, practical machine for up to 40 patients per year. Although LDR-3 is more cost effective for a greater number of patients, HDR would be recommended for more than 40 patients a year for practical reasons. Similarly, for 5 HDR compared with 2 LDR fractionations, LDR-3 would be recommended for up to 20 patients per year and HDR for a greater number of patients. Recommendations for other HDR/LDR fractionations and annual number of patients seen can be derived from the model. This recommendation is based on no cost sharing with other sites. Cost sharing was beyond the scope of this analysis, though the principles are similar to the ones used. The model may be adapted to help equipment decision-making for a brachytherapy programme for an individual centre.

Brachytherapy↗
PubMed1994

Drug-induced disorders of bone metabolism. Incidence, management and avoidance.

Calcium homeostasis depends upon the interplay of intestinal calcium absorption, renal excretion and skeletal mobilisation of calcium, mediated through bone formation and resorption, which are closely coupled in the adult skeleton. Serum calcium is extremely important for maintenance of normal cellular functions and is regulated by the major calciotropic hormones, parathyroid hormone (PTH), 1,25-dihydroxy-vitamin D and calcitonin. Certain drugs can interfere with calcium metabolism by effects at different stages in calcium metabolism, and a knowledge of the mechanism of drug action is generally helpful in understanding the various resultant clinical skeletal syndromes. Corticosteroids, for example, have profound effects at multiple stages of calcium metabolism, resulting in decreased bone formation and enhanced bone resorption leading to accelerated osteoporosis. Drugs such as aluminium and anticonvulsants impair mineralisation, leading to osteomalacia. Other drugs, such as fluoride, are employed for their known effects on bone, but in excess dosage can be harmful by producing mineralisation defects. Management of these conditions will be discussed in this review.

Adrenal Cortex Hormones↗
PubMed1994

Research utilization in critical care: an exemplar.

The authors describe the process and outcome of implementing a research-based pain management protocol in four adult critical care units at a large, Midwestern tertiary care center. The project was initiated and directed by members of the divisional research committee. Strategies used to change practice included determining if pain management was a problem via quality assessment monitors, surveying nurses regarding their knowledge and attitude toward pain management, educating staff members about the research base for the practice change, using change champions in each unit, and developing a core group of nurses in each unit to facilitate the change. Outcomes of this research utilization project include a 41% decline in the number of patients in pain, a 44% decline in pain intensity, and improvement in nurses knowledge about pain.

Clinical Nursing Research↗