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Biomedical subjects

J Hurst

Publications and source records attributed to J Hurst.

At least 37 records · Page 2Linked to original sources

Pulmonary atelectasis after reconstruction with a latissimus dorsi myocutaneous flap.

Atelectasis is the most common postoperative complication encountered in head and neck surgery. Risk factors include preexisting pulmonary disease, type of surgery performed, and the length of anesthetic. It is controversial whether reconstruction of defects with regional myogenous flaps predisposes to atelectasis. The latissimus dorsi myocutaneous flap requires the patient to be placed on his side for a period of time. Whether it is the position or the surgery that contributes to the development of atelectasis has not been examined. Eighteen patients underwent latissimus dorsi myocutaneous flap reconstruction following major ablative procedures for head and neck cancer. The cutaneous area transferred ranged from 70 to 225 cm2 (mean, 128 cm2). The flap size ranged from 7 x 10 to 15 x 15 cm. The majority of flaps were 10 x 15 cm or greater. These patients were compared to 18 patients who did not undergo pedicled myocutaneous chest flap reconstruction. Patients were matched for age, sex, length of operation, site of primary, and stage of disease. Postoperative atelectasis was radiographically detected in 89% of flap patients vs. 79% of controls. Major atelectasis was encountered in 16% of patients undergoing flap surgery vs. 11% of patients in the control group. Patients with large cutaneous paddles on the flaps (> 120 cm2) had significantly more atelectasis than patients with smaller cutaneous paddles (P<.05, chi-squared). The incidence of radiographic postoperative atelectasis in patients having a latissimus dorsi myocutaneous flap is high. The size of the skin paddle harvested as well as the position change may contribute to this.

Female↗

Increased synthesis of specific eicosanoids in rejected corneal grafts.

PURPOSE: Corneal injury stimulates the formation of both prostaglandins (PG) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE), the major lipoxygenase metabolite. The purpose of this study was to investigate the metabolism of arachidonic acid (AA) in a model of corneal graft rejection. METHODS: Corneal tissue from Dutch belted rabbits was transplanted to vascularized corneas of New Zealand white rabbits. Rejected corneas were removed at the endstage of allograft failure. The allograft, the host corneal rim, the contralateral control cornea rim of equal size and normal Dutch belted cornea from the same site as the allograft were incubated with 0.25 microCi [3H]AA and the released eicosanoids were analyzed by high-performance liquid chromatography. RESULTS: The host corneal rims, adjacent to the failed allografts, produced up to five times as much 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE) as contralateral control corneal rims. Additionally, prostaglandin E2 (PGE2) formation in the host rims increased 100% above controls, and 12(S)-HETE and PGE2 synthesis in the rejected corneal graft also increased. 12(R)-HETrE, an endogenous corneal angiogenic factor, was not detected in rejected corneas. CONCLUSIONS: The results point to the importance of selective AA pathways as the source key inflammatory components found in rejected allografts.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

A study of FRAXE in mentally retarded individuals referred for fragile X syndrome (FRAXA) testing in the United Kingdom.

The folate-sensitive fragile site FRAXE is located in proximal Xq28 of the human X chromosome and lies approximately 600 kb distal to the fragile X syndrome (FRAXA) fragile site at Xq27.3. The cytogenetic expression of FRAXE is thought to be associated with mental handicap, but this is usually mild compared to that of the more common fragile X syndrome that is associated with the expression of the FRAXA fragile site. The exact incidence of FRAXE mental retardation is uncertain. We describe here the results of a U.K. survey designed to assess the frequency of FRAXE in a population of individuals referred for fragile X syndrome testing and found to be negative for expansion events at the FRAXA locus. No FRAXE expansion events were found in 362 cytogenetically negative males studied, and one expansion event was identified in a sample of 534 males for whom cytogenetic analyses were either unrecorded or not performed. Further FRAXE expansion events were detected in two related females known to be cytogenetically positive for a fragile site in Xq27.3-28. To gain insight into the FRAXE phenotype, the clinical details of the identified FRAXE male plus three other FRAXE individuals identified through previous referrals for fragile X syndrome testing are presented. For the population studied, we conclude that FRAXE mental retardation is a relatively rare but significant form of mental retardation for which genetic diagnosis would be appropriate.

Base Sequence↗

Determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIIa and fibrinogen by means of surface plasmon resonance.

The binding reaction between purified human platelet glycoprotein IIb-IIIa and fibrinogen was investigated by real-time measurements using the surface-plasmon-resonance sensor technology. In these experiments, either glycoprotein IIb-IIIa or fibrinogen was immobilized on a sensor surface. The time-dependent change in surface coverage that occurred immediately upon contact with a solution of the complementary protein was then detected. The ability to record this dynamic event from its initiation allowed the collection of kinetic and thermodynamic data over an extended time period. These data indicated that initially, in fast reaction, a reversible low-affinity complex with an equilibrium dissociation constant, Kd, of 155-180 nM was formed. In a subsequent slower reaction this complex was transformed into a more stable high-affinity complex with a Kd of 20-70 nM. Efficient dissociation of the high-affinity complex could only be induced in the presence of a competitive inhibitor such as RGDV. These data demonstrate that the binding between glycoprotein IIb-IIIa and fibrinogen is not a single monophasic reaction, but is composed of at least two consecutive processes both with their own kinetics.

Amino Acid Sequence↗

Transcriptional activation by hypersensitive site three of the human beta-globin locus control region in murine erythroleukemia cells.

In this paper we describe a complete deletional analysis of hypersensitive site three (HS3) of the human beta-globin Locus Control Region (LCR). The previously defined core fragment consists of 6 footprinted regions, with multiple binding sites for the erythroid-specific factor GATA-1 and G-rich motifs that can interact with ubiquitous factors such as Sp1 and TEF-2. We show in this paper that the 5' half of this fragment is the most important for activity in murine erythroleukemia (MEL) cells. A fragment containing footprints 1-4 can stimulate transcription of a linked human beta-globin gene to levels of about 40% of that obtained with footprints 1-6. Constructs containing either footprints 1-3 or 3-6 cannot be distinguished from the beta-globin gene alone. We further show that binding sites for the erythroid-specific factor NF-E2 can co-operatively interact with parts of the HS3 core fragment, and that HS3 requires elements upstream from -103 in the human beta-globin promoter for full activity. The importance of these results is discussed in the context of the regulation of the genes in the human beta-globin cluster.

Animals↗

Structure/activity relationships in porphobilinogen oxygenase and horseradish peroxidase. An analysis using synthetic hemins.

The apo-enzymes of porphobilinogen oxygenase and horseradish peroxidase were reconstituted with hemin IX, deuterohemin IX, 2,4-diacetyldeuterohemin IX, 2-vinyl-4-deuterohemin IX and hemin I. The apoproteins did not reconstitute with the dimethyl or diethyl esters of hemin IX. The native enzymes and the synthetic hemoproteins showed similar oxygenase activities toward porphobilinogen in the presence of dithionite and oxygen. They also showed peroxidase activity in the presence of H2O2, which was affected by the side-chain substitution pattern of the hemes. Oxygenase activities, however, were not affected by the heme structure. Iron chelators completely inhibited the oxygenase, but not the peroxidase activities. The EPR spectra of the native and synthetic porphobilinogen oxygenase showed that dithionite reduction produced a rapid disappearance of the high-spin heme-iron signal at g = 6.0. It reappeared 1 min later but the enzyme retained its catalytic activity. The changes in the EPR spectra could be correlated with the biphasic kinetics of the oxygenase reaction which was very fast during the first minute and then decreased to a half-value rate. The oxygenase reaction was inhibited by addition of superoxide dismutase during the fast rate phase, but not during the slower phase. These results could be explained by the formation of a superoxide anion during the first minute of the oxygenase reaction, after which a protein-stabilized radical (g = 2.0) is generated (very likely a tyrosyl radical). The latter then oxidizes the substrate porphobilinogen and facilitates its reaction with O2 to give oxopyrrolenines.

Animals↗

The regulation of human globin gene switching.

This paper describes the mechanism of regulation of the human beta-globin on the basis of a number of natural mutations and experiments in transgenic mice. From these data we conclude that this multigene locus is regulated at a number of different levels involving specific interactions between the Locus Control Region (LCR) and the individual genes. Most important is the action of stage specific transcription factors acting on sequences immediately flanking the genes. In addition, specificity is obtained through specific interaction of the genes with the LCR and through competition of the genes for interaction with the LCR.

Animals↗

A novel model of a metastatic human breast tumour xenograft line.

The GI-101 human breast tumour xenograft line is unique in that it spontaneously metastasizes to the lungs of athymic murine hosts from subcutaneous trochar implants. Both tumour and lung metastases are positive for normal human breast tissue markers. GI-101 also is positive for the p53 antigen but negative for the c-erbB-2 oncogene.

Animals↗

Total quality management: a matter of quality polarity analysis and management.

Alvin Zander claims that group members are often more concerned with personal needs and rights than those of the organization. People tend to have their attention on only half (the upside of their preferred pole and the downside of the other) of the whole "picture" of a polarity. By making a complete, accurate diagram of the entire polarity and continually updating and using it, people can promote collaboration and effectiveness despite the automatic tendency for people to be both blind to the entire situation and individualistically undermining successful management of the polarity over time. In other words, most efforts to produce noteworthy and lasting results in successful implementation of total quality management most likely will be limited--or result in failure--due to the fact that nursing managers, staff, and administrators view autocratic management and employee empowerment as separate choices to be made and are unclear that their day-to-day action impacts both direction and empowerment continually. Polarity analysis and management tend to integrate what appear to be personal and individual needs with those of others in a collaborative partnership. When addressing any polarity, it is important to acknowledge that people at all levels of the organization potentially are paradoxically the greatest resources and the biggest barriers to unprecedented breakthrough results. Overzealous action to reduce autocratic leadership will subsequently affect empowerment negatively and thus ultimately erode direction. Likewise overzealous action to increase empowerment will promote a lack of focus and finally erode organization and compliance. As any group of people begins to experience the recurrence of the ups and downs of both poles, there is increased frustration, resignation, and sense of ineffectiveness.

Choice Behavior↗

Female twin with Hunter disease due to nonrandom inactivation of the X-chromosome: a consequence of twinning.

We report the occurrence of Hunter disease (mucopolysaccharidosis type II) in a karyotypically normal girl who was one of identical twins. Molecular studies showed nonrandom X-inactivation in both her fibroblasts and lymphocytes, while her normal twin showed equal usage of both X chromosomes. In view of previous reports of 7 pairs of identical female twins in which one had Duchenne muscular dystrophy, it seems that twinning may be strongly associated with nonrandom X-inactivation, and is not specific to the properties of the disease causing gene.

DNA Probes↗

Ellis-van Creveld syndrome in a Western Australian aboriginal community. Postaxial polydactyly as a heterozygous manifestation?

OBJECTIVE: To report two children with Ellis-van Creveld syndrome in an extended kindred of Western Australian Aboriginal descent. Furthermore, to document two family members with isolated postaxial polydactyly of the feet as probable heterozygous manifestations of the Ellis-van Creveld gene. CLINICAL FEATURES: Male and female second cousins with short limbs, postaxial polydactyly and cardiac malformations are described. CONCLUSIONS: It is proposed that founder effect and random genetic drift resulted in a relatively high frequency of the Ellis-van Creveld gene in the Aboriginal people of Western Australia. In addition, further evidence is provided for the postulate that isolated postaxial polydactyly is a heterozygous manifestation of the gene.

Ellis-Van Creveld Syndrome↗