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G Wright

Publications and source records attributed to G Wright.

At least 55 records · Page 3Linked to original sources
PubMed2000

Short-term exposure to homocysteine depresses rat aortic contractility by an endothelium-dependent mechanism.

The effect of short-term exposure to homocysteine (Hcy) on the contractile characteristics of rat aortic tissue was assessed both in vitro and in vivo. The contractile response of Hcy-treated aortic rings in culture for 1 or 4 days was unchanged from control responses. By comparison, aortic rings from animals injected with Hcy showed marked attenuation of response compared with controls injected with saline, cysteine or methionine. The contractile response to K+ was decreased within 24 hours of Hcy injection, whereas the response to both K+ (-27%) and noradrenaline (-56%) was significantly decreased by 4 days. In contrast, the contractile response to phorbol-12,13-dibutyrate was not different between Hcy and control groups. Intimal rubbing completely restored the responsiveness of Hcy-treated tissue to K+ and noradrenaline. By comparison, L-NAME only partially restored contractile responsiveness, while the cyclooxygenase inhibitor indomethacin had no effect on contractile attenuation induced by Hcy. Western blot analysis showed a 2-fold increase of endothelial nitric oxide synthase (eNOS) and a 3-fold increase in inducible nitric oxide synthase (iNOS) protein expression in the aortic endothelial cells from Hcy-injected rats. The results indicate an early detectable effect of Hcy on the in vivo contractile properties of vascular smooth muscle. The effect is endothelium-mediated and may vary depending on the agonist studied. The mechanism is uncertain but appears to involve increased nitric oxide (NO) production. Finally, the data suggest that attenuation of contraction may not be due to a direct effect of Hcy but that the compound is modified or acts indirectly in vivo.

Animals↗
PubMed2000

First trimester diagnosis of acardiac twins.

OBJECTIVE: To describe ultrasonographic findings from 5 to 17 weeks of gestation in monozygotic twin pregnancy resulting in acardia of one twin. METHODS: Transvaginal ultrasonographic examinations were performed using a 7.5 MHz probe at weekly intervals from week 5-11. Uterine artery PI were measured using color Doppler flow. Embryonic heart rates were determined with M-mode. RESULTS: A monochorionic gestational sac containing 2 embryos demonstrated embryonic cardiac activity between 5 and 7 weeks. One twin lost cardiac activity at 7 weeks. A diagnosis of acardiac twins was made at 1 weeks when growth of the lower extremities and no development above the thorax as well as reversal of blood flow through the umbilical cord of the acardiac twin was noted by 14 weeks. CONCLUSION: Ultrasonographic demonstration of independent embryonic heart rates from 5-6 weeks and reversal of blood flow through the umbilical cord of the acardiac twin suggest that the primary pathogenesis in acardia is cardiac dysmorphogenesis secondary to reversal of blood flow rather than primary cardiac agenesis. Acardiac twins can spontaneously ligate connection with their viable twin. Acardiac twinning is a rare complication of multifetal gestation occurring in 1% of monozygotic twin pregnancies or 1 in 35000 births (1). Acardius, as the name implies, is anomaly in which the heart is absent. Acardius can only occur in multiple gestations since its circulation must be maintained by vascular anastomosis with an accompanying fetus (2). Although little doubt exists that intrauterine growth of the acardiac twin is achieved by the perfusion afforded from the normal co-twin via vessel anastomosis in the placenta, the pathogenesis of acardia has been disputed. Some authors (3-5) have presented evidence supporting the concept that the primary defect is one of cardiac embryogenesis (dysmorphogenesis) and that the vascular anastomosis between the vessels, although necessary for the intrauterine survival of the acardiac twin, is not responsible for the cardiac findings. Others (6-8) believe that the primary cause is an abnormal vascular communication between embryos leading to reversed flow of blood to the hemodynamically disadvantaged or recipient twin, with the resulting secondary atrophy of the heart and dependent organs. Inadequate perfusion of the recipient twin is responsible for the development of characteristic set of anomalies including acardia and acephalus. The hemodynamically advantaged or pump twin is structurally normal, but is at risk for in utero cardiac failure and without treatment dies on 50% to 75% of cases (9). Ultrasonography has assumed increasing importance in prenatal diagnosis of congenital anomalies (10). Using this technique, intrauterine diagnosis of acardiac twins has been made as early as 18 weeks of gestation allowing umbilical cord ligation of the acardiac twin at 19 weeks of gestation and uncomplicated birth of abnormal twin at 36 weeks of gestation (11). We now report intrauterine diagnosis of acardiac twins during the first trimester of pregnancy. Unique aspects of the case suggest the pathogenesis of acardia involves arterioarterial anastomosis of placental vessels with retrogade blood flow into the recipient twin and not primary arrest in cardiac development. Further, spontaneous ligation of the vascular connection is documented followed by an uncomplicated delivery of a normal infant at term.

Diseases in Twins↗
PubMed1999

A novel element and a TEF-2-like element activate the major histocompatibility complex class II transactivator in B-lymphocytes.

Major histocompatibility complex (MHC) class II molecules play a central role in immune responses, and transcription of this family of genes requires the MHC class II transactivator (CIITA). CIITA has four promoters, which are transcribed in a tissue-specific manner. CIITA promoter III is constitutively active in mature B-lymphocytes. This report now describes the minimal 319-base pair promoter region necessary for maximal transcriptional activity in B-lymphocytes. Ultraviolet light and dimethylsulfate in vivo genomic footprinting analyses reveal five occupied DNA sequence elements present in intact B-lymphocytes. Functional analysis of these elements using promoter deletions and site-specific mutations demonstrates that at least two of the sites occupied in vivo are critical for transcriptional activity. In vitro protein/DNA analysis suggests that one of the sites is a TEF-2-like element and the other is occupied by a novel transcription activator. In addition, nuclear factor-1 associates with the promoter both in vivo and in vitro. In myeloma cell lines, loss of CIITA transcription correlates with a completely unoccupied CIITA promoter III. These findings suggest that CIITA transcription in B-lymphocytes is activated through at least two strong promoter elements, while loss of expression in myeloma cells is mediated through changes in promoter assembly.

B-Lymphocytes↗
PubMed1999

No effect of aluminium upon the hydrolysis of ATP in the coronary circulation of the isolated working rat heart.

Adenosine 5'-triphosphate (ATP) is now recognised as an important extracellular signalling molecule. Its action at a number of specific receptors is mediated by the activity of ectonucleotidases. We have optimised a high performance liquid chromatography (HPLC) method to allow the simultaneous determination of ATP, and the products of its hydrolysis, in the coronary effluent of an isolated working rat heart. The method is extremely sensitive allowing picomolar quantities of product to be determined. We have used this method to investigate the influence of aluminium on the hydrolysis of ATP by an ecto-ATPase located in the luminal surface of the coronary endothelium of the rat heart. Aluminium did not influence the hydrolysis of ATP by this enzyme.

Adenosine Triphosphate↗
PubMed1999

The effects of superoxide and the peripheral benzodiazepine receptor ligands on the mitochondrial processing of manganese-dependent superoxide dismutase.

The mitochondrion imports and processes the vast majority of the proteins that constitute its structural elements and metabolic pathways. To study mitochondrial precursor processing in the context of the cellular environment, we employed the baculovirus expression system to overexpress the prototypical precursor protein, human manganese-dependent superoxide dismutase (hMn-SOD). It was found that superoxide produced by hyperoxic culture conditions (95% O2 atm) or the redox cycling agent paraquat caused a lesion of the import/processing of precursor hMn-SOD in the baculovirus model. The oxidation of key sulfhydryl groups as a component of the mitochondrial processing lesion was implicated by the observation that the sulfhydryl reducing agent dithiothreitol was completely effective in preventing the block of hMn-SOD processing induced by paraquat. Interestingly, the peripheral benzodiazepine receptor (PBzR) agonists PK11194, Ro5-4864, and protoporphyrin IX were all found to enhance mitochondrial processing of the hMn-SOD precursor protein, suggesting a role for the PBzR in the regulation of mitochondrial import of proteins. Collectively, our results suggest a possible redox-regulated mechanism of mitochondrial protein import that may lead to less efficient precursor protein uptake by mitochondria under severely oxidizing conditions.

Animals↗
PubMed1999

Structure to 1.9 A resolution of a complex with herpes simplex virus type-1 thymidine kinase of a novel, non-substrate inhibitor: X-ray crystallographic comparison with binding of aciclovir.

Treatment of herpes infections with nucleoside analogues requires as an initial step the activation of the compounds by thymidine kinase. As an aid to developing more effective chemotherapy, both for treatment of recurrent herpes infection and in gene therapy systems where thymidine kinase is expressed, two high-resolution X-ray structures of thymidine kinase have been compared: one with the relatively poor substrate aciclovir (Zovirax), the other with a synthetic inhibitor having an N2-substituted guanine. Both compounds have similar binding modes in spite of their size difference and apparently distinct ligand properties.

Acyclovir↗
PubMed1999

Evaluation of a lumped parameter model for isolated working rat hearts.

When a mechanical model of the rat aortic input impedance is perfused with a pulsatile pump, the computed values of the impedance components vary linearly with flow rate and are interactive. When the model is perfused by an isolated rat heart, the total load upon the left ventricle consists of the model and coronary impedances in parallel. Adenosine triphosphate induces changes in coronary impedance, and the redistribution of cardiac output from the model to the coronary circulation causes flow-related changes in the model impedance. Thus, the mechanical model does not provide a constant load for the isolated heart, because of variations in both the model and coronary impedances.

Adenosine Triphosphate↗
PubMed1999

Reducing costs of laparoscopic hysterectomy.

STUDY OBJECTIVE: To establish the role of laparoscopic hysterectomy using reuseable surgical equipment. DESIGN: Prospective, observational study (Canadian Task Force classification II-2). SETTING: Tertiary major teaching hospital. PATIENTS: Fifty consecutive women carefully selected for laparoscopic hysterectomy. INTERVENTIONS: The ultrasonically activated (harmonic) scalpel was used for coagulative cutting of pedicles and ligaments attached to the uterus and adnexa, backed by bipolar diathermy. No nonabsorbable material was left in the pelvis at the conclusion of the procedures. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, uterine weight, histology, operating time, recovery, analgesic requirements, and hospital stay were recorded. Complications were noted and critically assessed for constructive quality assurance appraisal. Outcomes were satisfactory according to both patients and gynecologists. CONCLUSION: This pilot study suggests that the method is an efficacious, cost-effective, and well-controlled technique of laparoscopic hysterectomy.

Adult↗
PubMed1999

Intravascular ATP and coronary vasodilation in the isolated working rat heart.

1. Adenosine-5'-triphosphate (ATP) is a potent coronary vasodilator. Because of the efficient hydrolysis of ATP, adenosine-5'-diphosphate (ADP) and adenosine-5'-monophosphate (AMP) by ectonucleotidases located in the coronary endothelium ATP-induced vasodilation may be mediated via both P1 (AMP and adenosine) and P2Y (ATP and ADP) receptors. We have used the change in total coronary resistance (TCR) induced by intravascular ATP in the isolated working rat heart to determine both the component of the vasodilation mediated via P2Y receptors and the identity of the subclass of receptor involved. 2. The dose response for ATP revealed a half maximal effect at an apparent ATP concentration of 0.08 +/- 0.009 microM. The response was saturated at apparent ATP concentrations greater than 0.23 microM. Contrary to much of the current literature, the perfusion of a 0.25 microM concentration of adenosine resulted in the identical response to an equimolar concentration of ATP suggesting a significant role for adenosine in coronary vasodilation. 3. The non-selective P1 receptor antagonist 8-(p-Sulfophenyl)theophylline (8-SPT) was used to show that the response to ATP was mediated via both P1 and P2Y receptors. Whilst 8-SPT abolished the effect of adenosine it reduced the effect of ATP by only 50%. Thus, at a saturating concentration of ATP, P1 and P2Y receptors were shown to contribute equally to the observed vasodilation. 4. Uridine-5'-triphosphate (UTP), ADP and adenosine-5'-O-thiotriphosphate (ATP gamma S) were used to characterize the component of coronary vasodilation that was mediated via P2Y receptors. UTP at 0.25 microM was ineffective and did not induce vasodilation. Perfusion with 0.25 microM ADP resulted in a vasodilation that was identical to 0.25 microM ATP. In the absence of 8-SPT the perfusion of 0.25 microM ATP gamma S produced a vasodilation that was significantly (P < 0.05) less than ATP. However, the vasodilation due to ATP gamma S, like that of adenosine, but unlike that of both ATP and ADP, was abolished in the presence of 8-SPT. The ability of ADP to induce vasodilation combined with both the lack of response to UTP and the ability of 8-SPT to abolish the vasodilation induced by ATP gamma S suggested very strongly that the component of ATP-induced coronary vasodilation in the isolated working rat heart that was mediated via P2Y receptors was achieved by the action of ADP (and not ATP) at P2Y1 receptors. 5. These results suggest that the vasodilatory action of intravascular ATP in the coronary circulation should be attributed to the dual and equal activities of adenosine and ADP acting at P1 and P2Y1 receptors respectively.

Adenosine Triphosphate↗
PubMed1998

Action of Al-ATP on the isolated working rat heart.

ATP is an important extracellular messenger in the coronary vasculature of the heart. To be effective its extracellular concentration must be tightly controlled and this is achieved via ectonucleotidases located in the luminal surface of the coronary endothelium. Al-ATP is a potent inhibitor of the hydrolysis of ATP and we speculated that Al-ATP released by cells into the blood would disrupt the signalling function of extracellular ATP. We tested this hypothesis by perfusing isolated working Wistar rat hearts with buffers containing either ATP or Al-ATP. The functional parameters measured were, coronary flow, heart rate and pulsatile power. A number of control perfusions including adenosine, ATP-gamma-S and Al were used to identify those effects which might be specific to ATP and Al-ATP. Al-ATP did not appear to inhibit the function of the endothelial ectonucleotidases. Both ATP and Al-ATP produced a significant increase in coronary flow and this could be attributed to a coronary vasodilation. Interestingly, whilst the effect of ATP was reversible that of Al-ATP was not. ATP caused a reduction in heart rate which was potentiated by aluminium. The negatively chronotropic effect of Al-ATP was mediated via a mechanism which was either distinct from or in addition to the similar response known to be caused by adenosine. We have demonstrated for the first time an influence of Al-ATP on heart function. Perhaps more pertinently we present the first evidence that Al-ATP may influence the function of ATP-specific receptors.

Adenosine Triphosphatases↗
PubMed1998

Circular permutation of betaB2-crystallin changes the hierarchy of domain assembly.

The betagamma-crystallins form a superfamily of eye lens proteins comprised of multiple Greek motifs that are symmetrically organized into domains and higher assemblies. In the betaB2-crystallin dimer each polypeptide folds into two similar domains that are related to monomeric gamma-crystallin by domain swapping. The crystal structure of the circularly permuted two-domain betaB2 polypeptide shows that permutation converts intermolecular domain pairing into intramolecular pairing. However, the dimeric permuted protein is, in fact, half a native tetramer. This result shows how the sequential order of domains in multi-domain proteins can affect quaternary domain assembly.

Animals↗
PubMed1998

Birth after cryopreservation of immature oocytes with subsequent in vitro maturation.

OBJECTIVE: To establish the clinical feasibility of using cryostored germinal vesicle oocytes for IVF and ET. DESIGN: Case report. SETTING: Private infertility clinic. PATIENT(S): A 28-year-old woman with tubal infertility undergoing IVF therapy. INTERVENTION(S): Oocytes collected after ovarian stimulation were frozen without insemination or were inseminated, fertilized, and frozen as cleavage stage embryos. No fresh oocyte or embryo transfer was undertaken. All oocytes were thawed, and those that survived were used for IVF-ET. MAIN OUTCOME MEASURE(S): Oocyte cryosurvival, in vitro maturation, fertilization, embryo development, and pregnancy outcome. RESULT(S): None of 16 mature oocytes survived thawing; however, three of 13 germinal vesicle oocytes survived. After 30 hours in vitro maturation two oocytes had matured and underwent intracytoplasmic sperm injection with the partner's sperm. Both fertilized normally and were transferred to the patient. The woman delivered an apparently healthy female infant at 40 weeks. CONCLUSION(S): This case report proves the feasibility if not the efficiency of using immature oocytes for cryostorage, coupling both cryopreservation and in vitro maturation.

Adult↗
PubMed1998

Home, school, and community partnerships: integrating issues of race, culture, and social class.

The current review is an examination of home-school-community partnerships utilizing an ecological approach to understand the influences of race, culture, and social class. The ecological approach recognizes that families and schools are embedded in communities, and that these settings influence each other and the development of children. The roles of race, culture, and social class in the development of partnerships between the home, school, and community settings are explored. Race, culture, and social class may interact with parent and family attributes, teacher and school qualities, and community context. These factors are often misunderstood either through under investigation or lack of integration. The implications for future research, practice, and policy are discussed.

Adult↗
PubMed1998

Clinical application of human egg cryopreservation.

Clinical egg cryopreservation has been applied during a 4-year period with some limited success. Mostly mature and a few immature eggs were frozen slowly and thawed rapidly in 1,2-propanediol and sucrose, and subsequently inseminated by intracytoplasmic sperm injection (ICSI). Three studies were performed in which: (i) it was established that 55% of aged unfertilized mature eggs survive freezing; (ii) in 22 cycles of thawed donated eggs cryosurvival was 24% with 15 cycles reaching transfer, and five pregnancies were initiated, one of which went to term at 39 weeks with fraternal twin boys, and one remains ongoing at 37 weeks; and (iii) in five cycles, where in-vitro fertilization patients had some of their own eggs frozen/ thawed, cryosurvival of mature eggs was poor at only 2.2%, although 44% sibling germinal vesicle (GV) stage eggs survived. A normal female infant delivered at 40 weeks arose from transfer of two embryos where GV eggs underwent in-vitro maturation post-thaw and were fertilized by ICSI. Pregnancies reported here and by others indicate a burgeoning awareness of the potential benefits of egg cryopreservation, prompting cautious optimism for the future of this technology.

Adult↗
PubMed1998

The development of a quality model: measuring effective midwifery services (MEMS).

In a wider debate on defining and measuring quality in health care, there is a particular need for frameworks for understanding and managing quality in specific specialties. This article addresses the definition and measurement of quality in maternity care. It develops a pro forma for monitoring and hence managing midwifery quality.

Economic Competition↗