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A McNair

Publications and source records attributed to A McNair.

At least 19 recordsLinked to original sources
PubMed2001

A role for HNF-3 in the regulation of the HNF-1 gene of the Atlantic salmon.

Hepatocyte nuclear factors -1 (HNF-1) and -3 (HNF-3) are hepatocyte-enriched transcription factors that are central to the establishment and maintenance of the liver phenotype in vertebrates. In the present study we demonstrate that, in the Atlantic salmon, asHNF-3 regulates the expression of the gene for asHNF-1. Multiple putative binding sites for asHNF-3 were identified within the 5' flanking region of the HNF-1 gene using a computer-based algorithm, and these were confirmed to be functional by electrophoretic mobility shift assays. In transient transfection assays it was shown that co-expression of asHNF-3 leads to a decrease in the promoter activity of the 5' flanking region of the asHNF-1 gene.

Animals↗
PubMed2000

Synergistic activation of the Atlantic salmon hepatocyte nuclear factor (HNF) 1 promoter by the orphan nuclear receptors HNF4 and chicken ovalbumin upstream promoter transcription factor I (COUP-TFI).

Hepatocyte nuclear factor 1 (HNF1) is a liver-enriched transcription factor that plays an important role in transcriptional networks involved in liver function. The promoters of mammalian HNF1 genes contains a single binding site for another liver-enriched transcription factor, the nuclear hormone receptor HNF4. A transcriptional hierarchy involving HNF4-mediated activation of the HNF1 promoter has been proposed to be of crucial importance in maintaining the differentiated hepatocyte phenotype. Here we present evidence that the Atlantic salmon HNF1 promoter contains three nuclear-hormone-receptor-binding sequences. Gel-shift assays showed that these motifs are recognized with different affinities by HNF4 and the orphan nuclear receptors chicken ovalbumin upstream promoter transcription factors COUP-TFI and COUP-TFII. In hepatoma cells, the site showing highest affinity for HNF4 appears to be crucial for promoter activity. Transfection experiments in non-hepatic cells indicated that the salmon HNF1 promoter was activated by both HNF4 and COUP-TFs. We also identified a promoter fragment encompassing the two more distal nuclear-hormone-binding sites that was activated by HNF4, unaffected by COUP-TF and showed a strong synergistic activation by HNF4/COUP-TF. Results are presented detailing these interactions in relation to the salmon HNF1 promoter architecture.

Animals↗
PubMed2000

A prospective, randomized comparison of the ease and safety of variceal ligation using a multiband vs. a conventional ligation device.

BACKGROUND AND STUDY AIMS: Recent advances in endoscopic technology have led to the development of multiple-banding devices which avoid the use of an overtube in endoscopic variceal ligation. In the present study we prospectively examined the safety and efficacy of one such device compared with the conventional single-band ligator. PATIENTS AND METHODS: A total of 45 patients undergoing band ligation were randomly assigned to receive ligation using conventional techniques (n = 22), or multiband ligation (n = 23). RESULTS: The use of the multiband device was associated with a significant reduction in sedation requirements (midazolam 7.1 mg vs. 9.9 mg, P < 0.01, multiband vs. conventional, respectively), less discomfort (4% vs. 23% severe discomfort, P < 0.05). The total time of the endoscopic session was reduced in the multiband group (8 minutes 25 seconds vs. 12 minutes 21 seconds, P < 0.01), as was the time required for application of all the bands (2 minutes 22 seconds vs. 5 minutes 34 seconds, P < 0.001), and average time taken per individual band application (36 seconds vs. 1 minute 36 secs, P < 0.01). In three patients who underwent ligation using the conventional method, the procedure was stopped because of trauma secondary to overtube application. CONCLUSIONS: Multiband ligation is safer, quicker, and associated with less patient discomfort and morbidity when compared with conventional ligation.

Adult↗
PubMed2000

Atlantic salmon HNF-3/forkhead: cDNA sequence, evolution, expression, and functional analysis.

We report the isolation and characterization of a cDNA encoding an HNF-3 family member (as HNF-3) from Atlantic salmon (Salmo salar L). The important functional domains of HNF-3 proteins that have been characterized previously are revealed by segments of high identity along the alignment of the asHNF-3 with winged helix/forkhead amino acid sequences isolated from other species. A comparison of asHNF-3 cDNA and genomic DNA indicated that there were no introns present in the asHNF-3 gene. Expression of asHNF-3 protein in adult salmon tissues was not exclusive to liver but was also present in the pancreas and intestine. An RT-PCR analysis performed on salmon development showed that asHNF3 expression is detectable before gastrulation at the mid blastula transition stage. Functional analysis of the asHNF-3 protein using a characterized HNF-3 consensus binding site demonstrated that the protein can recognize and bind to specific HNF-3 consensus sequences. We also report the identification of a novel HNF3 binding site in the promoter of the Atlantic salmon transferrin gene.

Amino Acid Sequence↗
PubMed1999

Thrombin is effective in arresting bleeding from gastric variceal hemorrhage.

Gastric variceal hemorrhage is associated with a high morbidity and mortality. We report the efficacy and safety of bovine thrombin in the treatment of bleeding gastric varices. At endoscopy 52 patients with hematemesis were diagnosed with bleeding gastric varices. Patients were treated by intravariceal injection with bovine thrombin and underwent further endoscopy at 72 hr and then at two-week intervals. Initial hemostasis was achieved in 49/52 patients (94%). Bleeding-related mortality at 72 hr after the index bleed was 3/52 (6%). The mean amount of thrombin used to achieve initial hemostasis was 1070 IU (range 400-2000 IU) and no adverse drug effects were observed. The median number of treatment sessions required to achieve gastric variceal ablation was 2 (range 1-3). At six weeks, 9 of 49 surviving patients (18%) rebled and one further patient died. The six-week mortality in patients treated with thrombin was 4/52 (8%). In conclusion, safe and effective hemostasis of bleeding gastric varices can be achieved by intravariceal injection with thrombin.

Adult↗
PubMed1997

The clinical diversity and role of chemotherapy in lymphoproliferative disorder in liver transplant recipients.

BACKGROUND/AIMS: Post-transplant lymphoproliferative disorder is a well-documented complication with an incidence ranging from 2 to 10%, depending on the organ transplanted. Yet despite our increased understanding of the pathophysiology of this disease and the various treatments available, the mortality remains high at 60-80%. We present the clinical and histological features of ten adult liver transplant recipients with post-transplant lymphoproliferative disorder presenting over a 15-year period and review the therapeutic options. METHODS: CD20/CD45RO immunostaining was used for T/B-cell markers; polymerase chain reaction and in-situ hybridisation for Epstein-Barr virus genome detection; kappa/lambda immunostaining and gene rearrangement analysis for clonality. RESULTS: There were six females and four males (age range 24-56) with onset of post-transplant lymphoproliferative disorder-symptoms ranging from 3 to 72 months post transplant. Sites of post-transplant lymphoproliferative disorder included liver (n=4), lymph nodes (n=5), bone marrow (n=2), lungs (n=2), kidneys (n=2), brain, ovaries,: and pancreas (n=1). All lesions were classified as high-grade lymphoma, of B-cell lineage (9 tested); Epstein-Barr virus genome was detected in 7/10 cases. Three tumours were monoclonal; four were polyclonal and three undetermined. Treatment included immunosuppression reduction, antiviral therapy with acyclovir and/or chemotherapy (CHOP or VAPEC-B). Survival times for those patients not treated with chemotherapy were from 9 days to 30 months, whereas those receiving chemotherapy had remission times of 4 to 48 months. CONCLUSIONS: Longer-term remissions can be achieved in patients treated with systemic chemotherapy, although not without morbidity. Clonality assessment is important but treatment decisions should be based primarily on clinical features of progression, as polyclonal tumours can behave as aggressively as monoclonal tumours.

Adult↗
PubMed1996

Hepatocyte nuclear factor 4 (HNF4) binding sites in the salmon HNF1 promoter.

We report the isolation and sequencing of a 1100-bp DNA fragment containing the salmon Hepatocyte Nuclear Factor 1 gene (sHNF1) promoter. The sHNF1 promoter cloned upstream of the chloramphenicol acetyl transferase (CAT) encoding gene is shown to be active in two cell lines of hepatic origin. DNasel footprint analysis of the proximal 400 bp reveals several protein-binding sites, including a CCAAT box, a potential site for Sp1, and three potential HNF4 binding sites. The sequence does not contain any canonical TATA box or initiator and sHNF1 transcription is initiated at four different sites spanning a region of 56 bp. Sequence comparison with the Xenopus laevis HNF1 promoter sequence did not show any significant similarity except in the region overlapping two of the potential HNF4 binding sites.

Animals↗
PubMed1995

Schistosoma mansoni: interaction of nuclear extracts with the CCAAT-binding site revealed by the gel shift assay.

Analysis of the 5'-flanking region of the gene encoding the 28-kDa glutathione S-transferase of Schistosoma mansoni (Sm28GST) indicated the presence of motifs identical to AP-1 and CCAAT-family transcription factor recognition sequences. Gel retardation experiments showed that nuclear extracts from adult S. mansoni bound to an oligodeoxynucleotide containing at CCAAT box. A DNA fragment corresponding to the region of Sm28GST containing the CCAAT motif was demonstrated to interact with schistosome nuclear proteins. This binding was dependent on the presence of the CCAAT pentanucleotide motif. Nuclear factor Y (NF-Y) is a member of the CCAAT transcription factor family that has absolute requirement for the CCAAT sequence and that is highly conserved throughout evolution. The results of a PCR-based strategy aimed at cloning the NF-YA protein of S. mansoni are presented.

Amino Acid Sequence↗
PubMed1994

Tissue expression of the Schistosoma mansoni 28 kDa glutathione S-transferase.

The expression of the Schistosoma mansoni 28 kDa glutathione S-transferase (Sm28) was studied using molecular (PCR, in situ hybridization), and immunocytochemical techniques. The presence of Sm28 was demonstrated in all developmental stages of the parasite except the intra-uterine immature egg. In the parenchyma of male and female adult worms the distribution of Sm28 was limited to a subpopulation of parenchymal cells and to the dorsal tubercles of the male. The tegument, the muscles, the digestive tract, the neural mass, the vitelline glands, and mature gametes were not immunoreactive. Immature germinal cells in both sexes, and the ootype in the female genital system, were found to express Sm28. Deposits of immunoreactive material on host skin following cercarial penetration, exfoliation from the male tubercles, and especially emission of Sm28 from eggs in hepatic granulomas are suspected to be a source of antigen during the parasite infection. The reduction in worm fecundity previously observed in immunization experiments may result from an antibody response directed against Sm28 present in the ootype. There was no cross-reactivity observed, under the experimental conditions used, between the anti-Sm28 sera and either vertebrate or invertebrate host tissue.

Animals↗
PubMed1993

Hepatitis delta virus and the host response: current status and future perspectives.

The demonstration that recombinant vaccinia can control the level of viraemia after HDV superinfection raises the possibility that established HBV carriers can be immunized against HDV. Furthermore the likelihood that this protective effect is dependent on the induction of a CTL response to HDV raises the possibility that the therapeutic effect of interferon operates by the induction of this cellular response. The failure of interferon to exert a direct inhibitory effect on HDV replication needs further investigation as does the nature of the immune responses involved in the protective effect induced by immunization with recombinant vaccinia.

Animals↗
PubMed1990

[Spirapril and nitrendipine in arterial hypertension. A comparison of therapeutic effects and tolerance].

In a double-blind, randomized parallel-group investigation, a new angiotensin-converting enzyme-inhibitor, spirapril, was compared with a calcium antagonist, nitrendipine, in 266 patients with mild to moderate hypertension (diastolic blood pressure 96-119 mmHg). The object was to reduce the diastolic blood pressure measured 24 hours after intake of medicine to less than or equal to 90 mmHg. After monotherapy for four weeks with either 20 mg nitrendipine once daily or 12 mg spirapril once daily, the dosages were doubled in the patients in whom the desired blood pressure had not been obtained. After treatment for eight weeks, 12.5 mg hydrochlorthiazide daily was employed as a supplement in patients who had not yet obtained satisfactory blood pressures. Both methods of treatment resulted a lower number of patients who responded and lesser decreases in blood pressure than anticipated. No differences were found in the decreases in blood pressure resulting from the two therapeutic methods. The effect of supplementary hydrochlorthiazide to spirapril treatment was as anticipated while the combination with nitrendipine only resulted in a marginally extra decrease in blood pressure. Nitrendipine resulted in significantly more side effects and more patients defected from the investigation on account of side effects in the nitrendipine group (27%) than in the spirapril group (7%). This investigation had documented the abilities of nitrendipine and spirapril to reduce blood pressure and the side effects associated with this but does not predict whether the preparations can be employed to prevent the complications of hypertension which constitute the indications for treatment. Supplementing nitrendipine therapy with hydrochlorthiazide is not recommended.

Double-Blind Method↗
PubMed1986

Severe hypertension with cerebral symptoms treated with furosemide, fractionated diazoxide or dihydralazine. Danish Multicenter Study.

Emergency treatment of acute, severe hypertension defined as diastolic blood pressure (DBP) greater than or equal to 135 mmHg combined with cerebral symptoms was prospectively monitored in a randomized multicenter study including 64 patients. Treatment was divided into two periods. In the first hour the patients were observed in the supine position after being given 40 mg furosemide intravenously. If DBP remained greater than 125 mmHg (n = 52), the patients were put on fractionated diazoxide administered intravenously (n = 28) or dihydralazine administered intramuscularly (n = 24). Blood pressure (BP) decreased with diazoxide from an average of 241/149 mmHg to 180/111 mmHg after 5 hours and with dihydralazine from 237/149 to 161/101 mmHg. The inter-individual BP response varied considerably. A clear and identical regression in neurological symptoms was observed on both drug regimens. No new neurological symptoms were seen to develop. It is concluded that a gradual fall in BP can be obtained after fractionated dosage of diazoxide (i.v.) as well as after dihydralazine (i.m.). The indication of acute parenteral therapy compared to less aggressive oral treatment is discussed.

Adult↗
PubMed1986

Reversibility of cerebral symptoms in severe hypertension in relation to acute antihypertensive therapy. Danish Multicenter Study.

Cerebral symptoms were registered in a multicenter study including 64 patients with severe hypertension, diastolic blood pressure (DBP) greater than or equal to 135 mmHg, and more or less pronounced hypertensive encephalopathy. The symptoms were: headache (70%), dizziness (35%), consciousness disturbances (28%), nausea (27%), paresis (23%), blurred vision (22%), paraesthesia (21%) and vomiting (14%). None had convulsions or coma. Initial treatment was furosemide i.v., and if DBP was greater than or equal to 125 mmHg after one hour, patients were randomized to treatment with either i.v. diazoxide (bolus injections of 75-150 mg) or i.m. dihydralazine (bolus injections of 6-12.5 mg). A gradual fall in blood pressure (BP) was obtained in all three groups. Along with BP reduction a substantial regression of neurological symptoms was registered. After 5 hours only minor cerebral symptoms were present without significant difference between diazoxide and dihydralazine. None developed cerebral complications. The study failed to show a significant correlation between BP reduction and regression of neurological symptoms graded semiquantitatively. Reduction of BP by titration using small repeated bolus injections is recommended, but oral treatment should be considered in the patients who are able to ingest peroral medication in spite of neurological symptoms.

Aged↗