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P Harrison

Publications and source records attributed to P Harrison.

At least 91 records · Page 5Linked to original sources
PubMed1996

Nucleotide sequence of ub52 from the cnidarian Acropora millepora reveals high evolutionary conservation.

We report the cDNA sequence encoding Ub52 from the cnidarian Acropora millepora. As in other eukaryotes, the N-terminal region of the deduced amino-acid sequence is a ubiquitin moiety and the C-terminal region CEP52, a protein component of the large ribosomal subunit. A millepora Ub52 is highly homologous (> 95% identical) with the corresponding Drosophila and vertebrate sequences, the cnidarian sequence having higher identity with these 'higher' metazoan homologs than does the corresponding Caenorhabditis elegans protein. However, the cnidarian sequence contains two unique substitutions in the ubiquitin moiety, Ser22 and Thr28. Northern analysis indicates that A. millepora Ub52 is encoded by a small (< 800 nt) mRNA present in eggs and is first expressed after the early gastrula stage in embryonic development.

Amino Acid Sequence↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Relative reactivity of platelets from thrombopoietin- and interleukin-6-treated dogs.

Previous reports have shown that interleukin-6 (IL-6) enhances the responsiveness of platelets to thrombin stimulation and has modest thrombocytopoietic effects in vivo. Thrombopoietin (TPO; mpl ligand) has been shown to have dramatic thrombocytopoietic effect in vivo, but little is known of its capacity to alter platelet function. In this study, a direct comparison of the effects of IL-6 and TPO on platelet function in dogs has been performed, with modest doses of TPO (1 microgram/kg/d) chosen to match or moderately exceed the platelet counts achieved with IL-6 (40 micrograms/kg/d) for 10 days. Platelet responsiveness to thrombin stimulation was assessed in TPO-treated, IL-6-treated, and control dogs by flow cytometric measurement of P-selectin expression. On day 5, the dose of thrombin promoting half maximal stimulation (EC50) of platelets was not significantly changed in TPO-treated dogs, whereas in IL-6-treated dogs the EC50 decreased to 73.1% +/- 6.1% (mean +/- 1 SD; n = 5) of control values (P < 0.01). These experiments were performed on both gel-filtered platelets and washed whole blood, indicating that the observed changes in EC50 were caused by cytokine-mediated alteration of platelets rather than plasma components. Because it has been shown that thiazole orange specifically labels a subpopulation of dog platelets that is less than 24 hours old, the thrombin responsiveness of these young, newly synthesized platelets was determined. The EC50 of thiazole orange-positive platelets from IL-6-treated dogs decreased dramatically by day 5 to 46.5% +/- 13.1% (n = 4) of control values (P < 0.001), whereas TPO-treated dogs did not significantly change. When TPO was directly incubated with platelets ex vivo, no effects on either thrombin-mediated P-selectin expression or adenosine diphosphate-induced fibrinogen binding were observed. These data show that IL-6 alters platelet function, as measured by reactivity to thrombin, whereas TPO does not. This divergence in function is observed even though TPO is equally, or more, effective at promoting platelet production under these experimental conditions.

Adenosine Diphosphate↗
PubMed1996

Peptide bond cleavage site determination of novel proteolytic enzymes found in ROS 17/2.8 cell lysates.

We have identified proteolytic activities in the rat osteoblastic osteosarcoma cell line ROS 17/2.8 which are capable of cleaving a peptide substrate for protein kinase C-mediated phosphorylation (PSPKC, Pro-Leu-Ser-Arg-Thr-Leu-Ser-Val-Ala-Ala-Lys). Using polyacrylamide gel electrophoresis conditions similar to those used to resolve small molecular weight proteins, the peptide bonds of PSPKC which are cleaved by the proteolytic activities present in ROS 17/2.8 cell lysates have been determined. These activities cleave the Ser-Arg, Thr-Leu, and Ser-Val peptide bonds. To date, no proteolytic activities present in osteoblast cell lysates have been described with the aforementioned peptide bond specificities, suggesting that these activities are novel. The PSPKC-cleaved peptide fragment pattern generated was similar for several different osteoblast cell lysates. Lysates generated from different rat tissues were also able to cleave PSPKC, but the peptide fragment pattern generated by ROS 17/2.8 cell lysates appeared to be unique amongst these tissues.

Amino Acid Sequence↗
PubMed1996

Cytokine-induced alteration of platelet and hemostatic function.

A number of nonplatelet-specific cytokines that augment platelet recovery following chemo/radiotherapy have been described. The members of the interleukin 6 (IL-6) family have properties that influence the hematopoietic system beyond their modest thrombocytopoietic effects. Studies performed in a canine model with IL-6 have shown that this factor augments plasma fibrinogen and von Willebrand factor (vWf) concentrations and decreases the level of free protein S. IL-6 appears to decrease the bleeding time in thrombocytopenic dogs, although this effect does not seem to be due to a direct influence of the factor on endothelial vWf or tissue factor production. The factor does not directly alter platelet function in vitro, but when administered to dogs, it increases the sensitivity of the platelets to activation by thrombin. Normal platelets injected into IL-6-treated dogs, and platelets from IL-6-treated dogs injected into normal animals, survive normally. Following injection of either IL-6 or the more specific thrombocytopoietic cytokine thrombopoietin (TPO), IL-6 increases platelet responsiveness to thrombin-induced activation to a greater extent than does TPO. The data show that IL-6 has certain properties that might be construed as prohemostatic, and these properties may prove to be useful clinically.

Animals↗
PubMed1996

Identification of proteolytic activities in ROS 17/2.8 cell lysates which cleave peptide substrates for protein kinase C-mediated phosphorylation.

We have observed two proteolytic activities in cell lysates from the rat osteoblastic osteosarcoma cell line ROS 17/2.8 which are capable of cleaving a peptide substrate for protein kinase C-mediated phosphorylation, and other peptides containing similar sequences. Both activities are inhibited by Pefabloc, a serine protease inhibitor, while one of the activities is inhibited by either EDTA or aprotinin. The protease inhibitors pepstatin, bestatin, E-64, leupeptin and phosphoramidon do not block either of these proteolytic activities.

Amino Acid Sequence↗
PubMed1996

Evidence of increased guanylate cyclase activation by acetylcysteine in fulminant hepatic failure.

Patients with fulminant hepatic failure (FHF) have a severe microcirculatory disturbance causing tissue hypoxia. Infusion of acetylcysteine improves survival and reduces the incidence of multiorgan failure by enhancing tissue oxygenation. Because the observed circulatory effects of acetylcysteine in FHF are similar to and synergistic with those produced by the microcirculatory vasodilator prostacyclin, we postulated that acetylcysteine might potentiate an endogenous vasodilator. Nitric oxide, a vasodilator that activates soluble guanylate cyclase, is a possible candidate as plasma cyclic 3',5'-guanosine monophosphate (cGMP) is raised in FHF, and in vitro acetylcysteine has been found to enhance soluble guanylate cyclase activity. To investigate this possible mechanism further, plasma cGMP was measured before and after acetylcysteine infusion in 24 patients with FHF and again in 6 patients after recovery from acute illness. cGMP levels were high in FHF during acute illness (median, 7.0 nmol/L [interquartile range, 2.6-10.0]) in comparison with levels taken after recovery (1.5 nmol/L [1.0-1.9]; P < .05). Levels rose further after acetylcysteine infusion in the FHF cases (mean increase, 204% [95% CI; 49 to +360]; P < .01) but not in the cases after recovery (38% [-7 to +84]). There were no significant changes in levels of plasma atrial natriuretic peptide (ANP) or cyclic adenosine monophosphate (cAMP) (mean increases, 8% [-6 to +22] and 17% [-9 to +43], respectively). The findings further support the hypothesis that the beneficial hemodynamic effects of acetylcysteine in FHF are mediated by enhancing the activity of the nitric oxide/soluble guanylate cyclase enzyme system.

Acetylcysteine↗
PubMed1996

Cardiorespiratory responses of patients with rheumatoid arthritis during bicycle riding and running in water.

BACKGROUND AND PURPOSE: The purpose of this study was to compare exercise during dry-land bicycle ergometry and running in water with a flotation device in individuals with rheumatoid arthritis. SUBJECTS: Eight individuals with adult-onset rheumatoid arthritis, between the ages of 30 and 40 years (X = 35.88, SD = 2.85), participated. METHODS: Each subject did a graded maximal exercise test on a stationary bicycle and in the water wearing a flotation device, while oxygen uptake (VO2), heart rate (HR), pain, rating of perceived exertion (RPE), minute ventilation (VE), respiration rate, tidal volume (VT), and respiratory exchange ratio (R) were monitored. RESULTS: Higher maximum RPE and R were seen during water running, whereas higher VE and VT were seen during bicycle riding. Heart rate, R, and plateauing VO2 data indicated that a true physiological peak VO2 was reached during the bicycle test. Peak VO2 and HR were similar for either water or bicycle exercise. These findings show that with both forms of exercise, subjects were able to reach training levels as set by the American College of Sports Medicine. CONCLUSION AND DISCUSSION: The water exercise, therefore, provides a means of exercising for individuals with rheumatoid arthritis. It allows them to reach the needed training levels in a comfortable aquatic environment.

Adult↗
PubMed1996

Status of nonoperative management of blunt hepatic injuries in 1995: a multicenter experience with 404 patients.

INTRODUCTION: Nonoperative management is presently considered the treatment modality of choice in over 50% of adult patients sustaining blunt hepatic trauma who meet inclusion criteria. A multicenter study was retrospectively undertaken to assess whether the combined experiences at level I trauma centers could validate the currently reported high success rate, low morbidity, and virtually nonexistent mortality associated with this approach. Thirteen level I trauma centers accrued 404 adult patients sustaining blunt hepatic injuries managed nonoperatively over the last 5 years. Seventy-two percent of the injuries resulted from motor vehicle crashes. The mean injury severity score for the entire group was 20.2 (range, 4-75), and the American Association for the Surgery of Trauma-computerized axial tomography scan grading was as follows: grade I, 19% (n = 76); grade II, 31% (n = 124); grade III, 36% (n = 146); grade IV, 10% (n = 42); and grade V, 4% (n = 16). There were 27 deaths (7%) in the series, with 59% directly related to head trauma. Only two deaths (0.4%) could be attributed to hepatic injury. Twenty-one (5%) complications were documented, with the most common being hemorrhage, occurring in 14 (3.5%). Only 3 (0.7%) of these 14 patients required surgical intervention, 6 were treated by transfusions alone (0.5 to 5 U), 4 underwent angio-embolization, and 1 was further observed. Other complications included 2 bilomas and 3 perihepatic abscesses (all drained percutaneously). Two small bowel injuries were initially missed (0.5%), and diagnosed 2 and 3 days after admission. Overall, 6 patients required operative intervention: 3 for hemorrhage, 2 for missed enteric injuries, and 1 for persistent sepsis after unsuccessful percutaneous drainage. Average length of stay was 13 days. Nonoperative management of blunt hepatic injuries is clearly the treatment modality of choice in hemodynamically stable patients, irrespective of grade of injury or degree of hemoperitoneum. Current data would suggest that 50 to 80% (47% in this series) of all adult patients with blunt hepatic injuries are candidates for this form of therapy. Exactly 98.5% of patients analyzed in this study successfully avoided operative intervention. Bleeding complications are infrequently encountered (3.5%) and can often be managed nonoperatively. Although grades IV and V injuries composed 14% of the series, they represented 66.6% of the patients requiring operative intervention and thus merit constant re-evaluation and close observation in critical care units. The optimal time for follow-up computerized axial tomography scanning seems to be within 7 to 10 days after injury.

Adolescent↗
PubMed1996

Role of non-transferrin bound iron in iron overload and liver dysfunction in long term survivors of acute leukaemia and bone marrow transplantation.

AIMS: To determine whether nontransferrin bound iron is present in the serum of long term survivors of acute leukaemia and bone marrow transplantation who have liver dysfunction as indicated by consistently raised serum aspartate aminotransferase (AST) activities. METHODS: Thirty eight patients, who were at least three years from the end of treatment, were studied. Serum samples were analysed for hepatitis C, hepatitis B, AST, ferritin, and non-transferrin bound iron. A bleomycin based assay was used to detect non-transferrin bound iron. Patient and blood bank records were examined to determine the number of units of transfused blood received by each patient. RESULTS: Ten patients had consistently raised serum AST activities. Of these, two had evidence of hepatitis C infection, one had chronic hepatitis B infection and one had chronic graft versus host disease affecting the liver. None of these four patients had detectable non-transferrin bound iron. The remaining six patients had no obvious reason for raised AST activities, but four had non-transferrin bound iron detectable in their serum as compared with only two out of 28 patients with normal AST activities. Patients with abnormal AST activities had higher serum ferritin concentrations than those with normal AST, though serum ferritin was raised in 21 of 28 patients without liver dysfunction. CONCLUSION: Non-transferrin bound iron may be found in this group of patients, suggesting that iron overload is the cause of the observed liver dysfunction. Non-transferrin bound iron may also be a more specific indicator of iron overload than the serum ferritin concentrations.

Adult↗
PubMed1996

Chronic hepatitis C in long term survivors of haematological malignancy treated in a single centre.

AIMS: To investigate the impact of hepatitis C virus (HCV) infection in long term survivors of haematological malignancy treated before the introduction of blood donor screening in September 1991. METHOD: Patients were tested for evidence of HCV infection by third generation enzyme linked immunosorbent assays, a recombinant immunoblot assay and reverse transcriptase polymerase chain reaction. Serum aspartate aminotransferase activities were measured. The number and type of blood component units received by each patient were recorded. RESULTS: Forty two patients were studied who had received a total of 7143 blood component units. Two patients (4.8%) were found to have HCV infection, both had histological evidence of chronic active hepatitis, and one is now receiving treatment with alpha-interferon. Both of these patients had been missed by the ongoing look-back programme which aims to detect recipients of all known HCV infected blood components. CONCLUSION: Although HCV infection affects a minority of long term survivors of haematological malignancy, infected patients may benefit from alpha-interferon treatment. The screening of all patients treated for haematological malignancy before September 1991 is advocated.

Adult↗