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Biomedical subjects

P Harrison

Publications and source records attributed to P Harrison.

At least 181 records · Page 10Linked to original sources

Fat embolism--a review.

The subject of fat embolism is of recurring interest to those managing trauma. This article covers the topic of fat embolism in general, and presents a case of fulminant fat embolism syndrome which highlights the importance of clinical expertise, and whatever technological aids are available to diagnose and appropriately treat this relatively rare, but highly significant form of the syndrome. Fulminant fat embolism syndrome has a very high mortality and should be watched for in patients who have experienced major trauma.

Adult↗

Endothelium specific Weibel-Palade bodies in a continuous human cell line, EA.hy926.

Weibel-Palade bodies are ultrastructurally defined organelles found only in vascular endothelial cells. Because endothelium in corpo is very dispersed, isolation and further characterization of this organelle has been dependent on increasing the number of cells in culture. However, primary isolates of endothelial cells have a limited replication potential and tend to senesce in culture. In this report, EA.hy926, a continuously replicating cell line derived from human endothelium, is shown to contain Weibel-Palade bodies. Electron micrographs demonstrate the ultrastructural characteristics of these tissue-specific organelles and their cytoplasmic distribution in EA.hy926 cells. Von Willebrand factor, which has been shown to exist in Weibel Palade bodies, is demonstrated by immunofluorescence in discrete rod-shaped organelles whose size, shape, and distribution are consistent with that of Weibel-Palade bodies in primary endothelial cell cultures. Rapid release of von Willebrand factor can be induced by calcium ionophore, and large multimeric forms of the protein are found in EA.hy926 cells. These two properties are consistent with the function currently ascribed to Weibel Palade bodies: storage of multimerized von Willebrand factor. Thus ultrastructural, immunologic, and functional data establish the existence of this as yet poorly understood tissue-specific organelle in a continuous, vigorously replicating human cell line.

Calcimycin↗

Pharmacokinetics of fenbendazole in dogs.

Fenbendazole was administered to dogs at a dose rate of 20 mg/kg body weight on a single occasion in gelatin capsules, on 5 consecutive days in feed, and on a single occasion as an alginate suspension. It was also administered at a dose rate of 100 mg/kg body weight on a single occasion in feed. Following single administration of 20 mg/kg fenbendazole mean maximum concentrations (Cmax) of the parent drug and its known active sulphoxide metabolite were 0.42 +/- 0.05 and 0.31 +/- 0.05 microgram/ml, respectively. Mean times until maximum concentrations were achieved (tmax) were 12.67 +/- 4.18 and 15.33 +/- 2.81 h, respectively, and areas under the plasma concentration-time curves (AUC) were 5.83 +/- 0.65 and 4.60 +/- 0.57 microgram.h/ml, respectively. Administration in feed increased the apparent bioavailability and administration for 5 consecutive days provided sustained plasma concentrations, generally greater than 0.2 microgram/ml. Administration as an alginate did not increase bioavailability or extend the persistence in plasma. It did increase the tmax to 16.80 +/- 2.93 and 20.00 +/- 2.53 h for fenbendazole and its sulphoxide metabolite, respectively. Increasing the dose from 20 mg/kg to 100 mg/kg did not substantially increase the Cmax or AUC.

Administration, Oral↗

Molecular and developmental biology of the Cnidaria--basic aspects and phylogenetic implications.

Cnidarians are generally considered to be the most primitive group of eumetazoans. They are therefore of considerable interest for comparative studies of metazoan development and evolution. The application of molecular techniques to cnidarians can provide important insights into developmental processes and phylogenetic relationships both within the phylum Cnidaria and among the eumetazoa. This paper reviews current knowledge of molecular and developmental biology of cinidarians with particular emphasis on tropical scleractinian corals and soft corals from the Great Barrier Reef region. Nucleotide sequencing of the histone gene cluster has unequivocally established that cnidarians are typical eumetazoans. Repeated sequence analysis has been applied to the staghorn corals, and implies a major divergence within this group, which corresponds with differences in sperm ultrastructure. Recent developmental studies of corals have indicated that some species have an unusual method of germ layer formation. Molecular events associated with this process, and with other important developmental stages, are currently under investigation. Other areas of current research interest, including targets for PCR-based investigations into cnidarian phylogeny, are highlighted.

Animals↗

GATAAG; a cis-control region binding an erythroid-specific nuclear factor with a role in globin and non-globin gene expression.

An erythroid-specific nuclear protein factor binds to a sequence motif (GATAAG) which is present in the promoter region of the mouse alpha and beta major globin genes, and in the erythroid-specific promoter of the human porphobilinogen deaminase (PBG-D) gene. The protein activity is conserved across species, being found in mouse erythroleukaemia (MEL) cells, chicken erythrocytes, the human erythroid K562 and KMOE cell lines, but not in a variety of non-erythroid mouse tissues or in HeLa cells. Functional analysis of this element in the alpha globin gene promoter by stable transfection experiments show that the GATAAG motif resides in a 68 bp sequence which has a stimulatory effect on transcription in mouse erythroleukaemia but not fibroblast cells. The GATAAG motif is conserved in the promoters and 3' enhancers of a variety of globin and non-globin genes implying that it is a cis-element involved in the tissue-specific up-regulation of several genes that are co-expressed during erythroid cell differentiation.

Animals↗

Comparison of the in vitro characteristics of von Willebrand factor in British and commercial factor VIII concentrates.

Qualitative/quantitative analysis of von Willebrand factor antigen (vWf:Ag) in either heat or solvent/detergent treated factor VIII concentrates, used for haemophilia replacement therapy, was undertaken to assess their suitability for the treatment of vWD. For the first time immunoaffinity purified vWf:Ag (Monoclate by-product) was also evaluated by in vitro assessment. Potencies of vWf:Ag varied considerably but were consistently higher (28.9-420.5 iu/ml) than factor VIII:C (one-stage) activity (8.13-42.44 iu/ml). The functional activity of vWf was assessed by either Ristocetin Cofactor (vWf:RCo) or collagen binding methods (vWf:CBA) with typical vWf:RCo/vWf:Ag ratios ranging from 0.08 to 0.94. Multimeric analysis confirmed that in vitro biological activity was dependent on the presence of the high molecular weight forms of vWf:Ag. A significant correlation (r = 0.95) between vWf:RCo activity and collagen binding was observed in all of the concentrates with the exception of the immunopurified product. The data suggest that either NHS 8Y (mean vWfRCo/vWf:Ag = 0.94), Haemate P (mean vWf:RCo/vWf:Ag = 0.69) and high purity Octapharma V.I (vWf:RCo/vWf:Ag = 0.82) which contain medium/high MW vWf:Ag multimers are likely to be most cost-effective in the treatment of symptomatic severe vWD patients than other currently available concentrates.

Chemical Phenomena↗

Uptake of plasma fibrinogen into the alpha granules of human megakaryocytes and platelets.

The origin of platelet alpha-granule fibrinogen (Fg), whether from endogeneous synthesis or exogeneous derivation, remains unknown. Although Fg biosynthesis by megakaryocytes (MK) has been suggested, recent studies have demonstrated that certain alpha-granular proteins originate primarily from plasma. To study the origin of alpha-granule Fg, platelet-associated Fg was measured by ELISA and Western blotting, and localized by immunofluorescence and immunoelectron microscopy in a patient with symptomatic congenital afibrinogenemia before and after replacement therapy with cryoprecipitate. alpha-Granule Fg was detected in the majority of platelets as early as 24 h postinfusion, suggesting that direct platelet uptake was occurring. Platelet Fg reached a maximum value of 42.5% of normal values at 3 d postinfusion and was localized in the alpha-granules, while plasma levels followed a typical half-life profile. Significant alpha-granule Fg was still detectable at 13 d postinfusion, with plasma Fg virtually absent. Studies on cultured CFU-MKs from the patient also confirmed that MKs can incorporate exogeneous Fg into alpha-granules. These results indicate that platelet alpha-granule Fg can be derived from the circulating plasma pool and that Fg uptake can occur in both platelets and MKs.

Adult↗

Paedophilia and hyperprolactinaemia.

The case of a man presenting with paedophilia who has found to be hyperprolactinaemic is described. There is possibly a link between paedophilia and endocrine disorders.

Adult↗

Uncoordinated expression of fibrinogen compared with thrombospondin and von Willebrand factor in maturing human megakaryocytes.

The localization of three known alpha-granule proteins, thrombospondin (TSP), von Willebrand factor (vWF), and fibrinogen (Fg) has been studied in human megakaryocytes (MK) by immunofluorescence and immunoelectron microscopy. For this study, highly purified populations of MK were prepared from human bone marrow either by counterflow centrifugal elutriation or by cell culture from normal subjects and from two patients with megakaryoblastic leukemia. In normal bone marrow immature MK, TSP, and vWF were observed in the Golgi-associated vesicles and in small immature alpha-granules; in mature MK, they were found in the matrix of the mature large alpha-granules. Surprisingly, Fg was detected neither in the Golgi area, nor in the small precursors of alpha-granules; it was only found in the mature alpha-granules but this labeling was generally weaker than in blood platelets. In order to confirm these differences between the expression of Fg and vWF or TSP additional studies were performed on cultured maturing MK: immunofluorescent and ultrastructural immunogold labeling confirmed that vWF appeared early in the maturation while the same immature MK were negative for Fg. In the late maturation stage, the three proteins were detected in the alpha-granules. In order to know whether Fg was lately synthesized or endocytosed from the outside medium, normal MK were grown in the presence of either normal or afibrinogenemic plasma, and normal serum. Fg was detected only in the alpha-granules of MK grown in normal plasma. Similar results were observed with malignant MK, whose maturation was independent of the culture conditions. In conclusion, this study brings immunocytochemical evidence that vWF and TSP are synthesized by immature MK, whereas Fg appears later in the MK alpha-granules and its expression is dependent of the presence of an exogenous Fg source.

Adult↗

Chromatography of the VIII/vWF complex on dextran sulphate sepharose.

The applicability of Dextran Sulphate (DS) agarose in the purification of the VIII/vWf complex from cryoprecipitate was investigated. The elution profiles indicate high affinity of the VIII/vWf complex for the matrix. With application of combined salt/pH gradients good resolution of VIII/vWf from most of the applied proteins can be achieved. VIII/vWf normally elutes as a single component (70-90% vWf:Ag and vWf:RCo) with modest yields of factor VIII (30-40%) VIII:C and 50-70% VIII:Ag) providing calcium ions are present. Addition of L-lysine, Histidine and Arginine (all 1.0M) inhibit binding of proteins to the matrix. Alternatively, higher yields of VIII:C can be obtained (80% VIII:C and 100% VIII:Ag) by the application of L-lysine gradients (0-0.6M) but with loss of resolution from Fn and slight dissociation of VIII:C from vWf:Ag.

Chromatography, Affinity↗

The effects of dance team participation on female adolescent physical fitness and self-concept.

The purpose of this study was to determine to what extent female physical fitness and self-concept are affected by dance team participation in high school. Eight dancers were tested once prior to and once four months after dance team participation. Eight participants from physical education classes, matched for age, weight, height, grade, and race, were tested once at the same time as the second dance team test. Physiological tests were maximum oxygen uptake, sit-and-reach, one-repetition maximum bench press, skinfolds, and hydrostatic weighing. The self-concept tests were Coopersmith Self-Esteem Inventory, Tennessee Self-Concept Scale, and Body Cathexis Scale. Dependent one-tailed t tests were run to determine differences between dance team pre- and posttests and control and dance team posttests. Dance subjects increased maximum oxygen uptake and one-repetition maximum bench press in addition to improving their body composition as evidenced by a significant decrease in total skinfolds and a near significant decrease in percent body fat. The dance team had a significantly higher maximum oxygen uptake than did controls. No other significant differences were seen between groups. Dance team participants significantly improved physical self and social self on the Tennessee Self-Concept Scale. No other significant differences were seen. A factor that may have affected the self-concept results in this study was low dance team status, due to a combination of unsuccessful previous dance teams and a losing football season. Within the limitations of this study, these results indicate that physical fitness is improved as a result of dance team participation; however, self-concept seems to be affected only minimally, if at all, as compared with participation in physical education classes.

Adolescent↗