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Biomedical subjects

S Harrison

Publications and source records attributed to S Harrison.

At least 73 records · Page 4Linked to original sources
PubMed1998

The manufacturing process for recombinant factor IX.

Advances in recombinant DNA manufacturing technology have now made possible the production of a highly purified and active recombinant factor IX (rFIX) product. Recombinant factor IX was developed by (1) stable insertion of the genes for both factor IX and PACE-SOL (a truncated, soluble serine protease needed to enhance the capacity of cells to remove the amino-terminal propeptide from rFIX) into Chinese hamster ovary cells; (2) selection of a cell line that was capable of expressing high amounts of active rFIX while growing in bioreactors containing a completely defined culture medium that does not contain blood or plasma products; and (3) inclusion of four independent chromatography steps, none of which require monoclonal antibodies. Furthermore, rFIX has been extensively tested to demonstrate similarity to plasma-derived factor IX and has been shown to be a consistent, high-purity product. For example, a high-specific-activity product (276+/-23 IU/mg) has been consistently produced throughout 65 consecutive batches from five consecutive manufacturing campaigns. Thus, rFIX offers a consistent and high-purity source of factor IX treatment for patients with hemophilia B.

Animals↗
PubMed1997

Spatial pattern formation in an insect host-parasitoid system

Spatial models in ecology predict that populations may form patchy distributions within continuous habitats, through strong predator-prey or host-parasitoid interactions combined with limited dispersal. Empirical support of these models is provided. Parasitoids emanating from a population outbreak of tussock moths (Orgyia vetusta) suppressed the growth of nearby experimental populations of the moth, while experimental populations farther away were able to grow. This result explains the observed localized nature of tussock moth outbreaks and illustrates how population distributions can be regulated by dynamic spatial processes.

Journal Article↗
PubMed1997

Inhibition of intracellular Ca2+ signalling, cytotoxicity and antitumor activity of the herbicide oryzalin and its analogues.

PURPOSE: Studies were conducted on oryzalin (3,5-dinitro-N,N-di(n-propyl)sulfanilamide), a widely used dinitroaniline sulfonamide herbicide, which was identified from plant extracts as an inhibitor of mitogen- and growth factor-mediated intracellular free Ca2+ ([Ca2+]i) signalling in mammalian cells. METHODS AND RESULTS: Oryzalin inhibited vasopressin, bradykinin and platelet-derived growth factor [Ca2+]i signalling in Swiss 3T3 fibroblasts with IC50 values of 14, 16 and 18 microM, respectively. 45Ca2+ uptake into nonmitochondrial stores of saponin-permeabilized Swiss 3T3 cells was inhibited by oryzalin with an IC50 of 34 microM. Oryzalin inhibited colony formation of HT-29 colon carcinoma cells with an IC50 of 8 microM and inhibited the growth of a number of other cancer cell lines and primary human tumors in vitro with IC50 values in the range 3 to 22 microM. A number of oryzalin analogues were studied and an association was found between the ability to inhibit [Ca2+]i signalling and inhibition of the growth of HT-29 human colon cancer cells (P = 0.001) and of CCRF-CEM human leukemia cells (P = 0.016). Oryzalin at doses up to 600 mg/kg administered orally or subcutaneously daily to mice for 3 to 10 days beginning a day after tumor inoculation inhibited the growth of murine B16 melanoma by 63% but showed no appreciable activity when administered subcutaneously or intraperitoneally to mice beginning a number of days after tumor inoculation against a variety of human tumor xenografts. The peak plasma concentration of oryzalin following repeated subcutaneous administration of oryzalin at 600 mg/kg per day to mice was 37 microM and of its major metabolite N-depropyl oryzalin was 53 microM. CONCLUSION: It is unlikely that the absence of significant antitumor activity of oryzalin is a result of the inability to achieve adequate plasma concentrations.

3T3 Cells↗
PubMed1997

Liaison psychiatry and psychology in dentistry.

Dentists are trained to provide treatment for patients with straightforward problems that respond to routine therapy and do not recur. However, patients may present to dentists and complain solely of physical symptoms such as toothache, headache, and facial pain: only after much inappropriate treatment these symptoms are revealed to be due to emotional disturbance. The dentist may spend hours investigating such patients, in some of whom dental pathology may be present, but the symptoms and ensuing disability cannot be satisfactorily explained as a result. There are other patients who are preoccupied by physical symptoms or by their appearance. In others, anxiety may manifest itself as a phobia, or a dysmorphic concern about certain aspects of their appearance. This article reviews the role of liaison psychiatry and psychology in dentistry.

Dental Anxiety↗
PubMed1997

Does short-term group therapy affect unexplained medical symptoms?

This paper describes an intensive time-limited group-therapy program conducted in a busy surgical clinic by two nursing staff with the support of a consultant psychiatrist. Nineteen patients with chronic idiopathic facial pain were recruited to the study and underwent weekly group therapy over 8 weeks. At the end of the study period, results showed decreases in pain, anxiety and depression scores, along with an improvement in the patients coping skills. The findings support the use of group psychological interventions undertaken by appropriately trained nursing staff in reducing symptoms associated with chronic idiopathic facial pain.

Adult↗
PubMed1997

The effect of okadaic acid on non-adrenergic non-cholinergic contraction in guinea-pig isolated bronchus.

1. We have investigated the role of phosphatases in modulating contractile responses to electrical field stimulation (EFS), methacholine, substance P and capsaicin in guinea-pig isolated main bronchus by use of the phosphatase 1 and 2A inhibitor okadaic acid. 2. Non-adrenergic non-cholinergic (eNANC) contractile responses were elicited by EFS (3 Hz, 20 s, 0.5 ms max. voltage) in the guinea-pig isolated main bronchus in the presence of the non-selective muscarinic antagonist, atropine (1 microM), the non-selective beta-adrenoceptor antagonist; propranolol (1 microM), the neutral endopeptidase inhibitor thiorphan (10 microM) and the cyclo-oxygenase inhibitor, indomethacin (5 microM). Okadaic acid significantly attenuated eNANC contractile responses (% inhibition) elicited by EFS (0.01 microM, 15.2 +/- 26.9%; 0.03 microM, 30.4 +/- 13.9%; 0.01 microM, 39.8 +/- 5.1%; 0.3 microM, 59.5 +/- 8.7%; 1 microM 77.8 +/- 7.8%; P < 0.05, n = 4). In contrast, the inactive analogue 1-Nor okadaone (0.3 microM) failed to attenuate significantly eNANC contractile responses (% inhibition elicited by 1-Nor okadaone, -1.25 +/- 8.5% vs dimethylsulphoxide (DMSO), -13.5 +/- 21.5%; P > 0.05, n = 4). 3. Cholinergic contractile responses were elicited by EFS (1-30 Hz, 10 s, 0.5 ms max. voltage) in guinea-pig isolated bronchus in the presence of the nitric oxide synthase inhibitor, N omega-nitro-L-arginine methyl ester (L-NAME, 30 microM). Okadaic acid failed to attenuate significantly the contractile (% methacholine Emax) response elicited by EFS at all frequencies tested compared with the control (1 Hz, control, 22 +/- 7.9% vs okadaic acid, 18 +/- 7.7%; 3 Hz, control, 26 +/- 6.9% vs okadaic acid, 27 +/- 9.1%; 10 Hz, control, 36 +/- 7.6% vs okadaic acid, 33 +/- 8.9%; 30 Hz, control, 50 +/- 7.6% vs okadaic acid, 42 +/- 14%; P > 0.05, n = 4). 4. Okadaic acid (0.3 microM) failed to alter significantly the contractile potency (pD2) to capsaicin (okadaic acid, 9.0 +/- 0.5, vs DMSO, 9.2 +/- 0.4; P > 0.05 n = 6), substance P (okadaic acid, 7.6 +/- 0.3 vs DMSO, 8.2 +/- 0.2; P > 0.05 n = 7) or methacholine (okadaic acid, 6.4 +/- 0.2 vs DMSO, 6.4 +/- 0.3; P > 0.05 n = 4). 5. Okadaic acid (0.01-1 microM) did not appear to reverse substance P-induced tone. The maximal relaxant response (% reversal of substance P-induced tone) mediated by okadaic acid (1 microM) was 33 +/- 11.7% (n = 4), this was not significantly different from the DMSO (0.8%) or a time-dependent fall in tone of 34.3 +/- 23.1% (n = 4) and 33 +/- 15.8% (n = 4), respectively. Okadaic acid (0.3 microM) failed to augment isoprenaline-induced relaxation responses in substance P contracted bronchus (okadaic acid, 6.5 +/- 0.4 vs DMSO, 5.9 +/- 0.3; P > 0.05, n = 9). 6. These results indicate that protein phosphatases appear to regulate the release of sensory neuropeptides from airway sensory nerves in response to electrical field stimulation.

Animals↗
PubMed1997

Immunologic responses to vaccinia vaccines administered by different parenteral routes.

To develop a less reactogenic but equally immunogenic vaccine, this study of 91 human volunteers compared the safety and immunogenic potency of a new, cell culture-derived vaccinia virus vaccine administered intradermally and intramuscularly with the licensed vaccinia vaccine administered by scarification. Cutaneous pox lesions developed in a higher proportion of scarification vaccinees. Scarification and intradermal vaccine recipients who developed cutaneous pox lesions had more local reactions but also achieved significantly higher cell-mediated and neutralizing antibody responses than those who did not develop pox lesions. Although less reactogenic, intradermal or intramuscular administration of vaccinia vaccine without the concomitant development of a cutaneous pox lesion induced lower immune responses.

Antibodies, Viral↗
PubMed1997

Glial development in the Drosophila CNS requires concomitant activation of glial and repression of neuronal differentiation genes.

Two classes of glial cells are found in the embryonic Drosophila CNS, midline glial cells and lateral glial cells. Midline glial development is triggered by EGF-receptor signalling, whereas lateral glial development is controlled by the gcm gene. Subsequent glial cell differentiation depends partly on the pointed gene. Here we describe a novel component required for all CNS glia development. The tramtrack gene encodes two zinc-finger proteins, one of which, ttkp69, is expressed in all non-neuronal CNS cells. We show that ttkp69 is downstream of gcm and can repress neuronal differentiation. Double mutant analysis and coexpression experiments indicate that glial cell differentiation may depend on a dual process, requiring the activation of glial differentiation by pointed and the concomitant repression of neuronal development by tramtrack.

Animals↗
PubMed1996

The indirect immunobead test for seminal antisperm antibodies and fertilization rates at in-vitro fertilization.

A series of 183 patients with positive indirect immunobead tests on semen was studied to determine the correlation in semen between specific antibody types, binding sites, antibody concentration, and fertilizing ability. IgM was present in only 44 ejaculates and was present in sufficient quantity to cause significant binding to immunobeads (i.e. >20% of motile donor spermatozoa) in only three of them. There was no correlation between the percentages of motile donor spermatozoa that bound IgA and IgG immunobeads but the two classes of beads generally bound to the same region of the spermatozoa. A total of 63 couples went on to attempt in-vitro fertilization (IVF) treatment, all with mature eggs recovered. Of these mature eggs, 44% were fertilized and cleaved normally in comparison to 68% in a group of patients with tubal disease. Fertilization rates in individuals followed a bimodal distribution with a substantial number of couples experiencing zero or very poor rates (0-20%), the mode for the remainder lying between 60 and 80%. The fertilization rate tended to decrease as the amount of antibody increased. The percentage of donor spermatozoa that bound to immunobeads, taken as the greater of IgA and IgG, was selected by logistic regression as a significant predictor of poor fertilization (rate <=25%). The predictive power of the equation was improved by including the motile normal sperm concentration but the equation could only account for a small proportion of the total variation in fertilization rate. The presence of antibodies to the sperm head was highly correlated with the antibody concentration but was not selected as a predictor of fertilization. We conclude that the nature of the antigen against which the seminal antisperm antibody is directed may be as important as the antibody concentration in affecting sperm function. There seems to be little practical value in measuring IgM in seminal plasma.

Adult↗
PubMed1996

End of the line? Tramtrack and cell fate determination in Drosophila.

Cell differentiation reflects the balance of two opposing influences, pathways which confer specialized properties on specific cells or groups of cells, and antagonising mechanisms which modulate responsiveness to such differentiative cues. It appears that the zinc finger protein Tramtrack (Ttk) fulfils the latter function in the CNS and PNS of Drosophila. Ttk seems to be able to inhibit neural development by down-regulating competence to respond to neuralising signals. We speculate, however, that restriction of neural competence is merely one example of a more general ability of Ttk to influence differentiation and that, given its widespread expression profile, Ttk might be implicated in a number of differentiative events.

Animals↗
PubMed1996

Health Management Guide. Disease management.

Disease management has been described as a comprehensive, integrated approach to care and reimbursement based on the natural course of a disease. It requires a management approach which brings together research evidence, best practice and inter-professional and inter-agency working. Starting with the ideal of continuity of care for individual patients, it implies structured co-ordination of care over time and across primary, secondary and tertiary settings. The appeal of disease management is that it promises reduced costs, combined with increased quality of care and patient satisfaction. But the concept is open to different definitions and interpretations and its effectiveness in improving UK healthcare is still largely untested. This Health Management Guide removes the mystique behind disease management and puts it in the context of existing knowledge and practice. Treating it as a concept, rather than a specific technique, it distinguishes between its different potential applications, offers practical guidance on implementation, and reports on how NHS organisations are taking it forward.

Asthma↗
PubMed1996

General practice fundholding in the UK National Health Service: evidence to date.

The published evidence on the effects of General Practitioner Fundholding, a major feature of the 1991 reorganization of the UK National Health Service, is reviewed with regard to the source and character of the evidence, as well as the findings on the outputs (including referrals, prescribing, service shifts, and the attitudes of various actors); the processes (inter- and intra-organizational); and the inputs (costs). An overall assessment based on this evidence is presented; the latest political and organisational developments in NHS primary care are outlined; and the future of GP fundholding is discussed.

Cost-Benefit Analysis↗
PubMed1995

The eastern Australian childhood nevus study: prevalence of atypical nevi, congenital nevus-like nevi, and other pigmented lesions.

BACKGROUND: Various melanocytic lesions are frequently observed. An understanding of phenotypic factors and environmental stimuli that are associated with these lesions may help explain their pathogenesis. OBJECTIVE: This study was undertaken to determine the prevalence of atypical nevi, blue nevi, cafe-au-lait macules, congenital nevus-like nevi, halo nevi, nevi spili, nevi 5 mm or more in diameter, and skin-colored melanocytic nevi in a population of schoolchildren and to explore risk factors including solar radiation in the development of these melanocytic lesions. METHODS: A cross-sectional study was performed by the same medical investigators to examine schoolchildren in three Australian cities that span a wide range of latitudes. RESULTS: Data from 1123 white Australian schoolchildren, 6 to 15 years of age, were analyzed. Acquired melanocytic nevi (atypical nevi, nevi > or = 5 mm in diameter, and skin-colored nevi) were more likely to develop in older fair-skinned subjects who had freckles and lived closest to the equator. Café-au-lait macules and congenital nevus-like nevi were observed in 36.3% and 4.4% of the total population, respectively. Prevalence for both these types of melanocytic lesions increased significantly with decreasing latitude. Halo nevi were present in 5.3% of the subjects and were usually solitary. These lesions were related to the presence of atypical nevi primarily by virtue of their size rather than of other features of clinical atypia. CONCLUSION: Like melanocytic nevi in general, large and atypical nevi are strongly influenced by geographic location and, by implication, degree of solar radiation. The same can be said for congenital nevus-like nevi, which suggests that many so-called congenital nevi are in fact acquired early in life.

Adolescent↗