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Biomedical subjects

S Reid

Publications and source records attributed to S Reid.

At least 19 recordsLinked to original sources

In vivo induction of massive proliferation, directed migration, and differentiation of neural cells in the adult mammalian brain.

The development of an in vivo procedure for the induction of massive proliferation, directed migration, and neurodifferentiation (PMD) in the damaged adult central nervous system would hold promise for the treatment of human neurodegenerative disorders such as Parkinson's disease. We investigated the in vivo induction of PMD in the forebrain of the adult rat by using a combination of 6-hydroxydopamine lesion of the substantia nigra dopaminergic neurons and infusions of transforming growth factor alpha (TGFalpha) into forebrain structures. Only in animals with both lesion and infusion of TGFalpha was there a rapid proliferation of forebrain stem cells followed by a timed migration of a ridge of neuronal and glial progenitors directed toward the region of the TGFalpha infusion site. Subsequently, increasing numbers of differentiated neurons were observed in the striatum. In behavioral experiments, there was a significant reduction of apomorphine-induced rotations in animals receiving the TGFalpha infusions. These results show that the brain contains stem cells capable of PMD in response to an exogenously administered growth factor. This finding has significant implications with respect to the development of treatments for both acute neural trauma and neurodegenerative diseases.

Animals↗

A controlled trial of an educational pamphlet to prevent disability after occupational low back injury.

STUDY DESIGN: Randomized controlled trial. OBJECTIVE: To test the ability of an educational pamphlet to improve recovery in terms of pain, work status, and health care utilization after occupational low back injury. BACKGROUND: Low back pain and disability persist as occupational health problems of epidemic proportions. Because interventions based on biomechanical models have had limited impact, recent educational approaches to preventing back problems have stressed psychosocial recovery issues. METHODS: A pamphlet was developed by compiling activity resumption, self-care, and attitudinal advice from recent publications. The pamphlet was sent at random to half of all consenting workers reporting back pain within 11 days of occupational injury between 7/96 and 6/97. Three and 6 months later, back pain, work status, health care use, and pamphlet impact outcomes were assessed through structured telephone interviews. RESULTS: Of the 726 eligible workers, 486 consented to participate. Consenters and nonconsenters and intervention and control groups were similar in initial demographic variables. The pamphlet had no statistically significant impact at the 0.05 significance level on pain severity or reduction, health care visits, or work absence. Of the 229 pamphlet recipients, 129 thought it had provided useful information, but only 25 thought it had helped them return to work more quickly. CONCLUSIONS: In this trial, a pamphlet stressing psychosocial recovery issues did not prevent or reduce postinjury pain, health care use, or work absence.

Adult↗

Long-term impact on a closed household of pet cats of natural infection with feline coronavirus, feline leukaemia virus and feline immunodeficiency virus.

A closed household of 26 cats in which feline coronavirus (FCoV), feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) were endemic was observed for 10 years. Each cat was seropositive for FCoV on at least one occasion and the infection was maintained by reinfection. After 10 years, three of six surviving cats were still seropositive. Only one cat, which was also infected with FIV, developed feline infectious peritonitis (FIP). Rising anti-FCoV antibody titres did not indicate that the cat would develop FIP. The FeLV infection was self-limiting because all seven of the initially viraemic cats died within five years and the remainder were immune. However, FeLV had the greatest impact on mortality. Nine cats were initially FIV-positive and six more cats became infected during the course of the study, without evidence of having been bitten. The FIV infection did not adversely affect the cats' life expectancy.

Animals↗

Bacteriological quality of raw oysters in Trinidad and the attitudes, knowledge and perceptions of the public about its consumption.

In Trinidad and Tobago, raw oyster cocktails are a delicacy, but they are generally believed to be responsible for illness in the consumer. The microbial loads of raw oysters, condiments/spices and ready-to-consume oyster cocktails were determined in four sampling areas. Questionnaires were also administered to 72 oyster vendors to determine practices that affect the bacteriological quality of the products. Three hundred members of the public were interviewed to determine the attitudes, knowledge and perceptions of the public about raw oyster consumption. The mean total aerobic plate count (TAPC) per g of 50 samples each, of raw oysters, condiments/spices and ready-to-consume raw oyster cocktails averaged from 1.0 x 10(7)+/-4.3 x 10(7) to 1.4 x 10(8)+/-6.4 x 10(8), 2.0 x 10(5)+/-1.0 x 10(6) to 2.0 x 10(7)+/-1.4 x 10(8), and 4.3 x 10(5)+/-1.0 x 10(6) to 2.2 x 10(6)+/-1.0 x 10(7), respectively. The difference for each product among the four areas was statistically significant (P < or = 0.05; chi2). Using a recommended maximum standard of TAPC per g of 5.0 x 10(5), 115 (57.5%), 27 (13.5%) and 51 (25.5%) of 200 samples each, of raw oysters, condiments/spices and oyster cocktails, respectively, were considered unfit for human consumption. Amongst vendor practices, source of oyster harvest and length of time between separation of oyster meat from shell and sale, significantly affected the mean TAPC per g and the prevalence of unfit oyster cocktail samples. Consumption of raw oyster cocktails was more prevalent amongst males (73.6%) than females (26.4%) (P < 0.002), East Indians (63.2%) as compared with other respondents (36.8%) (P < 0.001), individuals < or = 40 years old (82.1%) than in individuals > 40 years of age (17.9%) (P < 0.01), and in individuals who were aware that raw oysters are considered to be a sexual enhancer (86.8%) as compared to those who did not have this perception (11.3%) (P < 0.03). Fear of falling ill prevented 44 (37.9%) of 116 non-consumers from eating oyster cocktails, while 13 of 106 consumers (12.3%) reported having experienced an oyster-borne illness. The rather high prevalence of raw oyster cocktails found to be unfit for human consumption, coupled with the perceptions and attitudes of the consumers about the product, pose a significant health risk to the public.

Animals↗

Seasonality, social zeitgebers and mood variability in entrainment of mood. Implications for seasonal affective disorder.

BACKGROUND: Seasonal variations in mood (seasonality) appear to be entrained to light, a physical zeitgeber. We hypothesised that people high in seasonality may be responsive to a range of zeitgebers, because of greater mood variability. We investigated whether the moods of people high in seasonality were more strongly entrained to the calendar week, a social zeitgeber, and whether any such effect was dependent on variability of mood. METHODS: 53 participants (14 male, 39 female; overall mean age=30) completed a daily mood report, over 56 consecutive days. Participants also completed the Seasonality Score Index (SSI) of the Seasonal Pattern Assessment Questionnaire. Each participant's time series of daily mood was analysed by spectral analysis to quantify the strength of their weekly mood cycle. RESULTS: Participants with high SSI scores (> or =11) had significantly stronger weekly mood cycles than those with low SSI scores (<11), and significantly greater variability in mood. Covarying for mood variability reduced the difference between high and low SSI groups in mean strength of weekly mood cycle to non-significance. LIMITATIONS: The time series of moods obtained was relatively short, and moods among high seasonal participants may have been affected by seasonal weather variability. CONCLUSIONS: People high in seasonality appear to be more responsive to external zeitgebers, and this could be linked to their greater variability in mood. The integration of research on mood variability with research on SAD appears to be warranted.

Adult↗

Philadelphia-positive T-ALL in a patient with follicular lymphoma.

Follicular lymphoma is a B cell malignancy prone to transformation into a large cell diffuse histology. This progression may be multi-clonal as determined by IgH rearrangement. Similar multi-clonal occurrences have been described in immunocompromised patients. However, the lymphoma cells remain predominantly of B cell type. Rarely, composite lymphomas with diffuse T cell histology have been reported arising from follicular lymphoma. The development of T cell leukaemia in a patient with a pre-existing B cell malignancy is an extremely rare event. The occurrence of T cell acute lymphoblastic leukaemia (T-ALL) following follicular lymphoma (FL) has not previously been reported. We report a case of Philadelphia positive (Ph+) T cell ALL developing in a patient who previously had FL which may give some insight into the cell of origin and the defects responsible for malignant transformation of the lymphocytes.

Adult↗

Targeted early rescue surfactant in ventilated preterm infants using the click test.

OBJECTIVE: To determine whether use of the click test, a rapid bedside test of surfactant function, results in earlier and more appropriate surfactant administration in ventilated preterm infants than does usual early rescue treatment. STUDY DESIGN: Ventilated preterm infants (n = 126) with inspired oxygen >/=25% and mean airway pressure >/=7 cm H(2)O were randomized in gestational strata (<28 weeks and 28-36 weeks) to have surfactant therapy determined by the click test or by usual clinical and chest radiograph criteria. The treatment group had the click test performed on a tracheal aspirate as soon as possible after intubation and, if negative or equivocal (surfactant deficient), surfactant was given. The control group had surfactant given as soon as possible based on clinical and chest radiograph diagnoses of respiratory distress syndrome. RESULTS: In infants of <28 weeks' gestation, use of the click test resulted in significantly earlier surfactant therapy (median time: 50 vs 159 minutes) and a reduction in the number of infants receiving surfactant (48% vs 79%). In infants of 28 to 36 weeks' gestation, there was no difference in time to surfactant (median time: 300 vs 268 minutes) or in the number of infants receiving surfactant. Neonatal morbidity and mortality were similar in click test and control groups. CONCLUSIONS: Use of the click test in ventilated, extremely premature infants results in significantly earlier and more appropriately targeted administration of surfactant than does early rescue therapy based on clinical and radiograph criteria. A randomized trial of targeted early rescue surfactant therapy versus prophylactic surfactant therapy in infants of <28 weeks' gestation is warranted. The click test has the potential to improve clinical outcomes and reduce costs.

Diagnostic Techniques, Respiratory System↗

Optimized production of recombinant bluetongue core-like particles produced by the baculovirus expression system.

The baculovirus-expression vector system (BEVS) has been widely used for the experimental production of many human and animal single- and multi-unit vaccines, heterologous proteins, and viral insecticides. In this work, the production of recombinant bluetongue virus core-like particles (CLPs), using Sf9 cells in shaker-suspension culture with the SF900 II medium (GIBCO, NY), has been studied. This system involved the simultaneous production of two proteins, VP7 and VP3, and was shown to achieve high volumetric productivities. The key parameters of the time of infection (TOI), and the multiplicity of infection (MOI) were studied. The results show that the peak-volumetric yields and cell-specific yields achieved using low MOIs at low-cell densities were the same as those obtained following infections with a high MOI at high-cell densities. This work establishes the feasibility of using low MOIs in the baculovirus system to produce complex multiprotein particles.

Animals↗

Plasma estradiol FSH and LH concentration after dominant follicle aspiration in the cow.

This work investigates the estrogenic role of the dominant follicle with regard to regulation of plasma FSH and LH concentration. Eight Holstein-Friesian cows were used for aspiration of the dominant follicle using ultrasound guidance during the early, mid and late stages of the luteal phase. Blood samples were collected at 15-min intervals from 4 h before until 7 h after aspiration. Plasma progesterone concentration increased from 0.7 to 7.2 ng mL-1 from early to mid luteal phase and then fell slightly to 5.9 ng mL-1 in the late luteal phase, but remained unaffected by follicle puncture. The follicular aspirate contained a thousandfold higher estradiol, than plasma concentration but its estradiol:progesterone ratio remained at around 2 at each stage of the luteal phase. Aspiration caused plasma estradiol concentration to fall from 1.4 to 0.7, 1.8 to 1.0 and 1.7 to 0.8 pg mL-1 in the early, mid and late stages of the luteal phase, respectively (P < 0.05). At the same time, mean plasma FSH concentration was increased from 1.1 to 1.8, 1.7 to 2.9 and 0.8 to 1.9 ng mL-1 (P < 0.05), respectively. The results suggest that estradiol secreted from dominant follicles selectively regulates gonadotropin secretion, since aspiration of the dominant follicle at any stage of the cycle affected circulating FSH but did not appear to influence the mean LH concentration.

Animals↗

Crystal structures of thrombin complexed to a novel series of synthetic inhibitors containing a 5,5-trans-lactone template.

The binding modes of four active site-directed, acylating inhibitors of human alpha-thrombin have been determined using X-ray crystallography. These inhibitors (GR157368, GR166081, GR167088, and GR179849) are representatives of a series utilizing a novel 5, 5-trans-lactone template to specifically acylate Ser195 of thrombin, resulting in an acyl complex. In each case the crystal structure of the complex reveals a binding mode which is consistent with the formation of a covalent bond between the ring-opened lactone of the inhibitor and residue Ser195. Improvements in potency and selectivity of these inhibitors for thrombin are rationalized on the basis of the observed protein/inhibitor interactions identified in these complexes. Occupation of the thrombin S2 and S3 pockets is shown to be directly correlated with improved binding and a degree of selectivity. The binding mode of GR179849 to thrombin is compared with the thrombin/PPACK complex [Bode, W., Turk, D., and Karshikov, A. (1992) Protein Sci. 1, 426-471] as this represents the archetypal binding mode for a thrombin inhibitor. This series of crystal structures is the first to be reported of synthetic, nonpeptidic acylating inhibitors bound to thrombin and provides details of the molecular recognition features that resulted in nanomolar potency.

Binding Sites↗

Enhanced myeloid progenitor cell cycling and apoptosis in mice lacking the chemokine receptor, CCR2.

Chemokines regulate hematopoiesis in part by influencing the proliferative status of myeloid progenitor cells (MPC). Human MCP-1/murine JE, a myelosuppressive chemokine, specifically binds C-C chemokine receptor 2 (CCR2). Transgenic mice containing a targeted disruption in CCR2 that prevents expression of CCR2 mRNA and protein and have MPC that are insensitive to inhibition by MCP-1 and JE in vitro were assessed for potential abnormalities in growth of bone marrow (BM) and spleen MPC. MPC in both unseparated and c-kit+lin- populations of BM from CCR2-deficient (-/-) mice were in a greatly increased proliferation state compared with CCR2 littermate control (+/+) mice, an effect not apparent with progenitors from spleens of CCR2 (-/-) mice. Increased cycling status of CCR2 (-/-) BM MPC did not result in increased numbers of nucleated cells or MPC in BM or spleens of CCR2 (-/-) mice. Possible reasons for this apparent discrepancy were highlighted by flow cytometric analysis of c-kit+lin- BM cells and colony formation by MPC subjected to delayed addition of growth factors. The c-kit+lin- population of BM cells from CCR2 (-/-) mice had a significantly higher percentage of apoptotic cells than those from CCR2 (+/+) BM. However, elevated apoptosis was not associated with decreased numbers of c-kit+lin- cells. The increased percentage of apoptotic c-kit+lin- cells was due to elevated apoptosis within the c-kitdimlin-, but not the c-kitbrightlin-, subpopulations of cells. Consistent with enhanced apoptosis of phenotypically defined cells, MPC from CCR2 (-/-) BM and purified c-kit+lin- cells demonstrated decreased cell survival in vitro upon delayed addition of growth factors. The data suggest that signals received by CCR2 limit proliferation of progenitor cells in the BM, but also enhance survival of these cells.

Animals↗

The future of the immunisation schedule: recommendations of a workshop.

The Ministry of Health convened a workshop in June 1998 on the future of the immunisation schedule. Your comments are invited on the recommendations of the workshop. PRINCIPLES BEHIND THE SCHEDULE: Improve on-time immunisation coverage as the priority. Reaching the last 20% will cost at least as much as the first 80% and is vital to achieve the aims of the immunisation programme (disease elimination and improved control). Obtain regular secure coverage data, derived from a tracking system that ensures children are followed up. Assess compliance with early childhood centre immunisation checks at entry and improve if necessary. Establish an expert committee to advise on the immunisation schedule and policies. Keep the schedule as simple as possible. Accept that vaccines are not generic and future schedule recommendations may be vaccine-specific. Involve providers in the process of change. PROPOSED CHANGES: Move the second dose of measles-mumps-rubella vaccine from age 11 years to around five years. Consider moving the third visit from five to four months to achieve earlier protection against pertussis. Consider adding a fifth dose of pertussis vaccine. Change to acellular pertussis vaccine, once suitable vaccines are available. Change to inactivated polio vaccine, once suitable vaccines are available. Consider omitting the fourth dose of polio vaccine. Consider introducing an adult immunisation schedule with fewer adult tetanus-diphtheria boosters.

Adult↗

p21(cip-1/waf-1) deficiency causes deformed nuclear architecture, centriole overduplication, polyploidy, and relaxed microtubule damage checkpoints in human hematopoietic cells.

A recent hypothesis suggests that tumor-specific killing by radiation and chemotherapy agents is due to defects or loss of cell cycle checkpoints. An important component of some checkpoints is p53-dependent induction of p21(cip-1/waf-1). Both p53 and p21 have been shown to be required for microtubule damage checkpoints in mitosis and in G1 phase of the cell cycle and they thus help to maintain genetic stability. We present here evidence that p21(cip-1/waf-1) deficiency relaxes the G1 phase microtubule checkpoint that is activated by microtubule damage induced with nocodazole. Reduced p21(cip-1/waf-1) expression also results in gross nuclear abnormalities and centriole overduplication. p53 has already been implicated in centrosome regulation. Our findings further suggest that the p53/p21 axis is involved in a checkpoint pathway that links the centriole/centrosome cycle and microtubule organization to the DNA replication cycle and thus helps to maintain genomic integrity. The inability to efficiently upregulate p21(cip-1/waf-1) in p21(cip-1/waf-1) antisense-expressing cells in response to microtubule damage could uncouple the centrosome cycle from the DNA cycle and lead to nuclear abnormalicies and polyploidy. A centrosome duplication checkpoint could be a new target for novel chemotherapy strategies.

Cell Cycle↗

The proteasome regulates caspase-dependent and caspase-independent protease cascades during apoptosis of MO7e hematopoietic progenitor cells.

Withdrawal of trophic support from growth factor-dependent MO7e human myeloid progenitor cells induces apoptosis characterized by DNA fragmentation and degradation of the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs). Inhibitors of caspase (ICE) protease family members did not inhibit apoptosis or DNA fragmentation induced by factor withdrawal, but blocked degradation of DNA-PKcs. Thus, caspase activity accounts for only a component of the apoptotic program in MO7e hematopoietic cells. The protease inhibitor TPCK, but not other protease inhibitors, blocked DNA fragmentation, but not degradation of DNA-PKcs during apoptosis of MO7e cells. Thus, caspase-independent and caspase-dependent protease cascades mediate distinct features of MO7e cell apoptosis. The proteasome inhibitors calpain inhibitor I and lactacystin promoted DNA fragmentation, degradation of DNA-PKcs and apoptosis of MO7e cells. The ability of lactacystin to promote DNA fragmentation was abrogated by TPCK, but not by caspase inhibitors, whereas the ability of lactacystin to promote degradation of DNA-PKcs was blocked by caspase inhibitors, but not by TPCK. Thus, caspase-dependent and caspase-independent protease cascades are downstream of and regulated by the proteasome, which plays a central role in regulating the multiple protease cascades that induce apoptosis.

Apoptosis↗

Yield, biological activity, and field performance of a wild-type Helicoverpa nucleopolyhedrovirus produced in H. zea cell cultures.

This paper reports studies of the in vitro production of a virus from Helicoverpa armigera (HaSNPV) and its possible use as a specific Helicoverpa/Heliothis larvicide. Growth kinetics of Helicoverpa zea (H. zea) cells and virus occlusion body yields were compared in three SF900II-based media, namely, SF900II (serum-free), SF900II + 1% serum, or SF900II + 10% serum. Viable cell densities were usually higher in the media supplemented with serum than in the serum-free medium; however, in the serum-free medium, cell diameters were 1.7 times greater (i.e., individual cell volumes were five times larger). Both volumetric production of virus occlusion bodies and production per cell were higher in the serum-free medium than in the media supplemented with serum. However, the infectivity of the occlusion bodies from the serum-free medium was less than that with those from the medium supplemented with 10% serum, when compared in bioassays employing newly hatched larvae. The infectivity of the in vitro produced occlusion bodies was also less than that of in vivo produced occlusion bodies in a commercially available virus product, GemStar. High levels of infection of H. armigera larvae obtained in a preliminary field assessment on preflowering tomatoes using the in vitro produced occlusion bodies indicated the suitability of the in vitro process for biopesticide production.

Animals↗