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Biomedical subjects

L Adamson

Publications and source records attributed to L Adamson.

At least 19 recordsLinked to original sources

Generation of DC-based vaccine for therapy of B-CLL patients. Comparison of two methods for enriching monocytic precursors.

BACKGROUND: The generation of Ag-loaded DC under good manufacturing practice (GMP) conditions is logistically challenging and further compounded when the starting precursors need to be purified from B-CLL patients who have overwhelming numbers of circulating B-CLL cells and decreased numbers of monocytes. METHODS: We have previously demonstrated that DC with endocytosed B-CLL apoptotic bodies are powerful stimulators of anti-leukemic T cells. In this study we compared counterflow elutriation and immunomagnetic separation for enriching monocyte precursors, and evaluated the feasibility of generating DC from B-CLL patients and the effects of cryopreservation. RESULTS: Monocyte yield from a single leukapheresis product of a B-CLL patient varied from 1 x 108 to 10 x 108 total cells, from which 40-200 x 106 mature DC could be produced. Adequate numbers of monocytes could not be enriched from one patient with 0.2% monocytes in the leukapheresis product, and the target of 50 x 106 DC was barely achieved in another patient with 0.9% monocytes in the pheresed cells. These results suggested that successful production of DC is dependent on a minimum frequency of 1% CD14(+) monocytes in the leukapheresis product. Cryopreservation of tumor cell-loaded DC yielded a recovery rate of 86+/-4.4% upon thawing, with a total viability of 90+/-2.8%. Most importantly, cryopreserved Ag-loaded DC retained their morphology, phenotype and function. DISCUSSION: The results demonstrate that adequate numbers of functional DC required for clinical therapy can be generated from patients who have >1% of CD14(+) monocytes in the leukapheresis product. Moreover, Ag-loaded DC can be cryopreserved and recovered without significant change in phenotype or function.

Cancer Vaccines↗

Effects of human plasma proteins on maturation of monocyte-derived dendritic cells.

Dendritic cells (DC) are a promising tool for vaccine therapy due to their unique properties as antigen presenting cells and their ability to prime naïve T cells. Increasing evidence suggests that maturation stage of DC critically influences the fate of the immune response. Generation of monocyte-derived DC for clinically applicable immunotherapy requires the use of well-defined components and stringent culture conditions. An alternative strategy is to use human autologous serum. However, its constituents are not stable and reflect the inflammatory condition of the donor. In order to investigate whether DC properties are influenced by proteins present in the plasma, we matured human monocyte-derived DC with four main plasma components: fibrinogen, fibronectin, plasminogen or C-reactive protein. These purified proteins were added at various concentrations on day 6 after the initial differentiation induced by IL-4 and GM-CSF. The maturation was assessed by phenotyping of maturation-associated marker (CD83) and co-stimulatory molecule CD86 as well as IL-12 production. Functional properties of DC were assessed by endocytic activity and mixed leukocyte culture. Our results indicate that fibrinogen had DC-maturation effect comparable to poly-I:C, TNF-alpha and PGE(2) as a positive control, but it failed to induce IL-12 production. The other plasma proteins had no effect on DC maturation. CRP at high concentration had rather inhibitory effect on DC induced lymphocyte function. We conclude that none of the tested plasma components and acute phase proteins sufficiently induce fully competent mature DC. This finding is important for the preparation of human DC-based vaccines supplemented by autologous sera.

Antigens, CD↗

Domestic violence screening and intervention programmes for adults with dental or facial injury.

BACKGROUND: Domestic violence exists in all communities across the world. Healthcare services have a pivotal role in the identification, assessment and response to domestic violence. As the face is a common target in assault, dentists and oral and maxillofacial surgeons are in a unique position to screen for domestic violence in the context of presentation of dental and facial injury. Owing to lack of training, dentists and oral and maxillofacial surgeons may not be the best persons to give advice to someone experiencing domestic violence. Improper advice such as encouragement to leave an abusive relationship may escalate the frequency of violence. It may be more appropriate to refer to specialist agencies for intervention and support. It would, therefore be useful to know whether screening and intervention programmes are effective. OBJECTIVES: (1) To assess the benefits and harms of intervention programmes employed to reduce and or prevent domestic violence in adults with dental and/or facial injuries.(2) To assess the benefits and harms of screening and the use of different screening tools in the detection of the proportion of adult victims of domestic violence who present with dental and/or facial injury. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, CINAHL, PsycINFO and Lilacs databases. No language restrictions were applied. Personal contacts were used and international domestic violence organisations were contacted to identify any unpublished trials. Last search was done February 2004. SELECTION CRITERIA: Randomised controlled trials involving adults aged 16 years and over presenting with dental and/or facial injury relating to domestic violence in any healthcare setting. DATA COLLECTION AND ANALYSIS: Screening of eligible studies was conducted in duplicate and independently by two reviewers. Results were to be expressed as random effects models using weighted mean differences for continuous outcomes and relative risk for dichotomous outcomes with 95% confidence interval. Heterogeneity was to be investigated including both clinical and methodological factors. MAIN RESULTS: No eligible randomised controlled trials (RCTs) were identified. REVIEWERS' CONCLUSIONS: There is no evidence to support or refute that screening for domestic violence in adults with dental or facial injury is beneficial nor that it causes harm. Screening tools to detect domestic violence exist but no RCTs have specifically evaluated their effectiveness for patients presenting with facial and or dental injuries. There is also lack of evidence that intervention programmes are effective at reducing frequency of physical assaults and at reducing the severity of facial injuries.

Domestic Violence↗

Development of a technology platform for large-scale clinical grade production of DC.

BACKGROUND: Clinical studies require protocols where a sufficient number of well-characterized highly immunogenic DC are produced according to good manufacturing practice (GMP) guidelines. METHODS: In the present study, using leukapheresis products from 10 cancer patients, we validated an elutriation technology for large-scale clinical grade production of monocyte-derived DC. RESULTS: The elutriation method gave a very high purity (mean+/-SD) (86+/-5.3%) and recovery (66+/-10.4%) of monocytes. Specifically for the two monocyte-rich fractions (3 and 4,) the recovery was 42+/-13% of viable cells that could be further differentiated into immature DC in hydrophobic culture bags using GM-CSF and IL-4. The immature DC exhibited<1% CD83+ expression and >98% phagocytic activity. Maturation with TNF-alpha or poly I:C resulted in DC with expression of CD80+, CD86+ and HLA-DR+ (>99%) and CD83+ (80+/-11.9%), as well as producing IL-12p70 and lacking phagocytic activity (<5%). This cell product can be cryopreserved with cell viability >85% and cell recovery >80% after thawing. DISCUSSION: The elutriation procedure, when optimized and if the monocyte content of the starting material exceeds 5%, does not require further selection or depletion using affinity approaches.

Antigens, CD↗

Insulin-like growth factor type 1 upregulates uncoupling protein 3.

In this study the expression of uncoupling protein 3 (UCP3) and its regulation by insulin-like growth factor 1 (IGF-I) and insulin in human neuroblastoma SH-SY5Y cells were characterized. Reverse transcriptase-PCR, Western blot, and immunofluorescence analysis showed that SH-SY5Y cells express UCP3 natively. IGF-I induced a time- and concentration-dependent induction of UCP3 protein reaching a twofold expression after 72 h with 10 nM IGF-I. Extremely high insulin concentrations (860 nM) and 10 nM trIGF-I, a truncated form of IGF-I with the same affinity for the IGF-I receptor as the full-length IGF-I, but with lower activity on the insulin receptor, also upregulated UCP3. We conclude that SH-SY5Y cells express UCP3 natively and that the expression is regulated by IGF-I via the IGF-I receptor.

Carrier Proteins↗

The Illawarra Coordinated Care Trial: better outcomes with existing resources?

The Illawarra Coordinated Care Trial was one of nine Australian trials undertaken to see whether different models of coordinated care could improve the health of people with multiple service needs within existing resources. This paper summarises the findings of an extensive local evaluation and discusses the impact of the trial on clients and service providers. It examines the main findings related to the principal trial hypothesis and points to lessons that might inform the next round of trials.

Aged↗

Altered fetal pituitary-adrenal function in the ovine fetus treated with RU486 and meloxicam, an inhibitor of prostaglandin synthase-II.

Term and preterm labor are associated with increased fetal hypothalamic-pituitary-adrenal (HPA) activation and synthesis of prostaglandins (PGs) generated through the increased expression of prostaglandin H synthase-II (PGHS-II) in the placenta. Inhibition of PGHS-II has been advocated as a means of producing uterine tocolysis, but the effects of such treatment on fetal endocrine functions have not been thoroughly examined. Because PGE(2) is known to activate the fetal HPA axis, we hypothesized that administration of meloxicam, a PGHS-II inhibitor, to sheep in induced labor would suppress fetal HPA function. Chronically catheterized pregnant ewes were treated with RU486, a progesterone receptor antagonist, to produce active labor, and then treated with either high-maintenance-dose meloxicam, graded-maintenance-dose meloxicam, or a saline infusion. Maternal uterine contraction frequency increased 24 h after the RU486 injection and the animals were in active labor by 48 +/- 4 h. RU486 injection led to increased concentrations of PGE(2), ACTH, and cortisol in the fetal circulation, and increased concentrations of 13,14 dihydro 15-ketoprostaglandin F(2 alpha) (PGFM) in the maternal circulation. Uterine activity was inhibited within 12 h of beginning meloxicam infusion at both infusion regimes. During meloxicam infusion there were significant decreases in fetal plasma PGE(2), ACTH, and cortisol concentrations, and PGFM concentrations in maternal plasma. In control animals, frequency of uterine contractions, maternal plasma PGFM, fetal plasma PGE(2), ACTH, and cortisol concentrations increased after RU486 administration, and continued to rise during saline infusion until delivery occurred. We conclude that RU486-provoked labor in sheep is associated with activation of fetal HPA function, and that this is attenuated during meloxicam treatment to a level considered compatible with pregnancy maintenance.

6-Ketoprostaglandin F1 alpha↗

Effectiveness of the National Death Index for establishing the vital status of older women in the Australian Longitudinal Study on Women's Health.

OBJECTIVE: To assess the effectiveness of the National Death Index (NDI) in identifying participants in the oldest cohort of the Australian Longitudinal Study on Women's Health (ALSWH) who had died between 1996 and 1998. METHODS: Identifying information for each woman was matched with the NDI using a probabilistic algorithm and clerical review. Differences in full name, date of birth, State of residence and date of last contact were used to assess the probability of a true match. RESULTS: NDI identified 410 matches of death records for 409 women; 386 were categorised as true matches and 23 were doubtful matches. Responses to the follow-up survey confirmed that for six of the doubtful matches the women had died, 16 were alive and the vital status of one woman remained unconfirmed at 30 June 1998. Twelve deaths, known to have occurred before July 1998, were not identified through NDI. The sensitivity of the NDI for identifying known deaths was 95%. Detailed identifying information, particularly the middle name, was important for accurate identification of the vital status. CONCLUSIONS: Using surname, all given names, gender, date of birth, State of residence and age at last contact as matching variables, the NDI was an effective tool for identifying women who had died. IMPLICATIONS: Routinely collected mortality data in the NDI are useful for the practice of epidemiology.

Aged↗

Adolescent identity--a qualitative approach: self-concept, existential questions and adult contacts.

In-depth interviews were performed with 12 adolescents (Swedish students, 16-19 years). Three questions were probed; what do adolescents say on the subjects of (a) themselves, (b) their existential questions, and (c) their adult contacts. The first two questions were aimed at elucidating the process of identity development, the last one at factors that may be influencing this process. The results showed that (a) balancing and controlling one's own needs and wishes in relation to others' was a central issue, (b) existential questions mainly concerned the personal future, (c) adult contacts outside the family were scarce and (d) all respondents expressed a need for adult contacts as sources of knowledge and experience. The conclusions are that identity formation during late adolescence consists of integrative issues where adults play a specific and important role.

Adolescent↗

General practitioner screening for melanoma: sensitivity, specificity, and effect of training.

OBJECTIVE: To measure the performance of trained and untrained general practitioners (GPs) in screening men and women aged 50 or more for melanomas. METHODS: GPs trained in melanoma diagnosis, untrained GPs, and skin cancer specialists examined groups of volunteers, each of which included a small number of subjects with prediagnosed suspicious pigmented lesions (SPLs) that were subsequently excised for histopathological examination. RESULTS: Trained and untrained GPs achieved mean sensitivities of 0.73 and 0.71, and mean predictive values of 0.40 and 0.37, respectively, for the detection of prediagnosed SPLs. When the SPLs had been excised and examined histopathologically, reanalysis showed mean sensitivities of 0.98 and 0.95, mean specificities of 0.52 and 0.49, and mean positive predictive values of 0.24 and 0.22 for the detection of subjects with melanomas by trained and untrained GPs respectively. Trained GPs were significantly better than untrained GPs at diagnosing as melanomas SPLs that subsequently proved to be melanomas (p = 0.04). CONCLUSIONS: GPs in this study achieved high sensitivities in screening older Australian men and women for melanomas, but at the cost of low specificities and positive predictive values. Training in melanoma diagnosis had no significant effect on sensitivity, specificity, and positive predictive value for screening. Data from the study were tested in a model of population screening for melanomas, and costs per life year saved for men aged 50-70 ranged from $A11,852 to $A40,259 depending upon the screening interval and whether the GPs excised the SPLs diagnosed, or referred all patients to skin cancer specialists; this would be as cost effective as cervical cancer screening.

Female↗

The research and educational priorities of rural occupational therapists.

The aim of this pilot research project was to identify the research and educational priorities of occupational therapists practising in rural New South Wales. Eight participants were recruited in the south-western region of the State. The Delphi technique was used to obtain the most reliable consensus of the research participants. Priorities emerged in four designated areas: (1) research that would be of value to clients; (2) research that would be of value in providing community care for clients; (3) research that would be of value in facilitating health promotion and disease prevention; and (4) research that would be of value to professional and educational needs. In the final phase of the study, 23 high priorities were identified. The findings of the study suggest directions for research and continuing education in occupational therapy which may benefit rural practitioners and their clients.

Attitude of Health Personnel↗

Self-concept and questions of life: identity development during late adolescence

The purpose of the present study was to explore identity development in late adolescent (18-20) years. Three areas were examined: (a) self-concept, (b) existential questions; content and communication patterns, and (c), connections between (a) and (b). The population consisted of 44 Swedish college students. Three methods were used: a questionnaire, the writing of a short essay and a self-evaluation test, Structural Analysis of Social Behavior (SASB). The results demonstrated a positive and stable self-concept for the majority of the group, and that questions of life mainly concerned questions of future. The quality of the self-concept (positive vs. negative) was significantly related to how subjects experienced adults' interest in their existential questions. Several issues are discussed: the importance of the social environment for identity development not only during early childhood but also during adolescence, the use of the SASB method in this age group and the need for placing processes of integration into focus in research concerning late adolescence.

Journal Article↗

Crying in !Kung San infants: a test of the cultural specificity hypothesis.

The pattern of crying and fretting behavior during the first two years is described for 46 !Kung San infants from a hunter-gatherer society in northwestern Botswana. Despite markedly different caretaking practices predisposing to quieter infants, crying and fretting were significantly greater during the first three months, and a peak pattern was present. Measurement of crying 'intensity' indicated that it was predominantly short and fretful. The results support the concept that the early peak pattern is not specific to infants in western industrialized societies, and may represent a behavior universal to the human species. The caretaking differences between societies primarily appear to affect crying duration rather than its frequency and pattern in early infancy.

Arousal↗

Characterization of two genome types of adenovirus type 31 isolated in Stockholm during 1987.

The authors isolated during 1987 seven adenovirus type 31 (Ad31) within a 9-month period. The isolates were obtained from urine, throat, and feces, implying a systemic spread of the infection. Most patients displayed gastrointestinal symptoms, but some had respiratory symptoms and fever. All of the strains differed by restriction endonuclease analysis from the prototype strain (1315) by an additional Bgl II restriction site. Ad31 isolates 1-6 could be divided into two groups by the enzymes Bam HI, Msp I, and Xho I. Each enzyme gave rise to the same group distribution: isolates 1-3 and 4-6, respectively. Digestion with Bst EII, Hind III, Kpn I, and Sma I resulted in identical patterns for isolates 1-6. Isolate 7, however, demonstrated a DNA deletion of approximately 0.8 kbp, but it was otherwise identical to isolates 4-6. In conclusion, two separate genome types of Ad31 were isolated, one of which included a DNA deletion mutant. The increased isolation rate may reflect an epidemiological situation, as the same isolation procedure had been used both before and after this period.

Adenovirus Infections, Human↗

Fibrinogen Aarhus and factor XIII induced polymerization and gel formation.

Fibrinogen Aarhus is an abnormal fibrinogen for which the clotting time with thrombin is greatly prolonged both in plasma and in the isolated fibrinogen. The whole blood clotting time is only slightly prolonged. The patient with this fibrinogen has no bleeding tendency. In this report we have investigated fibrinogen Aarhus in two alternative, thrombin independent polymerization and gelation pathways. These pathways are the factor XIII dependent oligomerization and gelation of fibrinogen, and heteropolymer (fibrinogen-fibronectin) formation which also is catalysed by factor XIII. Both of these reactions are qualitatively the same in fibrinogen Aarhus as in normal fibrinogen, but the rate of oligomerization is somewhat slower in fibrinogen Aarhus. This may depend on impaired association between factor XIII and fibrinogen Aarhus.

Blood Coagulation Disorders↗

Application of an enzyme-linked immunosorbent assay (ELISA) to von Willebrand factor (vWF) and its derivatives.

Sandwich ELISA systems were developed to measure human von Willebrand factor (vWF). In one system the microtitre plates were coated with goat F(ab')2 to vWF. The F(ab')2 different molecular forms in the soluble phase. VWF antigen bound by the F(ab')2 antibody was subsequently determined by using horse-radish peroxidase labeled goat Fab' to vWF. In plasma 3 X 10(-4) units of vWF per ml could be detected with this system. In a different approach the antigen bound by the F(ab')2 antibody was probed by monoclonal antibodies to multimeric as well as to the reduced and carboxymethylated (RCM) form of vWF. Using these monoclonals and RCM-as well as native plasma as antigen, the total antigen and the relative proportion of multimeric forms in the sample were estimated.

Animals↗