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Biomedical subjects

K Higgins

Publications and source records attributed to K Higgins.

At least 19 recordsLinked to original sources
PubMed2003

Anger management training: the effects of a structured programme on the self-reported anger experience of forensic inpatients with learning disability.

Within the current political climate, there is an increasing burden on mental health professionals to achieve accuracy in risk assessment and prediction. The accurate assessment and treatment of anger can make a valuable contribution towards alleviating this burden as part of a comprehensive treatment package. This study describes an anger management training programme provided to a group of three forensic inpatients with learning disability. An ABA single case study design was used, with anger levels assessed at weekly intervals before, during and after the programme. The results suggested that anger management training is useful with this client group, with established tools, such as the Novaco Anger Scale, the Spielberger State-Trait Anger Expression Inventory and the Modified Overt Aggression Scale, allowing the impact of the programme on anger levels to be evaluated. There is an indication that maintenance treatment is required to prevent anger levels increasing to pretest levels following treatment.

Adult↗
PubMed2001

The BMP family member Gdf7 is required for seminal vesicle growth, branching morphogenesis, and cytodifferentiation.

Epithelial-mesenchymal interactions play an important role in the development of many different organs and tissues. The secretory glands of the male reproductive system, including the prostate and seminal vesicles, are derived from epithelial precursors. Signals from the underlying mesenchyme are required for normal growth, branching, and differentiation of the seminal vesicle epithelium. Here, we show that a member of the BMP family, Gdf7, is required for normal seminal vesicle development. Expression and tissue recombination experiments suggest that Gdf7 is a mesenchymal signal that acts in a paracrine fashion to control the differentiation of the seminal vesicle epithelium.

Animals↗
PubMed2001

Metapopulation extinction caused by mutation accumulation.

Theory suggests that the risk of extinction by mutation accumulation can be comparable to that by environmental stochasticity for an isolated population smaller than a few thousand individuals. Here we show that metapopulation structure, habitat loss or fragmentation, and environmental stochasticity can be expected to greatly accelerate the accumulation of mildly deleterious mutations, lowering the genetic effective size to such a degree that even large metapopulations may be at risk of extinction. Because of mutation accumulation, viable metapopulations may need to be far larger and better connected than would be required under just stochastic demography.

Genetics, Population↗
PubMed2000

Microparticles in MF59, a potent adjuvant combination for a recombinant protein vaccine against HIV-1.

Novel adjuvant formulations involving PLG microparticles with entrapped recombinant protein antigens (env gp120 and p24 gag) from human immunodeficiency virus type-1 (HIV-1), dispersed in the emulsion adjuvant MF59 were evaluated as potential HIV-1 vaccine candidates in mice and baboons. In mice, the adjuvant combination induced significantly enhanced antibody responses in comparison to either adjuvant used alone. In addition, the polylactide co-glycolide polymer (PLG) microparticles and MF59 combination induced CTL activity against HIV-1 p24 gag. In baboons, the adjuvant combination induced significantly enhanced antibody titers after a single dose of gp120, but the responses were comparable to gp120 in MF59 alone after boosting. Both MF59+gp120 alone and PLG/gp120 in MF59 induced neutralizing antibodies against a T cell line-adapted (TCLA) strain and a primary isolate of HIV-1. In contrast to the observations with gp120, immunization in baboons with PLG/p24 in MF59 induced significantly enhanced antibody responses after boosting, in comparison to immunization with MF59 alone + p24.

AIDS Vaccines↗
PubMed2000

Experimental evolution in Heterandria formosa, a livebearing fish: group selection on population size.

Group selection has historically been an important and controversial subject in evolutionary biology. There is now a compelling body of evidence, both theoretical and experimental, that group selection not only can be effective, but can be effective in situations when individual selection is not. However, experiments in which true population-level traits have been shown to evolve in response to group selection are currently limited to two species of flour beetle in the genus Tribolium and RNA viruses. Here we report the results of an experiment wherein we imposed group selection via differential extinction for increased and decreased population size at 6-week intervals, a true population-level trait, in the poeciliid fish Heterandria formosa. In contrast to most other group selection experiments, we observed no evolutionary response after six rounds of group selection in either the up- or down-selected lines. Populational heritability for population size was low, if not actually negative. Our results suggest that group selection via differential extinction may be effective only if population sizes are very small and/or migration rates are low.

Animals↗
PubMed1999

Australia's notifiable diseases status, 1998. Annual report of the National Notifiable Diseases Surveillance System.

In 1998 there were 85,096 notifications to the National Notifiable Diseases Surveillance System; slightly lower than in 1997 (89,579). The number of measles cases remained low, and well below the number reported in the outbreak years of 1993 and 1994. Rubella notifications further decreased and remained low in 1998. The Measles Control Campaign from August to November 1998, did not impact significantly on the number of measles or rubella cases reported for 1998. Notifications of Haemophilus influenzae type b reached a record low since surveillance began in 1991, and appeared to have stabilised at a low rate since the introduction of the conjugated vaccine in 1992. The previously reported outbreak of pertussis in 1997 tapered off in early 1998. Food-borne disease, or detection of disease, appeared to be on the rise with an increase in notification rates of campylobacteriosis and salmonellosis. Notifications of hepatitis A decreased, correcting the previous high number of notifications in 1997. Sexually transmissible diseases (STDs) increased. Notifications for chlamydial infection were the highest for all sexually transmitted diseases and third highest for all notifiable diseases. Notifications of gonococcal infection also continued to rise and have doubled since 1991, whilst notifications for syphilis increased slightly after falling steadily over recent years. Arbovirus infections of concern in 1998 were dengue outbreaks in Far North Queensland and the first case of Japanese Encephalitis for mainland Australia, highlighting the importance of surveillance of arboviruses and vectors for their detection and management.

Australia↗
PubMed1999

Population pharmacokinetics. A regulatory perspective.

The application of population approaches to drug development is recommended in several US Food and Drug Administration (FDA) guidance documents. Population pharmacokinetic (and pharmacodynamic) techniques enable identification of the sources of inter- and intra-individual variability that impinge upon drug safety and efficacy. This article briefly discusses the 2-stage approach to the estimation of population pharmacokinetic parameters, which requires serial multiple measurements on each participant, and comprehensively reviews the nonlinear mixed-effects modelling approach, which can be applied in situations where extensive sampling is not done on all or any of the participants. Certain preliminary information, such as the compartment model used in describing the pharmacokinetics of the drug, is required for a population pharmacokinetic study. The practical design considerations of the location of sampling times, number of samples/participants and the need to sample an individual more than once should be borne in mind. Simulation may be useful for choosing the study design that will best meet study objectives. The objectives of the population pharmacokinetic study can be secondary to the objectives of the primary clinical study (in which case an add-on population pharmacokinetic protocol may be needed) or primary (when a stand-alone protocol is required). Having protocols for population pharmacokinetic studies is an integral part of 'good pharmacometric practice'. Real-time data assembly and analysis permit an ongoing evaluation of site compliance with the study protocol and provide the opportunity to correct violations of study procedures. Adequate policies and procedures should be in place for study blind maintenance. Real-time data assembly creates the opportunity for detecting and correcting errors in concentration-time data, drug administration history and covariate data. Population pharmacokinetic analyses may be undertaken in 3 interwoven steps: exploratory data analysis, model development and model validation (i.e. predictive performance). Documentation for regulatory purposes should include a complete inventory of key runs in the analyses undertaken (with flow diagrams if possible), accompanied by articulation of objectives, assumptions and hypotheses. Use of diagnostic analyses of goodness of fit as evidence of reliability of results is advised. Finally, the use of stability testing or model validation may be warranted to support label claims. The opinions expressed in this article were revised by incorporating comments from various sources and published by the FDA as 'Guidance for Industry: Population Pharmacokinetics' (see the FDA home page http:/(/)www.fda.gov for further information).

Data Interpretation, Statistical↗
PubMed1998

A comparison of the prevalence of HIV infection and injecting risk behaviour in urban and rural samples in Scotland.

AIMS: To compare the prevalence of HIV infection and injecting risk behaviour among injecting drug users from urban and rural areas. DESIGNS: Two samples of injecting drug users were recruited using a multi-site sampling strategy. Respondents were first interviewed by trained interviewers then specimens of saliva were collected for anonymous testing for antibodies to HIV. SETTING: Respondents were recruited from drug treatment services and street sites. PARTICIPANTS: Respondents were eligible for inclusion in the study if they had "ever" injected a drug and were currently using drugs. MEASUREMENTS: Measurements taken included self-reported patterns of drug use and injecting risk behaviour. Specimens of saliva were tested for the presence of HIV infection using GACELISA with reactive specimens confirmed by Western blot analysis. FINDINGS: Our data indicate that there are two separate populations which are geographically discrete but broadly similar in profile and current injecting risk behaviour. The prevalence of HIV infection among IDUs from Dundee city was found to be 26.8% (95% CI, 20.2%-33.0%) compared with 3.7% (95% CI, 0.13%-15.8%) for IDUs from rural Tayside. This marked difference in prevalence of HIV infection we attribute to a high level of injecting risk among urban IDUs between 1980 and 1984, limited migration from the urban epicentre of infection and a reluctance among rural IDUs to share with IDUs outside their immediate social and kinship networks. CONCLUSIONS: Although current levels of injecting risk behaviour are similar in our urban and rural samples, rural IDUs may be less likely to contract HIV from their fellow injectors because of the lower prevalence of HIV infection and more closed sharing networks within the rural population. The implications of this for the development and expansion of drug services are considered.

Adult↗
PubMed1996

Hypertext support for remedial students and students with learning disabilities.

Student use of pop-up text windows that support or extend information found in a high school social studies text provides a detailed look into the instructional effectiveness of a set of hypermedia study guides. Twenty-five students, 19 male and 6 female, with a mean age of 14.6 years participated in this study. Thirteen were students with learning disabilities and 12 were remedial students. Findings from the study indicate that hypertext (text-only) support provides adequate reinforcement to move remedial students and students with learning disabilities toward continued, unprompted use of a hypermedia study guide, and that short-term and long-term retention of information can be expected from text-only information support. Students who had access to the hypermedia study guides exhibited better information retention than students who did not use the hypermedia study guides.

Adolescent↗
PubMed1995

Regulated expression of Ly-6A.2 is important for T cell development.

Ly-6A.2 is a surface protein on T cells that may play a role in lymphocyte activation. The regulation of Ly-6A.2 expression during T cell lymphopoiesis has been intriguing. It is one of the earliest markers expressed on pluripotent hemopoietic stem cells and is present on both primitive and mature T cells, but its expression is extinguished in the thymus during key developmental stages. To determine whether Ly-6A.2 is active on developing T cells, as well as the significance of its developmental regulation, Ly-6A.2 was expressed throughout T cell development under control of the T cell-specific human CD2 enhancer in transgenic mice. The constitutive overexpression of Ly-6A.2 in vivo led to a marked impairment in the generation of thymocytes. Development was arrested at the time in thymic development when Ly-6A.2 expression is normally turned off. These results indicate that the regulated expression of Ly-6A.2 in thymocytes may be important for normal development. Moreover, these findings demonstrate that Ly-6A.2 is active in the thymic microenvironment.

Animals↗
PubMed1995

Over-expression of CD3 epsilon transgenes blocks T lymphocyte development.

We have reported previously that mice carrying > 30 copies of the human CD3 epsilon transgene completely lose their T lymphocytes and NK cells (36). Here we demonstrate by immunohistology that in the most severely immunodeficient mouse, tg epsilon 26, the thymus is very small, has sizeable vacuoles and does not contain recognizable T lymphocytes except for a small percentage of Thy-1+ cells and B cells. Cell surface phenotyping and TCR alpha and -beta rearrangement studies confirm that the arrest in T lymphocyte development precedes the arrest in rag-1null, rag-2null and TCR beta nuli mice. Since the T cell progenitors in which the arrest occurred were absent in the transgenic mice, indirect approaches were taken to examine the causes of the block in T cell development. Analyses of 12 independently established mutant mouse lines, generated with five different transgenic constructs, revealed that the severity of the abrogation in T cell development was dependent on the number of copies of transgenes. Since the number of transgene copies generally correlated with the levels of expression of the transgenic CD3 epsilon proteins, we concluded that over-expression of the CD3 epsilon protein was the likely cause of the block in T lymphocyte development. The T cell immunodeficiency was caused by either the human or the murine CD3 epsilon protein. Since transgene coded mRNAs were found in significantly higher quantities than endogenous CD3 epsilon mRNAs in fetal thymi on days 13 and 14 of gestation, over-expression took place very early in development, probably prematurely. Over-expression of the CD3 epsilon transgene in thymocyte precursors may therefore affect T lymphocyte development in the absence of TCR and possibly in the absence of the other CD3 proteins. More importantly, over-expression of the CD3 epsilon protein in thymocytes of mice with a low copy number of transgenes had a significant effect on late thymic development. Over-expression of the CD3 epsilon protein in immature thymocytes mimicked the effects caused by exposure of CD4- CD8- thymocytes to anti-CD3 epsilon treatment: apoptosis and lack of TCR beta expression. We therefore speculate that in the homozygous tg epsilon 26 animals the arrest in T cell development was caused by excessive signal transduction events rather than by a toxic effect of the transgenic protein.

Amino Acid Sequence↗
PubMed1995

Resistance of chimpanzees immunized with recombinant gp120SF2 to challenge by HIV-1SF2.

OBJECTIVE: To determine whether vaccination with recombinant HIV-1SF2 gp120 in a novel oil-in-water adjuvant emulsion, MF59, protects chimpanzees against challenge with HIV-1SF2, the homologous virus isolate. METHODS: Two vaccinated chimpanzees and two control animals were challenged with 25-50 animal infectious doses of a stock of HIV-1SF2 that had been grown in mitogen-activated human peripheral blood mononuclear cells (PBMC). The animals were monitored by a series of serologic [enzyme-linked immunosorbent assay (ELISA), Western blot, and neutralization assays] and virologic [virus culture, RNA and DNA polymerase chain reaction (PCR)] assays for infection. RESULTS: Both control animals showed evidence of seroconversion in ELISA and Western blot assays. In addition, virus was detected in the early, acute phase of infection of both control animals by (1) plasma RNA PCR, (2) virus culture, and (3) PBMC DNA PCR assays. One vaccinated animal showed no serologic or virologic evidence of infection. The other vaccinated animal has not seroconverted, and there was no evidence of plasma viremia. However, virus was detected at early timepoints in this animal's PBMC, and transient lymphoproliferation to HIV-1 proteins not in the vaccine was observed. These observations suggest that the former animal was protected from challenge while the latter may have experienced a transient or curtailed infection. CONCLUSION: Two types of vaccine-induced protective immune responses were observed when chimpanzees immunized with rgp120SF2 were challenged with the homologous virus isolate: a response consistent with the 'sterilizing immune response' documented in the chimpanzee model in previous studies, as well as one that did not completely protect from infection, showing curtailment of the acute phase and a failure of the animal to seroconvert.

AIDS Vaccines↗
PubMed1994

A block in both early T lymphocyte and natural killer cell development in transgenic mice with high-copy numbers of the human CD3E gene.

A severe immunodeficiency involving a complete loss of T lymphocytes and natural killer cells was observed in independent lines of transgenic mice containing > 30 copies of the human CD3E gene (pL12). T-cell- natural killer (NK)- mice could also be generated by using a gene fragment pL12 delta 1 (without exons 4A and 5) coding for the CD3-epsilon transmembrane region and its 55-amino acid nonenzymatic cytoplasmic tail. The abnormally small thymus gland in the homozygous transgenic animals, which was approximately 1% the size of a wild-type thymus, contained only a few (2-4%) prethymocytes with a Thy-1+Pgp-1+IL-2R alpha- CD3-4-8- phenotype. In mice with lower copy numbers of the transgene thymocyte development was blocked at the Thy-1+Pgp-1-IL-2R alpha+CD3-4-8- stage, and normal NK activity was detected. Mice generated with high-copy numbers of a transgene pL12 delta 2 (pL12 delta 1 minus exons 6), coding for a truncated protein from which the CD3-epsilon extracellular domain, its transmembrane region, and most of its cytoplasmic region were absent, contained normal numbers of T lymphocytes and NK cells. These transgene effects suggested that recruitment of signal-transduction molecules by the cytoplasmic tail of this protein played an important role in the abrogation of both lineages. Taken together these observations support the notion that T lymphocytes and NK cells stemmed from a common precursor.

Animals↗