The cytoskeleton and motor proteins of human schistosomes and their roles in surface maintenance and host-parasite interactions

Schistosomes are parasitic blood flukes, responsible for significant human disease in tropical and developing nations. Here we review information on the organization of the cytoskeleton and associated motor proteins of schistosomes, with particular reference to the organization of the syncytial tegument, a unique cellular adaptation of these and other neodermatan flatworms. Extensive EST databases show that the molecular constituents of the cytoskeleton and associated molecular systems are likely to be similar to those of other eukaryotes, although there are potentially some molecules unique to schistosomes and platyhelminths. The biology of some components, particular those contributing to host-parasite interactions as well as chemotherapy and immunotherapy are discussed. Unresolved questions in relation to the structure and function of the tegument relate to dynamic organization of the syncytial layer. (C) 2004 Wiley Periodicals, Inc.

Pioglitazone inhibits cell growth and reduces matrix production in human kidney fibroblasts

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, and small studies have suggested a beneficial effect on renal function, but their effects on. extracellular matrix (ECM) turnover are unknown. The aims of this study were to investigate the effects of the PPAR-gamma agonist pioglitazone on growth and matrix production in human cortical fibroblasts (CF). Cell growth and ECM production and turnover were measured in human CF in the presence and absence of 1 and 3 muM pioglitazone. Exposure of CF to pioglitazone caused an antiproliferative (P < 0.0001) and hypertrophic (P < 0.0001) effect; reduced type IV collagen secretion (P < 0.01), fibronectin secretion (P < 0.0001), and proline incorporation (P < 0.0001); decreased MMP-9 activity (P < 0.05); and reduced tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 secretion (P < 0.001 and P < 0.0001, respectively). These effects were independent of TGF-beta1. A reduction in ECM production was similarly observed when CF were exposed to a selective PPAR-gamma agonist (L-805645) in concentrations that caused no toxicity, confirming the antifibrotic effects of pioglitazone were mediated through a PPAR-gamma-dependent mechanism. Exposure of CF to high glucose conditions induced an increase in the expression of collagen IV (P < 0.05), which was reversed both in the presence of pioglitazone (1 and 3 muM) and by L-805645. In summary, exposure of human CIF to pioglitazone causes an antiproliferative effect and reduces ECM production through mechanisms that include reducing TIMP activity, independent of TGF-beta1. These studies suggest that the PPAR-gamma agonists may have a specific role in ameliorating the course of progressive tubulointerstitial fibrosis under both normoglycemic and hyperglycemic states.

A Drug-Based Intervention Study on the Importance of Buffaloes for Human Schistosoma Japonicum Infection around Poyang Lake, People’s Republic of China

Schistosomiasis japonica is a zoonosis of major public health importance in southern China. We undertook a drug intervention to test the hypothesis that buffalo are major reservoirs for human infection in the marshlands/lake areas, where one million people are infected. We compared human and buffalo infection rates and intensity in an intervention village (Jishan), where humans and buffalo were treated with praziquantel, and a control village (Hexi), where only humans were treated, in the Poyang Lake region. Over the four-year study, human incidence in Jishan decreased but increased in Hexi. Adjustment of incidence by age, sex, water exposure, year, and village further confirmed the decreased human infection in Jishan. Chemotherapy for buffaloes resulted in a decrease in buffalo infection rates in Jishan, which coincided with the reduction in human infection rates there in the last two years of the study. Mathematical modeling predicted that buffalo are responsible for 75% of human transmission in Jishan. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene.

How can experience in clinical and community settings contribute to early medical education? A BEME systematic review

Review date: Review period January 1992-December 2001. Final analysis July 2004-January 2005. Background and review context: There has been no rigorous systematic review of the outcomes of early exposure to clinical and community settings in medical education. Objectives of review: (1) Identify published empirical evidence of the effects of early experience in medical education, analyse it, and synthesize conclusions from it. (2) Identify the strengths and limitations of the research effort to date, and identify objectives for future research. Search strategy: Ovid search of. BEI, ERIC, Medline, CIATAHL and EMBASE Additional electronic searches of: Psychinfo, Timelit, EBM reviews, SIGLE, and the Cochrane databases. Hand-searches of: Medical Education, Medical Teacher, Academic Medicine, Teaching and Learning in Medicine, Advances in Health Sciences Education, Journal of Educational Psychology. Criteria: Definitions: Experience: Authentic (real as opposed to simulated) human contact in a social or clinical context that enhances learning of health, illness and/or disease, and the role of the health professional. Early: What would traditionally have been regarded as the preclinical phase, usually the first 2 years. Inclusions: All empirical studies (verifiable, observational data) of early experience in the basic education of health professionals, whatever their design or methodology, including papers not in English. Evidence from other health care professions that could be applied to medicine was included. Exclusions: Not empirical; not early; post-basic; simulated rather than 'authentic' experience. Data collection: Careful validation of selection processes. Coding by two reviewers onto an extensively modified version of the standard BEME coding sheet. Accumulation into an Access database. Secondary coding and synthesis of an interpretation. Headline results: A total of 73 studies met the selection criteria and yielded 277 educational outcomes; 116 of those outcomes (from 38 studies) were rated strong and important enough to include in a narrative synthesis of results; 76% of those outcomes were from descriptive studies and 24% from comparative studies. Early experience motivated and satisfied students of the health professions and helped them acclimatize to clinical environments, develop professionally, interact with patients with more confidence and less stress, develop self-reflection and appraisal skill, and develop a professional identity. It strengthened their learning and made it more real and relevant to clinical practice. It helped students learn about the structure and function of the healthcare system, and about preventive care and the role of health professionals. It supported the learning of both biomedical and behavioural/social sciences and helped students acquire communication and basic clinical skills. There were outcomes for beneficiaries other than students, including teachers, patients, populations, organizations and specialties. Early experience increased recruitment to primary care/rural medical practice, though mainly in US studies which introduced it for that specific purpose as part of a complex intervention. Conclusions: Early experience helps medical students socialize to their chosen profession. It. helps them acquire a range of subject matter and makes their learning more real and relevant. It has potential benefits for other stakeholders, notably teachers and patients. It can influence career choices.

An inverse methodology for high frequency RF head coil design with pre-emphasized B1 field in MRI

An inverse methodology to assist in the design of radio-frequency (RF) head coils for high field MRI application is described in this work. Free space time-harmonic electromagnetic Green's functions and preemphasized B1 field are used to calculate the current density on the coil cylinder. With B1 field preemphasized and lowered in the middle of the RF transverse plane, the calculated current distribution can generate an internal magnetic field that can reduce the EM field/tissue interactions at high frequencies. The current distribution of a head coil operating at 4 T is calculated using inverse methodology with preemphasized B1 fields. FDTD is employed to calculate B1 field and signal intensity inside a homogenous cylindrical phantom and human head. A comparison with conventional RF birdcage coil is reported here and demonstrated that inverse-method designed coil with preemphasized B1 field can help in decreasing the notorious bright region caused by EM field/tissue interactions in the human head images at 4 T.

An equivalent distributed magnetic current based FDTD method for the calculation of e-fields induced by gradient coils in MRI

This paper evaluates a low-frequency FDTD method applied to the problem of induced E-fields/eddy currents in the human body resulting from the pulsed magnetic field gradients in MRI. In this algorithm, a distributed equivalent magnetic current (DEMC) is proposed as the electromagnetic source and is obtained by quasistatic calculation of the empty coil's vector potential or measurements therein. This technique circumvents the discretizing of complicated gradient coil geometries into a mesh of Yee cells, and thereby enables any type of gradient coil modeling or other complex low frequency sources. The proposed method has been verified against an example with an analytical solution. Results are presented showing the spatial distribution of gradient-induced electric fields in a multilayered spherical phantom model and a complete body model.

Interactions between serotonergic genotype and amino acid transmitter receptor expression in human alcoholics

Serotonin can modulate the activity of neural reward pathways that are strongly implicated in mediating the effects of chronic alcohol misuse, and its treatment, in human subjects. In previous work and as discussed elsewhere at this meeting, we and others have found consistent differences in the parameters of GABA and glutamate receptors, and the expression of their component subunit transcripts and proteins, in areas of the alcoholic brain that are altered by alcoholism. We did not fi nd clear changes in GABA and glutamate transport function in such samples, but a series of microarray analyses showed consistent upregulation of the presynaptic GABA/betaine transporter SLC6A12. Microarray studies showed no signifi cant differences in the expression of transcripts associated with 5HT transmission; however, only a small number of such elements were present on the arrays. Here we partitioned GABAA and NMDA pharmacology, and subunit mRNA and protein expression, measured in samples of frontal and motor cortex obtained at autopsy from alcoholics without comorbid disease, alcoholics with liver cirrhosis, and controls, according to 5HTTLPR (SLC6A4) and 5HT1B (HTR1B) polymorphisms. We found no effect of these genotypes on the expression of GABAA receptor gene products, but there was a signifi cant mRNA Transcript X Area X Group X 5HTTLPR Interaction with NMDA subunit isoform expression measured by Real Time PCR with GAPDH normalization. Further analysis showed the effect to be selective for alcoholics with cirrhosis, to be most marked in the pathologically vulnerable frontal cortex, and to vary with subunit transcript (F2,76 = 6.545, P = 0.002). NR1 expression was most affected, followed by NR2A, with NR2B expression least altered. Pilot data suggest 5HT1B genotype may also modulate NMDA subunit expression. Interactions between amino acid and serotonin transmission may infl uence susceptibility to alcohol dependence or pathogenesis

Dppa3 is a marker of pluripotency and has a human homologue that is expressed in germ cell tumours

We identified a transcript named 11M2 on the basis of its strong male-specific expression pattern in the developing mouse gonad. 11M2 was found to be expressed by gonad primordial germ cells (PGCs) of both sexes and down-regulated in female PGCs as they enter prophase I of the first meiotic division, similar to the expression of Oct4. Mouse EST analysis revealed expression only in early-stage embryos, embryonic stem cells and pre-meiotic germ cells. 11M2 corresponds to a recently reported gene variously known as PGC7, stella or Dppa3. We have identified the human orthologue of Dppa3 and find by human EST analysis that it is expressed in human testicular germ cell tumours but not in normal human somatic tissues. The expression patterns of mouse and human DPPA3, in undifferentiated embryonic cells, embryonic germ cells and adult germ cell tumours, together suggest a role for this gene in maintaining cell pluripotentiality.