Analysis of the intracellular barriers encountered by nonviral gene carriers in a model of spatially controlled delivery to neurons.

Background: Neuron-specific, nonviral gene delivery vehicles are useful tools for the potential treatment of neurological disease and spinal cord injury. For minimally invasive, peripheral administration, gene carriers must efficiently mediate uptake at axon terminals, retrograde axonal transport, vesicular escape, and nuclear entry. The design of improved vehicles will benefit from an understanding of the barriers that limit nonviral delivery to neurons.

Application of an environmentally sensitive fluorophore for rapid analysis of the binding and internalization efficiency of gene carriers.

Nonviral gene carriers must associate with and become internalized by cells in order to mediate efficient transfection. Methods to quantitatively measure and distinguish between cell association and internalization of delivery vectors are necessary to characterize the trafficking of vector formulations. Here, we demonstrate the utility of nitro-2,1,3-benzoxadiazol-4-yl (NBD)-labeled oligonucleotides for discrimination between bound and internalized gene carriers associated with cells.

Nonviral approaches for neuronal delivery of nucleic acids.

The delivery of therapeutic nucleic acids to neurons has the potential to treat neurological disease and spinal cord injury. While select viral vectors have shown promise as gene carriers to neurons, their potential as therapeutic agents is limited by their toxicity and immunogenicity, their broad tropism, and the cost of large-scale formulation. Nonviral vectors are an attractive alternative in that they offer improved safety profiles compared to viruses, are less expensive to produce, and can be targeted to specific neuronal subpopulations.

Prolonged somatostatin therapy may cause down-regulation of SSTR-like GPCRs on Schistosoma mansoni.

Background & Objectives: Chemotherapy with praziquantel remains the only control measure to Schistosoma mansoni infections to date. The neuropeptide hormone somatostatin gives relief from gastrointestinal disturbances, liverpathology, and reduces egg production in S. mansoni infected mice, suggesting an interaction of somatostatin with the parasite rather than with the host alone.

Sexually transmitted infection health-care seeking behaviour in the Netherlands: general practitioner attends to the majority of sexually transmitted infection consultations.

Health-care seeking behaviour for sexually transmitted infection (STI)-related symptoms is not well known in the Netherlands. Within the framework of a large representative study, the second National Survey of General Practice (NIVEL 2001), 9687 persons aged 18 years and older were interviewed about their STI and STI-related health-care seeking behaviour. In total, 1.

Evaluation of an LC8-binding peptide for the attachment of artificial cargo to dynein.

The limited cytoplasmic mobility of nonviral gene carriers is likely to contribute to their low transfection efficiency. This limitation could be overcome by mimicking the viral strategy of recruiting the dynein motor complex for efficient transport toward the host cell nucleus. A promising approach for attaching artificial cargo to dynein is through an adaptor peptide that binds the 8 kDa light chain (LC8) found in the cargo-binding region of the dynein complex.

Lessons learned from a population-based chlamydia screening pilot.

We evaluated process organization and response optimization in a home-based Chlamydia trachomatis (Ct) screening project in the Netherlands among 15- to 29-year-old women and men. The method used was computer-supported data flow, from population sampling to informing participants of the result. A new test kit or a letter reminded non-respondents after six weeks.

[A girl with hereditary myotonia due to an exceptional sodium channel mutation].

A 22-month-old girl had cramps and stiffness of her muscles. After medical history, physical examination and an EMG, a short differential diagnosis based on the symptoms of myotonia was made. Initially, the symptoms were incorrectly assumed to be due to Becker's myotonia, an autosomal recessive condition caused by a mutation in the chloride channel.

An improved RT-PCR method for the detection of killer-cell immunoglobulin-like receptor (KIR) transcripts.

Killer cell immunoglobulin-like receptors (KIRs) are expressed on human natural killer (NK) cells and a proportion of T cells. As the specificity of these NK and T cells is, at least in part, determined by the combination of KIRs they express, it is important to be able to determine the KIR expression pattern of NK and T cell clones to understand their function. However, for most KIR genes, specific reagents to detect expression are currently either unavailable or sensitive to allelic variations.

Dppa2 and Dppa4 are closely linked SAP motif genes restricted to pluripotent cells and the germ line.

Despite the enormous medical potential of ESCs, the molecular mechanisms conferring the ability to differentiate into all cell types of the embryo remain elusive. We used an in silico approach to identify genes expressed exclusively in mouse preimplantation embryos and pluripotent cell lines. Two of these genes were developmental pluripotency-associated gene 2 (Dppa2) and Dppa4, which we show are closely linked genes encoding putative nuclear SAP domain proteins expressed in human and mouse pluripotent stem cells and germ cell tumor-derived embryonal carcinoma cells.

Gold nanoparticles as a versatile platform for optimizing physicochemical parameters for targeted drug delivery.

The development of targeted vehicles for systemic drug delivery relies on optimizing both the cell-targeting ligand and the physicochemical characteristics of the nanoparticle carrier. A versatile platform based on modification of gold nanoparticles with thiolated polymers is presented in which design parameters can be varied independently and systematically. Nanoparticle formulations of varying particle size, surface charge, surface hydrophilicity, and galactose ligand density were prepared by conjugation of PEG-thiol and galactose-PEG-thiol to gold colloids.

Description of the ICTI consortium: an integrated approach to the study of Chlamydia trachomatis infection.

The use of an integrated approach to the study of Chlamydia trachomatis infection of the female genital tract, presented at the mini-symposium "Chlamydia trachomatis infections" and described in the thesis of Joseph M. Lyons, has resulted in the creation of the ICTI consortium. The ICTI consortium is based on strong interaction and collaboration between basic scientists, clinicians, epidemiologists, and health care policy makers.

Prevalence of urogenital Chlamydia trachomatis infections in the Netherlands suggests selective screening approaches. Results from the PILOT CT Population Study.

Chlamydia trachomatis screening is being considered in the Netherlands, but policy recommendations are hampered by the lack of population-based data. We studied the prevalence of chlamydia infection in 15-29-year-old women and men in a national representative sample of 21,000 inhabitants of rural and urban areas in the Netherlands. Of this sample, 41% responded by sending in urine and an answered questionnaire, while 11% returned a refusal card.

Acceptability of self-taken vaginal swabs and first-catch urine samples for the diagnosis of urogenital Chlamydia trachomatis and Neisseria gonorrhoeae with an amplified DNA assay in young women attending a public health sexually transmitted disease clinic.

Objectives: Public health efforts are needed to encourage young women to get tested for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC).

Goal: To assess the acceptability and feasibility of 2 noninvasive diagnostic approaches.

Study Design: Participants of this cross-sectional survey were 413 young women (age 16-35) who underwent STD testing by self-taken vaginal swab (SVS) and a first-catch urine sample (FCU) by nucleic acid amplification test (BDProbTec) and filled out a questionnaire.

Population prevalence of Chlamydia trachomatis and Neisseria gonorrhoeae in the Netherlands. Should asymptomatic persons be tested during population-based Chlamydia screening also for gonorrhoea or only if chlamydial infection is found?

Background: Screening and active case finding for Chlamydia trachomatis (CT) is recommended to prevent reproductive morbidity. However insight in community prevalence of gonococcal infections and co-infections with Neisseria gonorrhoea (NG) is lacking.

Methods: Nested study within a large population-based Chlamydia Screening Pilot among 21.

Prevalence of STI related consultations in general practice: results from the second Dutch National Survey of General Practice.

Background: The role of the GP in the care of sexually transmitted infections (STIs) is unclear.

Aim: We studied the prevalence of STI related consultations in Dutch general practice in order to obtain insight into the contribution of the GP in STI control.

Design Of Study: A descriptive study.

Systematic screening for Chlamydia trachomatis: estimating cost-effectiveness using dynamic modeling and Dutch data.

Objective: To estimate the cost-effectiveness of a systematic one-off Chlamydia trachomatis (CT) screening program including partner treatment for Dutch young adults.

Methods: Data on infection prevalence, participation rates, and sexual behavior were obtained from a large pilot study conducted in The Netherlands. Opposite to almost all previous economic evaluations of CT screening, we developed a dynamic Susceptible-Infected-Susceptible (SIS) model to estimate the impact of the screening program on the incidence and prevalence of CT in the population.

Management of Chlamydia cases and their partners: results from a home-based screening program organized by municipal public health services with referral to regular health care.

Background: We evaluated the management of Chlamydia trachomatis cases and partners found in a systematic home-based chlamydia screening project in the Netherlands among 15- to 29-year-old women and men, organized by the Municipal Public Health Services (MHS).

Methods: Infected participants (165/8339 = 2%) were referred to regular curative services. The treating physician provided feedback on treatment and partner notification.

Reinfections, persistent infections, and new infections after general population screening for Chlamydia trachomatis infection in the Netherlands.

Objectives: The objectives of this study were to determine the rate of new infections and reinfections or persistent infections with Chlamydia trachomatis to define appropriate screening intervals and to identify risk factors for reinfection.

Design: This was a cross-sectional study among a subsample of participants in a population-based screening.

Setting: This study was conducted in urban and rural areas in The Netherlands.

Analysis of Esg1 expression in pluripotent cells and the germline reveals similarities with Oct4 and Sox2 and differences between human pluripotent cell lines.

Establishment of pluripotent epiblast cells is a critical event during early mammalian development because all somatic lineages and the primordial germ cells (PGCs) are derived from them. The epiblast and PGCs are in turn the precursors of pluripotent embryonic stem cells and embryonic germ cells, respectively. Although PGCs are specialized cells, they express several key pluripotency-related genes, such as Oct4 and Sox2.

Annexin XI co-localises with calcyclin in proliferating cells of the embryonic mouse testis.

Mammalian sex determination relies on the expression of SRY, which triggers a tightly regulated cascade of gene expression leading to male differentiation. Many elements of this pathway remain to be identified. Here, we characterise Annexin XI (Anxa11), a gene whose major site of embryonic expression was within the undifferentiated and differentiating testis.

[Summary of the practice guideline 'The STD consultation' from the Dutch College of General Practitioners].

The practice guideline on STD consultations from the Dutch College of General Practitioners sets out guidelines for the diagnosis and treatment of Chlamydia-infection, gonorrhoea, syphilis, trichomoniasis, genital herpes condylomata acuminata, hepatitis B, HIV-infection and pubic lice. Testing for Chlamydia-infection is always indicated if an STD is suspected but the necessity of also testing for gonorrhoea, syphilis, hepatitis B or HIV-infection depends on the likely risk. For the diagnosis of Chlamydia in a symptomatic woman it advises taking material from the cervix and urethra.

Acceptability and consequences of screening for chlamydia trachomatis by home-based urine testing.

Objective: The objective of this study was to study the acceptability and consequences of home-based chlamydia (CT) screening by Municipal Health Services (MHS) among 15- to 29-year-old participants.

Study: This study consisted of a cross-section of 156 CT-positives and 600 random sampled CT-negatives after receiving the result of their CT test.

Results: Thirty-eight percent of the men and 59% of the women responded.