Cognitive and functional decline in adults aged 75 and older.

Objectives: To simultaneously examine the influence of functional disability on the development of cognitive impairment and the influence of cognitive status on the development of functional disability over time and compare findings across ethnic groups.

Design: A population-based longitudinal study.

Setting: Galveston County, Texas.

Hybrid tetanus toxin C fragment-diphtheria toxin translocation domain allows specific gene transfer into PC12 cells.

To study the mechanism by which genes can efficiently be transferred into specific cell types, we have constructed several novel, single-chain multicomponent proteins by recombining the nontoxic C fragment of tetanus toxin and the translocation domain of diphtheria toxin together with the DNA-binding fragment of GAL4 transcription factor, for transportation of plasmid DNA into neuronal cells. The C fragment of tetanus toxin provided neuronal selectivity, the translocation domain of diphtheria toxin permitted endosomal escape, and the GAL4 domain provided binding to DNA. To assess the cellular tasks of each component in gene transfer, different combinations of these fragments were produced by polymerase chain reaction, expressed in Escherichia coli, and purified under native conditions from the soluble proteins.

Clinical study of a urinary competitve ELISA for neural thread protein in Alzheimer disease.

AD7C-NTP (neural thread protein) is a approximately 41-kD brain protein that is selectively elevated in Alzheimer disease (AD). AD7C-NTP is associated with the pathologic changes of AD, and overexpression of the AD7C-NTP gene is associated with cell death similar to that found in the AD brain. A newly developed competitive ELISA (enzyme-linked immunosorbent assay) was tested in urine samples from patients with AD, patients with non-AD dementia, and healthy normal individuals.

First and second transmembrane segments of alpha3, alpha4, beta2, and beta4 nicotinic acetylcholine receptor subunits influence the efficacy and potency of nicotine.

The first three transmembrane segments (M1-M3) of human nicotinic acetylcholine receptors (nAChRs) have been implicated in determining the efficacy of nicotine by studies of alpha3/alpha4 subunit chimeras. Nicotine has full efficacy on the alpha4beta2 nAChR and partial efficacy on the alpha3beta2 nAChR. Now, we have exchanged individually three amino acids between the alpha4 and the alpha3 subunits at positions 226(M1), 258(M2), and 262(M2).

Nerve growth factor, neuropeptides, and mast cells in ultraviolet-B-induced systemic suppression of contact hypersensitivity responses in mice.

The induction of systemic immunosuppression following ultraviolet B radiation exposure has been linked with the release of inflammatory and immunomodulatory mediators by cells of the epidermis and dermis. Nerve growth factor has not previously been linked with ultraviolet-B-induced immunosuppressive effects. Nerve growth factor antibodies abrogated ultraviolet-B-induced systemic suppression of contact hypersensitivity responses in BALB/C mice.

Small primary sensory neurons innervating epidermis and viscera display differential phenotype in the adult rat.

Target tissues contribute to the phenotype and function of sensory neurons. Due to lack of appropriate markers for trkA expressing sensory axons and terminals, the detailed peripheral projection of these neurons is unclear. In this study, the peripheral projections of trkA immunoreactive neurons are characterized using the combined techniques of immunohistochemistry and retrograde tracing.

Neurotrophin 3 is increased in the spontaneously hypertensive rat.

Objective: To determine whether the noradrenergic sympathetic hyperinnervation in the spontaneously hypertensive rat (SHR), a genetic model of essential hypertension, is associated with changes in neurotrophin 3 (NT3) concentrations.

Methods: NT3 levels were measured using a sensitive enzyme-linked immunosorbent assay (ELISA) in the superior cervical ganglia (SCG), heart, mesenteric artery (MA) and blood of postnatal and mature SHR and normotensive Wistar-Kyoto (WKY) rats.

Results And Conclusions: NT3 levels in SHR are significantly higher in the SCG during the first 4 postnatal weeks, and in the heart and MA from 2 to 10 weeks of age, compared with levels in WKY rats.

Deciding about prophylactic oophorectomy: what is important to women at increased risk of ovarian cancer?

Background: Little is known about the factors that women at increased risk of ovarian cancer consider to be important when deciding about prophylactic oophorectomy, surgery to remove the ovaries before they develop cancer.

Methods: Women who had undergone prophylactic oophorectomy (surgical group; n = 30) were compared with women who remained on the ovarian screening program (nonsurgical group; n = 28) on their importance ratings for a number of relevant decision-making factors.

Results: The most important decision-making factor across all subjects was reducing risk of ovarian cancer, but the single best predictor of group membership was the importance attributed to reducing cancer worry.

Comparison of wheat germ agglutinin-horseradish peroxidase and biotinylated dextran for anterograde tracing of corticospinal tract following spinal cord injury.

Established methods for monitoring regeneration of the corticospinal tract involve anterograde labelling of the cortical motor neuron. While wheat germ agglutinin-horseradish peroxidase conjugate has been used to anterogradely label these neurons, we demonstrate that this technique may not completely label the whole axon and fine terminal processes when this tracer is administered in dried form. An alternative method is described for anterograde labelling of cortical motor neurons using biotinylated dextran.

Prophylactic oophorectomy versus screening: psychosocial outcomes in women at increased risk of ovarian cancer.

This study investigated the psychosocial outcome of prophylactic oophorectomy versus regular screening in women at increased risk of ovarian cancer. Women who had undergone prophylactic oophorectomy (n=29) were compared with women who remained on the ovarian screening programme (n=28). Assessments were made retrospectively by postal questionnaire.

Release of immunoreactive brain-derived neurotrophic factor in the spinal cord of the rat following sciatic nerve transection.

Using the antibody microprobe method, the sites of spinal release of immunoreactive brain-derived neurotrophic factor (BDNF) was studied in normal rats, and rats with prior sciatic nerve transection. In normal rats, a significant basal release of immunoreactive BDNF was found in the superficial dorsal horn. Following sciatic nerve transection (performed 14 days previously), release of BDNF was found throughout the whole of the dorsal horn, extending into deeper laminae.

Ultrastructural localization of brain-derived neurotrophic factor in rat primary sensory neurons.

In a previous study we have shown that brain-derived neurotrophic factor (BDNF) is present in a subpopulation of small- to medium-sized sensory neurons in the dorsal root ganglia (DRG) and is anterogradely transported in both the peripheral and central processes. Within the spinal cord, BDNF is localized to varicosities of sensory nerve terminals in laminae I and II of the dorsal horn. This study raised the question of whether BDNF is localized in synaptic vesicles of the afferent nerve terminals.

Stimulation of corticospinal tract regeneration in the chronically injured spinal cord.

Acute spinal cord injury models have proved popular in studies aimed at identifying factors capable of influencing axonal regeneration within the central nervous system. In these models, the test factors (e.g.

Cancer risk perceptions and distress among women attending a familial ovarian cancer clinic.

Of 230 women referred to a familial ovarian cancer clinic, 196 (85%) completed a questionnaire before they attended. The data collected included pre-counselling risk perceptions and an assessment of distress. Respondents were more likely to underestimate (44%) than overestimate (19%) their risk.

Psychosocial effects of living with an increased risk of breast cancer: an exploratory study using telephone focus groups.

Research to date has mainly focused on the short-term psychological impact of genetic risk counselling for breast cancer. This study aimed to explore the long-term consequences for women of being informed about an increased risk of breast cancer in terms of: the effect on their everyday lives, their coping strategies and their unmet needs in terms of the current service. The participants were 25 women with a family history of breast cancer who had received genetic risk counselling and had consequently been receiving clinical surveillance for at least 2 years.

Neurotrophin 4/5 immunoassay: identification of sources of errors for the quantification of neurotrophins.

Neurotrophin 4/5 (NT4/5) is the least understood member of the mammalian neurotrophin family. Precise and reliable determinations of endogenous NT4/5 levels are essential to understand its physiology. Immunoassay has been used for neurotrophin quantification for over three decades.

GPs' views on their role in cancer genetics services and current practice.

Background: Increasing demand for cancer genetics services has necessitated an urgent review of how these services are organized and, in particular, identification of an effective role for primary care.

Objectives: We aimed to assess the views of GPs on their role in cancer genetics services and their confidence in performing that role; to assess their understanding of cancer genetics, current practice and referral behaviour; and to identify needs for information and training to enable GPs to play an effective role in these services.

Method: A cross-sectional questionnaire survey of GPs was conducted through general practices in SE Scotland; 397 (response rate 59.

Measurement of neurotrophin 4/5 in rat tissues by a sensitive immunoassay.

Neurotrophin 4/5 (NT4/5) is a member of the neurotrophin family known to exert survival and other effects on a variety of neurons including those within the motor, sensory and central populations. Although mRNA(NT4/5) has been found in various effector tissues of the rat and human, the concentration of NT4/5 protein in tissues has not been reported previously due to lack of suitable methodology. We present here a quantitative two-site enzyme-linked immunosorbent assay for the estimation of NT4/5 in pre- and postnatal rat tissues.

Injured primary sensory neurons switch phenotype for brain-derived neurotrophic factor in the rat.

Peripheral nerve injury results in plastic changes in the dorsal root ganglia and spinal cord, and is often complicated with neuropathic pain. The mechanisms underlying these changes are not known. We have now investigated the expression of brain-derived neurotrophic factor in the dorsal root ganglia with histochemical and biochemical methods following sciatic nerve lesion in the rat.

Ethnic variation in the health burden of self-reported diabetes in adults aged 75 and older.

Objective: The health burden of self-reported diabetes was compared across three ethnic groups of older adults.

Methods: Analysis of variance and logistic regression were used to compare ethnic differences in the rates of co-morbid chronic health conditions, complications, and disability for older diabetics vs non-diabetics, in a sample of 173 Mexican Americans, 201 African Americans, and 181 non-Hispanic whites, all aged 75 and older.

Results: The prevalence of self-reported diabetes was significantly higher in older Mexican Americans (17.

Satellite-cell-derived nerve growth factor and neurotrophin-3 are involved in noradrenergic sprouting in the dorsal root ganglia following peripheral nerve injury in the rat.

Injury to a peripheral nerve induces in the dorsal root ganglia (DRG) sprouting of sympathetic and peptidergic terminals around large-diameter sensory neurons that project in the damaged nerve. This pathological change may be implicated in the chronic pain syndromes seen in some patients with peripheral nerve injury. The mechanisms underlying the sprouting are not known.

Upregulation of brain-derived neurotrophic factor and neuropeptide Y in the dorsal ascending sensory pathway following sciatic nerve injury in rat.

An immunohistochemical study was undertaken to examine the changes of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) in the nucleus gracilis of rats following sciatic nerve transection. The results showed that BDNF-immunoreactivity (-ir) in the gracile nucleus was significantly increased after the nerve injury. The upregulation was apparent 24 h after nerve lesion, remaining robust up to 56 days postlesion.