Parkinsonian signs and substantia nigra neuron density in decendents elders without PD

Substantia nigra (SN) neurons were counted on single, transverse caudal midbrain sections from 217 male participants in the Honolulu-Asia Aging Study, aged 74-97 years at death. Quadrants areas within the SN were determined with a planimeter and neuronal density was expressed as neurons/mm(2) for 10 Parkinson's disease (PD) cases, 29 incidental Lewy body cases, and 178 controls with neither condition. Mean densities in all quadrants were significantly lower in the PD group compared with the other groups (p = 0.006). This relationship was strongest in the ventrolateral quadrant. In a subgroup of 50 controls who were examined with the Unified Parkinson's Disease Rating Scale an average of 2.1 years prior to death, there was an association of stooped posture (p = 0.009), postural instability (p = 0.013), body bradykinesia (p = 0.048), and gait disturbance (p = 0.05) with neuron density in the dorsolateral quadrant; and impaired speech (p = 0.014), abnormal facial expression (p = 0.022), and difficulty rising from a chair (p = 0.032) with neuron density in the dorsomedial quadrant. There was a significant association of increasing number of signs present with decreasing neuron density in both quadrants (p = 0.001 for trend). Low SN neuron density may be the basis for parkinsonian signs in the elderly without PD.     

Spatially and temporally restricted chemoattractive and chemorepulsive cues direct the formation of the nigro-striatal circuit

Identifying cellular and molecular mechanisms that direct the formation of circuits during development is thought to be the key to reconstructing circuitry lost in adulthood to neurodegenerative disorders or common traumatic injuries. Here we have tested whether brain regions situated in and around the developing nigro-striatal pathway have particular chemoattractive or chemorepulsive effects on mesencephalic dopamine axons, and whether these effects are temporally restricted. Mesencephalic explants from embryonic day (E)12 rats were either cultured alone or with coexplants from the embryonic, postnatal or adult medial forebrain bundle region (MFB), striatum, cortex, brain stem or thalamus. Statistical analysis of axon growth responses revealed a potent chemoattraction to the early embryonic MFB (i.e. E12-15) that diminished (temporally) in concert with the emergence of chemoattraction to the striatum in the late embryonic period (i.e. E19+). Repulsive responses by dopaminergic axons were obvious in cocultures with embryonic brain stem and cortex, however, there was no effect by the thalamus. Such results suggest that the nigro-striatal circuit is formed via spatially and temporally distributed chemoattractive and chemorepulsive elements that: (i) orientate the circuit in a rostral direction (via brain stem repulsion); (ii) initiate outgrowth (via MFB attraction); (iii) prevent growth beyond the target region (via cortical repulsion); and (iv) facilitate target innervation (via striatal chemoattraction). Subsequent studies will focus on identifying genes responsible for these events so that their products may be exploited to increase the integration of neuronal transplants to the mature brain, or provide a means to (re)establish the nigro-striatal circuit in vivo.     

Environmental enrichment affects striatal graft morphology and functional recovery

Environmental conditions and behavioural experience can affect neuronal function and morphology. It is less well known whether such factors also influence the growth, integration and functional recovery provided by neural grafts placed within the damaged brain. Here we report on the effects of differential housing conditions on striatal graft morphology and functional recovery after striatal lesions. Rats were pretrained on a skilled bilateral forelimb task, the staircase test, and lesioned unilaterally in the lateral dorsal striatum with quinolinic acid. One group of lesioned animals was given suspension grafts of E15 whole ganglionic eminence implanted into the lesioned striatum. Following transplantation, the animals were housed either in standard cages (four per cage) or in enriched environment housing conditions (10 per cage) with tunnels, ladders and increased living space available for exploration, social interaction and play. The differentially housed animals were retested on the skilled staircase test at two separate time points. Repeated testing, environmental enrichment and transplantation positively influenced behavioural recovery. Partial recovery was observed bilaterally amongst the grafted animals in both housing conditions. Nevertheless, the grafted animals housed in the enriched environment performed significantly better in the final test compared with all of the other experimental groups. The grafts survived equally well under both housing conditions but the grafts of animals housed in the enriched environment contained larger projection neurons and were somewhat better reinnervated by dopaminergic afferents. An increased level of striatal brain-derived neurotrophic factor was observed in the control animals housed under the enriched compared with the standard conditions. The results indicate that an enriched environment can affect both graft function and graft morphology through as yet unknown mechanisms.     

Altered thyroid status in lake trout (Salvelinus namaycush) exposed to co-planar 3,3',4,4',5-pentachlorobiphenyl

Recent studies indicate that co-planar 3,3',4,4',5-pentachlorobiphenyl (PCB) congeners or their metabolites may disrupt thyroid function in fishes. Although co-planar PCB have been detected at microgram per kilogram levels in fish from contaminated areas, few studies have examined mechanisms whereby, co-planar PCBs may alter thyroid function in fish. We treated immature lake trout by intraperitoneal (i.p.)-injection or dietary gavage with vehicle containing 0, 0.7, 1.2, 25 or 40 microg 3,3',4,4',5-pentachlorobiphenyl (PCB 126) per kgBW. Blood and tissue samples were collected at various times up to 61 weeks following exposure. The treatments produced sustained dose-dependent elevations of tissue (PCB 126) concentrations. Thyroid epithelial cell height (TECH), plasma thyroxine (T4) and 3,3',5-triiodo-l-thyronine (T3) concentrations, hepatic 5'-monodeiodinase, hepatic glucuronidation of T4 and T3, as well as plasma T4 kinetics and fish growth were analyzed. Exposure to the highest doses of PCB 126 caused increased TECH, plasma T4 dynamics and T4-glucuronidation (T4-G). PCB 126 did not affect 5'-monodeiodinase and T3-glucuronidation (T3-G) and there were no effects on fish growth or condition. Because T3 status and growth were unaffected, the thyroid system was able to compensate for the alterations caused by the PCB 126 exposure. It is clear that concentrations of co-planar PCBs similar to those found in predatory fish from contaminated areas in the Great Lakes are capable of enhancing metabolism of T4. These changes may be of significance when T4 requirements are high for other reasons (e.g. periods of rapid growth, warm temperatures, metamorphosis, and parr-smolt transformation).     

Alcohol consumption and risk of colon cancer: evidence from the national health and nutrition examination survey I epidemiologic follow-up study

The epidemiologic findings on the relationship between alcohol consumption and colon cancer are inconsistent. The National Health and Nutrition Examination Survey (NHANES) I Epidemiologic Follow-Up Study (NHEFS) included a prospective cohort population representative of the general U.S. population, which had not been fully utilized for examining the risk between colon cancer and alcohol drinking. The NHEFS consisted of 10,220 participants prospectively followed over a decade. Alcohol consumption, amount and type of beverage, and drinking patterns at baseline were considered in examination of the effect of alcohol consumption on the risk of colon cancer. The consumption of one or more alcoholic beverages a day at baseline was associated with approximately a 70% greater risk of colon cancer [relative risk (RR)=1.69; 95% confidence interval (CI)=1.03, 2.79], with a strong positive dose-response relationship (P=0.04). This association appeared to be exclusively related to daily drinking of one or more drinks of liquor (RR=2.48; 95% CI=1.66, 4.53). Additionally, more than a 70% increased risk of colon cancer was observed for more than 34 yr of alcohol drinking history compared with nondrinkers (RR=1.73; 95% CI=1.08, 2.78). Overall, alcohol consumption was significantly associated with increased risk of colon cancer. The most important factor for colon cancer seems to be liquor consumption.     

Early childhood hearing loss: a frequently overlooked cause of speech and language delay

The explosion of information regarding the genetics of hearing loss, the extraordinary effectiveness of early intervention, and the widespread practice of universal newborn hearing screening make for exciting times for those who serve young children who are deaf or hard-of-hearing and their families. These rapid changes in the knowledge base and practice standards also require the cooperation and help of pediatricians to enable children to take full advantage of available opportunities to optimize development of early communication.     

Demonstrating the case that AD is a vascular disease: epidemiologic evidence

Alzheimer's disease (AD) is the most frequent type of dementia in old age. The pathology of AD is not well understood. One hypothesis states that AD has a vascular basis. This hypothesis is controversial because AD has traditionally been studied and treated as a separate disease from vascular dementia. This article reviews the epidemiologic evidence supporting an association between AD and two major vascular risk factors-blood pressure and diabetes. Both methodologic and biologic explanations for these associations are discussed.     

Bereaved Orthodox Jewish families and their community: a cross-cultural perspective

This article examines the laws and customs of bereavement in Orthodox Jewish families and their community. It considers definitions of bereavement, the need for health care team members' cross-cultural understanding of bereavement, the community's role, and the role of the community health nurse and health care team with this particular group.