Survey of food safety awareness among HIV positive individuals

Though opioids are known to have neuroprotective properties, little information is available on the functional state of opioidergic receptors following focal cerebral ischaemia. The present study investigated the evolution of the Bmax and Kd for [3H]DAMGO, [3H]DADLE, and [3H]U69,593, respectively, for the mu, delta, and kappa opioidergic receptors after permanent focal cerebral ischaemia in mice. While the various Kd were unchanged, mu and delta Bmax values were precociously decreased in frontoparietal cortices, earlier than kappa receptors, reflecting infarct extension with time. The Bmax values for mu and delta receptors were also altered in non-infarcted tissues, such as tissues at risk (e.g., temporal auditory cortex) and exofocal (e.g., contralateral and non-infarcted) cortices. These results suggest that, in non-infarcted areas, the observed changes reflect functional modifications to focal ischaemia.     

The p35/Cdk5 kinase is a neuron-specific Rac effector that inhibits Pak1 activity

Cyclin-dependent kinase 5 (Cdk5) and its neuron-specific regulator p35 are essential for neuronal migration and for the laminar configuration of the cerebral cortex. In addition, p35/Cdk5 kinase concentrates at the leading edges of axonal growth cones and regulates neurite outgrowth in cortical neurons in culture. The Rho family of small GTPases is implicated in a range of cellular functions, including cell migration and neurite outgrowth. Here we show that the p35/Cdk5 kinase co-localizes with Rac in neuronal growth cones. Furthermore, p35 associates directly with Rac in a GTP-dependent manner. Another Rac effector, Pak1 kinase, is also present in the Rac-p35/Cdk5 complexes and co-localizes with p35/Cdk5 and Rac at neuronal peripheries. The active p35/Cdk5 kinase causes Pak1 hyperphosphorylation in a Rac-dependent manner, which results in down-regulation of Pak1 kinase activity. Because the Rho family of GTPases and the Pak kinases are implicated in actin polymerization, the modification of Pak1, imposed by the p35/Cdk5 kinase, is likely to have an impact on the dynamics of the reorganization of the actin cytoskeleton in neurons, thus promoting neuronal migration and neurite outgrowth.     

Lyme arthritis synovial gamma delta T cells respond to Borrelia burgdorferi lipoproteins and lipidated hexapeptides

Lyme arthritis synovial fluid contains a large proportion of gamma delta T cells that proliferates upon stimulation with the causative spirochete, Borrelia burgdorferi. A panel of Borrelia-reactive gamma delta T cell clones was derived from synovial fluid of two patients with Lyme arthritis. Each of six gamma delta clones from one patient used the V delta 1 TCR segment but had otherwise unique CDR3 sequences and diverse V gamma segment usage. Stimulation of the V delta 1 clones was optimal in the presence of Borrelia, dendritic cells, and exogenous IL-2, which was reflected by proliferation, TCR down-modulation, as well as induction of CD25 and Fas ligand expression. Stimulation by B. burgdorferi-pulsed dendritic cells withstood chemical fixation and was not restricted to class I or class II MHC, CD1a, CD1b, or CD1c. In contrast, anti-gamma delta antibody potently inhibited proliferation. Extraction of B. burgdorferi lipoproteins with Triton X-114 enriched for the stimulatory component. This was confirmed using lipidated vs nonlipidated hexapeptides of Borrelia outer surface proteins. These observations suggest that synovial V delta 1 T cells may mediate an innate immune response to common lipoprotein products of spirochetes.     

Structure-based design of a lysozyme with altered catalytic activity

Here we show that the substitution Thr 26-->His in the active site of T4 lysozyme causes the product to change from the alpha- to the beta-anomer. This implies an alteration in the catalytic mechanism of the enzyme. From the change in product, together with inspection of relevant crystal structures, it is inferred that wild-type T4 lysozyme is an anomer-inverting enzyme with a single displacement mechanism in which water attacks from the alpha-side of the substrate. In contrast, the mutant T26H is an anomer-retaining enzyme with an apparently double displacement mechanism in which a water molecule attacks from the opposite side of the substrate. The results also show that the mechanism of wild-type T4 lysozyme differs from that of hen egg-white lysozyme even though both enzymes are presumed to have evolved from a common precursor.     

Association between bleomycin hydrolase and Alzheimer's disease in caucasians

A recent study showed modest evidence for an increased frequency of the bleomycin hydrolase (BH) V/V genotype in Alzheimer's disease (AD) patients compared with non-demented controls. To test this hypothesis, we examined this polymorphism in 621 rigorously evaluated patients and 502 control subjects (all caucasian) but were unable to detect an association between BH and AD even after controlling for age, gender, and apolipoprotein E (ApoE) genotype. We conclude that this polymorphism does not account for inherited susceptibility to AD in the populations represented in this sample.     

Relationship between ApoE, MRI findings, and cognitive function in the Cardiovascular Health Study

BACKGROUND AND PURPOSE: We determined the relationship between apolipoprotein (Apo)E, MRI, and low cognitive scores. METHODS: The relationship between age, education, ApoE genotype, MRI examination of the brain, subclinical and clinical cardiovascular disease, and low (<80) score on the Modified Mini-Mental State Examination (3MSE, as modified by Teng and Chui) was evaluated for 3469 black and white participants in the Cardiovascular Health Study (CHS) in years 5 and 6 of the study. The participants were followed for up to 3 years. RESULTS: The prevalence of scores <80 in years 5 and 6 of the CHS was 8.2% for participants without and 20.4% for those with prior history of stroke. Age, race, and education were important determinants of low 3MSE scores. The prevalence of ApoE-4 (odds ratio [OR], 1.6 [1.1 to 2.1]) was directly related to scores <80, as was high ventricular volume (OR, 1.6 [1.2 to 2.3]), high white matter grade (OR, 1.4 [1.1 to 1.9]), and infarctlike lesions (OR, 1.6 [1.2 to 2.1]) on the MRI in the multivariate analysis. A five-point or greater decline in scores over up to 3 years was more often observed for participants with low 3MSE scores at year 5, at older ages, with lower education, and experiencing incident stroke (OR, 3.6 [1.2 to 10.6]), ApoE-4 genotype (OR, 1.8 [1.4 to 2.3]), and with MRI findings of high ventricular volume (OR, 2.0 [1.5 to 2.7]), and infarctlike lesions (OR, 1.2 [0.9 to 1.5]). CONCLUSIONS: These results demonstrate that vascular changes on MRI, measures of brain atrophy, ApoE-4, and age, education, and race are associated with low cognitive scores among older individuals. The MRI of the brain provides valuable information related to cognitive tests and decline over time. The potential exists for using MRI measurements to identify high-risk individuals for dementia and to test potential interventions to reduce the risk of dementia.     

A randomized walking trial in postmenopausal women: effects on physical activity and health 10 years later

BACKGROUND: It is important to determine if permanent lifestyle changes may result from physical activity interventions and whether health may be affected by these changes. OBJECTIVE: To conduct a 10-year follow-up of physical activity and self-reported health status in participants of a randomized clinical trial of walking intervention. METHODS: Of the original 229 volunteer postmenopausal women who participated in the original clinical trial, 196 (N = 96 intervention and 100 controls) completed the 10-year follow-up telephone interview. The interview protocol included questions on self-reported walking for exercise and purposes other than exercise, the Paffenbarger sport and exercise index, functional status, and various chronic diseases and conditions. RESULTS: The median values for both usual walking for exercise and total walking were significantly higher for walkers compared with controls (for both, P = .01), with median differences of 706 and 420 kcal/wk, respectively. After excluding women who reported heart disease during the original trial, 2 women in the walking group (2%) and 11 women in the control group (12%) reported physician-diagnosed heart disease over the last 10 years (P = .07). There were also fewer hospitalizations, surgeries, and falls among women in the walking group, although these differences were not statistically significant (P>.05). CONCLUSIONS: Although limited by self-report, this study may be the first to demonstrate long-term exercise compliance to a randomized control trial in older women and to suggest that health benefits may have ensued as a result of these increased activity levels.     

Partial agonists and full antagonists at the human and murine bradykinin B1 receptors

OBJECTIVE: To examine the incidence of first diagnosis of invasive squamous cell carcinoma (SCC) of the skin over time. DESIGN: Retrospective, population-based incidence study. SETTING: Enumerated, geographically isolated, semiurban population served by the Mayo Clinic and its affiliated hospitals and the Olmsted Medical Center, including its affiliated hospital in Rochester, Minn. METHODS: Using the Rochester Epidemiology Project databases that capture virtually all medical care provided to the residents of Rochester, we identified and reviewed records of all documented residents in whom histologically proven, invasive SCC of the skin was first diagnosed between 1984 and 1992. Age and sex stratum-specific rates were calculated, and age-adjusted rates observed over time for individuals aged 35 years or older were analyzed using Poisson regression. Adjusted rates were compared with the results of other studies. RESULTS: Review of 1630 records identified 511 incidence cases of SCC. Tumors located on the head and neck accounted for 66.4% of tumors in females and 72.9% in males. The annual age- and sex-specific incidence rates per 100,000 increased from 0 cases among males aged 0 to 14 years to 1286.0 cases among males aged 85 years or older. Over time, the annual age-adjusted incidence rates per 100,000 females rose from 46.5 (95% confidence interval [CI], 32.4-60.6) for the 1984 to 1986 period to 99.6 (95% CI, 80.4-118.7) for the 1990 to 1992 period and were 71.2 (95% CI, 61.7-80.8) overall. The corresponding rates for males were 125.9 (95% CI, 95.3-156.4), 191.0 (95% CI, 156.9-225.0), and 155.5 (95% CI, 137.0-174.0). The age- and sex-adjusted SCC incidence rates for the period from 1987 to 1989 and 1990 to 1992 exceeded those for the period from 1984 to 1986 (P = .03 and P < .001, respectively). Our age-adjusted rates for SCC were within the ranges seen in other white populations from temperate climates. CONCLUSION: The frequencies of first diagnosis of SCC are increasing at rates beyond those explainable by demographic shifts alone.     

Immunoglobulins and transient paraproteins in sera of patients with the Wiskott-Aldrich syndrome: a follow-up study

Immunoglobulin levels of individual classes and IgG subclasses and the occurrence of homogeneous immunoglobulins--paraproteins--were studied longitudinally in the sera of three patients with the Wiskott-Aldrich syndrome; Common findings in all three patients were great variations in the immunoglobulin levels, restricted heterogeneity of the immunoglobulins, the frequent appearance of transient homogeneous immunoglobulins and the presence of serum antibodies against bovine milk proteins. A partial and selective deficiency involving mainly the T immune system is postulated as an explanation for these findings.