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M C Morris

Publications and source records attributed to M C Morris.

At least 19 recordsLinked to original sources
PubMed2007

A non-covalent peptide-based strategy for siRNA delivery.

The major obstacle to clinical development of siRNAs (short interfering RNAs), like for most of the nucleic-acid-based strategies, is their poor cellular uptake and bioavailability. Although several viral and non-viral strategies have been proposed to improve siRNA delivery, their applications in vivo remain a major challenge. We have developed a new strategy, based on a short amphipathic peptide, MPG, that is able to form stable nanoparticles with siRNA. MPG-based particles enter the cell independently of the endosomal pathway and can efficiently deliver siRNA in a fully biologically active form into a variety of cell lines and in vivo. This short review will discuss the mechanism and the potency of the MPG strategy for siRNA delivery both in vitro and in vivo.

Animals↗
PubMed2006

Associations of vegetable and fruit consumption with age-related cognitive change.

OBJECTIVE: To examine the association between rates of cognitive change and dietary consumption of fruits and vegetables among older persons. METHODS: The authors conducted a prospective cohort study of 3,718 participants, aged 65 years and older of the Chicago Health and Aging Project. Participants completed a food frequency questionnaire and were administered at least two of three cognitive assessments at baseline, 3-year, and 6-year follow-ups. Cognitive function was measured using the average z-score of four tests: the East Boston Tests of immediate memory and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test. RESULTS: The mean cognitive score at baseline for the analyzed cohort was 0.18 (range: -3.5 to 1.6), and the overall mean change in score per year was a decline of 0.04 standardized units. In mixed effects models adjusted for age, sex, race, and education, compared with the rate of cognitive decline among persons in the lowest quintile of vegetable intake (median of 0.9 servings/day), the rate for persons in the fourth quintile (median, 2.8 servings/day) was slower by 0.019 standardized units per year (p = 0.01), a 40% decrease, and by 0.018 standardized units per year (p = 0.02) for the fifth quintile (median, 4.1 servings/day), or a 38% decrease in rates. The association remained significant (p for linear trend = 0.02) with further control of cardiovascular-related conditions and risk factors. Fruit consumption was not associated with cognitive change. CONCLUSION: High vegetable but not fruit consumption may be associated with slower rate of cognitive decline with older age.

Aged↗
PubMed2005

Cell-penetrating peptides: tools for intracellular delivery of therapeutics.

The main problem of therapeutic efficiency lies in the crossing of cellular membranes. Therefore, significant effort is being made to develop agents which can cross these barriers and deliver therapeutic agents into cellular compartments. In recent years, a large amount of data on the use of peptides as delivery agents has accumulated. Several groups have published the first positive results using peptides for the delivery of therapeutic agents in relevant animal models. These peptides, called cell-penetrating peptides (CPPs), are short peptides (fewer than 30 residues) with a net positive charge and acting in a receptor- and energy-independent manner. Here, we give an extensive review of peptide-mediated delivery systems and discuss their applications, with particular focus on the mechanisms leading to cellular internalization.

Amino Acid Sequence↗
PubMed2004

Blood pressure and late-life cognitive function change: a biracial longitudinal population study.

OBJECTIVE: To examine the relation of blood pressure (BP) to subsequent decline in cognitive function among persons age 65 or over. METHODS: All persons age 65 or over in a geographically defined community were invited to participate in a longitudinal study of problems of the elderly. Interviews were conducted in the participants' homes and included two BP measures and four tests of cognitive function. Follow-up interviews 3 and 6 years after baseline repeated the cognitive function tests. These analyses included 4,284 individuals who had baseline and at least one follow-up measure of cognitive function. The average of z scores of the individual cognitive function tests was used as a global measure of cognitive function. RESULTS: In random effects analyses controlling for age, sex, education, and race, there was no significant linear association of either systolic or diastolic BP with 6-year change in global cognitive function score. There was no significant curvilinear association with systolic BP. In tests for a curvilinear association with diastolic BP, there was a suggestion of increased decline among those with low or high diastolic BP (p = 0.03 for the quadratic diastolic term). At baseline, 50% of participants took some type of medication affecting BP. CONCLUSION: In this community population where BP treatment was common, there was no association of either high systolic or high diastolic BP at the beginning of the observation interval with 6-year cognitive decline.

Aged↗
PubMed2004

Dietary fat intake and 6-year cognitive change in an older biracial community population.

OBJECTIVE: To examine whether consumption of different types of fat is associated with age-related change in cognition. METHODS: The authors related fat consumption to 6-year change in cognitive function among 2,560 participants of the Chicago Health and Aging Project, ages 65 and older, with no history of heart attack, stroke, or diabetes at baseline. Fat intake was measured by food frequency questionnaire. Cognitive function was measured at baseline and 3-year and 6-year follow-ups, using the average z score of four cognitive tests: the East Boston Tests of Immediate and Delayed Recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test. RESULTS: In separate mixed models adjusted for demographic and cardiovascular risk factors and intakes of antioxidant nutrients and other dietary fats, higher intakes of saturated fat (p for trend = 0.04) and trans-unsaturated fat (p for trend = 0.07) were linearly associated with greater decline in cognitive score over 6 years. These associations became stronger in analyses that eliminated persons whose fat intake changed in recent years or whose baseline cognitive scores were in the lowest 15%. Inverse associations with cognitive decline were observed in these latter restricted analyses for high intake of monounsaturated fat and a high ratio of polyunsaturated to saturated fat intake. Intakes of total fat, vegetable and animal fats, and cholesterol were not associated with cognitive change. CONCLUSION: A diet high in saturated or trans-unsaturated fat or low in nonhydrogenated unsaturated fats may be associated with cognitive decline among older persons.

Age Factors↗
PubMed2004

Combination of a new generation of PNAs with a peptide-based carrier enables efficient targeting of cell cycle progression.

The design of potent systems for the delivery of charged and noncharged molecules that target genes of interest remains a challenge. We describe a novel technology that combines a new generation of peptide nucleic acids (PNAs), or HypNA-pPNAs, with a new noncovalent peptide-based delivery system, Pep-2, which promotes efficient delivery of PNAs into several cell lines. We have validated the potential of this technology by showing that Pep2-mediated delivery of an antisense HypNA-pPNA chimera directed specifically against cyclin B1 induces rapid and robust downregulation of its protein levels and efficiently blocks cell cycle progression of several cell lines, as well as proliferation of cells derived from a breast cancer. Pep-2-based delivery system was shown to be 100-fold more efficient in delivering HypNA-pPNAs than classical cationic lipid-based methods. Whereas Pep-2 is essential for improving the bioavailability of PNAs and HypNA-pPNAs, the latter contribute significantly to the efficiency and specificity of the biological response. We have found that Pep-2/HypNA-pPNA strategy promotes potent antisense effects, which are approximately 25-fold greater than with classical antisense oligonucleotide directed specifically against the same cyclin B1 target. Taken together, these data demonstrate that peptide-mediated delivery of HypNA-pPNAs constitutes a very promising technology for therapeutic applications.

Antisense Elements (Genetics)↗
PubMed2004

Dietary niacin and the risk of incident Alzheimer's disease and of cognitive decline.

BACKGROUND: Dementia can be caused by severe niacin insufficiency, but it is unknown whether variation in intake of niacin in the usual diet is linked to neurodegenerative decline. We examined whether dietary intake of niacin was associated with incident Alzheimer's disease (AD) and cognitive decline in a large, prospective study. METHODS: This study was conducted in 1993-2002 in a geographically defined Chicago community of 6158 residents aged 65 years and older. Nutrient intake was determined by food frequency questionnaire. Four cognitive tests were administered to all study participants at 3 year intervals in a 6 year follow up. A total of 3718 participants had dietary data and at least two cognitive assessments for analyses of cognitive change over a median 5.5 years. Clinical evaluations were performed on a stratified random sample of 815 participants initially unaffected by AD, and 131 participants were diagnosed with 4 year incident AD by standardised criteria. RESULTS: Energy adjusted niacin intake had a protective effect on development of AD and cognitive decline. In a logistic regression model, relative risks (95% confidence intervals) for incident AD from lowest to highest quintiles of total niacin intake were: 1.0 (referent) 0.3 (0.1 to 0.6), 0.3 (0.1 to 0.7), 0.6 (0.3 to 1.3), and 0.3 (0.1 to 0.7) adjusted for age, sex, race, education, and ApoE e4 status. Niacin intake from foods was also inversely associated with AD (p for linear trend = 0.002 in the adjusted model). In an adjusted random effects model, higher food intake of niacin was associated with a slower annual rate of cognitive decline, by 0.019 standardised units (SU) per natural log increase in intake (mg) (p = 0.05). Stronger associations were observed in analyses that excluded participants with a history of cardiovascular disease (beta = 0.028 SU/year; p = 0.008), those with low baseline cognitive scores (beta = 0.023 SU/year; p = 0.02), or those with fewer than 12 years' education (beta = 0.035 SU/year; p = 0.002) CONCLUSION: Dietary niacin may protect against AD and age related cognitive decline.

Aged↗
PubMed2003

Cognitive activity and cognitive decline in a biracial community population.

BACKGROUND: Frequent participation in cognitively stimulating activities has been associated with reduced risk of AD in several prospective studies. However, the association of cognitive activity with cognitive decline, the principal manifestation of AD, is not well understood. METHODS: More than 4,000 older residents of a geographically defined biracial community of Chicago were interviewed at approximately 3-year intervals for an average of 5.3 years. Each interview included administration of four cognitive function tests from which a previously established global measure was derived. At baseline, each person rated frequency of participation in cognitively stimulating activities (e.g., reading a magazine) from which a previously established composite measure of cognitive activity was derived. RESULTS: Cognitive activity scores ranged from 1 to 5 (mean = 3.14, SD = 0.66), with higher scores indicating more frequent participation. More frequent cognitive activity was associated with reduced cognitive decline during follow-up. In a model that controlled for baseline level of cognition, age, sex, race, and education, a 1-point increase in cognitive activity score was associated with an approximately 19% decrease in annual rate of cognitive decline (p < 0.001). This effect remained when we controlled for depressive symptoms and chronic medical conditions (p < 0.001), and when we excluded persons with evidence of memory impairment at baseline (p < 0.001). CONCLUSION: Frequent participation in cognitively stimulating activities is associated with reduced cognitive decline in older persons.

Aged↗
PubMed2003

Noncompliance after kidney transplantation: a systematic review.

We performed a systematic review of the literature on medical noncompliance after kidney transplantation in the cyclosporine era. We wished to define commonalities that may help the clinician identify patients for early intervention. We found that patients who were at a higher risk of noncompliance after kidney transplants were younger, female, unmarried, and non-Caucasians. Patients who were recipients of living donor transplants and had been transplanted for a longer time with a history of a previous transplant were also at risk of noncompliance. We also found that patients displaying emotional problems, such as anxiety, hostility, depression, distress, lack of coping, and avoidant behaviors, were also at risk for noncompliance after kidney transplantation.

Female↗
PubMed2003

Minimizing harm in agricultural animal experiments in New Zealand.

Intrusive agricultural experiments published in New Zealand in the last five years are reviewed in terms of the degree of animal suffering involved, and the necessity for this suffering in relation to research findings. When measured against animal welfare criteria of the Ministry of Agriculture, thirty-six studies inflicted "severe" or "very severe" suffering. Many of these experiments had questionable short-term applications, had an application restricted to agricultural production or economic growth, or could have been modified to prevent or reduce suffering.

Agriculture↗
PubMed2002

Cognitive activity and incident AD in a population-based sample of older persons.

BACKGROUND: Participation in cognitively stimulating activities is hypothesized to be associated with risk of AD, but knowledge about this association is limited. METHODS: A biracial community in Chicago was censused, persons aged 65 years and older were asked to participate in an interview, and 6,158 of 7,826 (79%) eligible persons did so. As part of the interview, persons rated current frequency of participation in seven cognitive activities (e.g., reading a newspaper) and nine physical activities (e.g., walking for exercise) from which composite measures of cognitive and physical activity frequency were derived. Four years later, 1,249 of those judged free of AD were sampled for a detailed clinical evaluation of incident disease and 842 (74% of those eligible) participated. RESULTS: The composite measure of cognitive activity ranged from 1.28 to 4.71 (mean 3.30; SD 0.59), with higher scores indicating more frequent activity. A total of 139 persons met National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD on clinical evaluation. In a logistic regression model adjusted for age, education, sex, race, and possession of the APOE epsilon4 allele, a one-point increase in cognitive activity score was associated with a 64% reduction in risk of incident AD (OR 0.36; 95% CI 0.20 to 0.65). By contrast, weekly hours of physical activity (mean 3.5; SD 5.1) was not related to disease risk (OR 1.04; 95% CI 0.98 to 1.10). Education was associated with risk of AD and a similar trend was present for occupation, but these effects were substantially reduced when cognitive activity was added to the model. CONCLUSION: Frequency of participation in cognitively stimulating activities appears to be associated with risk of AD and may partially explain the association of educational and occupational attainment with disease risk.

Aged↗
PubMed2002

The changing epidemiological pattern of hepatitis A in England and Wales.

Sera from an age-stratified sample of 4188 individuals, submitted for diagnostic purposes to 15 public health laboratories in England and Wales in 1996, were tested for hepatitis A antibody. The serological profiles were consistent with declining incidence in the past. This hypothesis was tested by comparing the serological profiles of Ashford, Leeds and Preston public health laboratories with those from sera collected during a previous study in the same laboratories in 1986/7. A comparison of equivalent 10 year birth cohorts revealed that significant hepatitis A seroconversion had only continued in Ashford. However, it is probable that most seroconversions are due to vaccination and immigration rather than continuing viral transmission. Further population-based surveys collecting more in-depth social and demographic data are needed to confirm the main factors influencing hepatitis A seroprevalence and to explain the regional differences.

Adolescent↗
PubMed2002

Oral fluid collection by post--a pilot study of two approaches.

This pilot study aimed to assess the feasibility of the postal collection of oral fluid samples for surveillance purposes and the effect of two different approaches on the response rates. This cross-sectional, antibody prevalence study collected oral fluid samples and questionnaire data from randomly selected individuals, aged under 45 y, through the post. The individuals were recruited from four general practice registers. In a one stage approach patients were sent the oral fluid kit with the initial invitation letter. In a two stage approach the kits were sent out after written consent had been received. There was little difference in the overall response rates between the two approaches (38% two stage and 41% one stage), though the response rate for the one stage approach was 10% higher in the under-20-y-olds in practices from areas of greater deprivation. The low response partly reflected poor uptake in young adults who may need to be approached through more targeted surveys. In the other age groups additional reminders could prove a cost-effective way of increasing the response rate further.

Adolescent↗
PubMed2001

Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study.

BACKGROUND: It is uncertain whether high blood pressure increases the risk of developing Alzheimer disease (AD). OBJECTIVE: To examine the association between incident AD and blood pressure measured up to 13 years before diagnosis. DESIGN: Longitudinal cohort study conducted from 1982 to 1988, with blood pressure measured every 3 years in home interviews, and in 1973 for a portion (60%) of the sample. SETTING: Community of East Boston, Mass. PARTICIPANTS: Six hundred thirty-four subjects 65 years or older and without AD were selected as a stratified random sample of participants of the East Boston Established Populations for Epidemiologic Studies of the Elderly. MAIN OUTCOME MEASURE: Alzheimer disease was diagnosed by a neurologist using a structured clinical evaluation. RESULTS: High blood pressure was not associated with an increased risk of AD in logistic regression models adjusted for age, sex, and level of education. There was no association with systolic pressure measured 13 years before diagnosis (odds ratio = 1.03/10 mm Hg; 95% confidence interval, 0.80-1.32) and an inverse association with systolic pressure measured 4 years before diagnosis (odds ratio = 0.82/10 mm Hg; 95% confidence interval, 0.72-0.95). Associations for diastolic pressure were in the same direction as those for systolic pressure except with wider confidence intervals. The odds ratios were not materially different with further adjustment for cardiovascular risk factors and diseases. CONCLUSION: In this large community study, high blood pressure was not associated with an increased risk of AD.

Aged↗