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Biomedical subjects

M C Morris

Publications and source records attributed to M C Morris.

At least 55 records · Page 3Linked to original sources
PubMed1998

Kinetics of dimerization and interactions of p13suc1 with cyclin-dependent kinases.

The impact of p13suc1 on the conformation and regulation of cyclin-dependent kinases (cdks) and cyclins was investigated by spectroscopic and rapid kinetic approaches. In the absence of phosphorylation on cdks, p13suc1 formed stable complexes, mainly stabilized by hydrophobic interactions, specifically with cdk2 and cdc2. The presence of cyclin A, associated with cdk2 or cdc2, increased the stability of the interaction between cdk2 and p13suc1 by a factor of 2. However, cyclin A did not modify the association rate of p13suc1 to cdk2, but the dissociation rate, which was decreased 3-fold. Moreover, binding of p13suc1 to cdk2 resulted in a 2-fold decrease in the release of nucleotide from cdk2, indicating that p13suc1 induces a marked change in the structure of the nucleotide binding site of cdks. On the basis of the structure of cdk2/CksHs1 complex and on our kinetic results, we propose that the binding of Cks proteins to C-lobe of cdk2 is stabilized by the presence of cyclin A and that it may modify the orientation of the loop carrying residues 14 and 15 and their consequent access for dephosphorylation by cdc25 phosphatases. Finally, we have shown that dimerization of p13suc1 in the presence of zinc abolishes its interaction with cdks, which suggests that the binding of p13suc1 to cdk2 or cdk2/cyclin A may be regulated by dimerization of p13suc1 in vivo.

Amino Acid Sequence↗
PubMed1998

Response to a mail nutritional survey in an older bi-racial community population.

PURPOSE: We conducted a pilot study of a mail food frequency questionnaire among a bi-racial sample of 200 persons 65 years and older, selected from participants of an ongoing community study. METHODS: Up to three successive mailings were followed by personal contact with nonresponders. Response to the mail survey was higher in whites (81%) than in blacks (53%). Personal contact was important to achieving high and uniform response (94%) in both racial groups. RESULTS: Those responding to the mailed questionnaires were also more likely to be older and higher educated. The vast majority of questionnaires returned by mail were complete; 85% had fewer than 15 missing items out of 152 questions. CONCLUSIONS: A mail nutritional survey is a feasible method of dietary assessment in older, white populations, but personal contact with nonresponders may be required for comparable participation among blacks.

Black or African American↗
PubMed1998

Paediatric nephrotic syndrome in Auckland, New Zealand.

OBJECTIVE: To review children with nephrotic syndrome in Auckland, New Zealand. METHODS: All children admitted to Auckland Children's Hospital between January 1984 and December 1994 with nephrotic syndrome and a renal biopsy had their charts retrospectively reviewed and the appropriate information summarised. RESULTS: Fifty-seven children biopsied with nephrotic syndrome were available for review. The mean age at diagnosis was 5.4 years, standard deviation (SD) 3.9 years, with mean follow-up of 5.7 years. The histologies of the renal biopsies were: minimal change nephrotic syndrome (MCNS) in 37%, focal segmental glomerulosclerosis in 19%, membranoproliferative glomerulonephritis (MPGN) in 23% and other causes in 21%. Maori children were most likely to have MPGN. Steroid resistance was present in 66% of children. End stage renal failure developed in 26% of patients and chronic renal failure in 4% of patients. CONCLUSION: In this series the proportion of children with MCNS is low and significant numbers of children with nephrotic syndrome progressed to chronic renal failure and end stage renal failure.

Adolescent↗
PubMed1998

Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease.

Oxidative stress may play a role in neurologic disease. The present study examined the relation between use of vitamin E and vitamin C and incident Alzheimer disease in a prospective study of 633 persons 65 years and older. A stratified random sample was selected from a disease-free population. At baseline, all vitamin supplements taken in the previous 2 weeks were identified by direct inspection. After an average follow-up period of 4.3 years, 91 of the sample participants with vitamin information met accepted criteria for the clinical diagnosis of Alzheimer disease. None of the 27 vitamin E supplement users had Alzheimer disease compared with 3.9 predicted based on the crude observed incidence among nonusers (p = 0.04) and 2.5 predicted based on age, sex, years of education, and length of follow-up interval (p = 0.23). None of the 23 vitamin C supplement users had Alzheimer disease compared with 3.3 predicted based on the crude observed incidence among nonusers (p = 0.10) and 3.2 predicted adjusted for age, sex, education, and follow-up interval (p = 0.04). There was no relation between Alzheimer disease and use of multivitamins. These data suggest that use of the higher-dose vitamin E and vitamin C supplements may lower the risk of Alzheimer disease.

Aged↗
PubMed1997

A new peptide vector for efficient delivery of oligonucleotides into mammalian cells.

The development of antisense and gene therapy has focused mainly on improving methods for oligonucleotide and gene delivery into cells. In the present work, we describe a potent new strategy for oligonucleotide delivery based on the use of a short peptide vector, termed MPG (27 residues), which contains a hydrophobic domain derived from the fusion sequence of HIV gp41 and a hydrophilic domain derived from the nuclear localization sequence of SV40 T-antigen. The formation of peptide vector/oligonucleotide complexes was investigated by measuring changes in intrinsic tryptophan fluorescence of peptide and of mansyl-labelled oligonucleotides. MPG exhibits relatively high affinity for both single- and double-stranded DNA in a nanomolar range. Based on both intrinsic and extrinsic fluorescence titrations, it appears that the main binding between MPG and oligonucleotides occurs through electrostatic interactions, which involve the basic-residues of the peptide vector. Further peptide/peptide interactions also occur, leading to a higher MPG/oligonucleotide ratio (in the region of 20/1), which suggests that oligonucleotides are most likely coated with several molecules of MPG. Premixed complexes of peptide vector with single or double stranded oligonucleotides are delivered into cultured mammalian cells in less than 1 h with relatively high efficiency (90%). This new strategy of oligonucleotide delivery into cultured cells based on a peptide vector offers several advantages compared to other commonly used approaches of delivery including efficiency, stability and absence of cytotoxicity. The interaction with MPG strongly increases both the stability of the oligonucleotide to nuclease and crossing of the plasma membrane. The mechanism of cell delivery of oligonucleotides by MPG does not follow the endosomal pathway, which explains the rapid and efficient delivery of oligonucleotides in the nucleus. As such, we propose this peptide vector as a powerful tool for potential development in gene and antisense therapy.

3T3 Cells↗
PubMed1997

Interactions of cyclins with cyclin-dependent kinases: a common interactive mechanism.

The formation of cdk-cyclin complexes has been investigated at the molecular level and quantified using spectroscopic approaches. In the absence of phosphorylation, cdk2, cdc2, and cdk7 form highly stable complexes with their "natural" cyclin partners with dissociation constants in the nanomolar range. In contrast, nonphosphorylated cdc2-cyclin H, cdk2-cyclin H, and cdk7-cyclin A complexes present a 25-fold lower stability. On the basis of both the structure of the cdk2-cyclin A complex and on our kinetic results, we suggest that interaction of any cyclin with any cdk involves the same hydrophobic contacts and induces a marked conformational change in the catalytic cleft of the cdks. Although cdks bind ATP strongly, they remain in a catalytically inactive conformation. In contrast, binding of the cyclin induces structural rearrangements which result in the selective reorientation of ATP, a concomitant 3-fold increase in its affinity, and a 5-fold decrease of its release from the active site of cdks.

Adenosine Triphosphate↗
PubMed1997

The hyperventilation of cirrhosis: progesterone and estradiol effects.

Progesterone and estradiol are metabolized in the liver and are elevated in patients with cirrhosis. Progesterone stimulates ventilation by activating progesterone receptors in the central nervous system; estradiol may facilitate progesterone's actions by increasing progesterone receptors. This study evaluated whether progesterone and estradiol contribute to the respiratory alkalosis common in cirrhotic patients. Arterial blood gases and progesterone and estradiol levels were obtained in 50 patients with cirrhosis. Multiple linear regression revealed a statistically significant correlation between PaCO2 and progesterone and estradiol (r = .54, P < .05). Patients with severe hyperventilation (PaCO2 < or = 30 mm Hg) had statistically higher levels of progesterone and estradiol than did patients with mild hyperventilation (30 < PaCO2 < or = 35) or normal ventilation (PaCO2 > 35) (P < .05). Although the progesterone levels were two orders of magnitude lower than those associated with hyperventilation in pregnant patients, the increased ventilatory effect may be because of the altered blood-brain barrier (BBB) present in cirrhotic patients. Progesterone and estradiol appear to contribute to the hyperventilation in cirrhotic patients.

Adult↗
PubMed1997

[New strategy for RNA vectorization in mammalian cells. Use of a peptide vector].

A major barrier for gene delivery is the low permeability of nucleic acids to cellular membranes. The development of antisenses and gene therapy has focused mainly on improving methods of oligonucleotide or gene delivery to the cell. In this report we described a new strategy for RNA cell delivery, based on a short single peptide. This peptide vector is derived from both the fusion domain of the gp41 protein of HIV and the nuclear localization sequence of the SV40 large T antigen. This peptide vector localizes rapidly to the cytoplasm then to the nucleus of human fibroblasts (HS-68) within a few minutes and exhibits a high affinity for a single-stranded mRNA encoding the p66 subunit of the HIV-1 reverse transcriptase (in a 100 nM range). The peptide/RNA complex formation involves mainly electrostatic interactions between the basic residues of the peptide and the charges on the phosphate group of the RNA. In the presence of the peptide-vector fluorescently-labelled mRNA is delivered into the cytoplasm of mammalian cells (HS68 human fibroblasts) in less than 1 h with a relatively high efficiency (80%). This new concept based on a peptide-derived vector offers several advantages compared to other compounds commonly used in gene delivery. This vector is highly soluble and exhibits no cytotoxicity at the concentrations used for optimal gene delivery. This result clearly supports the fact that this peptide vector is a powerful tool and that it can be used widely, as much for laboratory research as for new applications and development in gene and/or antisense therapy.

Cells, Cultured↗
PubMed1997

The responses of Lucilia cuprina to odours from sheep, offal and bacterial cultures.

The responses of gravid female Lucilia cuprina to odours from sheep urine, faeces and gut mucus, and to odours from liver/sodium sulphide mixtures was tested using a bioassay which measured the movement and probing response of walking flies. The same bioassay was used to test the response to odours from cultures of bacteria isolated from liver/sodium sulphide and liver/water mixtures. A significant movement towards odours from faeces, gut mucus and urine was observed. Odours from cultures of the bacteria Proteus mirabilis, Dermatophilus congolensis and Serratia marcescens also elicited significant movement. A probing response was elicited by odours from gut mucus, fresh urine, liver/sodium sulphide mixtures and cultures of P.mirabilis, D.congolensis and gram-positive species. Odours from cultures of Pseudomonas aeruginosa, Enterobacter aerogenes and Citrobacter freundii did not elicit significant movement or probing. The movement and probing responses are discussed with reference to the possible uses of the substances tested as a bait for attracting L.cuprina.

Animals↗
PubMed1996

Is a randomized trial of antioxidants in the primary prevention of Alzheimer disease warranted?

Alzheimer disease is a common condition that severely affects both persons with the illness and their families. Prevention of Alzheimer disease is an urgent priority, but study of potentially modifiable risk factors for the illness is at an early stage. Laboratory studies suggest that oxidative mechanisms may be involved in the pathogenesis of Alzheimer disease and raise the possibility that antioxidant nutrients could be used in disease prevention. Observational studies suggest that antioxidant nutrients may have protective effects against a number of other common chronic diseases, including cardiovascular disease and cancer. Because the protective effects, if any, of antioxidant nutrients are likely to be small to moderate in magnitude, large-scale randomized trials of primary prevention will likely be necessary to resolve this issue, and a major question is how quickly to progress to expensive and time consuming trials needed to provide more definitive evidence. This is a difficult question, but the severity of the disease, the current absence of preventive strategies and the likelihood that observational studies alone will not provide clear resolution of the issue all suggest that it may be prudent to strongly consider such trials in the near future.

Alzheimer Disease↗
PubMed1995

Fish consumption and cardiovascular disease in the physicians' health study: a prospective study.

The authors examined the association between dietary intake of fish and omega 3 fatty acids from seafood and the risk of cardiovascular disease in a prospective cohort study of 21,185 US male physicians who are participants in the Physicians' Health Study. In 4 years of follow-up, there were 281 incident cases of total (fatal and nonfatal) myocardial infarction, 173 cases of stroke, and 121 cardiovascular deaths. There was no evidence for association between dietary intake of fish and any cardiovascular endpoint, including myocardial infarction, stroke, and cardiovascular death. The relative risks of total myocardial infarction, adjusted for age and randomized treatment assignment, for categories of fish intake were: 1.0 for < 1 meal/week (referent), 1.6 (95% confidence interval (Cl) 1.1-2.3) for 1 fish meal/week; 1.4 (95% Cl 1.0-2.0) for 2-4 fish meals/week; and 1.2 (95% Cl 0.6-2.2) for > or = 5 fish meals/week; chi 2 for trend = 0.9, p = 0.34. The relative risks were similar for omega 3 fatty acid intake and for specific types of fish, and did not change after adjustment for history of hypertension, hypercholesterolemia, diabetes mellitus, or angina pectoris, parental history of myocardial infarction before age 60 years, obesity, exercise, smoking, alcohol use, saturated fat intake, and vitamin supplement use. These data do not support the hypothesis that moderate fish consumption lowers the risk of cardiovascular disease.

Aged↗
PubMed1994

Dietary fats and blood pressure.

This chapter reviews the evidence from epidemiologic studies and controlled clinical trials dealing with dietary fats and blood pressure. Trials studying the effect on blood pressure of n-3 polyunsaturated fatty acids from fish oil show a dose-response hypotensive effect that may be restricted to patients with atherosclerotic cardiovascular disease. However, fish oil is not a practical therapy for hypertension given the large dose required (10 capsules per day) for a small effect (3-4 mmHg). From numerous studies, it is clear that saturated and n-6 polyunsaturated fats have no effect on blood pressure. Monounsaturated fats also have no effect but fewer studies have examined this relation.

Blood Pressure↗
PubMed1993

The effect of fish oil on blood pressure in mild hypertensive subjects: a randomized crossover trial.

We conducted a double-blind, crossover trial with 18 healthy, untreated mildly hypertensive subjects to test the effect on blood pressure of 6 or 12 g fish oil/d (50% n-3 fatty acids) as compared with an olive oil placebo. Blood pressure was measured every 6 wk in the clinic and three times daily by subjects using a semiautomated device in their homes. Compliance was determined biochemically. No significant changes in home or clinic blood pressure measurements were noted for either dose after 6 or 12 wk of treatment. Clinic blood pressure after 12 g fish oil/d was slightly lower than after placebo treatment by -0.8/-0.4 mm Hg [95% CI: systolic blood pressure (-4.4, +2.8); diastolic blood pressure (-3.2, +2.4)]. Blood pressure changes were not correlated with compliance, baseline dietary fish consumption, or blood pressure. Moderate doses of fish oil did not have a substantial effect on blood pressure. We conclude that fish oil is not a practical treatment for mild hypertension.

Blood Pressure↗
PubMed1993

Does fish oil lower blood pressure? A meta-analysis of controlled trials.

BACKGROUND: In a meta-analysis of 31 placebo-controlled trials on 1356 subjects, we examined the effect of omega-3 fatty acids in fish oil on blood pressure by grouping studies that were similar in fish oil dose, length of treatment, health of the subjects, or study design. METHODS AND RESULTS: The mean reduction in blood pressure caused by fish oil for the 31 studies was -3.0/-1.5 mm Hg (95% confidence intervals: systolic blood pressure: -4.5, -1.5; diastolic blood pressure: -2.2, -0.8). There was a statistically significant dose-response effect when studies were grouped by omega-3 fatty acid dose: -1.3/-0.7 mm Hg at doses < or = 3 g/d, -2.9/-1.6 mm Hg at 3.3 to 7 g/d, and -8.1/-5.8 mm Hg at 15 g/d. Both eicosapentaenoic acid and docosahexaenoic acid were significantly related to blood pressure response. There was no effect on blood pressure in eight studies of "healthy" persons (mean reduction, -0.4/-0.7 mm Hg) at an overall mean dose of 4.2 g omega-3 fatty acids/d. By contrast, there was a significant effect of -3.4/-2.0 mm Hg in the group of hypertensive studies with a mean fish oil dose of 5.6 g/d and on systolic blood pressure only in six studies of hypercholesterolemic patients (-4.4/-1.1 mm Hg) with a mean dose of 4.0 g/d. A nonsignificant decrease in blood pressure was observed in four studies of patients with atherosclerotic cardiovascular disease (-6.3/-2.9 mm Hg). Variations in the length of treatment (from 3 to 24 weeks), type of placebo, and study design (crossover or parallel groups) did not appear to account for inconsistent findings among studies. CONCLUSIONS: There is a dose-response effect of fish oil on blood pressure of -0.66/-0.35 mm Hg/g omega-3 fatty acids. The hypotensive effect may be strongest in hypertensive subjects and those with clinical atherosclerotic disease or hypercholesterolemia.

Adult↗
PubMed1991

Evaluation of commercial enzyme immunoassays for detection of hepatitis delta antigen and anti-hepatitis delta virus (HDV) and immunoglobulin M anti-HDV antibodies.

Panels of hepatitis B virus surface antigen-positive sera from drug abusers were used to evaluate 14 commercial enzyme immunoassays from six companies for detecting hepatitis delta virus (HDV) markers. For detecting hepatitis delta virus antigen (HDAg), the Wellcome, Pasteur and Noctech assays had 100% sensitivity for all 42 HDAg-positive serum specimens that were confirmed in-house; the Organon reagents gave 59.5% sensitivity without detergent and 64.3% sensitivity with detergent, but there were 14 discrepant results with and without detergent. The Sorin assay detected HDAg in only 10 of the positive samples (23.8% sensitivity). For the detection of antibody to HDV (anti-HDV) all six commercial enzyme immunoassays were reactive with all 36 anti-HDV-positive specimens that were confirmed in-house. There were no false-positive results with the Wellcome, Noctech, or Sorin assay, but one specimen was false positive by the Organon assay. One HDAg-positive specimen gave a false anti-HDV-positive result in the Abbott assay and an equivocal result in the Pasteur assay (97.8% specificity). For the detection of immunoglobulin M anti-HDV, the Wellcome, Noctech, and Sorin assays agreed for the 38 positives confirmed in-house, except for one false negative with the Sorin test. We conclude that there has been a substantial improvement over previously evaluated assays in sensitivity and specificity of commercial assays for anti-HDV detection, and the sensitivities of immunoglobulin M anti-HDV assays are also comparable. However, there are still major differences in sensitivity among some assays for HDAg detection.

Antibodies, Viral↗
PubMed1990

Acute limb ischemia due to arterial embolism of tumor.

Arterial tumor embolism is a rare occurrence. We report such an embolus causing acute limb ischemia which was the first indication of malignancy in a patient who subsequently proved to have malignant melanoma.

Acute Disease↗