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J Potter

Publications and source records attributed to J Potter.

At least 37 records · Page 2Linked to original sources
PubMed2000

Associations between dietary intake and Ki-ras mutations in colon tumors: a population-based study.

Ki-ras mutations are thought to be early events in the carcinogenic process leading to colon tumors. Dietary factors associated with colon cancer may be associated with these mutations. Data from a population-based, multicenter, case-control study of colon cancer were used to determine whether dietary factors are associated with Ki-ras mutations. Ki-ras mutations were detected by direct sequencing of codons 12 and 13 of the Ki-ras gene on exon 1 from DNA obtained from archival tissue. Ki-ras data were available for 1428 cases with valid interview data; data from 2410 controls were available for comparison with cases positive and negative for Ki-ras mutations. Mutations in the Ki-ras gene were detected in 32% of tumors. Of these mutations, 32.8% were G-->A transitions in the second base of codon 12 (2G-->A). Other than cruciferous vegetables, there were no nutrients or foods associated specifically with Ki-ras mutations [odds ratio (OR) for high intake relative to low intake, 0.7; 95% confidence interval (CI), 0.5-1.0]. However, evaluation of specific types of Ki-ras mutations revealed that for each of the most common types of mutation, dietary associations existed. Dietary factors involved in DNA methylation pathways were associated with 2G-->A mutations. Comparison of individuals with and without Ki-ras mutations revealed that individuals with low levels of dietary folate (OR, 0.7; 95% CI, 0.4-1.3), vitamin B6 (OR, 0.5; 95% CI, 0.3-1.0), vitamin B12 (OR, 0.6; 95% CI, 0.3-1.1), and high levels of alcohol (OR, 0.7; 95% CI, 0.4-1.1) were less likely to have a 2G-->A mutation. Individuals with high levels of dietary carbohydrate (OR, 2.0; 95% CI, 0.9-4.4) and a high glycemic index (OR, 1.9; 95% CI, 0.8-4.6) were more likely to have a G-->A transition mutation in the second base of codon 13 (5G-->A). Individuals with high levels of dietary fat (OR, 1.6; 95% CI, 0.8-3.2), saturated fat (OR, 1.7; 95% CI, 0.8-3.5), and monounsaturated fat (OR, 1.9; 95% CI, 1.0-3.7) were more likely to harbor a 2G-->T mutation. Low levels of cruciferous vegetable intake and high levels of processed meat intake also were associated with fewer 5G-->A, as reflected by the ORs (OR, 0.4; 95% CI, 0.2-1.0 and OR, 0.4; 95% CI 0.2-0.8, respectively). These data suggest that diet may be involved in disease pathways represented by specific Ki-ras mutations. However, given the limited information currently available on associations between specific genetic mutations in colon tumors and diet, these findings also should be viewed as hypothesis generating.

Adult↗
PubMed2000

Associations between cigarette smoking, lifestyle factors, and microsatellite instability in colon tumors.

BACKGROUND: Microsatellite instability (MSI) has been reported to occur in approximately 10%-15% of colon tumors. MSI is characterized by the presence of mutations in tandemly repeated DNA sequences known as microsatellites. Some individuals with unstable tumors have inherited mutations in mismatch repair genes, but MSI is also observed in sporadic colon cancer. It is unknown whether lifestyle factors associated with colon cancer, such as physical activity, body size, cigarette smoking, or use of aspirin and/or nonsteroidal anti-inflammatory drugs, contribute to MSI in sporadic tumors. METHODS: Data from a population-based, case-control study of colon cancer were used. Case subjects were between 30 and 79 years of age at the time of diagnosis and included both men and women. Questionnaire data were used to obtain information on lifestyle factors. Tumor MSI was determined with the use of a panel of 10 tetranucleotide repeats and two mononucleotide repeats. A total of 1510 case subjects had valid questionnaire data and tumor DNA from which we were able to obtain MSI status. Questionnaire data were compared with lifestyle factors reported by 2410 population-based control subjects. All statistical tests were two-sided. RESULTS: MSI-positive (MSI(+)) tumors were most common in older people and women and in the proximal colon. Patients with MSI(+) tumors were more likely to smoke 20 or more cigarettes a day than case subjects with MSI-negative (MSI(-)) tumors (odds ratio for being a smoker = 1.6 [95% confidence interval = 1.0-2.5] for men and 2.2 [95% confidence interval = 1.4-3.5] for women). The association between MSI(+) tumors and cigarette smoking was strongest among case subjects who started to smoke at a young age, smoked for 35 or more years, and were either current smokers or had stopped fewer than 15 years before diagnosis. A statistically significant linear trend of increased risk of MSI(+) tumors was observed with increasing amount smoked (P<.01). CONCLUSIONS: This study suggests that smoking cigarettes statistically significantly contributes to MSI in colon tumors. We estimate that approximately 21% of MSI in colon tumors may be attributable to cigarette smoking.

Adult↗
PubMed2000

Decreased UDP-GlcNAc levels abrogate proliferation control in EMeg32-deficient cells.

The hexosamine pathway provides UDP-N:-acetylhexosamine donor substrates used in cytosolic and Golgi-mediated glycosylation of proteins and for formation of glycosylphosphatidylinositol (GPI) anchors, which tether proteins to the outer plasma membrane. We have recently identified the murine glucosamine-6-phosphate (GlcN6P) acetyltransferase, EMeg32, as a developmentally regulated enzyme on the route to UDP-N:-acetylglucosamine (UDP-GlcNAc). Here we describe embryos and cells that have the EMeg32 gene inactivated by homologous recombination. Homozygous mutant embryos die at around embryonic day (E) 7.5 with a general proliferative delay of development. In vitro differentiated EMeg32(-/-) ES cells show reduced proliferation. Mouse embryonic fibroblasts (MEFs) deficient for EMeg32 exhibit defects in proliferation and adhesiveness, which could be complemented by stable re-expression of EMeg32 or by nutritional restoration of intracellular UDP-GlcNAc levels. Reduced UDP-GlcNAc levels predominantly translated into decreased O-GlcNAc modifications of cytosolic and nuclear proteins. Interestingly, growth-impaired EMeg32(-/-) MEFs withstand a number of apoptotic stimuli and express activated PKB/AKT. Thus, EMeg32-dependent UDP-GlcNAc levels influence cell cycle progression and susceptibility to apoptotic stimuli.

Acetyltransferases↗
PubMed2000

Severe liver degeneration and lack of NF-kappaB activation in NEMO/IKKgamma-deficient mice.

Phosphorylation of IkappaB, an inhibitor of NF-kappaB, is an important step in the activation of the transcription factor NF-kappaB. Phosphorylation is mediated by the IkappaB kinase (IKK) complex, known to contain two catalytic subunits: IKKalpha and IKKbeta. A novel, noncatalytic component of this kinase complex called NEMO (NF-kappaB essential modulator)/IKKgamma was identified recently. We have generated NEMO/IKKgamma-deficient mice by gene targeting. Mutant embryos die at E12.5-E13.0 from severe liver damage due to apoptosis. NEMO/IKKgamma-deficient primary murine embryonic fibroblasts (MEFs) lack detectable NF-kappaB DNA-binding activity in response to TNFalpha, IL-1, LPS, and Poly(IC) and do not show stimulus-dependent IkappaB kinase activity, which correlates with a lack of phosphorylation and degradation of IkappaBalpha. Consistent with these data, mutant MEFs show increased sensitivity to TNFalpha-induced apoptosis. Our data provide in vivo evidence that NEMO/IKKgamma is the first essential, noncatalytic component of the IKK complex.

Animals↗
PubMed2000

Is dosage of physiotherapy a critical factor in deciding patterns of recovery from stroke: a pragmatic randomized controlled trial.

BACKGROUND AND PURPOSE: The best treatment and management of stroke patients has been shown to be in stroke units by multidisciplinary rehabilitation teams. Since the composition of stroke units differs it is important to know the extent to which the different components contribute to this results. Physiotherapy is one component of most rehabilitation teams and recent systematic reviews have shown that patients with stroke receiving more physiotherapy achieve more recovery from disability. However, information about the actual amounts of physiotherapy needed to achieve this result is not known. METHOD: A pragmatic, randomized, single-blind, controlled trial comparing recovery from disability in subjects receiving the current standard amount of 30 minutes' physiotherapy with those receiving double that amount (60 minutes). The study included measures of physical performance and function, psychological aspects of anxiety and depression, and perceived control over recovery. RESULTS: Some 114 subjects were recruited to the study; full six-week data are available for 104 subjects and six-month data for 93 subjects. Comparison of initial to six-week difference scores in the control and intervention groups of the whole sample did not show a significant difference. Scrutiny of the recovery curves of the whole sample showed that, in half the sample, three distinct patterns of recovery were demonstrated. CONCLUSION: These results suggest that doubling the physiotherapy time available for patients in a stroke unit will not provide a measurable benefit for all patients. The subgroup analysis of patterns of recovery must be regarded as speculative, but provides the basis for hypotheses about those likely to respond well to more intensive therapy.

Activities of Daily Living↗
PubMed2000

Differential engraftment of genetically modified CD34(+) and CD34(-) hematopoietic cell subsets in lethally irradiated baboons.

OBJECTIVE: To test gibbon ape leukemia virus (GALV) pseudotype vector transduction of marrow subpopulations that contribute to hematopoietic reconstitution in vivo. MATERIALS AND METHODS: Autologous CD34(+) Lin(-), CD34(+) Lin(+), and CD34(-) Lin(-) marrow cells, transduced by coculture with PG13/LN, PG13/LNX, and PG13/LNY vector-producing cells, respectively, were transplanted in three female baboons. Two female baboons also were transplanted with fresh allogeneic CD34(-)Lin(-) marrow cells from MHC-matched male siblings and, to ensure survival, with autologous CD34(+)Lin(-) and CD34(+)Lin(+) marrow cells transduced with PG13/LN and PG13/LNX, respectively. The LN, LNX, and LNY vectors are identical except for different length sequences at the 3' end of the bacterial neomycin phosphotransferase (neo) gene. RESULTS: LN(+) and LNX(+) cells from CD34(+)Lin(-) and CD34(+)Lin(+) cells, respectively, but no LNY(+) from CD34(-)Lin(-) cells were detectable in blood and marrow of all animals after transplant. LN(+), CD34(+)Lin(-) cells contributed to reconstitution of the T, B, and myeloid lineages. LNX(+), CD34(+)Lin(+) cells contributed only to B and myeloid lineages. Male cells, CD34(-)Lin(-), were detected by polymerase chain reaction in blood and marrow of the two allogeneic transplanted animals at estimated frequencies of </=0.001% 1 month after transplant in both animals. Male cells became undetectable in one animal and have remained detectable, with declining frequency, in the other for more than 15 months. In this animal, no male CD34(+) or colony-forming cells have been detected. CONCLUSIONS: CD34(+)Lin(-) and CD34(+)Lin(+) marrow cells can serve as targets for GALV pseudotype retrovirus-mediated gene transfer. CD34(+)Lin(-) cells contribute to reconstitution of all hematopoietic lineages. Autologous CD34(-)Lin(-) cells were either not transduced by GALV pseudotype retrovirus vectors using current approaches or did not contribute significantly to reconstitution, as suggested by allogeneic transplants.

Animals↗
PubMed2000

Factors affecting the dissolution and degradation of oriental mustard-derived sinigrin and allyl isothiocyanate in aqueous media.

Sinigrin, the predominant glucosinolate in the oriental mustard Brassica juncea, is mainly degraded upon the enzymatic action of myrosinase under normal conditions to give allyl isothiocyanate (AITC) in an aqueous media. Because AITC is considered to be the principal nematicidal ingredient in B. juncea, its stability in aqueous media is an important issue in achieving efficient nematode control. Pure sinigrin and AITC were found to be relatively stable in buffered water in the pH range of 5.00-7.00 but less stable at pH 9.00. Both sinigrin and AITC were more stable in soil water (supernatant of a 1:1 water/air-dried soil mixture) than in buffered water at the same pH range of 5.00-9.00. Sinigrin dissolved from the mustard bran or ground seed into water very quickly and was degraded by codissolved myrosinase to AITC. The AITC that formed from the degradation of sinigrin was found to be more stable in the soil water than in the buffered water. Buffer capacity was considered to be one of the factors that contributed to the stabilization of AITC in the soil water, but other unknown factors from both bran or seed and soil may also have contributed to the stabilization.

Glucosinolates↗
PubMed2000

Associations between family history of cancer and genes coding for metabolizing enzymes (United States).

OBJECTIVE: Family history of cancer has been a useful tool to identify highly penetrant genes. However, the association between family history and low-penetrance genes that are prevalent in the population, is less well understood. While epidemiologists have studied low-penetrance genes in association studies at the population level, geneticists have often favored family studies to identify low-penetrance genes in the same manner that these families have been used to identify high-penetrance genes. In this study, we evaluated the association between family history of cancer and molecular variants of three genes: N-acetyltransferases (NAT2), glutathione-S-transferases (GSTM-1), and methylenetetrahydrofolate reductase (MTHFR). These genes were examined because of their plausible functional significance and their association with cancer risk in some studies. METHODS: In a large multi-centered study of colon cancer, reported family history of cancer in first-degree relatives was used to classify cases and controls separately as having a family history of colorectal cancer, hormone-related cancers, smoking-related cancers, prostate cancer, and any cancer. RESULTS: With three weak exceptions, we did not observe significant associations between any of these genes and family history of cancer. The ability of family history to positively predict the presence of variants of low-penetrance genes that may carry an elevated risk ranged from 41% to 60%; low-penetrance variants accurately predicted a family history of cancer 9 to 17% of the time. Assessment of the likelihood of having a family history of cancer given the combination of genetic and environmental factors, showed that those who smoked 20 or more cigarettes per day were more likely to have a family history of a smoking-related cancer irrespective of genotype. CONCLUSIONS: People with a family history of cancer are not more likely to have a variant of low-penetrance genes than those without a family history of cancer. Family studies may not be efficient methods to study low-penetrance genes.

Adult↗
PubMed2000

Computer recording of standard tests of visual neglect in stroke patients.

OBJECTIVE: To determine whether a computer-based method for recording standardized assessment of neglect identifies abnormalities in the 'process' as well as in the 'outcome' of such tasks. DESIGN: Prospective sequential assessment of patients admitted to a stroke rehabilitation unit. SUBJECTS: All consecutive patients with right-sided cerebrovascular accident confirmed on computerized tomography (CT) scan including 30 patients with neglect, 57 patients without neglect. An age-matched control group of 13 subjects. INTERVENTION: All patients were tested using the standard Rivermead Behavioural Inattention Test (BIT) and by computer recording of two standard tests for assessing neglect (line bisection and Albert's test). Age-matched controls were tested using computer recording of the two standard tests. MAIN OUTCOME MEASURES: Neglect was defined using the BIT with a cut-off score of 129. Computer recording measured the 'outcome' of tasks, i.e. the deviation from midline and omissions in cancellation, as well as the 'process' of tasks, i.e. time between cancellations, components of cancellation time including premovement, movement and drawing time, and the starting point for cancellation. RESULTS: The computer recording identified significant differences in 'outcome' and 'process' which distinguished neglect from non-neglect patients. There were significant differences between non-neglect patients and age-matched controls with regard to 'process' measures but not with regard to 'outcome' measures. CONCLUSIONS: Computer recording of standard tests for assessing neglect identifies novel impairments with regard to the process of carrying out tasks. These impairments may be used to investigate changes in neglect with time, the response of neglect to treatment and to explore further the neuropsychological changes associated with neglect in stroke patients.

Aged↗
PubMed2000

Evaluation of the PuriLens contact lens care system: an automatic care system incorporating UV disinfection and hydrodynamic shear cleaning.

PURPOSE: This study evaluates lens care using the PuriLens System, an advanced way to clean and disinfect soft hydrophilic lenses using subsonic agitation and UV radiation, respectively. METHODS: A two-period crossover lens cleaning and safety investigation was conducted using 80 patients. Disinfecting efficacy was tested in accordance with standard FDA protocols. Lens compatibility was studied with Group I and Group IV lenses during the equivalent of a 6-month care regimen by measuring: lens power, base curve, wet diameter, refractive index, clarity, and tint. Safety was evaluated through slit-lamp findings, wearing time, comfort, and visual acuity. RESULTS: The mean wearing time of patients in the study was 13.79 hours. No slit lamp findings greater than grade 2 were noted. Visual acuity was 20/25 or better in 92.5% of examinations. None of the patients lost more than two lines of acuity. Lens surface evaluation showed no deposits (grade 0) to very slight deposits (grade 1) in 94.4% of examinations. Lenses cleaned with the PuriLens System were cleaner by a statistically significant margin (P=0.02) compared to lenses digitally cleaned with a leading multi-purpose solution (ReNu, Bausch & Lomb). Overall, neither the Group I nor Group IV lenses were affected after 180 cleaning cycles. CONCLUSIONS: The PuriLens System provides automatic lens care compliance, superior antimicrobial efficacy, and eliminates the need for daily digital cleaning.

Adolescent↗
PubMed1999

Treatment of mandibular angle fractures with a malleable noncompression miniplate.

PURPOSE: This study evaluated the results in patients treated for fractures of the mandibular angle with a single, thin, malleable miniplate designed for use in the midface. PATIENTS AND METHODS: Forty-six patients with 51 fractures of the mandibular angle were treated by open reduction and internal fixation using one noncompression, thin, malleable miniplate and 1.3-mm self-threading screws placed through a transoral incision. No patient was placed into postsurgical maxillomandibular fixation. They were prospectively studied for complications. RESULTS: Seven patients (15.2%) experienced complications. All were considered minor and did not require hospitalization. Three had asymptomatic fracture of the bone plate, but at the time of diagnosis the fracture had already healed and it required no treatment. Two patients had fracture of the bone plate with continued fracture mobility requiring maxillomandibular fixation. Three minor infections occurred requiring intraoral incision and drainage. CONCLUSIONS: The use of this small bone plate for fractures of the angle of the mandible provided adequate fixation in most cases but was associated with an unacceptable incidence of plate fracture. However, the results also indicate that the fixation requirements for angle fractures is less than previously thought.

Adolescent↗
PubMed1999

Guidelines for management of hypertension: report of the third working party of the British Hypertension Society.

Use non-pharmacological measures in all hypertensive and borderline hypertensive people. Initiate antihypertensive drug therapy in people with sustained systolic blood pressures (BP) >/=160 mm Hg or sustained diastolic BP >/=100 mm Hg. Decide on treatment in people with sustained systolic BP between 140 and 159 mm Hg or sustained diastolic BP between 90 and 99 mm Hg according to the presence or absence of target organ damage, cardiovascular disease or a 10-year coronary heart disease (CHD) risk of >/=15% according to the Joint British Societies CHD risk assessment programme/risk chart. In people with diabetes mellitus, initiate antihypertensive drug therapy if systolic BP is sustained >/=140 mm Hg or diastolic BP is sustained >/=90 mm Hg. In non-diabetic hypertensive people, optimal BP treatment targets are: systolic BP <140 mm Hg and diastolic BP <85 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <150/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some hypertensive people. In diabetic hypertensive people, optimal BP targets are; systolic BP <140 mm Hg and diastolic BP <80 mm Hg. The minimum acceptable level of control (Audit Standard) recommended is <140/<90 mm Hg. Despite best practice, these levels will be difficult to achieve in some people with diabetes and hypertension. In the absence of contraindications or compelling indications for other antihypertensive agents, low dose thiazide diuretics or beta-blockers are preferred as first-line therapy for the majority of hypertensive people. In the absence of compelling indications for beta-blockade, diuretics or long acting dihydropyridine calcium antagonists are preferred to beta-blockers in older subjects. Compelling indications and contraindications for all antihypertensive drug classes are specified. For most hypertensives, a combination of antihypertensive drugs will be required to achieve the recommended targets for blood pressure control. Other drugs that reduce cardiovascular risk must also be considered. These include aspirin for secondary prevention of cardiovascular disease, and primary prevention in treated hypertensive subjects over the age of 50 years who have a 10-year CHD risk >/=15% and in whom blood pressure is controlled to the audit standard. In accordance with existing British recommendations, statin therapy is recommended for hypertensive people with a total cholesterol >/=5 mmol/L and established vascular disease, or 10-year CHD risk >/=30% estimated from the Joint British Societies CHD risk chart. Glycaemic control should also be optimised in diabetic subjects. Specific advice is given on the management of hypertension in specific patient groups, ie, the elderly, ethnic subgroups, diabetes mellitus, chronic renal disease and in women (pregnancy, oral contraceptive use and hormone replacement therapy). Suggestions for the implementation and audit of these guidelines in primary care are provided.

Antihypertensive Agents↗
PubMed1999

A preliminary investigation into the use of virtual environments in memory retraining after vascular brain injury: indications for future strategy?

PURPOSE: In a preliminary investigation of the use of Virtual Environments (VEs) in neurorehabilitation, this study compares the effects of active and passive experience of a VE on two types of memory in vascular brain injury patients and controls. METHOD: Forty-eight patients with vascular brain injury and 48 non-impaired control participants were randomly assigned to active and passive VE conditions. The active participants explored a virtual bungalow seeking a particular object; the passive participants observed, but did not control movement through the VE, also seeking the object. Afterwards, both active and passive participants completed spatial recognition and object recognition tests. RESULTS: Expectedly, the patients were impaired relative to the controls but were able to perform the virtual tasks. Active participation in the VE enhanced memory for its spatial layout in both patients and controls. On object recognition, active and passive patients performed similarly, but passive controls performed better than active controls. CONCLUSIONS: The findings are discussed in relation to their implications for memory rehabilitation strategies.

Adult↗
PubMed1999

Integrated designs for gene discovery and characterization.

Recent advances, including near completion of the human genome map, ever improving high-throughput technologies, and successes in discovering chronic disease-related genes, have stimulated the further development of genetic epidemiology. The primary mission of genetic epidemiology is to discover and characterize genes, whether independent of or interactive with environmental factors, that cause human diseases. To accomplish such a mission, genetic epidemiology needs to integrate both genetic and epidemiologic approaches. One of the challenges facing such an integrated approach is the identification of study designs that are efficient for both gene discovery and characterization. Because designs for gene discovery alone and designs for gene characterization alone have been elaborated in the other two panels, the focus of this paper is to describe those designs that may be useful for discovery and characterization jointly, including case-family and case-control-family designs. Examples of integrated designs are described, and studies of breast cancer conducted at the Fred Hutchinson Cancer Research Center are used for illustration. Finally, related analytic issues are also discussed.

Breast Neoplasms↗
PubMed1999

The Physical Activity for Total Health (PATH) Study: rationale and design.

PURPOSE: Physical activity has been associated with a decreased risk for breast cancer. Mechanisms for this association may involve hormonal pathways. The Physical Activity for Total Health study is testing the effect of a 1-yr moderate intensity physical activity intervention on the endogenous sex hormone profile of postmenopausal women in a randomized controlled study. METHODS: Women (N = 168) who are aged 55-75 yr, not using sex hormones, sedentary, nonsmokers, have no endocrine-related disease or cancer, and with body mass index of 25.0 or greater, are eligible. Women are recruited through mass mailings and media advertising and are randomized to either a 1-yr moderate intensity aerobic and strength training exercise program (monitored group exercise sessions plus home exercise) or a control program (stretching classes). RESULTS: Serum hormones to be assayed at baseline and at the end of the study include: total estrone, total estradiol, free estradiol, percent bioavailable estradiol, estrone sulfate, sex hormone binding globulin, albumin, testosterone, free testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone sulfate, insulin, glucose, and triglycerides. Other outcome measures include: the ratio of urinary 2-hydroxyestrone: 16alpha-hydroxyestrone (an estrogen metabolite ratio that may be associated with risk for breast cancer), weight, body mass index, total fat mass, and body fat distribution (waist:hip circumference ratio, DEXA scan, and abdominal fat measured by computed tomography). CONCLUSION: This study is the first to examine the effect of change in physical activity level on sex hormones in postmenopausal women. It will provide insight into possible mechanisms through which physical activity might be associated with reduced risk of breast cancer.

Aged↗