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Biomedical subjects

C M Anderson

Publications and source records attributed to C M Anderson.

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

Telephone counseling as adjuvant treatment for nicotine replacement therapy in a "real-world" setting.

BACKGROUND: Physicians prescribing nicotine replacement therapy (NRT), or health plans covering NRT, often want their patients to receive adjuvant behavioral treatment. However, how to do that in a "real world" is unclear. This paper reports results from a public health program that uses proactive telephone counseling as support for physician advice and provides adjuvant treatment for NRT users. METHODS: Participants were NRT users (N = 8,832) who called the California Smokers' Helpline, a statewide cessation service that provides proactive counseling, one session before NRT use and multisessions after the smokers received NRT. After receiving NRT, some participants discontinued the counseling while others continued with follow-up sessions. A subset of the 8,832 participants (n = 664) was interviewed 13 months later for quitting status. RESULTS: After receiving NRT, 79% of the participants continued with counseling and received 4.2 sessions on average, while 21% of them received only one session. Overall, 82.8% of all participants made a quit attempt. Nicotine patch users were more likely to make an attempt than nicotine gum users (85.2% vs 66.3%), but the relapse probability was the same for these attempts. Those who received multiple counseling were more likely to make an attempt than those receiving single counseling (84.4% vs 77.1%) and were more likely to stay quit for 1 year (25.6% vs 16.1%). CONCLUSIONS: Proactive telephone counseling is a promising adjuvant treatment for NRT users in a "real-world" setting: a convenient referral service for supporting health plans or physicians who advise their patients to quit smoking.

Adolescent↗
PubMed2000

Disparity between association and linkage analysis for HNF1A G319S in type 2 diabetes in Canadian Oji-Cree.

In parallel experiments designed to find the genetic determinants of type 2 diabetes in Oji-Cree, we identified several linked chromosomal regions, using genomic scanning, in addition to a private diabetes-associated mutation, namely HNF1A G319S, using candidate gene sequencing. The genome scan did not identify the region harboring HNF1A as being linked with diabetes. Also, the HNF1A mutation, when used directly in sib-pair linkage analysis, was not linked with diabetes. However, HNF1A G319S was very strongly associated with diabetes, predicted the clinical severity of diabetes, and performed well as a diagnostic predictive test for diabetes in the Oji-Cree. Despite the failure of linkage analysis to identify HNF1A as a determinant of type 2 diabetes, we feel justified in interpreting that G319S has a very important pathogenic role in Oji-Cree diabetes, based upon the highly suggestive association studies. The probable etiologic heterogeneity of type 2 diabetes in the Oji-Cree created a situation in which association analysis was much more sensitive to detect a relationship between HNF1A S319 and diabetes than was linkage analysis. The effectiveness of linkage analysis will probably be limited in study samples that have an even greater complexity of genetic background and/or disease etiology. Thus, the absence of linkage does not always mean that a genomic variant is not an important determinant of a complex disease. Furthermore, our experience confirms the value of using several complementary strategies to identify susceptibility genes for a complex disease.

Alleles↗
PubMed2000

The changing prognosis of melanoma.

Cutaneous melanoma is a significant and increasing clinical problem. Knowing accurately the prognosis in a given patient is critical for treatment decisions and for optimal patient education. In this article we discuss the most current information regarding prognostic factors in early-stage and advanced malignant melanoma. Tumor thickness and ulceration are the most important predictors for primary melanoma. Number of positive lymph nodes is the most powerful predictor for stage III patients, and sites of disease and lactase dehydrogenase levels are the most useful predictors in metastatic disease.

Age Factors↗
PubMed2000

Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry.

Attention-deficit/hyperactivity disorder is a highly heritable and prevalent neuropsychiatric disorder estimated to affect 6% of school-age children. Its clinical hallmarks are inattention, hyperactivity and impulsivity, which often respond substantially to treatment with methylphenidate or dextroamphetamine. Etiological theories suggest a deficit in corticostriatal circuits, particularly those components modulated by dopamine. We developed a new functional magnetic resonance imaging procedure (T2 relaxometry) to indirectly assess blood volume in the striatum (caudate and putamen) of boys 6-12 years of age in steady-state conditions. Boys with attention-deficit/hyperactivity disorder had higher T2 relaxation time measures in the putamen bilaterally than healthy control subjects. Relaxation times strongly correlated with the child's capacity to sit still and his accuracy in accomplishing a computerized attention task. Daily treatment with methylphenidate significantly changed the T2 relaxation times in the putamen of children with attention-deficit/hyperactivity disorder, although the magnitude and direction of the effect was strongly dependent on the child's unmedicated activity state. There was a similar but nonsignificant trend in the right caudate. T2 relaxation time measures in thalamus did not differ significantly between groups, and were not affected by methylphenidate. Attention-deficit/hyperactivity disorder symptoms may be closely tied to functional abnormalities in the putamen, which is mainly involved in the regulation of motor behavior.

Attention Deficit Disorder with Hyperactivity↗
PubMed2000

Gender, obesity, hepatic nuclear factor-1alpha G319S and the age-of-onset of type 2 diabetes in Canadian Oji-Cree.

Among the Oji-Cree of northern Ontario, women have both a higher prevalence and an earlier onset of type 2 diabetes compared to men. We studied the relationship between HNF1A S319 and both the presence of and the age-of-onset of type 2 diabetes in women and men separately. We found that: 1) in women, there was a significant difference in the mean age-of-onset of type 2 diabetes according to HNF1A genotype; and 2) in men, there was no difference in the mean age-of-onset of type 2 diabetes according to HNF1A genotype. The findings indicate that HNF1A S319 is associated with increased susceptibility to type 2 diabetes in both men and women, but with earlier age-of-onset in women only. One factor that might account for the gender difference in the onset of HNF1A S319-associated type 2 diabetes is the greater prevalence and severity, and earlier onset of, obesity among female Oji-Cree.

Adolescent↗
PubMed2000

Differing effects of copper,zinc superoxide dismutase overexpression on neurotoxicity elicited by nitric oxide, reactive oxygen species, and excitotoxins.

Overexpression of Cu,Zn superoxide dismutase (SOD1) reduces ischemic injury in some stroke models but exacerbates injury in a neonatal stroke model and in other settings. The current study used a SOD1 transgenic (SOD1-Tg) murine cortical culture system, derived from the same mouse strain previously used for the stroke models, to identify conditions that determine whether SOD1 overexpression in neurons is protective or detrimental. The nitric oxide (NO) donors S-nitroso-N-acetylpenicillamine, spermine-NONOate, and diethylamine-NONOate produced less death in SOD1-Tg neurons than in wild-type neurons (p < 0.01). Also, NO produced markedly less 3-nitrotyosine in SOD1-Tg cells. In contrast, the superoxide generator menadione produced significantly greater death and nearly twice as much 2'7'-dichlorofluorescein fluorescence in SOD1-Tg neurons than in wild-type neurons, suggesting increased peroxide formation in the SOD1-Tg cells. No significant difference was observed in the vulnerability of the two cell types to H2O2, the product of the SOD reaction. Overexpression of SOD1 also had no effect on neuronal vulnerability to glutamate, N-methyl-D-aspartate, or kainate. These observations suggest that SOD1 overexpression can reduce neuronal death under conditions where peroxynitrite formation is a significant factor, but may exacerbate neuronal death under conditions of rapid intracellular superoxide formation or impaired H2O2 disposal.

Animals↗
PubMed2000

Association between nuclear lamin A/C R482Q mutation and partial lipodystrophy with hyperinsulinemia, dyslipidemia, hypertension, and diabetes.

Nuclear lamins A and C are encoded by LMNA and are present in terminally differentiated cells. Lamins participate in DNA replication, chromatin organization, arrangement of nuclear pores, nuclear growth, and anchorage of nuclear membranes. In several Canadian probands with partial lipodystrophy, since found to have a common ancestor, we identified a rare novel LMNA mutation, R482Q, that completely cosegregated with the partial lipodystrophy phenotype. We evaluated the relationship between quantitative metabolic phenotypes in both diabetic and nondiabetic carriers of LMNA R482Q and family controls, who were LMNA R482/R482 homozygotes. We found that when compared with LMNA R482/R482 homozygotes: (1) diabetic LMNA Q482/R482 heterozygotes had significantly higher glucose, glycosylated hemoglobin, triglycerides, insulin and C-peptide, and significantly lower HDL cholesterol; and (2) nondiabetic LMNA Q482/R482 heterozygotes had significantly higher triglycerides, insulin and C-peptide, and significantly lower HDL cholesterol. We also found that diabetic LMNA Q482/R482 heterozygotes were older and more likely to take antihypertensive medications. Thus, LMNA R482Q was associated with lipodystrophy, hyperinsulinemia, dyslipidemia, diabetes, and hypertension. The results indicate that perturbations in plasma lipids precede the plasma glucose abnormalities in LMNA Q482-associated hyperinsulinemia. Thus, rare mutations in a nuclear structural protein can be associated with markedly abnormal qualitative and quantitative metabolic phenotypes

Adolescent↗
PubMed2000

A centralised telephone service for tobacco cessation: the California experience.

OBJECTIVE: To provide an overview of the California Smokers' Helpline, an increasingly popular telephone program for tobacco cessation in California since 1992. As many states, regions, and nations are contemplating various telephone programs as part of large scale anti-tobacco campaigns, this paper presents a practical model. DESIGN: The Helpline provides Californians with free cessation services that include counselling, self help quit kits, and cessation related information. Services are provided in six spoken languages plus a line for the hearing impaired. The program is promoted statewide by media campaigns, health care providers, local tobacco control programs, and the public school system. SETTING: The Helpline is centrally operated through the University of California, San Diego and provides services statewide via telephone. RESULTS: The Helpline has served over 100 000 tobacco users and has become the chief cessation resource for the Comprehensive Tobacco Control Program in California. Media was the most important referral source for Helpline callers (50%), followed by health care providers (20%). About one third of the callers were ethnic minorities and 17% were 24 years old or younger. Compared to California smokers in general, the callers were more dependent on nicotine and more likely to live with other smokers, but they were also more likely to have tried to quit recently and were more ready to try again. Two randomised trials have demonstrated the efficacy of the Helpline's counselling protocol. CONCLUSION: A centralised helpline operation can be an accessible and effective service for tobacco users and should be included in any large scale, comprehensive tobacco control program.

Adolescent↗
PubMed2000

Peroxisome proliferator-activated receptor-gamma2 P12A and type 2 diabetes in Canadian Oji-Cree.

Among the Oji-Cree of northern Ontario, we previously identified a novel variant in the HNF1A gene, namely G319S, that was strongly associated with type 2 diabetes. However, the majority of subjects with diabetes did not have the HNF1A S319 variant, suggesting that there might be other genetic determinants of diabetes susceptibility. In the course of sequencing candidate genes in diabetic subjects who were homozygous for HNF1A G319/G319, we found that some of them had the PPARG A12 variant. After genotyping PPARG in the entire adult Oji-Cree population, we found that: 1) PPARG A12 was strongly associated with type 2 diabetes in women, but not men; 2) among women, the odds of being affected for carriers of PPARG A12 compared with noncarriers was 2.3 (95% confidence interval, 1.4-3.8); and 3) among women, affected carriers of PPARG A12 had a significantly earlier age-of-onset and/or age-at-diagnosis compared with noncarriers. When taken together with the previously reported association of diabetes with HNF1A in both men and women, the gender-specific association with PPARG A12 confirms that type 2 diabetes is etiologically complex in the Oji-Cree and that at least two genes are involved in determining susceptibility to the disease in these people.

Adult↗
PubMed2000

LMNA R482Q mutation in partial lipodystrophy associated with reduced plasma leptin concentration.

Mutations in LMNA, which encodes lamins A and C, have been found in patients with autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD). We analyzed the relationship between plasma leptin and the rare LMNA R482Q mutation in 23 adult FPLD subjects compared with 25 adult family controls with normal LMNA in an extended Canadian FPLD kindred. We found that the LMNA Q482/R482 genotype was a significant determinant of plasma leptin, the ratio of plasma leptin to body mass index (BMI), plasma insulin, and plasma C peptide (P= 0.015, P = 0.0007, P = 0.0004, and P < 0.0001, respectively), but not BMI (P = 0.67). Family members who were heterozygous for LMNA Q482/R482 had significantly lower plasma leptin and leptin:BMI ratio than unaffected R482/R482 homozygotes. Fasting plasma concentrations of insulin and C peptide were both significantly higher in LMNA Q482/R482 heterozygotes than in R482/R482 homozygotes. Multivariate regression analysis revealed that the LMNA R482Q genotype accounted for 40.9%, 48.2%, 86.9%, and 81.0%, respectively, of the attributable variation in log leptin, leptin:BMI ratio, log insulin, and log C peptide (P = 0.013, P = 0.0007, P = 0.0002 and P < 0.0001, respectively). The results indicate that a rare FPLD mutation in LMNA determines the plasma leptin concentration. It remains to be established whether the reduction in leptin results from the reduced adipose tissue mass in FPLD or from another subcellular effect of mutant LMNA. It also remains to be established whether the insulin resistance in FPLD is a consequence of the reduced plasma leptin or of another functional change resulting from mutant LMNA.

Adult↗
PubMed2000

Heterogeneity of nuclear lamin A mutations in Dunnigan-type familial partial lipodystrophy.

We previously identified a novel mutation, namely LMNA R482Q, that was found to underlie Dunnigan-type partial lipodystrophy (FPLD) and diabetes in an extended Canadian kindred. We have since sequenced LMNA in five additional Canadian FPLD probands and herein report three new rare missense mutations in LMNA: V440M, R482W, and R584H. One severely affected subject was a compound heterozygote for both V440M and R482Q. The findings indicated that 1) a spectrum of LMNA mutations underlies FPLD; 2) aberrant lamin A, and not lamin C, is likely to underlie FPLD, as R584H occurs within LMNA sequence that is specific for lamin A; 3) the V440M mutation may not cause lipodystrophy on its own; 4) compound heterozygosity for V440M and R482Q is associated with a relatively more severe FPLD phenotype, but not with complete lipodystrophy; and 5) variation in the severity of the phenotype might be related to environmental factors.

DNA↗
PubMed2000

The nuclear receptor corepressor (N-CoR) contains three isoleucine motifs (I/LXXII) that serve as receptor interaction domains (IDs).

Unliganded thyroid hormone receptors (TRs) repress transcription through recruitment of corepressors, including nuclear receptor corepressor (N-CoR). We find that N-CoR contains three interaction domains (IDs) that bind to TR, rather than the previously reported two. The hitherto unrecognized ID (ID3) serves as a fully functional TR binding site, both in vivo and in vitro, and may be the most important for TR binding. Each ID motif contains a conserved hydrophobic core (I/LXXII) that resembles the hydrophobic core of nuclear receptor boxes (LXXLL), which mediates p160 coactivator binding to liganded nuclear receptors. Although the integrity of the I/LXXII motif is required for ID function, substitution of ID isoleucines with leucines did not allow ID peptides to bind to liganded TR, and substitution of NR box leucines with isoleucines did not allow NR box peptides to bind unliganded TR. This indicates that the binding preferences of N-CoR for unliganded TR and p160s for liganded TR are not dictated solely by the identity of conserved hydrophobic residues within their TR binding motifs. Examination of sequence conservation between IDs, and mutational analysis of individual IDs, suggests that they are comprised of the central hydrophobic core and distinct adjacent sequences that may make unique contacts with the TR surface. Accordingly, a hybrid peptide that contains distinct adjacent sequences from ID3 and ID1 shows enhanced binding to TR.

Amino Acid Motifs↗
PubMed2000

Clinical utility of HNF1A genotyping for diabetes in aboriginal Canadians.

OBJECTIVE: To determine the diagnostic performance characteristics of HNF1A genotyping for diabetes and impaired glucose tolerance (IGT) in Canadian Oji-Cree Indians. RESEARCH DESIGN AND METHODS: We studied all Oji-Cree subjects > or = 50 years of age (96 subjects) who had participated in a community-wide prevalence survey for type 2 diabetes. Subjects were classified either as having "disease," which included type 2 diabetes and IGT, or not. All subjects were genotyped for the HNF1A G319S mutation. RESULTS: The prevalence of disease in this group was 65.7%, of whom 71.4% had type 2 diabetes. For a carrier of HNF1A S319, the specificity, sensitivity, and positive and negative predictive values were 97.0, 30.1, 95.0, and 42.1%, respectively. When the pretest disease prevalence was accounted for, the probability of disease after a positive test was 97.2%, and the probability of disease after a negative test was 42.2%. The values were very similar for the subgroup of subjects with type 2 diabetes alone. CONCLUSIONS: The HNF1A genotype appears to be the most specific genetic test yet reported for the prediction of a common multifactorial disease by applying present-day standards of clinical epidemiology in molecular genetics. A positive test result had particular diagnostic value in the Oji-Cree: a subject with HNF1A S319 was virtually certain of having diabetes or IGT by 50 years of age. In contrast, a subject without HNF1A S319 had a reduced risk compared with the age-specific prevalence but was not totally risk-free. Because HNF1A S319 was not the only predisposing factor for diabetes in the Oji-Cree, subjects without HNF1A S319 were still at some risk for diabetes or IGT.

Canada↗
PubMed2000

Infection-susceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area.

The MBL gene, encoding mannose-binding lectin, determines interindividual variation in susceptibility to certain infectious agents, such as Chlamydia pneumoniae. We examined whether infection-susceptibility alleles of MBL, called "non-A alleles," would be associated with increased carotid plaque area (CPA), an intermediate phenotype of atherosclerosis. In 164 subjects, we measured CPA with 2-dimensional ultrasound. We also determined traditional atherosclerosis risk factors and genotyped all subjects for MBL codons 52, 54, and 57. We used ANOVA to determine sources of variation for CPA and tested the hypothesis that the presence of a single MBL non-A "infection-susceptibility" allele was associated with increased CPA; 45.7% of subjects had at least one non-A allele. ANOVA showed that CPA was significantly associated with MBL genotype, age, smoking, hypertension, and hyperlipidemia (P < 0.05). When MBL was used as the sole independent variable in the regression analysis, the association with CPA was even more significant (P = 0.009). Subjects with at least one MBL non-A allele had significantly higher CPA than subjects homozygous for the MBL A allele and were significantly more likely to have CPA in excess of the sample median. Thus, infection-susceptibility alleles of MBL were associated with increased CPA in this study sample; these alleles may be a determinant of interindividual differences in atherosclerosis risk.

Adult↗
PubMed2000

Astrocyte glutamate transport: review of properties, regulation, and physiological functions.

Rapid removal of glutamate from the extracellular space is required for the survival and normal function of neurons. Although glutamate transporters are expressed by all CNS cell types, astrocytes are the cell type primarily responsible for glutamate uptake. Astrocyte glutamate uptake also plays a role in regulating the activity of glutamatergic synapses. Lastly, release of glutamate from astrocytes, via transporter reversal and other routes, can contribute to glutamate receptor activation. This review examines the mechanisms of astrocyte glutamate uptake and release, with particular focus on high-affinity Na(+)-dependent transporters. Transporter regulation, energetics, and physiological roles are discussed.

ATP-Binding Cassette Transporters↗
PubMed2000

Sex differences in workplace smoking policies: results from the current population survey.

OBJECTIVE: To determine the prevalence of smoking policies in indoor work environments in the United States, with a special focus on sex differences in the provision of these policies. METHOD: Information on the prevalence and restrictiveness of workplace smoking policies was obtained from 86,490 currently employed indoor workers (50,865 women and 35,625 men) 15 years of age and older who responded to the National Cancer Institute's Tobacco Use Supplement to the Current Population Survey, a cross-sectional survey of households in all 50 states and the District of Columbia conducted between 1995 and 1996. RESULTS: Eighty-six percent of respondents reported that their workplaces had official smoking policies, and 63% reported that their workplaces were smoke free. Women reported significantly higher rates of both official smoking policies and smoke-free workplaces than men, regardless of racial/ethnic or age group. CONCLUSION: The overall rates of worksite smoking restrictions, including the establishment of smoke-free workplaces, were higher than those reported in earlier surveys. Disparities in coverage will need to be reduced if all workers, regardless of sex, race, age, or industry of employment, are to be protected from the demonstrated hazards of environmental tobacco smoke.

Adolescent↗