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Biomedical subjects

J W Lynch

Publications and source records attributed to J W Lynch.

At least 19 recordsLinked to original sources
PubMed2006

The "Americanisation" of migrants: evidence for the contribution of ethnicity, social deprivation, lifestyle and life-course processes to the mid-20th century Coronary Heart Disease epidemic in the US.

We investigated the contribution of the large-scale immigration of White Europeans into the US between 1850 and 1930 to the timing and extent of the epidemic pattern of heart disease between 1900 and 1980. The analyses are based on data collected through the United States Federal Census from 1850 to the present. The hardcopy historical record confirms that census reports themselves and related monographs were concerned from 1850 with excessive mortality from heart disease of immigrants, particularly of Northern European origin and initially at least, their first-generation native-born children. Our analysis of the electronic database indicates a strong relationship between the percentage of US population foreign born and native born of foreign parentage and age adjusted mortality from heart disease. We identified a lag of 50 years giving the maximum linear correlation coefficient for men (r(2) = 0.92), and for women a shorter lag of 38 years and an earlier decline in Coronary Heart Disease (CHD) rates (r(2) = 0.96). Both the rise and fall of the CHD epidemic over an 80-year period correspond closely to the rise and fall of the foreign population in previous years. For the foreign born only, age adjusted negative binomial general estimated equation (GEE) models calculate the relative risk of dying of heart disease per 10% increase in proportion foreign born. There is an independent influence for men until 1930 and for women throughout the period from 1910 onwards. We conclude there is an impact of immigration on the pattern of the epidemic, mediated through a combination of factors, such as accumulated life-course susceptibility, deprived socio-economic conditions upon arrival, and the enthusiastic uptake of behaviours related to the classic risk factors of smoking, high saturated fat and salt diet. Our analysis provides a more contextualised understanding of the scale and timing of the epidemic of CHD in the US.

Censuses↗
PubMed2004

Trends in socioeconomic health inequalities in Korea: use of mortality and morbidity measures.

STUDY OBJECTIVE: To examine trends in educational mortality and morbidity inequalities in Korea. DESIGN: Census data (1990, 1995, 2000) and death certificate data (1990-91, 1995-96, 2000-01) were used for mortality. For morbidity, four waves (1989, 1992, 1995, and 1999) of Social Statistics Survey from Korea's National Statistical Office were used. Morbidity indicators were self rated health and self reported illness in the past two weeks. Trends were studied using indices for both the relative and absolute size of socioeconomic inequalities in health. SETTING: South Korea. Patients (or Participants): Representative annual samples of the adult population aged 30-59 in Korea. MAIN RESULTS: Based on trends in relative index of inequalities, the relative level of socioeconomic mortality inequality remained virtually unchanged in men and women in the past 10 years. Meanwhile, inequalities in self rated health have increased over time in both sexes. Most of the total increase in health inequalities happened between 1995 and 1999. Inequalities in self reported acute illness increased in the past 10 years. CONCLUSIONS: The rise in inequalities in morbidity requires increased social discourse and policy discussions about health inequalities in Korean society.

Adult↗
PubMed2004

Country of birth, socioeconomic position, and healthcare expenditure: a multilevel analysis of Malmö, Sweden.

STUDY OBJECTIVE: The principle of equity aims to guarantee allocation of healthcare resources on the basis of need. Therefore, people with a low income and persons living alone are expected to have higher healthcare expenditures. Besides these individual characteristics healthcare expenditure may be influenced by country of birth. This study therefore aimed to investigate the role of country of birth in explaining individual healthcare expenditure. DESIGN: Multilevel regression model based on individuals (first level) and their country of birth (second level). SETTING: The city of Malmö, Sweden. PARTICIPANTS: All the 52 419 men aged 40-80 years from 130 different countries of birth, who were living in Malmö, Sweden, during 1999. MAIN RESULTS: At the individual level, persons with a low income and persons living alone showed a higher healthcare expenditure, with regression coefficients (and 95% confidence intervals) being 0.358 (0.325 to 0.392) and 0.197 (0.165 to 0.230), respectively. Country of birth explained a considerable part (18% and 13%) of the individual differences in the probability of having a low income and living alone, respectively. However, this figure was only 3% for having some health expenditure, and barely 0.7% with regard to costs in the 74% of the population with some health expenditure. CONCLUSIONS: Malmö is a socioeconomically segregated city, in which the country of birth seems to play only a minor part in explaining individual differences in total healthcare expenditure. These differences seem instead to be determined by individual low income and living alone.

Adult↗
PubMed2003

Concentrations of four fecal steroids in wild baboons: short-term storage conditions and consequences for data interpretation.

One source of both bias and "noise" in fecal steroid analysis is temporal change in steroid concentrations resulting from duration or conditions of fecal sample storage. However, no consensus currently exists regarding correct procedures or precautions necessary for fecal sample storage, and conditions vary widely within field endocrinology literature. This study considered the effects of short-term, weeks-long, storage conditions on quantifiable fecal testosterone (fT), glucocorticoids (fGC), estrogens (fE), and progestagen (fP) metabolite concentrations in wild baboons (Papio cynocephalus). Quadruplicate subsamples of fecal samples (n=29) collected at Amboseli National Park and its environs were subjected to four different storage conditions prior to lyophilization, in order to determine the effects of storage on subsequent steroid concentrations, as assessed by 125I radioimmunoassays. As expected, the best alternative to the "initial condition" of lyophilization at three days after collection was to freeze fecal samples at -20 degrees C for two weeks prior to lyophilization. This storage method resulted in no significant change from initial steroid concentrations for fE, fT, or fP, although fGC showed a slight but significant decline. Storage for two weeks in a charcoal refrigerator caused a mean increase in all four steroid concentrations. However, the results from this storage condition were robust in terms of practical questions asked of the data: fE and fP values still reflected pregnant versus non-pregnant states in baboon females; a fGC profile constructed by age class resembled that created from the samples from the initial condition, although slightly inflated across age classes; and there were only moderate changes in relative fT concentrations across adult males. Knowledge of the effects of storage upon each steroid analyzed within one's study is a necessary component in determining the optimal compromise for storage protocol in a particular research project.

Androgens↗
PubMed2003

Biochemical and physiological validation of a corticosteroid radioimmunoassay for plasma and fecal samples in oldfield mice (Peromyscus polionotus).

The measurement of fecal steroids provides an increasingly important noninvasive technique for assessing reproduction, environmental stress, and aggression in populations of captive and free-living animals. In this paper, we validated the corticosterone (CORT) 125I-radioimmunoassay (ICN Pharmaceuticals) for plasma and fecal samples in a small rodent species, the oldfield mouse (Peromyscus polionotus subgriseus). The biochemical validations indicated that the assays accurately measured CORT concentrations in the plasma and corticosteroid concentrations in the feces. Physiological validation demonstrated that: (1) blood samples collected within 3 min of disturbing an animal's cage represented "baseline" CORT concentrations, and (2) fecal corticosteroid concentrations collected over a 24-h period closely tracked plasma CORT concentrations approximately 4 h earlier. These results demonstrate that the plasma CORT and fecal corticosteroid assays are sensitive enough to detect biologically meaningful alterations in corticosteroid concentrations in oldfield mice.

Adrenal Cortex Hormones↗
PubMed2003

Correlation of early lymphocyte recovery and progression-free survival after autologous stem-cell transplant in patients with Hodgkin's and non-Hodgkin's Lymphoma.

The importance of the association between early lymphocyte recovery and outcome has not been well studied in autologous stem cell transplantation (ASCT). In this retrospective study, we analyzed 90 consecutive patients with non-Hodgkin's and Hodgkin's lymphoma who underwent ASCT. Patients were divided into two groups: group 1 with absolute lymphocyte count (ALC) on day +15 below the median of 667/mm(3), and group 2 with ALC >or=667/mm(3). The median progression-free survival (PFS), but not overall survival (OS), was significantly longer in group 2 when compared to group 1 (16 months vs not reached P=0.02). Group 2 patients also had significantly shorter hospital stay, received higher CD34(+) cell dose, and had shorter time to neutrophil recovery. Multivariate analysis demonstrated day +15 ALC to be an independent prognostic indicator for PFS, but not OS, while CD34(+) cell dose and the number of pretransplant treatments were better predictors for both PFS and OS. We conclude that higher day +15 ALC may independently predict better PFS after ASCT for lymphoma patients; however, whether this merely reflects faster overall recovery caused by higher infused CD34(+) cell dose and less pretransplant therapy needs further investigation.

Adolescent↗
PubMed2003

Poor mobilization of peripheral blood stem cells is a risk factor for worse outcome in lymphoma patients undergoing autologous stem cell transplantation.

The effect of poor blood stem cells mobilization on the outcome of autologous stem cell transplantation (ASCT) has not been well studied. Our aim is to evaluate poor mobilization as a prognostic factor in lymphoma patients undergoing ASCT. We analyzed 90 consecutive patients with Hodgkin's (HD) and non-Hodgkin's lymphoma (NHL) who underwent ASCT. Poor mobilization was defined as the inability to obtain > or = 1 x 10(6) CD34+ cells/kg ideal body weight with two large volume aphereses. Patients were divided into 2 groups: group 1 = poor mobilizers, and group 2 = good mobilizers. The poor mobilizers received lower median transplant CD34+ cell dose (2 x 10(6) vs. 4.5 x 10(6)/kg for good mobilizers, P = 0.001), were more heavily pretreated (P = 0.01), and required higher number of aphereses for PBSC collection (P = 0.0006). The median progression-free survival (PFS) in groups 1 and 2 was 10 and 41 months (P = 0.04), while the median overall survival (OS) was 38 months and not reached (P = 0.02), respectively. Univariate analysis showed that > or = 3 pre-transplant treatments, CD34+ cell dose < or = 2 x 10(6), elevated LDH before transplant, and poor mobilization were significant prognostic factors for poor PFS, while only the first three were significant for worse OS. Multivariate analysis using these same four factors revealed that number of pre-transplant treatments (HR = 6.03, P = 0.001), CD34+ cell dose (HR = 0.1, P = 0.0007) were the only independent predictive factors for worse overall outcome. In conclusion, our data show that poor mobilization could indicate poor outcome in lymphoma patients undergoing ASCT, however, it is more likely to be a reflection of the heavy pre-transplant therapy and lower CD34+ cell dose re-infused in this group of patients.

Adolescent↗
PubMed2001

The surface accessibility of the glycine receptor M2-M3 loop is increased in the channel open state.

Mutations in the extracellular M2-M3 loop of the glycine receptor (GlyR) alpha1 subunit have been shown previously to affect channel gating. In this study, the substituted cysteine accessibility method was used to investigate whether a structural rearrangement of the M2-M3 loop accompanies GlyR activation. All residues from R271C to V277C were covalently modified by both positively charged methanethiosulfonate ethyltrimethylammonium (MTSET) and negatively charged methanethiosulfonate ethylsulfonate (MTSES), implying that these residues form an irregular surface loop. The MTSET modification rate of all residues from R271C to K276C was faster in the glycine-bound state than in the unliganded state. MTSES modification of A272C, L274C, and V277C was also faster in the glycine-bound state. These results demonstrate that the surface accessibility of the M2-M3 loop is increased as the channel transitions from the closed to the open state, implying that either the loop itself or an overlying domain moves during channel activation.

Amino Acid Substitution↗
PubMed2001

Ivermectin, an unconventional agonist of the glycine receptor chloride channel.

The effects of the antihelmintic, ivermectin, were investigated in recombinantly expressed human alpha(1) homomeric and alpha(1)beta heteromeric glycine receptors (GlyRs). At low (0.03 microm) concentrations ivermectin potentiated the response to sub-saturating glycine concentrations, and at higher (> or =0.03 microm) concentrations it irreversibly activated both alpha(1) homomeric and alpha(1)beta heteromeric GlyRs. Relative to glycine-gated currents, ivermectin-gated currents exhibited a dramatically reduced sensitivity to inhibition by strychnine, picrotoxin, and zinc. The insensitivity to strychnine could not be explained by ivermectin preventing the access of strychnine to its binding site. Furthermore, the elimination of a known glycine- and strychnine-binding site by site-directed mutagenesis had little effect on ivermectin sensitivity, demonstrating that the ivermectin- and glycine-binding sites were not identical. Ivermectin strongly and irreversibly activated a fast-desensitizing mutant GlyR after it had been completely desensitized by a saturating concentration of glycine. Finally, a mutation known to impair dramatically the glycine signal transduction mechanism had little effect on the apparent affinity or efficacy of ivermectin. Together, these findings indicate that ivermectin activates the GlyR by a novel mechanism.

Amino Acid Substitution↗
PubMed2001

Socioeconomic disparities in health change in a longitudinal study of US adults: the role of health-risk behaviors.

This study investigated the hypothesis that socioeconomic differences in health status change can largely be explained by the higher prevalence of individual health-risk behaviors among those of lower socioeconomic position. Data were from the Americans' Changing Lives study, a longitudinal survey of 3,617 adults representative of the US non-institutionalized population in 1986. The authors examined associations between income and education in 1986, and physical functioning and self-rated health in 1994, adjusted for baseline health status, using a multinomial logistic regression framework that considered mortality and survey nonresponse as competing risks. Covariates included age, sex, race, cigarette smoking, alcohol consumption, physical activity, and Body Mass Index. Both income and education were strong predictors of poor health outcomes. The four health-risk behaviors under study statistically explained only a modest portion of the socioeconomic differences in health at follow-up. For example, after adjustment for baseline health status, those in the lowest income group at baseline had odds of moderate/severe functional impairment in 1994 of 2.11 (95% C.I.: 1.40, 3.20) in an unadjusted model and 1.89 (95% C.I.: 1.23, 2.89) in a model adjusted for health-risk behaviors. The results suggest that the higher prevalence of major health-risk behaviors among those in lower socioeconomic strata is not the dominant mediating mechanism that can explain socioeconomic disparities in health status among US adults.

Adult↗
PubMed2001

Ecological analysis of teen birth rates: association with community income and income inequality.

OBJECTIVES: To examine whether per capita income and income inequality are independently associated with teen birth rate in populous U.S. counties. METHODS: This study used 1990 U.S. Census data and National Center for Health Statistics birth data. Income inequality was measured with the 90:10 ratio, a ratio of percent of cumulative income held by the richest and poorest population deciles. Linear regression and analysis of variance were used to assess associations between county-level average income, income inequality, and teen birth rates among counties with population greater than 100,000. RESULTS: Among teens aged 15-17, income inequality and per capita income were independently associated with birth rate; the mean birth rate was 54 per 1,000 in counties with low income and high income inequality, and 19 per 1,000 in counties with high income and low inequality. Among older teens (aged 18-19) only per capita income was significantly associated with birth rate. CONCLUSIONS: Although teen childbearing is the result of individual behaviors, these findings suggest that community-level factors such as income and income inequality may contribute significantly to differences in teen birth rates.

Adolescent↗
PubMed2001

A common inhibitory binding site for zinc and odorants at the voltage-gated K(+) channel of rat olfactory receptor neurons.

This study compared the effects of zinc and odorants on the voltage-gated K(+) channel of rat olfactory neurons. Zinc reduced current magnitude, depolarized the voltage activation curve and slowed activation kinetics without affecting inactivation or deactivation kinetics. Zinc inhibition was potentiated by the NO compound, S-nitroso-cysteine. The pH- and diethylpyrocarbonate-dependence of zinc inhibition suggested that zinc acted by binding to histidine residues. Cysteine residues were eliminated as contributing to the zinc-binding site. The odorants, acetophenone and amyl acetate, also reduced current magnitude, depolarized the voltage activation curve and selectively slowed activation kinetics. Furthermore, the diethylpyrocarbonate- and pH-dependence of odorant inhibition implied that the odorants also bind to histidine residues. Zinc inhibitory potency was dramatically diminished in the presence of odorants, implying competition for a common binding site. These observations indicate that the odorants and zinc share a common inhibitory binding site on the external surface of the voltage-gated K(+) channel.

4-Chloromercuribenzenesulfonate↗
PubMed2001

A single beta subunit M2 domain residue controls the picrotoxin sensitivity of alphabeta heteromeric glycine receptor chloride channels.

This study investigated the residues responsible for the reduced picrotoxin sensitivity of the alphabeta heteromeric glycine receptor relative to the alpha homomeric receptor. By analogy with structurally related receptors, the beta subunit M2 domain residues P278 and F282 were considered the most likely candidates for mediating this effect. These residues align with G254 and T258 of the alpha subunit. The T258A, T258C and T258F mutations dramatically reduced the picrotoxin sensitivity of the alpha homomeric receptor. Furthermore, the converse F282T mutation in the beta subunit increased the picrotoxin sensitivity of the alphabeta heteromeric receptor. The P278G mutation in the beta subunit did not affect the picrotoxin sensitivity of the alphabeta heteromer. Thus, a ring of five threonines at the M2 domain depth corresponding to alpha subunit T258 is specifically required for picrotoxin sensitivity. Mutations to alpha subunit T258 also profoundly influenced the apparent glycine affinity. A substituted cysteine accessibility analysis revealed that the T258C sidechain increases its pore exposure in the channel open state. This provides further evidence for an allosteric mechanism of picrotoxin inhibition, but renders it unlikely that picrotoxin (as an allosterically acting 'competitive' antagonist) binds to this residue.

Allosteric Regulation↗
PubMed2001

Characterization of a glycine receptor domain that controls the binding and gating mechanisms of the beta-amino acid agonist, taurine.

The beta-amino acid, taurine, is a full agonist of the human glycine receptor alpha1 subunit when recombinantly expressed in a mammalian (HEK293) cell line, but a partial agonist of the same receptor when expressed in Xenopus oocytes. Several residues in the Ala101-Thr112 domain have previously been identified as determinants of beta-amino acid binding and gating mechanisms in Xenopus oocyte-expressed receptors. The present study used the substituted cysteine accessibility method to investigate the role of this domain in controlling taurine-specific binding and gating mechanisms of glycine receptors recombinantly expressed in mammalian cells. Asn102 and Glu103 are identified as taurine and glycine binding sites, whereas Ala101 is eliminated as a possible binding site. The N102C mutation also abolished the antagonistic actions of taurine, indicating that this site does not discriminate between the putative agonist- and antagonist-bound conformations of beta-amino acids. The effects of mutations from Lys104-Thr112 indicate that the mechanism by which this domain controls beta-amino acid-specific binding and gating processes differs substantially depending on whether the receptor is expressed in mammalian cells or Xenopus oocytes. Thr112 is the only domain element in mammalian cell-expressed GlyRs which was demonstrated to discriminate between glycine and taurine.

Amino Acid Substitution↗
PubMed2001

Childhood socioeconomic position and cognitive function in adulthood.

BACKGROUND: Risk of dementia and Alzheimer's disease is higher among adults with limited education, and the less educated perform poorer on cognitive function tests. This study determines whether the socioeconomic environment experienced during childhood has an impact on cognitive functioning in middle age. METHODS: A population-based study of eastern Finnish men (n = 496) aged 58 and 64 for whom there were data on parent's socioeconomic position (SEP), their own education level, and performance on neuropsychological tests. Cognitive function was measured using the Trail Making Test, the Selective Reminding Test, the Verbal Fluency Test, the Visual Reproduction Test, and the Mini Mental State Exam. RESULTS: We found a significant and graded association between parental SEP (combined as an index) and cognitive function both prior to and after adjustment for respondent's education. Those from more disadvantaged backgrounds exhibited the poorest performance. When the separate components of the parental SEP measure were used, father's occupation and mother's education were independently associated with the respondent's score for three and five of the tests, respectively (there was no association with father's education and mother's occupation). After adjustment for the respondent's education, father's occupation was no longer associated with respondent's test score, however, the results were essentially unchanged for mother's education. CONCLUSIONS: Higher SEP during childhood and greater educational attainment are both associated with cognitive function in adulthood, with mothers and fathers each contributing to their offspring's formative cognitive development and later life cognitive ability (albeit in different ways). Improvements in both parental socioeconomic circumstances and the educational attainment of their offspring could possibly enhance cognitive function and decrease risk of dementia later in life.

Adult↗
PubMed2001

Stress-induced blood pressure reactivity and incident stroke in middle-aged men.

BACKGROUND AND PURPOSE: Exaggerated blood pressure reactivity to stress is associated with atherosclerosis and hypertension, which are known stroke risk factors, but its relation to stroke is unknown. Previous work also indicates that the association between reactivity and cardiovascular diseases may be influenced by socioeconomic status. METHODS: The impact of blood pressure reactivity and socioeconomic status on incident stroke was examined in 2303 men (mean age, 52.8+/-5.1 years) from a population-based, longitudinal study of risk factors for ischemic heart disease in eastern FINLAND: Reactivity was calculated as the difference between blood pressure measured during the anticipatory phase of an exercise tolerance test (before exercise) and resting blood pressure, measured 1 week earlier. Mean systolic reactivity was 20 mm Hg (+/-15.9), and mean diastolic reactivity was 8.6 mm Hg (+/-8.5). Socioeconomic status was assessed as years of education. One hundred thirteen incident strokes (90 ischemic) occurred in 11.2 (+/-1.6) years of follow-up. RESULTS: Men with exaggerated systolic reactivity (>/=20 mm Hg) had 72% greater risk of any stroke (relative hazard ratio [RH], 1.72; 95% CI, 1.17 to 2.54) and 87% greater risk of ischemic stroke (RH, 1.87; 95% CI, 1.20 to 2.89) relative to less reactive men. Moreover, men who were high reactors and poorly educated were nearly 3 times more likely to suffer a stroke than better educated, less reactive men (RH, 2.90; 95% CI, 1.66 to 5.08). Adjustment for stroke risk factors had little impact on these associations. Diastolic reactivity was unrelated to stroke risk. CONCLUSIONS: Excessive sympathetic reactivity to stress may be etiologically important in stroke, especially ischemic strokes, and low socioeconomic status confers added risk.

Adult↗