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A H Schnell

Publications and source records attributed to A H Schnell.

16 recordsLinked to original sources
PubMed2001

Segregation analyses of asthma and respiratory allergy: the Humboldt family study.

We performed segregation analyses of asthma and respiratory allergy based on data from 309 nuclear families comprising 1,053 individuals living in the town of Humboldt, Saskatchewan, in 1993, using the REGD program of the S.A.G.E. program package. For adults, information on asthma and history of respiratory allergy was provided by the subjects themselves, and for children by their parents. When asthma was considered as the trait in segregation analysis, models of no major effect, with or without familial effects, were rejected, but they were not rejected after adjusting for history of respiratory allergy. The major gene hypothesis was not rejected before adjusting for history of respiratory allergy. When respiratory allergy was analyzed as the trait, both major gene and multifactorial models fitted the data well, regardless of whether there was adjustment for asthma or not. Other covariates adjusted for in the segregation analyses were age, sex, number of household smokers, current smoking, number of household members, generation, and house type. The data suggest that a major gene related to respiratory allergy may explain the familial aggregation of asthma.

Adolescent↗
PubMed2001

Segregation analysis of asthma and respiratory allergy in population-based samples of families.

Class A regressive multiple logistic segregation models with a sibling covariate were used to investigate the underlying determinants of asthma and respiratory allergy (defined from specific IgE levels to inhaled allergens) in the randomly recruited Caucasian families from the Genetic Analysis Workshop 12 asthma data sets--Perth, Busselton, and Southampton. For asthma, both a purely multifactorial model and a major gene (dominant or recessive) model with multifactorial effects fitted the data. For respiratory allergy, a dominant, dominant with multifactorial effects and a purely multifactorial model all fitted the data. However, homogeneity of the three studies was rejected for both traits indicating that the three populations are significantly different and should be analyzed separately. This finding has implications for the meta-analysis of asthma linkage studies.

Adult↗
PubMed2001

Electrocardiographic prediction of abnormal genotype in congenital long QT syndrome: experience in 101 related family members.

INTRODUCTION: Previous studies showed that diagnosing congenital long QT syndrome (LQTS) is difficult due to variable penetrance and genetic heterogeneity, especially when subjects from multiple families with diverse mutations are combined. We hypothesized that a combination of clinical and ECG techniques could identify gene carriers within a single family with congenital LQTS. METHODS AND RESULTS: One hundred one genotyped members of a family with LQTS, including 26 carriers of a HERG mutation, underwent history and ECG analysis. Forty-eight family members also underwent exercise testing with QT and T wave alternans (TWA) analysis and 24-hour Holter monitoring with QT and heart rate variability analysis. A logistic regression model, which included age, gender, QTc, and QTc by age, provided the best prediction of gene carrier status, although there was substantial overlap (78%) of QTc among subjects with and without the mutation. QTc was not helpful as a discriminator in children < or = 13 years. TWA (observed infrequently) did not add significantly to the model's ability to predict abnormal genotype. CONCLUSION: Even in this homogeneous LQTS population, the phenotype was so variable that clinical and detailed ECG analyses did not permit an accurate diagnosis of gene carrier status, especially in children. Sustained microvolt TWA was a specific (100%) but insensitive (18%) marker for LQTS. Its ability to predict risk of arrhythmia in this population remains to be determined. Genetic testing serves an essential role in screening for carriers of LQTS.

Adolescent↗
PubMed2000

Major gene segregation of actinic prurigo among North American Indians in Saskatchewan.

Actinic prurigo is an idiopathic, familial photodermatosis seen especially in American Indians. Segregation analysis was performed on 12 Saskatchewan pedigrees with American Indian ancestry, comprising a total of 1,148 individuals, ascertained via probands diagnosed with actinic prurigo. Although a high degree of familial aggregation has been noted in the past and dominant inheritance has been suggested, no formal segregation analysis has been attempted. Actinic prurigo has a variable age of onset and, therefore, age at the time of censoring must be taken into account in the analysis. However, as these ages of 57% of the unaffected individuals were missing, an algorithm was devised to impute the missing ages from known birth years in the family based on the age differences among relatives and spouses. Using these imputed ages, simple dominant inheritance with incomplete penetrance and a single age of onset distribution was found. The method for imputing the ages at examination was evaluated, as was the correction for ascertainment, by using alternative methods and comparing the results. Regardless of the method used, a dominant mode of inheritance without any multifactorial component remained the best hypothesis.

Adolescent↗
PubMed2000

Genetic determinants of acute hypoxic ventilation: patterns of inheritance in mice.

Acutely lowering ambient O(2) tension increases ventilation in many mammalian species, including humans and mice. Inheritance patterns among kinships and between mouse strains suggest that a robust genetic influence determines individual hypoxic ventilatory responses (HVR). Here, we tested specific genetic hypotheses to describe the inheritance patterns of HVR phenotypes among two inbred mouse strains and their segregant and nonsegregant progeny. Using whole body plethysmography, we assessed the magnitude and pattern of ventilation in C3H/HeJ (C3) and C57BL/6J (B6) progenitor strains at baseline and during acute (3-5 min) hypoxic [mild hypercapnic hypoxia, inspired O(2) fraction (FI(O(2))) = 0.10] and normoxic (mild hypercapnic normoxia, FI(O(2)) = 0.21) inspirate challenges in mild hypercapnia (inspired CO(2) fraction = 0.03). First- and second-filial generations and two backcross progeny were also studied to assess response distributions of HVR phenotypes relative to the parental strains. Although the minute ventilation (VE) during hypoxia was comparable between the parental strains, breathing frequency (f) and tidal volume were significantly different; C3 mice demonstrated a slow, deep HVR relative to a rapid, shallow phenotype of B6 mice. The HVR profile in B6C3F(1)/J mice suggested that this offspring class represented a third phenotype, distinguishable from the parental strains. The distribution of HVR among backcross and intercross offspring suggested that the inheritance patterns for f and VE during mild hypercapnic hypoxia are consistent with models that incorporate two genetic determinants. These results further suggest that the quantitative genetic expression of alleles derived from C3 and B6 parental strains interact to significantly attenuate individual HVR in the first- and second-filial generations. In conclusion, the genetic control of HVR in this model was shown to exhibit a relatively simple genetic basis in terms of respiratory timing characteristics.

Acute Disease↗
PubMed1999

Model-based and model-free multipoint genome-wide linkage analysis of alcoholism.

We analyzed a subset of the Collaborative Study on the Genetics of Alcoholism (COGA) data set as provided by the 11th Genetic Analysis Workshop (GAW11). Linkage analyses were performed using each of the diagnostic criteria for alcoholism included in the data: the COGA criteria (DSM-III-R plus the Feighner criteria) and the narrower World Health Organization diagnosis ICD-10 criteria. Formal segregation analysis using these data was not attempted because only a subset of all the originally ascertained families was made available. Nevertheless, an attempt was made to estimate the best one-locus two-allele genetic model for these data. Model-based multipoint linkage analysis was performed using the results of our trait model fitting, and model-free multipoint linkage analysis was performed with an improved version of the Haseman and Elston linkage method for sib pairs.

Adolescent↗
PubMed1997

A new test statistic for linkage applied to bipolar disorder and marker D18S41.

We applied a new test statistic for linkage that removes the traditional assumption of equal female (theta f) and male (theta m) recombination fractions by testing Ho: theta f + theta m = 1 vs. HA: theta f + theta m < 1 to GAW10 Problem 1. Specifically we reanalyzed the reported possible linkage between a suggested susceptibility locus for bipolar affective disorder and marker D18S41 on chromosome 18 [Stine et al., 1995]. We used penetrance functions fitting the description of those used by Stine et al. [1995] assuming a continuous age-dependent logistic distribution. Maximum likelihood marker allele frequencies were estimated assuming Hardy-Weinberg equilibrium. Results from the traditional lod-score analyses do not strongly support the existence of linkage between the disease locus and marker D18S41. Similarly, the new test statistic for linkage failed to provide evidence in support of linkage. This was true whether dominant or recessive models of inheritance were assumed, and whether the analyses included all available pedigrees or were confined to paternally transmitted pedigrees. The appreciable difference found between our lod scores and those obtained by Stine et al. [1995] can be attributed to differences in the assumptions made regarding the age-dependent penetrance function, the marker allele frequencies, or both.

Alleles↗
PubMed1997

Modeling age of onset and residual familial correlations for the linkage analysis of bipolar disorder.

We applied regressive modeling to the data described by Stine et al. [1995] and further explored the possible linkage of bipolar disorder to marker D18S41 on chromosome 18. We performed analyses to determine age-dependent penetrance functions that best fit the data and that allow for residual familial correlations. Specifically, we introduce here a simple method to allow for a sibling correlations. that is not due to segregation at the linked locus, and then extend the results of Stine et al. [1995] by using the best fitting "regressive" model of this kind as input into a lod score linkage analysis. Although a formal segregation analysis was not attempted, a surprising finding was that, except for doubtful linkage to D18S41, there is little evidence for genetic transmission of bipolar disorder in these families.

Age of Onset↗
PubMed1997

Model-free age-of-onset methods applied to the linkage of bipolar disorder.

We performed Haseman-Elston regression on a set of bipolar pedigrees using each of three dependent variables: a binary trait indicating disease concordance or discordance, a binary trait adjusted for age-of-onset, and the residuals from a survival analysis. The latter two methods, which both adjust for age-of-onset, gave smaller p-values when previous analyses suggested linkage between disease and marker, but not when previous analyses were not suggestive of linkage.

Age of Onset↗
PubMed1993

Performance of subjects with probable Alzheimer disease and normal elderly controls on the Gollin Incomplete Pictures Test.

Our study was designed to evaluate perceptual ability measured by the Gollin Incomplete Pictures Test (in which subjects identify fragmented pictures of common objects) in Alzheimer Disease. We developed a standardized procedure for administering Gollin's test and compared the performance of 58 Alzheimer patients and 37 elderly controls on the Gollin, two design copying tests, the Mini-Mental State Examination, a verbal version of the Knox Cubes test, a recognition memory test, and a verbal fluency test. Alzheimer patients performed significantly more poorly than controls on all tests. Factor analysis demonstrated a visual perceptual factor, with loadings on the Gollin test and design copying, and three other factors representing primary memory, secondary memory, and language. Results indicate the Gollin test measures visual perceptual ability, but the precise nature of the task requires further study. Identification of fragmented pictures appears a practical and potentially useful measure for evaluating at least some aspects of visual perception in patients with generalized cognitive impairment.

Adult↗
PubMed1988

Lysosomes and pancreatic islet function. A quantitative estimation of crinophagy in the mouse pancreatic B-cell.

Ultrastructural studies of pancreatic islets have suggested that crinophagy provides a possible mechanism for intracellular degradation of insulin in the insulin-producing B-cells. In the present study, a quantitative estimation of crinophagy in mouse pancreatic islets was attempted by morphometric analysis of lysosomes containing immunoreactive insulin. Isolated islets were incubated in tissue culture for one week in 3.3, 5.5 or 28 mmol/l glucose. The lysosomes of the pancreatic B-cells were identified by morphological and enzyme-cytochemical criteria and divided into three subpopulations comprising primary lysosomes and insulin-positive or insulin-negative secondary lysosomes. Both the volume and numerical density of the primary lysosomes increased with increasing glucose concentration. The proportion of insulin-containing secondary lysosomes was highest at 5.5 and lowest at 3.3 mmol/l glucose. Insulin-negative secondary lysosomes predominated at 3.3 mmol/l glucose. Studies of the dose-response relationships of glucose-stimulated insulin biosynthesis and insulin secretion of the pancreatic islets showed that biosynthesis had an apparent Km-value for glucose of 7.0 mmol/l, whereas it was 14.5 mmol/l for secretion. The pronounced crinophagic activity at 5.5 mmol/l glucose may thus be explained by the difference in glucose sensitivity between insulin biosynthesis and secretion resulting in an intracellular accumulation of insulin-containing secretory granules. The predominance of insulin-negative secondary lysosomes at 3.3 mmol/l glucose may reflect an increased autophagy, whereas the predominance of primary lysosomes at 28 mmol/l glucose may reflect a generally low activity of intracellular degradative processes.

Animals↗
PubMed1986

Lysosomes and pancreatic islet function: intracellular insulin degradation and lysosomal transformations.

Previous observations indicate that substantial amounts of insulin are degraded intracellularly in isolated pancreatic islets exposed to low or physiological glucose concentrations. The intracellular degradation of insulin seems to occur by a crinophagic process. The aim of the present investigation was to elucidate the role of glucose both in the intracellular insulin degradation and in the lysosomal changes associated with crinophagy in the pancreatic islets. Isolated islets were maintained for 1 week in tissue culture at glucose concentrations of either 3.3 or 28 mmol/l. At both glucose concentrations experimental conditions producing both low and high rates of insulin secretion were examined. Differences in intracellular insulin degradation between the low and high insulin secretory conditions were estimated by measuring insulin biosynthesis and the total amounts of intracellular and extracellular insulin in the islet cultures. Primary and secondary lysosomes in the islets were strictly defined by morphological criteria and evaluated by ultrastructural morphometry. The intracellular degradation of insulin was significantly enhanced in the low-secretory conditions, irrespective of the glucose concentration. Also at both glucose concentrations, primary lysosomes occurred with higher frequency in islets with a high insulin secretion, whereas secondary lysosomes predominated in islets with a low rate of secretion. Thus, the degradative process is manifested as a transformation of lysosomes from their primary to their secondary form. Furthermore, it is suggested that glucose does not interfere directly with crinophagy but rather affects intracellular degradation of insulin in the pancreatic B cells by changing retention of secretory material.

Animals↗
PubMed1985

Lysosomes and pancreatic islet function. Glucose-dependent alterations of lysosomal morphology.

The relation between qualitative and quantitative glucose-dependent alterations of lysosomes in pancreatic islets and the function of the islets was studied. Isolated islets of the mouse were maintained in tissue culture for one week in either 28, 5.5 or 3.3 mmol/l glucose. Insulin biosynthesis, insulin secretion and insulin content of the cultured islets were determined. After culture, the islets were subjected to acid phosphatase cytochemistry and examined by electron microscopy and ultrastructural morphometry. Islets cultured in 28 mmol/l glucose both produced and secreted insulin rapidly. Such islets seemed, however, unable to maintain more than small amounts of granule-stored insulin. Islets cultured at the lower concentrations of glucose displayed a reduced insulin secretion, which apparently resulted in considerable amounts of intracellularly stored insulin. In all cultured islets different types of lysosomes, identified by their acid phosphatase reactivity, could be seen. Dense bodies, i.e., lysosomes characterized by a homogeneous, very fine, particulate content of high density, seemed to predominate at all concentrations of glucose. It is suggested that, in the islets, the dense bodies correspond morphologically to primary lysosomes. Other types of lysosomes with inclusions of various kinds, which were frequent at the two lower concentrations of glucose, may correspond to secondary lysosomes. Morphometry revealed differences between the size distributions of lysosomes in the three experimental groups. Thus, the average lysosomal size was inversely proportional to the concentration of glucose in the culture medium. However, the numerical density of lysosomes was greatest at the highest glucose concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Assessment of behavioral and affective symptoms in Alzheimer's disease.

Noncognitive behavioral symptoms occurring during the prior week were studied in 34 Alzheimer's disease (AD) patients and 21 spousal control subjects via caregiver and patient interviews using the Behavioral Pathology in Alzheimer's Disease Rating Scale and the Cornell Scale for Depression in Dementia. Delusional or paranoid features were reported in 13 subjects (38%) and hallucinations in six (18%); patients with these psychoticlike symptoms had lower scores on the Folstein's Mini-Mental State Examination. Other behavioral symptoms reported in AD patients included anxiety (50%) and activity disturbances (44%). Six AD subjects (18%) and two controls (10%) showed mild to moderate symptoms of depression; AD subjects were more likely than controls to show behavioral signs and symptoms of depression, but the two groups did not differ in terms of mood-related, cyclical, or physical signs and symptoms.

Aged↗