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Biomedical subjects

L E Mitchell

Publications and source records attributed to L E Mitchell.

33 records · Page 2Linked to original sources
PubMed1995

Evidence for an association between nonsyndromic cleft lip with or without cleft palate and a gene located on the long arm of chromosome 4.

Recent studies suggest that the familial aggregation of nonsyndromic cleft lip with or without cleft palate (CL +/- P) is likely to be attributable to the effects of several susceptibility loci, acting in a multiplicative fashion. Two potential CL +/- P susceptibility loci (CSL), transforming growth factor alpha (TGFA) and retinoic acid receptor (RARA), have been identified through association studies. In addition, recent evidence of linkage between CL +/- P and two markers (D4S175 and D4S192) in the region 4q25-4q31.3 raised the possibility that a CSL, with a larger effect than either TGFA or RARA, may reside within this region of the human genome. The present analyses were undertaken to determine whether D4S175 or D4S192 is significantly associated with CL +/- P in a sample of unrelated patients that have previously provided evidence of associations between CL +/- P and both TGFA and RARA. The results of these analyses provide further, tentative, evidence for the presence of a CSL locus on the long arm of chromosome 4 and help to refine the location of this locus in the region of D4S175 and D4S192.

Alleles↗
PubMed1994

Are air inlets necessary with Haemaccel?

Haemaccel is often used for the resuscitation of shocked patients. It is common practice to introduce an air inlet into the plastic container to increase the flow rate. We investigated how much difference an air inlet made. We compared the flow rates with no air inlet, a single air inlet, a 2 x 2 cm hole (equivalent to multiple air inlets) and a pressure infusion cuff. Although the use of an air inlet compared with no air inlet reduced the time to infuse 500 ml by 27 s, the difference was only clinically significant over the final 100 ml. A pressure cuff produced the fastest flow, reducing the time by 68 s. Use of an air inlet, however, precludes subsequent use of a pressure cuff. We recommend that the practice of using air inlets for Haemaccel and other similarly packaged products is abandoned.

Air↗
PubMed1994

Evidence for an association between dehydroepiandrosterone sulfate and nonfatal, premature myocardial infarction in males.

BACKGROUND: Several studies indicate that endogenous hormones play a role in the etiology of coronary artery disease, either as independent risk factors or indirectly, via an effect on lipids, lipoproteins, or other heart disease risk factors. METHODS AND RESULTS: The relation between endogenous hormone levels and premature (< 56-year-old patients) myocardial infarction was assessed in a retrospective study involving 49 male survivors of premature myocardial infarction and 49 age-matched, volunteer male controls. Serum samples were obtained for each subject the morning after a > or = 12-hour fast and frozen at -70 degrees C for subsequent hormonal analysis. Among the male patients, the average duration between the most recent myocardial infarction and blood sampling was 3.4 years (range, 0.7 to 19.2 years). Individuals reporting the use of any medications with the potential to alter lipid, lipoprotein, or hormone levels were excluded from these analyses. Dehydroepiandrosterone sulfate levels were significantly lower in the patients than in the control subjects. This association remained statistically significant even after accounting for the effects of total cholesterol, triglycerides, the ratio of total to high-density lipoprotein (HDL) cholesterol, HDL, apolipoprotein A-I, apolipoprotein A-II, apolipoprotein B, and body mass index. There were no significant differences in the levels of estradiol, testosterone, or free testosterone or the ratio of estradiol to testosterone between patients and control subjects. CONCLUSIONS: Our conclusions are limited by the retrospective nature of this study. However, these data indicate that serum dehydroepiandrosterone sulfate levels are inversely related to premature myocardial infarction in males and that this association is independent of the effects of several known risk factors for premature myocardial infarction.

Age Factors↗
PubMed1994

Commingling analysis of adiposity in an Indian population.

The distributions of five adiposity phenotypes were assessed for the presence of commingling in a sample of 756 adults (> or = 30 years old), residing in the Chittoor district of Andhra Pradesh, India. Three measures of generalized fatness (body mass index, the sum of six skinfolds and the sum of three trunk skinfolds) and two indicators of fat patterning (the ratio of trunk to extremity subcutaneous fat and the ratio of the subscapular skinfold to the sum of the subscapular and the supra-iliac skinfolds) were analysed. Each phenotype was adjusted for the effects of (i) age within sex, and (ii) age, energy intake and energy expenditure within sex. The distribution of each phenotype, under both adjustment schemes, was assessed for evidence of commingling. The commingling analyses were performed separately for males (n = 397) and females (n = 359), and evidence for heterogeneity in the distribution of each phenotype, by sex, was evaluated. There is evidence of commingling in the distribution of each phenotype, under both adjustment schemes. Conclusions regarding the distributions of these phenotypes are, however, influenced by the specific adjustments made to the data. In general, the measures of generalized fatness are more sensitive than measures of fat patterning to the specific adjustments applied to the data. Interestingly, and in contrast with the majority of commingling analyses of adiposity, the smallest components of the commingled distributions often have the lowest mean phenotypic value.

Adipose Tissue↗
PubMed1993

Cincinnati myocardial infarction and hormone family study: family resemblance for testosterone in random and MI families.

Familial correlations for total testosterone and free testosterone were examined in both random and nonrandom families participating in the Cincinnati Myocardial Infarction and Hormone Family Study (CIMIH). The non-random families were ascertained through Caucasian males who had survived a myocardial infarction (MI) prior to age 56 years, while random families were recruited largely through an adolescent boy maturation study. Eight sex-specific familial correlations were estimated (father-mother, father-son, father-daughter, mother-son, mother-daughter, son-son, daughter-daughter, and son-daughter) for each of the MI and random samples using maximum likelihood methods with appropriate ascertainment correction. These familial correlations were examined for differences between the random and MI samples, as well as for sex-specific familial patterns. The results suggest that total testosterone levels may have a limited role in determining MI risk, as evidenced by the overall heterogeneity between samples, and lower serum levels in MI than random probands. The pattern of correlations for both androgens suggests that a simple genetic model appears unlikely; however, familiarity cannot be ruled out. Although possible covariate effects such as age and sex may have masked some potentially significant results, especially in males, familiarity in females is suggested (correlations ranging from .3-.9). The relative stability of these hormones in females as compared to that in males may have contributed to its identification, and suggests the familial transmissibility may be associated with adrenal production and/or metabolic clearance of testosterone.

Adolescent↗
PubMed1993

The genetics of infantile hypertrophic pyloric stenosis. A reanalysis.

OBJECTIVE: To determine whether the existing family data for infantile hypertrophic pyloric stenosis (IHPS) are sufficient for the purposes of establishing the mode of inheritance of this condition. DESIGN: Reanalysis of the familial aggregation patterns exhibited by IHPS, using data from several published family studies. CONCLUSIONS: Due to several limitations of the available family data for IHPS, the results of this analysis should be interpreted cautiously. Within the context of these limitations, the familial recurrence pattern among monozygotic cotwins and more remote relatives of IHPS probands was found to be inconsistent with generalized single major locus inheritance. The familial recurrence pattern of IHPS is, however, compatible with multifactorial threshold inheritance or the effects of multiple interacting loci. Under a model of multiple interacting loci, no single locus can account for more than a fivefold increase in the risk to first-degree relatives of IHPS probands. In contrast to several earlier reports, this analysis does not support the existence of a maternal factor that contributes to the risk of IHPS in the offspring of affected females.

Diseases in Twins↗
PubMed1993

Assessment of adiposity in an Indian population: familial correlations.

Familial correlations for five measures of adiposity were assessed using data from 473 nuclear families residing in the Chittoor district of Andhra Pradesh, India. Fat patterning, measured as the ratio of trunk to extremity subcutaneous fat, and the ratio of the subscapular to the sum of the subscapular and suprailiac skinfolds, and three measures of generalized fatness: body mass index, the sum of six skinfolds and the sum of three trunk skinfolds were analyzed. Maximum likelihood estimates of the familial correlations were obtained for each phenotype, after adjusting for the effects of (1) age within sex, and (2) current levels of energy intake and expenditure, and age within sex. Hypotheses regarding sex-specific, and generational differences in these correlations were assessed for each phenotype, under both adjustment schemes. The strength and pattern of the familial correlations for the three measures of generalized fatness were markedly influenced by the specific adjustments applied to the data. In contrast, the familial correlations for the fat patterning phenotypes were quite similar under the two adjustment schemes. Comparison of our results with previously published data indicates that the familial correlations for a subset of these adiposity measures may be heterogeneous across populations.

Adipose Tissue↗
PubMed1993

The Cincinnati Myocardial Infarction and Hormone Family Study: family resemblance for dehydroepiandrosterone sulfate in control and myocardial infarction families.

Dehydroepiandrosterone sulfate (DHEAS) was examined in random (control) and nonrandom (case) families participating in the Cincinnati Myocardial Infarction and Hormone (CIMIH) family study. The case families were ascertained through white men who survived a myocardial infarction (MI) before the age of 56, whereas control families were recruited through advertisements and through an adolescent boy maturation study. Both familial correlations and genetic effects of DHEAS were investigated. First, maximum likelihood estimates of the sex-specific familial correlations (corrected for nonrandom ascertainment) suggested that there was significant heterogeneity between the two sampling types. This heterogeneity was isolated to the male sibling correlation, which was higher in the case than control families. Post hoc analyses suggested that the sibling group heterogeneity may be in part a function of age, since the control sample offspring were on average much younger than those in case families. No sex differences other than those for the siblings were noted in the familial correlations. Second, heritability was investigated in control families using a simple path model (TAU) that allowed for sex differences. The only significant model parameter was the sex-specific familiarity (combined polygenic and familial environmental effects), which was larger in females (74%) than in males (29%). In general, these analyses suggested that (1) DHEAS may play only a limited role in the increased risk for premature MI, and (2) the degree of heritable (familial) variation may be dependent on sex.

Adolescent↗
PubMed1993

Correlates of genetic risk for non-syndromic cleft lip with or without cleft palate.

Multivariate analysis was used to determine which characteristics: sex of the proband, sibling sex, severity of the proband's defect or family history, are the best predictors of recurrence risk among siblings of individuals with non-syndromic cleft lip with or without cleft palate (CL +/- P). Sibling recurrence risks are not significantly related to the sex of the proband. Severity of the proband's defect, classified by the extent of the lip defect (unilateral versus bilateral), was found to be a significant predictor of sibling recurrence, whereas involvement of the palate in the proband's defect was not. A positive family history of clefting (i.e. at least one affected first-degree relative in addition to the proband) and the sex of the sibling were also found to be significant predictors of sibling recurrence. The associations between sibling risk and family history, and sibling risk and bilaterality of the proband's defect appear to be mildly confounded. After adjusting for the effects of family history, the risk to siblings of probands with bilateral lip defects is twice the risk to siblings of probands with unilateral defects (O.R. = 2.00; 95% C.I. 1.25-3.19). A positive family history of clefting increases the risk to siblings by greater than 4-fold (O.R. = 4.49; 95% C.I. 2.74-7.35), after adjusting for the extent of the proband's lip defect. These results provide a rational strategy for identifying subsets of the 'at risk' population which have markedly different recurrence risks. This information is important for genetic counseling, since it allows for more precise estimation of sibling recurrence risks in individual cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Cleft Lip↗
PubMed1992

Mode of inheritance of nonsyndromic cleft lip with or without cleft palate: a reanalysis.

Nonsyndromic cleft lip with or without cleft palate (CL +/- P) is traditionally recognized as a multifactorial threshold trait (MFT). Recently, however, evidence for the involvement of a major gene in the etiology of CL +/- P has been reported. To assess the potential for major-gene involvement in the etiology of this trait, familial recurrence patterns from several family studies of CL +/- P were reanalyzed. The recurrence patterns in first-degree relatives of CL +/- P probands were found to be compatible with the expectations for either an MFT or a generalized single-major-locus (gSML) trait. The use of multiple thresholds based on proband sex, defect bilaterality, or palatal involvement did not help to discriminate between these models. However, the pattern of recurrence among MZ twins and more remote relatives of CL +/- P probands is not consistent with gSML inheritance but is compatible with either an MFT model or a model specifying multiple interacting loci. For such a model, no single locus can account for more than a sixfold increase in risk to first-degree relatives. These findings have important implications with regard to the feasibility of detecting linkage to loci conferring susceptibility to CL +/- P.

Cleft Lip↗
PubMed1991

Hazards of urocanic acid as a cosmetic ingredient.

Certain commercially available cosmetic products have been found to contain the ingredient urocanic acid. We have shown that the solar irradiation in vitro of one such lotion resulted in the formation of cis urocanic acid. The irradiated lotion, when applied topically to the skin of hairless mice, systemically suppressed the normal contact hypersensitivity reaction to 2,4-dinitrofluorobenzene by 68%. In addition, mice exposed to a minimally erythemal dose of ultraviolet B (280-320 nm) radiation, normally sub-immunosuppressive, showed a 56% suppression of the contact hypersensitivity reaction if they were irradiated through the topically applied cosmetic lotion.

Animals↗
PubMed1989

Molecular analysis of an alcohol dehydrogenase (Adh) gene from chromosome 1 of wheat.

We have cloned and determined the nucleotide sequence of a gene encoding alcohol dehydrogenase (Adh) from Triticum aestivum cv. Millewa. Southern analysis using cv. Chinese Spring nullisomic-tetrasomic and ditelosomic lines established that the cloned gene mapped to the long arm of chromosome 1A and does not correspond to any previously identified wheat Adh locus. Southern analysis also provided evidence for triplicate copies of this Adh gene on the homoeologous group 1 chromosomes, while Northern blots indicated that the homoeologous group 1 Adh genes, like several other plant Adh genes, are transcribed under anaerobic conditions. Sequence analysis indicates that the cloned gene has a structure similar to both monocot and dicot Adh genes with an open reading frame encoding a polypeptide of 379 amino acids. Sequences important for eucaryotic gene expression such as the TATA box, polyadenylation signal, and intron splice sites were found in the expected positions. The open reading frame is interrupted by 8 introns which are in identical positions with 8 of the 9 introns in maize and pea Adh genes, suggesting that during evolution there are processes occurring that result in the loss of introns. Sequence analysis also revealed that the cloned wheat Adh gene shared extensive homology with the barley Adh3 gene not only in the coding region but also in the noncoding regions. However, this homology is discontinuous as a result of a 1.8-kbp insertion (TLM), which is present in the cloned wheat Adh gene and absent in the barley Adh3 gene. Sequence analysis of this insertion reveals features characteristic of the short terminal inverted repeat class of eucaryotic transposable elements. We have no evidence for the transposition of the TLM element. However, Southern blots reveal multiple copies of sequences related to TLM in the wheat genome and in other closely related species, suggesting that transposition may once have played an important role in the evolution of the Gramineae family.

Alcohol Dehydrogenase↗
PubMedDate not supplied

Reproductive versus chronologic age as a predictor of low birth weight, preterm delivery and intrauterine growth retardation in primiparous women.

The effect of reproductive age (chronologic age at conception minus menarcheal age) and chronologic age on the risks of low birth weight, preterm delivery and intrauterine growth retardation were studied in 1198 primiparous women whose pregnancies ended in singleton live births at Yale-New Haven Hospital, 1980-1982. After adjustment for maternal race and other important confounding variables, neither young reproductive age (less than 8 years) nor young chronologic age (less than 20 years) were strongly related to any of the reproductive outcomes. Older chronologic age (greater than 29 years) was also not strongly related to any of these outcomes, but older reproductive age (greater than 15 years) was moderately associated with low birth weight (OR 1.9; 95% CI 0.9, 3.8) after adjusting for maternal race, religion and smoking status. In addition, extremely young reproductive age (less than 2 years) appeared to be associated with an increased risk of preterm delivery (OR 3.1; 95% CI 0.7, 14.6), but our sample was too small to adjust for confounding factors in this group of women. Reproductive age appears to reflect extremes in menarcheal age, whereas chronologic age does not, and this association may account for any relationship between reproductive age and pregnancy risk in primiparous women.

Adolescent↗