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Biomedical subjects

J A Simon

Publications and source records attributed to J A Simon.

At least 73 records · Page 4Linked to original sources
PubMed1995

The nonsurgical diagnosis of adenomyosis.

OBJECTIVE: To survey the nonsurgical diagnostic techniques for distinguishing adenomyosis, and to determine whether one technique offers diagnostic advantages. DATA SOURCES: We conducted a thorough search of the MEDLINE data base and identified English-language papers on adenomyosis published during the last 28 years. Reference lists of retrieved articles were also examined for additional source documents. METHODS OF STUDY SELECTION: We reviewed 238 articles. Papers on nonsurgical diagnostic techniques published in peer-reviewed journals were selected for inclusion. DATA EXTRACTION AND SYNTHESIS: We determined nonsurgical diagnostic techniques for distinguishing adenomyosis to be hysterosalpingography, abdominal ultrasound, transvaginal sonography, and magnetic resonance imaging (MRI). Studies were divided into these four categories, reviewed, and summarized accordingly. Recent reports suggest that noninvasive modalities, eg, transvaginal sonography and MRI, have, made possible the nonsurgical diagnosis of adenomyosis. CONCLUSION: Because of its widespread availability and patient tolerance, transvaginal sonography remains the primary screening modality for imaging the female pelvis. However, for cases in which sonography cannot detect adenomyosis, MRI provides a viable alternative and should be the definitive diagnostic modality of choice.

Abdomen↗
PubMed1995

Grb2 SH3 binding to peptides from Sos: evaluation of a general model for SH3-ligand interactions.

BACKGROUND: Grb2 acts as an adaptor protein in the transduction of signals from receptor tyrosine kinases to Ras. It binds to phosphotyrosine on the cytoplasmic tail of cell-surface receptors via its central SH2 domain, and to its immediate downstream target, Sos, via two SH3 domains. The basis of the Grb2-Sos interaction is not fully understood. We previously proposed a model for SH3 domain binding specificity, based on two solution structures of the Src SH3 domain complexed with high-affinity ligands, in which the ligands are bound in a polyproline type II conformation in two distinct orientations, class I and class II. Here, we have used this model to predict the identity and orientation of Grb2 SH3 ligands in the human Sos protein. RESULTS: Six contiguous fragments from the carboxy-terminal portion of hSos (amino acids 1000-1333), each containing a single potential SH3 binding site, were expressed in E. coli as GST fusion proteins. Four of these proteins were predicted to associate with SH3 domains. The amino-terminal Grb2 SH3 domain was shown to bind strongly to only these four fragments. CONCLUSIONS: We have used a general model for SH3-ligand interactions to predict the nature of Grb2 SH3 interactions with the hSos protein. Comparison of the four hSos sequences that bind Grb2 revealed a preference for the PXXPXR motif, consistent with the predicted class II-type binding interaction. The interaction between Grb2 and hSos peptides is predominantly via the amino-terminal SH3 domain, although the carboxy-terminal SH3 domain may increase the overall stability of the Grb2-hSos complex.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Serum fatty acids and the risk of stroke.

BACKGROUND AND PURPOSE: To examine the relationship between serum fatty acids, which reflect dietary intake, and stroke, we conducted a nested case-control study of 96 men with incident stroke and 96 control subjects matched by age, clinical center, treatment group, and date of randomization who were enrolled in the Multiple Risk Factor Intervention Trial. METHODS: After confirming the stability of the stored serum samples, we measured serum cholesterol ester and phospholipid fatty acid levels as the percentage of total fatty acids by gas-liquid chromatography and examined their association with incident stroke. Using stepwise conditional logistic regression that controlled for risk factors for stroke, we determined which fatty acids were independent correlates of stroke. RESULTS: In univariate models, a standard deviation (SD) increase (1.37%) in phospholipid stearic acid (18:0) was associated with a 37% increase in the risk of stroke, whereas an SD increase (0.06%) in phospholipid omega-3 alpha-linolenic acid (18:3) was associated with a 28% decrease in the risk of stroke (all P < .05). Only alpha-linolenic acid in the cholesterol ester fraction was associated with the risk of stroke in multivariate models: an SD increase (0.13%) in the serum level of alpha-linolenic acid was associated with a 37% decrease in the risk of stroke (P < .05). Systolic blood pressure and cigarette smoking were also independently associated with stroke risk. CONCLUSIONS: Our findings suggest that higher serum levels of the essential fatty acid alpha-linolenic acid are independently associated with a lower risk of stroke in middle-aged men at high risk for cardiovascular disease.

Adult↗
PubMed1995

Correlates of high-density lipoprotein cholesterol in Black girls and White girls: the NHLBI Growth and Health Study.

To determine the correlates of serum high-density lipoprotein cholesterol (HDL-C) in 9- and 10-year-old girls, data were examined from 624 Black girls and 773 White girls. Black girls had, on average, 3.6 mg/dL higher levels than White girls. Each 10-mm increase in sum of skinfolds was associated with a decrease of 1.4 mg/dL; each unit increase in the tricep/suprailiac skinfold ratio was associated with an increase of 2 mg/dL; and each 10% increase in polyunsaturated fat intake was associated with an increase of 3.4 mg/dL. The associations of sedentary activity and sexual maturation with HDL were mediated by differences in adiposity. Interventions to decrease adiposity may be important for the primary prevention of heart disease in women.

Black People↗
PubMed1994

Two binding orientations for peptides to the Src SH3 domain: development of a general model for SH3-ligand interactions.

Solution structures of two Src homology 3 (SH3) domain-ligand complexes have been determined by nuclear magnetic resonance. Each complex consists of the SH3 domain and a nine-residue proline-rich peptide selected from a large library of ligands prepared by combinatorial synthesis. The bound ligands adopt a left-handed polyproline type II (PPII) helix, although the amino to carboxyl directionalities of their helices are opposite. The peptide orientation is determined by a salt bridge formed by the terminal arginine residues of the ligands and the conserved aspartate-99 of the SH3 domain. Residues at positions 3, 4, 6, and 7 of both peptides also intercalate into the ligand-binding site; however, the respective proline and nonproline residues show exchanged binding positions in the two complexes. These structural results led to a model for the interactions of SH3 domains with proline-rich peptides that can be used to predict critical residues in complexes of unknown structure. The model was used to identify correctly both the binding orientation and the contact and noncontact residues of a peptide derived from the nucleotide exchange factor Sos in association with the amino-terminal SH3 domain of the adaptor protein Grb2.

Adaptor Proteins, Signal Transducing↗
PubMed1994

Dietary cation intake and blood pressure in black girls and white girls.

The authors examined the relative importance of dietary sodium, potassium, calcium, and magnesium intakes as correlates of blood pressure in a cross-sectional analysis of 987 black and 1,043 white 9- and 10-year-old girls from Richmond, California, Cincinnati, Ohio, and Washington, DC, who were enrolled in the National Heart, Lung, and Blood Institute Growth and Health Study between January 1987 and May 1988. Dietary intake was measured using a 3-day food record. Dietary cation intake was not associated with blood pressure in black girls. An inverse association between magnesium intake and diastolic (fifth Korotkoff phase) blood pressure was found in white girls (p < 0.01). After controlling for factors often associated with blood pressure, such as pulse rate, body mass index, and household income, the authors found that dietary magnesium intake (range, 53-511 mg/day) continued to be associated with diastolic (fifth Korotkoff phase) blood pressure in white girls, such that each 100-mg/day increase in intake was associated with a 3.22-mmHg decrease in diastolic pressure (95% confidence interval -5.70 to -0.75). However, after adjustment for dietary fiber intake, the authors were no longer able to discern an association between dietary magnesium intake and blood pressure. They conclude that the body mass index and pulse rate are the strongest correlates of blood pressure in 9- and 10-year-old black girls and white girls and that studies examining the relation between dietary magnesium and blood pressure should control for the effects of dietary fiber intake.

Black or African American↗
PubMed1994

Familial adenomyosis: a case report.

The persuasive data not only illustrate a familial tendency towards adenomyosis but also emphasize that adenomyosis can be diagnosed noninvasively and accurately by MRI. A possible familial predisposition toward or a direct familial cause of adenomyosis warrants further investigation.

Adult↗
PubMed1994

Adenomyosis: prospective comparison of MR imaging and transvaginal sonography.

PURPOSE: To prospectively compare conventional spin-echo magnetic resonance (MR) imaging and transvaginal sonography for the diagnosis of adenomyosis. MATERIALS AND METHODS: Twenty women with clinically suspected adenomyosis underwent MR imaging and transvaginal sonography performed within 3 months of each other. Pathologic proof was obtained in all cases. RESULTS: Seventeen patients were proved to have adenomyosis. The correct diagnosis was achieved with MR imaging in 15 of 17 cases. One false-positive and two false-negative diagnoses were made with MR imaging. With transvaginal sonography, nine of 17 cases of adenomyosis were correctly diagnosed. One false-positive and eight false-negative diagnoses occurred. The most frequent cause of false-negative diagnoses with transvaginal sonography was the misinterpretation of adenomyosis as leiomyomas (seven cases). CONCLUSION: MR imaging is significantly better (P < .02) than transvaginal sonography in the diagnosis of adenomyosis.

Adult↗
PubMed1993

Mutation hotspots due to sunlight in the p53 gene of nonmelanoma skin cancers.

To identify the sites in the p53 tumor suppressor gene most susceptible to carcinogenic mutation by sunlight, the entire coding region of 27 basal cell carcinomas (BCCs) of the skin was sequenced. Fifty-six percent of tumors contained mutations, and these were UV-like: primarily CC-->TT or C-->T changes at dipyrimidine sites. Such mutations can alter more than half of the 393 amino acids in p53, but two-thirds occurred at nine sites at which mutations were seen more than once in BCC or in 27 previously studied squamous cell carcinomas of the skin. Seven of these mutation hotspots were specific to skin cancers. Internal-cancer hotspots not located at dipyrimidine sites were not mutated in skin cancers; moreover, UV photoproducts were absent at these nucleotides. The existence of hotspots altered the process of inactivating p53 in BCC compared to other cancers: allelic loss was rare, but 45% of the point mutations were accompanied by a second point mutation on the other allele. At least one of each pair was located at a hotspot. Sunlight, acting at mutation hotspots, appears to cause mutations so frequently that it is often responsible for two genetic events in BCC development.

Aged↗
PubMed1993

Ascorbic acid and cholesterol gallstones.

Decreased activity of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the catabolism of cholesterol to bile acids, is known to result in increased biliary cholesterol concentration and supersaturation of bile. Supersaturation of bile by cholesterol is a necessary condition for cholesterol gallstone formation. In guinea pigs, the hepatic concentration of ascorbic acid affects the catabolism of cholesterol: hypovitaminosis C reduces cholesterol 7 alpha-hydroxylase activity. Cholesterol gallstones are frequently found in ascorbic acid-deficient guinea pigs. Risk factors for cholesterol gallstones in humans include obesity, aging, estrogen treatment, pregnancy and diabetes. Plasma ascorbic acid levels are reduced in these groups. Vegetarian diets, which typically have high ascorbic acid contents, protect against gallstones. Since ascorbic acid effects the rate-limiting step in the catabolism of cholesterol in the guinea pig and many human risk groups for cholesterol gallstones are associated with reduced ascorbic acid levels, ascorbic acid may play a contributory role in human gallbladder disease.

Animals↗
PubMed1993

Leuprolide acetate and bone mineral density measured by quantitative digitized radiography.

Quantitative digitized radiography uses low-energy photons to measure bone density with precision not available in older techniques. Using this method, lumbar spine density was evaluated in 12 women before and after 6 months of therapy with LA. A 2.9% decrement in mean bone density was documented. The reproducibility of quantitative digitized radiography suggests that this small degree of bone mineral loss is a real phenomenon and not an artifact of measurement. The clinical significance of this degree of bone mineral loss has yet to be established.

Adolescent↗
PubMed1993

Dietary vitamin C and serum lipids in black and white girls.

We examined the cross-sectional relation of dietary vitamin C intake to serum lipids in 1,825 preadolescent black and white girls. Dietary vitamin C intake exclusive of supplement use, determined by 3-day diet record, appeared unrelated to total serum cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels. Because other investigators have demonstrated an inverse association between vitamin C and total serum cholesterol in individuals with elevated total serum cholesterol levels, we analyzed the subgroup of 285 girls (142 blacks and 143 whites) with total serum cholesterol levels > or = 200 mg per dl. Multivariate analyses of this subgroup, which adjusted for saturated fat, polyunsaturated fat, monounsaturated fat, cholesterol, fiber, and energy intake and for body mass index, demonstrated negative association between vitamin C intake and total serum cholesterol. In girls with total serum cholesterol levels > or = 200 mg per dl, each 100 mg per day increase in dietary vitamin C intake (ranges 13-373 and 14-242 mg per day for blacks and whites, respectively) was associated with a total serum cholesterol decrease of 4 mg per dl (95% confidence limits = -10.34, 2.77) in blacks and 13 mg per dl (95% confidence limits = -22.99, -2.68) in whites. If the observed association is causal and generalizable, our results suggest that increased vitamin C intake could play an important role in the cholesterol homeostasis of females with elevated total cholesterol levels.

Ascorbic Acid↗
PubMed1993

The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone.

OBJECTIVES: To examine the effects of food ingestion and administered dose on the absorption of oral micronized P (Utrogestan; Besins-Iscovesco, Paris, France) and to compare the bioavailability of intramuscular versus oral routes of administration. DESIGN: Prospective, randomized, open label crossover protocol with 7 days between dosages. SETTING: Academic institution. PARTICIPANTS: Fifteen normal postmenopausal women. INTERVENTIONS: All subjects participated in three separate protocols: [1] micronized P (200 mg) or placebo under fasting or nonfasting conditions once daily for 5 days; [2] micronized P (100, 200, or 300 mg) once daily under fasting conditions for 5 days; and [3] micronized P (200 mg) or intramuscular P (50 mg in oil) administered once daily for 2 days. MAIN OUTCOME MEASURES: Serum P concentrations were measured in all groups. RESULTS: Concomitant food ingestion increased the area under the serum P concentration versus time curve (AUC0 to 24) and the maximum serum P concentration (Cmax) without affecting time to maximum serum concentration (Tmax) (P < 0.05). Micronized P absorption and elimination were first-order processes and exhibited dose-independent pharmacokinetics between 100 and 300 mg. After intramuscular P, Cmax was higher and Tmax occurred later compared with the oral P preparation. Oral P had lower relative bioavailability (8.6%) than intramuscular P. CONCLUSIONS: Absorption of micronized P was enhanced twofold in the presence of food. Both absorption and elimination were dose-independent, dose proportionality being confirmed. Bioavailability of the oral P was approximately 10% compared with intramuscular P.

Administration, Oral↗
PubMed1992

Calcium intake and blood pressure in elderly women.

The authors studied the relative importance of calcium intake as a correlate of blood pressure in a cross-sectional analysis of 6,517 nonblack women aged > or = 65 years from Portland, Oregon; Minneapolis, Minnesota; Baltimore, Maryland; and the Monongahela Valley near Pittsburgh, Pennsylvania, who enrolled in the Study of Osteoporotic Fractures in 1986. Dietary calcium intake was measured by using a modified food frequency questionnaire. There were weak associations between total calcium intake and blood pressure, such that each 1,000 mg/day increase in calcium intake was associated with a 1.5 mmHg decrease in systolic blood pressure (95% confidence interval -2.2 to -0.8, p < 0.0001) and a 0.5 mmHg decrease in diastolic pressure (95% confidence interval -0.8 to -0.20, p < 0.004). After adjustment for confounding variables, total calcium intake continued to have a weak inverse association only with diastolic blood pressure. The multivariate models revealed several stronger independent risk factors for blood pressure, including age, body mass index, alcohol consumption, and level of education (all p < 0.01). The small size of the inverse association between calcium intake and blood pressure limits its biological importance in this population of elderly women.

Aged↗