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Biomedical subjects

James E Heubi

Publications and source records attributed to James E Heubi.

At least 19 recordsLinked to original sources
PubMed2006

Potential of blood eosinophils, eosinophil-derived neurotoxin, and eotaxin-3 as biomarkers of eosinophilic esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by eosinophilic inflammation of the esophageal mucosa, and typically requires serial invasive endoscopic biopsy examinations to document the characteristic histologic features of the disorder. The aim of this study was to identify noninvasive biomarkers that correlated with disease activity and response to treatment as measured by esophageal eosinophilia. METHODS: A prospective, cross-sectional analysis was performed on 47 pediatric patients undergoing endoscopic evaluation of possible EE. Blood samples were collected for measurement of peripheral blood absolute eosinophil count (AEC) and levels of eosinophil-derived neurotoxin (EDN), eotaxin-1, -2, and -3, and interleukin-5. Stool samples were collected for measurement of EDN. Biomarker levels were correlated with esophageal eosinophil density, and differences in biomarker levels based on disease activity and treatment were determined. RESULTS: AEC, plasma EDN levels, and eotaxin-3 levels significantly correlated with esophageal eosinophil density (AEC: r = 0.56, P < .0001; EDN: r = 0.54, P < .0001; eotaxin-3: r = 0.32, P = .04), and were increased in patients with active EE vs controls (AEC: 440 vs 140 eosinophils/muL, P < .05; EDN: 50.3 vs 31.1 ng/mL, P = .01; eotaxin-3: 37.7 vs 11.5 pg/mL, P = .01). Cut-off values were established to maximize the sensitivity, specificity, and predictive values of these biomarkers alone and in combination. Eotaxin-1, eotaxin-2, interleukin-5, and fecal EDN levels did not correlate with esophageal eosinophil density, and were not increased in active EE vs controls or those with inactive EE. CONCLUSIONS: These data show that blood levels of AEC, EDN, and eotaxin-3 may have value as noninvasive biomarkers for monitoring EE.

Adolescent↗
PubMed2006

A randomized clinical trial of dietary calcium to improve bone accretion in children with juvenile rheumatoid arthritis.

OBJECTIVE: To examine a behavioral intervention (BI) to increase calcium intake in children with juvenile rheumatoid arthritis (JRA) on calcium intake and bone mass 6 and 12 months after treatment. STUDY DESIGN: A randomized trial compared a 6-session BI to a 3-session enhanced standard of care (ESC) with 49 children ages 4 to 10 years with JRA. Calcium intake was assessed via 3-day diet diaries. Total body bone mineral content (BMC), arms and legs BMC, and lumbar spine bone mineral density were assessed by dual energy x-ray absorptiometry. RESULTS: BI maintained an average calcium intake of 1500 mg/d at 6- and 12-month follow-up. This was greater than their baseline level of 972 mg/d, but not greater than the intake of 1300 mg/day maintained by ESC (P=.09). The BI had a 4% and 2.9% greater gain in total body bone mineral content than ESC at 6 and 12 months, respectively (P=.005), and a 7.1% and 5.3% greater gain in arms and legs BMC at 6 and 12 months than ESC (P=.0007). CONCLUSIONS: BI is effective in increasing calcium intake and BMC in children with JRA over a 12-month period.

Adult↗
PubMed2006

Effects of chenodeoxycholic acid and deoxycholic acid on cholesterol absorption and metabolism in humans.

Quantitative and qualitative differences in intralumenal bile acids may affect cholesterol absorption and metabolism. To test this hypothesis, 2 cross-over outpatient studies were conducted in adults with apo-A IV 1/1 or apo-E 3/3 genotypes. Study 1 included 11 subjects 24 to 37 years of age, taking 15 mg/kg/day chenodeoxycholic acid (CDCA) or no bile acid for 20 days while being fed a controlled diet. Study 2 included 9 adults 25 to 38 years of age, taking 15 mg/kg/day deoxycholic acid (DCA) or no bile acid, following the same experimental design and procedures as study 1. CDCA had no effect on plasma lipid concentrations, whereas DCA decreased (P < 0.05) plasma high-density lipoprotein (HDL)-cholesterol and tended to decrease (P = 0.15) low-density lipoprotein (LDL)-cholesterol. CDCA treatment enriched (P < 0.0001) bile with CDCA and increased cholesterol concentration in micelles, whereas meal-stimulated bile acid concentrations were decreased. DCA treatment enriched (P < 0.0001) bile with DCA and tended to increase intralumenal cholesterol solubilized in micelles (P = 0.06). No changes were found in cholesterol absorption, free cholesterol fractional synthetic rate (FSR), or 3-hydroxy-3 methylglutaryl (HMG) CoA reductase and LDL receptor messenger ribonucleic acid (mRNA) levels after CDCA treatment. DCA supplementation tended to decrease cholesterol absorption and reciprocally increase FSR and HMG CoA reductase and LDL receptor mRNA levels. Results of these 2 studies suggest that the solubilization of cholesterol in the intestinal micelles is not a rate-limiting step for its absorption.

Absorption↗
PubMed2006

Defects in bile acid biosynthesis--diagnosis and treatment.

Bile acid synthetic defects represent a specific category of metabolic liver disease. This article highlights the history and summarizes our analytical approach to the diagnosis and treatment of genetic defects in bile acid synthesis. By the application of mass spectrometry as a screening tool, it is possible to perform rapid diagnosis of potential inborn errors in bile acid synthesis from urinary bile acid analysis. Molecular techniques then afford the identification of specific mutations in genes encoding the enzymes responsible for bile acid synthesis. Using this approach, 6 of the 7 known genetic defects that are causes of progressive cholestatic liver disease, syndromes of fat-soluble vitamin malabsorption, or neurological disease, have been characterized. Bile-acid therapy using oral cholic acid has proven effective in most of these bile acid synthetic defects making early diagnosis crucial to optimum clinical prognosis.

Bile Acids and Salts↗
PubMed2006

Variability in the management of childhood constipation.

To assist primary care providers, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) published clinical practice guidelines for management of childhood constipation. A cross-sectional survey of pediatricians from across the United States was conducted to assess pediatricians' constipation management strategies, whether pediatricians are familiar with the NASPGHAN constipation guidelines, and reasons pediatricians refer constipated patients to a pediatric gastroenterologist. Overall, 75% of pediatricians used polyethylene glycol without electrolytes to treat childhood constipation, 8% of pediatricians were aware NASPGHAN had published constipation guidelines, and parental pressure was just one reason pediatricians referred constipated patients to a pediatric gastroenterologist.

Child, Preschool↗
PubMed2005

S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora.

BACKGROUND: The discovery of equol in human urine more than 2 decades ago and the finding that it is bacterially derived from daidzin, an isoflavone abundant in soy foods, led to the current nutritional interest in soy foods. Equol, unlike the soy isoflavones daidzein or genistein, has a chiral center and therefore can occur as 2 distinct diastereoisomers. OBJECTIVE: Because it was unclear which enantiomer was present in humans, our objectives were to characterize the exact structure of equol, to examine whether the S- and R-equol enantiomers are bioavailable, and to ascertain whether the differences in their conformational structure translate to significant differences in affinity for estrogen receptors. DESIGN: With the use of chiral-phase HPLC and mass spectrometry, equol was isolated from human urine and plasma, and its enantiomeric structure was defined. Human fecal flora were cultured in vitro and incubated with daidzein to ascertain the stereospecificity of the bacterial production of equol. The pharmacokinetics of S- and R- equol were determined in 3 healthy adults after single-bolus oral administration of both enantiomers, and the affinity of each equol enantiomer for estrogen receptors was measured. RESULTS: Our studies definitively establish S-equol as the exclusive product of human intestinal bacterial synthesis from soy isoflavones and also show that both enantiomers are bioavailable. S-equol has a high affinity for estrogen receptor beta (K(i) = 0.73 nmol/L), whereas R-equol is relatively inactive. CONCLUSIONS: Humans have acquired an ability to exclusively synthesize S-equol from the precursor soy isoflavone daidzein, and it is significant that, unlike R-equol, this enantiomer has a relatively high affinity for estrogen receptor beta.

Animals↗
PubMed2005

Effective dose of dual-energy X-ray absorptiometry scans in children as a function of age.

Effective dose, a parameter utilized to assess biological risk related to radiation exposure, may be used to evaluate risk associated with dual-energy X-ray absorptiometry (DXA). We estimated the effective dose from DXA (Hologic QDR 4500A) scans of the lumbar spine (fast array mode), total body, hip (fast array mode), and forearm for children ages 1, 5, 10, and 15 yr and for adults. Entrance dose incorporating backscatter was determined for each scan type. Depth-dose curves were derived using Plexiglas slabs simulating tissue attenuation. Organ depth was estimated using pediatric phantom models. For all scan types, the effective dose decreased as age increased. The effective dose values for a 1-yr-old and an adult, respectively, were 4.7 microSv and 2.2 microSv for a lumbar spine scan performed in fast array mode, 3.4/3.5 microSv and 1.8/2.1 microSv (male/female) for a total body scan, and 0.14 microSv and 0.03 microSv for a forearm scan. There were marked sex differences in the effective dose associated with hip scans (fast array mode) ranging from 15.2 microSv for a 1-yr-old male to 4.6 microSv for an adult female. A comprehensive uncertainty analysis indicated that the effective dose values were reliable within a factor of 3. With the exception of the hip scans in 1- and 5-yr-olds, the effective doses were below the negligible individual dose limit of 10 microSv/yr.

Absorptiometry, Photon↗
PubMed2005

Effects of early cholesterol intake on cholesterol biosynthesis and plasma lipids among infants until 18 months of age.

BACKGROUND: The endogenous cholesterol fractional synthesis rate (FSR) is related inversely to infant dietary cholesterol at 4 months of age; however, it remains to be established whether this effect is permanent, possibly contributing to later hypercholesterolemia. OBJECTIVE: To determine whether levels of dietary cholesterol in infancy induced changes in FSR and plasma lipid levels that persisted at 18 months. METHODS: A prospective clinical trial was conducted with 47 infants, from their first week of life until 18 months of age, who received human milk (HM) until weaned (n = 15) or were randomized to receive modified cow's milk formula (MCF) with added cholesterol (n = 15) or cow's milk formula (CF) (n = 17) for 12 months. Cholesterol contents of HM, MCF, and CF were 120, 80, and 40 mg/L, respectively. FSR and plasma lipid levels were measured at 4 and 18 months. RESULTS: At 4 months, total cholesterol and low-density lipoprotein cholesterol levels were higher for infants fed HM and MCF, compared with CF. High-density lipoprotein cholesterol levels were higher in the MCF group than in the HM and CF groups. FSR in the HM group (0.034 +/- 0.005 pools per day) was lower than that in the CF group (0.052 +/- 0.005 pools per day). There was no difference between the HM and MCF (0.047 +/- 0.005 pools per day) groups or between the MCF and CF groups. At 18 months, there were no differences in FSRs or plasma lipid profiles between the groups. CONCLUSION: Although cholesterol intake before weaning affects FSRs and plasma lipid profiles at 4 months, these differences do not persist after weaning to an unrestricted diet at 18 months. This provides additional evidence that there is no imprinting of FSR in infancy with differing dietary levels of cholesterol.

Animals↗
PubMed2004

Bile acid synthetic defects and liver disease: a comprehensive review.

Bile acid synthetic defects (BASD), uncommon genetic disorders that are responsible for approximately 2% of persistent cholestasis in infants, are reviewed with emphasis on morphology of associated liver disease. The associated liver diseases may be life threatening, and are treatable, usually by replacement of deficient primary bile acids. Specific diagnosis is made by analysis of body fluids (bile, blood, and urine) using fast atom bombardment-mass spectroscopy (FAB-MS) and gas chromatography-mass spectroscopy (GC-MS). Inborn errors have been demonstrated for four single enzymes involved in modification of the sterol nucleus and in five steps in modification of the side-chain to form cholic and chenodeoxycholic acids, the primary bile acids. With few exceptions, BASD cause liver diseases that vary from severe to mild depending on the defect. In three of four known defects of sterol nucleus modification, liver disease is progressive. Progression of liver disease is most rapid when the defect results in accumulation of toxic monohydroxy and unsaturated oxo-bile acids. Liver disease may be transient, delayed in onset and mild. Reduced bile flow caused by atypical bile acids contributes to cholestasis and may be the dominant factor in defects of side-chain synthesis, peroxisomal abiogenesis and S-L-O syndrome. Pathological findings may include intralobular cholestasis with giant cell transformation, prevalence of necrotic hepatocytes including giant cell forms, and hepatitic injury confined to the portal limiting plate where the smallest bile ductules may be injured and where fibrosis typically develops. Interlobular bile ducts are usually spared. Ultrastructure of liver reveals nonspecific changes with the possible exception of unusual canalicular morphology in some defects. The course of BASD may be modified by replacement of deficient primary bile acids, which produces beneficial feedback inhibition of abnormal bile acid production and enhances choluresis. Giant cell transformation is present in all symptomatic infants with BASD and seems to have a more consistent association with BASD than with the many other liver diseases in infants where it occurs. We hypothesize that immature hepatocytes of infants may fuse to form multinucleate hepatocytes whenever atypical or toxic bile acids are present and the pool of normal bile acids is critically reduced.

3-Hydroxysteroid Dehydrogenases↗
PubMed2004

Cholic acid supplementation enhances cholesterol absorption in humans.

BACKGROUND & AIMS: Qualitative and quantitative changes in intralumenal bile acid composition may alter cholesterol absorption and synthesis and low-density lipoprotein (LDL) receptor expression. The role of cholic acid (CA) in cholesterol absorption in humans remains unclear and, thus, was examined in the current study. METHODS: In a crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day (CA) or no bile acid supplement (control) while being fed a controlled diet (AHA heart-healthy diet). A liquid meal of defined composition was given on day 14 of the diet, and lumenal samples were collected. Thereafter, cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods from days 16 to 20. RESULTS: With CA treatment, bile was enriched significantly with CA (P < 0.0004) to 60.2% +/- 2.4% (mean +/- SEM) compared with 43.3% +/- 2.4% for controls. CA plus diet treatment significantly increased (P = 0.013) cholesterol absorption (72.6% +/- 2.9%) compared with diet treatment alone (60.4% +/- 2.9%). Percentage micellar cholesterol was increased by CA plus diet treatment vs. diet alone after meal ingestion (P = 0.004). Plasma total and high-density lipoprotein (HDL) and LDL cholesterol was unchanged with CA treatment. CONCLUSIONS: Thus, enrichment in lumenal bile with CA results in an increase in cholesterol absorption, an effect potentially mediated by enhanced cholesterol solubilization in micelles.

Absorption↗
PubMed2004

A novel, noninvasive method for the measurement of intestinal fat absorption.

BACKGROUND & AIMS: The goal of the study was to facilitate fat balance measurements with an appropriate intestinal marker for the transit of dietary fat and thereby eliminate the need for complete diet and fecal collections. METHODS: Dietary fat containing 5% sucrose polybehenate was fed in a semisynthetic diet to rats and mice. Fat absorption was calculated from the ratios of behenic acid to other fatty acids in diet and feces as analyzed by gas chromatography of fatty acid methyl esters. The method was validated by measuring absorption of well-absorbed (safflower oil) and poorly absorbed (olestra; calcium soaps) dietary fats. The animals were fed meals containing test fats for 2 or 3 days, and fecal samples were collected. Fecal samples of approximately 10 mg (single fecal pellet from mice) were assayed. RESULTS: The method yielded values that were consistent with complete absorption of safflower oil and the nonabsorbability of olestra and calcium soaps. The results were reproducible and consistent among individual fecal aliquots. The method was compared with traditional fat-balance methods in animals fed both high- and low-fat diets. CONCLUSIONS: Sucrose polybehenate is an appropriate marker that allows the rapid measurement of fat absorption by analyzing aliquots of <1% of total feces. The method is noninvasive, does not require isotope analyses, and can be carried out as part of an animal's normal feeding regimen. The method may be a facile technique to assess fat absorption measurements in humans.

Animals↗
PubMed2003

Determination of risk factors for Epstein-Barr virus-associated posttransplant lymphoproliferative disorder in pediatric liver transplant recipients using objective case ascertainment.

BACKGROUND: Previous studies have suggested an increased risk of Epstein-Barr virus-associated posttransplant lymphoproliferative disorder (EBV-PTLD) in patients receiving tacrolimus for immunosuppression. We hypothesized that after correction for confounding variables, immunosuppression with tacrolimus is not associated with an increased risk of EBV-PTLD. METHODS: Potential cases of EBV-PTLD, identified by chart review, were independently ascertained by three clinicians and defined using published criteria. Agreement in diagnosing EBV-PTLD was measured using Kappa coefficients. Unadjusted and adjusted relative risk estimates were determined using proportional hazards regression. RESULTS: Twenty-three cases of EBV-PTLD were identified in 221 patients, a proportion of 10.4% (95% confidence interval [CI]: 6.4%-14.4%). Multivariable analysis revealed that immunosuppression with tacrolimus was associated with an increased risk of EBV-PTLD (relative risk 3.10: 95% CI: 1.21-7.92), as was age at transplantation as a continuous variable (parameter estimate -0.15, P=0.03). Kappa coefficients in diagnosing EBV-PTLD and subclassifying as neoplastic and non-neoplastic EBV-PTLD were 0.73 (95% CI: 0.54-0.93) and 0.54 (95% CI: 0.40-0.68), respectively. Patients with neoplastic PTLD demonstrated a lower probability of survival than patients with non-neoplastic PTLD and non-cases. CONCLUSIONS: Immunosuppression with tacrolimus and young age at transplantation are associated with an increased risk of EBV-PTLD in children undergoing liver transplantation, although we cannot exclude detection bias as an explanation for this observed increase. Good agreement between observers can be achieved using previously published criteria for defining EBV-PTLD. Patients with neoplastic EBV-PTLD may have a worse prognosis, and thus identification of risk factors for the development of this subtype of the disorder may be more important.

Aging↗
PubMed2003

Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans.

Qualitative and quantitative changes in intraluminal bile acid composition may alter cholesterol absorption and synthesis and LDL receptor expression. In a randomized crossover design outpatient study, 12 adults aged 24-36 years took 15 mg/kg/day ursodeoxycholic acid (UDCA) or no bile acid supplement (control) for 20 days while being fed a controlled diet (AHA Step II). A liquid meal of defined composition was then given and luminal samples collected. Cholesterol absorption and cholesterol fractional synthetic rate (FSR) were assessed by stable isotopic methods. With UDCA treatment, bile was enriched significantly (P < 0.0001) to 40.6 +/- 2.6% (mean +/- SEM) compared with 2.2 +/- 2.6% for controls. Regardless, plasma total, HDL, and LDL cholesterol were unchanged with UDCA treatment. Intraluminal cholesterol solubilized in the aqueous phase during the entire collection was decreased (P = 0.012) in UDCA-treated subjects (101.0 +/- 7.2 mg/ml/120 min) compared with controls (132.5 +/- 7.2 mg/ml/120 min.). Percent micellar cholesterol was increased in UDCA-treated versus controls after meal ingestion. No changes were found in cholesterol absorption, FSR, or LDL receptor mRNA with UDCA treatment compared with controls. Thus, despite marked enrichment in luminal bile with UDCA and decreased cholesterol solubilization, no differences in cholesterol absorption or metabolism are found when diet and genetic differences in absorption are carefully controlled.

Adult↗
PubMed2003

Liver disease caused by failure to racemize trihydroxycholestanoic acid: gene mutation and effect of bile acid therapy.

BACKGROUND & AIMS: Inborn errors of bile acid metabolism may present as neonatal cholestasis and fat-soluble vitamin malabsorption or as late onset chronic liver disease. Our aim was to fully characterize a defect in bile acid synthesis in a 2-week-old African-American girl presenting with coagulopathy, vitamin D and E deficiencies, and mild cholestasis and in her sibling, whose liver had been used for orthotopic liver transplantation (OLT). METHODS: Bile acids were measured by mass spectrometry in urine, bile, serum, and feces of the patient and in urine from the unrelated recipient. RESULTS: Liver biopsy specimens showed neonatal hepatitis with giant cell transformation and hepatocyte necrosis; peroxisomes were reduced in number. High concentrations of (25R)3alpha,7alpha,12alpha-trihydroxy-5beta-cholestanoic acid in the urine, bile, and serum established a pattern similar to that of Zellweger syndrome and identical to the Alligator mississippiensis. Serum phytanic acid was normal, whereas pristanic acid was markedly elevated. Biochemical, MRI, and neurologic findings were inconsistent with a generalized defect of peroxisomal function and were unique. Analysis of the urine from the recipient of the deceased sibling's liver confirmed the same bile acid synthetic defect. A deficiency in 2-methylacyl-CoA racemase, which is essential for conversion of (25R)THCA to its 25S-isomer, the substrate to initiate peroxisomal beta-oxidation to primary bile acids, was confirmed by DNA analysis revealing a missense mutation (S52P) in the gene encoding this enzyme. Long-term treatment with cholic acid normalized liver enzymes and prevented progression of symptoms. CONCLUSIONS: This genetic defect further highlights bile acid synthetic defects as a cause of neonatal cholestasis.

Bile↗
PubMed2003

Bone mineral density in long-term survivors following pediatric liver transplantation.

We sought to estimate the prevalence of reduced bone mass, defined by lumbar spine bone mineral density (LS-BMD) (z-score < -2.0), and to determine the factors associated with LS-BMD after liver transplantation in children and adolescents. LS-BMD z-scores were measured in a sample of subjects who had undergone liver transplantation in childhood or adolescence using dual energy x-ray absorptiometry (DXA). One hundred nine patients underwent DXA. The mean age at transplantation was 4.3 years (median, 1.8 years), and mean duration since transplantation was 6.2 years (median, 5.8 years). The mean weight z-score was -0.130 (SD, 1.26). The mean LS-BMD z-score was -0.243 (SD, 1.27). Eight patients, or 7.3% (95% confidence interval [CI], 2.4% to 12.2%), had reduced bone mass. Compared with those without reduced bone mass, subjects with reduced bone mass were more likely to have been treated for rejection at least once (87.5% versus 51.5%; P =.07), and had greater cumulative exposure to prednisone during the year before DXA (92.3 versus 26.2 mg/kg/y; P =.001). Multiple linear regression determined that LS-BMD z-score was positively associated with time since transplantation and weight z-score and negatively associated with cumulative prednisone exposure. Serum 25-OH vitamin D was measured and reduced (< 15 ng/mL) in 5 of 87 patients, one of whom had reduced bone mass. In conclusion, the prevalence of reduced bone mass was 7.3% in our population. Only certain patients appear to be at risk for low BMD, including those with a history of rejection. Screening for reduced bone mass may be appropriate for these patients.

Absorptiometry, Photon↗
PubMed2003

Bioavailability, disposition, and dose-response effects of soy isoflavones when consumed by healthy women at physiologically typical dietary intakes.

The pharmacokinetics of isoflavones in 10 healthy women were determined from serum appearance/disappearance concentration profiles and urinary excretions after single-bolus ingestion of 10, 20 or 40 g of soy nuts delivering increasing amounts of the conjugated forms of daidzein (6.6, 13.2 and 26.4 mg) and genistein (9.8, 19.6 and 39.2 mg). Peak serum daidzein and genistein concentrations were attained after 4-8 h, and elimination half-lives were 8.0 and 10.1 h, respectively. There were no differences in the pharmacokinetics of daidzein and genistein between pre- and postmenopausal women, indicating absorption and disposition of isoflavones to be independent of age or menopausal status. A curvilinear relationship was observed between the bioavailability of daidzein and genistein, apparent from the area under the curve to infinity (AUC(inf)) of the serum concentration-time profiles and the amount of isoflavones ingested. The mean fraction of the isoflavones excreted in urine decreased with increasing intake when expressed as a percentage of the administered dose (63.2 +/- 8.0, 54.4 +/- 8.1 and 44.0 +/- 4.3%, respectively, for daidzein, and correspondingly, 25.2 +/- 5.3, 13.4 +/- 2.1 and 15.8 +/- 2.7% for genistein), underscoring the trend toward nonlinear pharmacokinetics. Equol was identified as a metabolite in 30% of women; it was present consistently in urine and blood from the same subjects. Its delayed appearance was consistent with colonic synthesis. On the basis of the pharmacokinetics, optimum steady-state serum isoflavone concentrations would be expected from modest intakes of soy foods consumed regularly throughout the day rather than from a single highly enriched product.

Adult↗
PubMed2003

Molecular genetics of 3beta-hydroxy-Delta5-C27-steroid oxidoreductase deficiency in 16 patients with loss of bile acid synthesis and liver disease.

The 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase (C(27) 3beta-HSD) is a membrane-bound enzyme of the endoplasmic reticulum that catalyzes an early step in the synthesis of bile acids from cholesterol. Subjects with autosomal recessive mutations in the encoding gene, HSD3B7, on chromosome 16p11.2-12 fail to synthesize bile acids and develop a form of progressive liver disease characterized by cholestatic jaundice and malabsorption of lipids and lipid-soluble vitamins from the gastrointestinal tract. The gene encoding the human C(27) 3beta-HSD enzyme was isolated previously, and a 2-bp deletion in exon 6 of HSD3B7 was identified in a well characterized subject with this disorder. Here, we report a molecular analysis of 15 additional patients from 13 kindreds with C(27) 3beta-HSD deficiency. Twelve different mutations were identified in the HSD3B7 gene on chromosome 16p11.2-12. Ten mutations were studied in detail and shown to cause complete loss of enzyme activity and, in two cases, alterations in the size or amount of the transcribed mRNA. Mutations were inherited in homozygous form in 13 subjects from 10 families and compound heterozygous form in four subjects from three families. We conclude that a diverse spectrum of mutations in the HSD3B7 gene underlies this rare form of neonatal cholestasis.

3-Hydroxysteroid Dehydrogenases↗