Biomedical subjects

David J Hart

Publications and source records attributed to David J Hart.

10 recordsLinked to original sources

PubMed2006

Quassinoid support studies: fused carbocycle synthesis from benzoic acid derivatives via 5-hexynyl and 6-heptynyl radical cyclizations.

Eight bromoalkynes were prepared from substituted benzoic acids and treated with n-Bu3SnH to provide trans-fused perhydroindans or cis- and trans-fused perhydronaphthalenes. Atom-transfer reactions that accompany the free radical reactions resulted in several tandem radical cyclizations with formation of up to three carbon-carbon bonds in a single reaction. The relationship between these reactions and an approach to the quassinoid family of natural products is also described.

Journal Article↗

PubMed2005

Differential kinetic behavior and distribution for pteroylglutamic acid and reduced folates: a revised hypothesis of the primary site of PteGlu metabolism in humans.

Single (13)C(6)-labeled doses of pteroylmonoglutamic acid (PteGlu: 634 nmol; n = 14), (6S-)5-formyltetrahydrofolic acid (431-569 nmol; n = 16), or [(15)N(1-7)]-intrinsically labeled spinach (mainly 5-methyltetrahydrofolate) (588 nmol; n = 14) were fed to fasting adult volunteers. Plasma-labeled 5-methyltetrahydrofolic acid responses were monitored for 8 h. There was a slower rate of increase in plasma-labeled 5-methyltetrahydrofolic acid and longer time to peak (171 +/- 9 min; mean +/- SEM) following an oral dose of [(13)C(6)]PteGlu than either [(13)C(6)]5-formyltetrahydrofolic acid (54 +/- 10 min) or [(15)N(1-7)]spinach folate (60 +/- 13 min) suggesting saturated metabolic capacity for the biotransformation of PteGlu. Mathematical modeling generated a significantly higher mean "apparent absorption" for 5-formyltetrahydrofolic acid (38%) and spinach folate (44%) than for PteGlu (24%). The high "relative absorption" of reduced folates to PteGlu was unexpected given that PteGlu itself, from (14)C-tracer mass balance experiments, is almost completely absorbed. Although it is ubiquitously accepted that a physiological dose of PteGlu is reduced and methylated in the epithelial cells of the small intestine, and that essentially only 5-methyltetrahydrofolic acid is exported into the hepatic portal vein (HPV), as is the case for absorbed reduced 1-carbon-substituted folates, modeling indicated greater liver sequestration when PteGlu was used as the test dose, suggesting that PteGlu enters the HPV unaltered and that the liver is the primary site of initial metabolism. Because of the observed differential plasma response and the hypothesized difference in the site of initial metabolism, the historical use of PteGlu as a "reference folate" in studies of folate bioavailability is seriously questioned.

Erythrocytes↗

PubMed2005

Anterior cervical spinal cord tethering after anterior spinal surgery: case report.

OBJECTIVE AND IMPORTANCE: This is the first reported case of anterior cervical spinal cord tethering after anterior spinal surgery. A mechanistic hypothesis is presented to explain the observed phenomenon. CLINICAL PRESENTATION: A patient developed cervical myelopathy 2 years after multiple anterior cervical discectomies complicated by cerebrospinal fluid leakage. She demonstrated reflex and motor changes as well as neuropathic pain. INTERVENTION: An anterior corpectomy was performed, with opening of the dura and detethering of an arachnoid band and then fusion and plating. CONCLUSION: Reflex and motor changes improved, but pain did not. We hypothesize that mechanical deformation and scar formation after cerebrospinal fluid leakage may have led to tethering of the spinal cord.

Adult↗

PubMed2004

Pediatric sacral fractures.

STUDY DESIGN: Retrospective review. OBJECTIVES: To examine the epidemiologic, anatomic, mechanistic, and outcome characteristics in pediatric patients with sacral fractures and to look for correlation with the adult literature regarding sacral fractures and previous classification systems. SUMMARY OF BACKGROUND DATA: A review of the current literature reveals no systematic attempts to apply the results of studies of sacral fractures in adults to those in the pediatric population. METHODS: We reviewed all 4876 cases of pediatric trauma at 1 children's hospital over a 7-year period. Eight children had documented sacral fractures. Their charts were reviewed, and follow-up interviews were conducted. RESULTS: All patients suffered either motor vehicle accidents or falls from height. Three patients' injuries were confined to the pelvic rim including the sacrum. Mean follow-up was 38 months. Six patients had Denis Zone I injuries, 1 patient had a Zone II injury (no neurologic deficits in either category), and 1 patient had a Zone III injury with significant neurologic injury. Only this patient required surgical intervention. Long-term recovery was good in those without comorbid injuries. CONCLUSIONS: Pediatric sacral fractures are rare (0.16% of pediatric trauma). As is the case in adults, most fractures are not associated with neurologic injury. Diagnosing pediatric sacral fractures requires high clinical suspicion and thorough radiographic evaluation. Correlation of neurologic injury with certain fracture types may be possible, but will require larger studies to be confirmed.

Adolescent↗

PubMed2004

Kinetics of gastro-intestinal transit and carotenoid absorption and disposal in ileostomy volunteers fed spinach meals.

BACKGROUND: Reports of low carotenoid absorption from food sources has undermined their postulated 'protective' role as one of the active agents in diets rich in vegetable matter. AIM OF THE STUDY: This study quantified beta-carotene and lutein absorption from a representative green vegetable with different degrees of processing, using both mass balance and metabolic modelling of triglyceride-rich lipoprotein plasma fraction (TRL) response. METHODS: Whole or chopped-leaf cooked spinach was fed to volunteers (n = 7, paired) with vegetable oil (40 g) in yoghurt. Blood and ileal effluent samples were collected for up to 24 h. Effluent and TRL samples were analysed for lutein and beta-carotene by HPLC. A digesta transit model was used to describe meal transit and a single compartment model used to predict percentage absorption from the plasma TRL response. RESULTS: Mass balance showed 25% of lutein and beta-carotene were absorbed from chopped spinach, compared with 25% beta-carotene and 40 % lutein from whole-leaf spinach. Increased lutein absorption correlated to slower gastrointestinal (GI) transit for the whole-leaf meal. An area under the curve (AUC) response for the TRL fraction, found in 50% of cases, was not confined to those with the greatest percentage absorption. Absorption by mass balance and TRL AUC indicate a half-life of newly absorbed carotenoid around 11 min CONCLUSION: GI residence time appears to have an effect on the absorption of lutein but not beta-carotene. Rapid clearance is probably the main reason for absence of measurable plasma concentration excursions. Lack of plasma response cannot be interpreted as lack of carotenoid absorption without knowledge of the absorption and disposal kinetics.

Antioxidants↗

PubMed2004

Rational design of lipid for membrane protein crystallization.

The lipidic cubic phase has been used to grow crystals of membrane proteins for high-resolution structure determination. However, the original, so-called, in meso method does not work reliably at low temperatures, where proteins are generally more stable, because the hosting lipid turns solid. The need existed therefore for a lipid that forms the cubic phase and that supports crystal growth at low temperatures. We created a database of phase diagrams and used it to design such a lipid. X-ray diffraction showed that the new lipid exhibits designed phase behavior. Further, it produces diffraction quality membrane protein crystals by the in meso method at 6 degrees C. This demonstrates that lipidic materials, like their protein counterparts are amenable to rational design. The same approach as used in this study should find application in extending the range of membrane proteins crystallizable by the in meso method and in tailoring transport of cubic phases for controlled delivery and uptake.

Carbon↗

PubMed2003

Acid-promoted Prins cyclizations of enol ethers to form tetrahydropyrans.

Trifluoroacetic acid efficiently catalyzes Prins cyclizations of enol ethers 8 to provide tetrahydropyrans 9 and 10. These tetrahydropyrans are isolated with combined yields of 42-85% and stereoselectivities at C(4) ranging from 95:5 to 50:50 depending on the nature of the substituent R. Unique byproducts of these cyclizations that reveal the presence of underlying equilibria have been isolated and identified. [reaction: see text]

Catalysis↗

PubMed2003

Is there more to folates than neural-tube defects?

The purpose of the present paper is to review our current understanding of the chemistry and biochemistry of folic acid and related folates, and to discuss their impact on public health beyond that already established in relation to neural-tube defects. Our understanding of the fascinating world of folates and C1 metabolism, and their role in health and disease, has come a long way since the discovery of the B-vitamin folic acid by Wills (1931), and its first isolation by Mitchell et al. (1941). However, there is still much to do in perfecting methods for the measurement of folate bioavailability, and status, with a high extent of precision and accuracy. Currently, examination of the relationships between common gene polymorphisms involved in C1 metabolism and folate bioavailability and folate status, morbidity, mortality and longevity is evaluated as a series of individual associations. However, in the future, examination of the concurrent effects of such common gene polymorphisms may be more beneficial.

Ascorbic Acid↗

PubMed2002

Determination of 5-methyltetrahydrofolate (13C-labeled and unlabeled) in human plasma and urine by combined liquid chromatography mass spectrometry.

The association of folates with the prevention of neural tube defects and reduced risk of other chronic diseases has stimulated interest in the development of techniques for the study of their bioavailability in humans. Stable isotope protocols differentiate between oral and/or intravenous test doses of folate and natural levels of folate already present in the body. An liquid chromatography/mass spectrometry (LC/MS) procedure is described that has been validated for the determination of [13C]5-methyltetrahydropteroyl monoglutamic acid ([13C]5-CH3H4PteGlu) in plasma and urine, following oral dosing of volunteers with different labeled folates. Folate binding protein affinity columns were used for sample purification prior to LC/MS determination. Chromatographic separation was achieved using a Superspher 100RP18 (4 microm) column and mobile phase of 0.1 mol/L acetic acid (pH 3.3):acetonitrile (90:10; 250 microL/min). Selected ion monitoring was conducted on the [M-H](-) ion: m/z 458 and 459 for analyzing 5-CH3H4PteGlu; m/z 464 [M+6-H](-) to determine 5-CH3H4PteGlu derived from the label dose; m/z 444 for analysis of 2H4PteGlu internal standard, and m/z 446 and 478 to confirm that there was no direct absorption of unmetabolized compounds. Calibration was linear over the range 0-9 x 10(-9) mol/L; the limits of detection and quantification were 0.2 x 10(-9) and 0.55 x 10(-9) mol/L, respectively. The mean coefficient of variation of the ratios (m/z 463/458) was 7.4%. The method has potential applications for other key folates involved in one-carbon metabolism.

Carbon Isotopes↗

PubMedDate not supplied

The vertical hydraulic conductivity of an aquitard at two spatial scales.

Aquitards protect underlying aquifers from contaminants and limit recharge to those aquifers. Understanding the mechanisms and quantity of ground water flow across aquitards to underlying aquifers is essential for ground water planning and assessment. We present results of laboratory testing for shale hydraulic conductivities, a methodology for determining the vertical hydraulic conductivity (K(v)) of aquitards at regional scales and demonstrate the importance of discrete flow pathways across aquitards. A regional shale aquitard in southeastern Wisconsin, the Maquoketa Formation, was studied to define the role that an aquitard plays in a regional ground water flow system. Calibration of a regional ground water flow model for southeastern Wisconsin using both predevelopment steady-state and transient targets suggested that the regional K(v) of the Maquoketa Formation is 1.8 x 10(-11) m/s. The core-scale measurements of the K(v) of the Maquoketa Formation range from 1.8 x 10(-14) to 4.1 x 10(-12) m/s. Flow through some additional pathways in the shale, potential fractures or open boreholes, can explain the apparent increase of the regional-scale K(v). Based on well logs, erosional windows or high-conductivity zones seem unlikely pathways. Fractures cutting through the entire thickness of the shale spaced 5 km apart with an aperture of 50 microns could provide enough flow across the aquitard to match that provided by an equivalent bulk K(v) of 1.8 x 10(-11) m/s. In a similar fashion, only 50 wells of 0.1 m radius open to aquifers above and below the shale and evenly spaced 10 km apart across southeastern Wisconsin can match the model K(v).

Geological Phenomena↗