A practical and facile route for the preparation of 18-norandrostan-17-ones from androstan-17-ones using SmI(2)-promoted cyclization and dehydroxylation.
Explore the source record for details and available documents.
Androstanes↗
Biomedical subjects
H Hu
Publications and source records attributed to H Hu.
A broad role for the zinc finger protein ZNF202 in human lipid metabolism.
The ZNF202 gene resides in a chromosomal region linked genetically to low high density lipoprotein cholesterol in Utah families. Here we show that the ZNF202 gene product is a transcriptional repressor that binds to elements found predominantly in genes that participate in lipid metabolism. Among its targets are structural components of lipoprotein particles (apolipoproteins AIV, CIII, and E), enzymes involved in lipid processing (lipoprotein lipase, lecithin cholesteryl ester transferase), and several genes involved in processes related to energy metabolism and vascular disease. Based on the linkage and apparent transcriptional function of ZNF202, we propose that ZNF202 is a candidate susceptibility gene for human dyslipidemia.
Alternative Splicing↗
Ornithine decarboxylase activity and its gene expression are increased in benign hyperplastic prostate.
BACKGROUND: Ornithine decarboxylase (ODC) is the first key enzyme in the polyamine biosynthesis pathway. Polyamine is believed to participate in cellular proliferation and differentiation. To study the relationship between ODC and the pathogenesis of benign prostatic hyperplasia (BPH), the polyamine levels, ODC activities, and expression of ODC mRNA in benign hyperplastic and normal human prostates were assayed. METHODS: Polyamine contents and ODC activities in tissue extracts were determined by reverse-phase high-performance liquid chromatography and spectrophotometric procedures, respectively. The ODC mRNA levels were assayed by Northern blot analysis. RESULTS: The contents of putrescine, spermidine, and spermine in BPH tissues were 2.2, 3.4, and 6.0 times higher than those in normal tissues, respectively; the ODC activity of BPH tissue was about 3.2 times higher than in normal tissue; the expression level of ODC mRNA in the BPH tissues was greater than that of normal tissues. CONCLUSIONS: The findings imply that 1) the increased ODC activity and polyamine content in prostatic tissue may correlate with the pathogenesis of BPH, and 2) the high level of ODC activity is induced by the overexpression of ODC mRNA.
Adult↗
The multidimensional filter diagonalization method.
The theory of the multidimensional filter diagonalization method (FDM) described in the previous paper (V. A. Mandelshtam, 2000, J. Magn. Reson. 144, 343-356 (2000)) is applied to NMR time signals with up to four independent time variables. Direct projections of the multidimensional time signals produce new kinds of 2D spectra. The resolution obtained by FDM can be far superior to that obtained by conventional phase-sensitive FT processing, and correlation peaks in heteronuclear and homonuclear experiments can be condensed to sharp singlets, removing all spin-spin couplings. Examples of singlet-HSQC and singlet-TOCSY spectra show big gains in resolution. It is not necessary to have a finely digitized spectrum, in which the individual multiplet components are resolved, for the methods to work. Examples of FDM spectra, ranging from simple organic molecules and steroids to metalloproteins, are shown.
Artifacts↗
Fragment constant method for prediction of fish bioconcentration factors of non-polar chemicals.
A fragment constant method for prediction of fish bioconcentration factor (BCF) was established based on experimental BCF values for 80 non-polar chemicals from nine classes. The model was evaluated using coefficients of determination and mean residuals, which are 0.995 and 0.1836, respectively. Jackknife tests were applied to examine the robustness of the prediction model on a class-by-class basis.
Animals↗
Estimation of bioconcentration factors of nonionic organic compounds in fish by molecular connectivity indices and polarity correction factors.
A bioconcentration factor (BCF) estimation model for a wide range of nonionic organic compounds was developed on the basis of molecular connectivity indices and polarity correction factors. The nonlinear topological modeling using polarity correction factors resulted in the best BCF estimation quality for all of the 239 compounds studied, with a mean absolute estimation error of 0.478 log units. Residual analysis indicated that the estimation errors came from many sources including BCF measurement, test species, and selection of descriptors. Statistical robustness of the developed model was validated by modified jackknifed tests where random deletion of a set of compounds and specific deletion of a class of compounds were both performed. Comparison between the MCI-based (molecular connectivity indices) model and a Kow-based (octanol/water partition coefficient) model revealed that the BCF estimation based on topological parameters was as good as that achieved by Kow.
Animals↗
Exposure to metals.
Metals, particularly heavy metals such as lead, cadmium, and arsenic, constitute significant potential threats to human health in both occupational and environmental settings. Lead exposure is of particular concern because of ongoing exposure to thousands of workers in the US and recent research indicating that asymptomatic lead exposure can result in chronic toxicity manifestations, such as hypertension, kidney impairment, and cognitive disturbances. Mercury is neurotoxic, even at the relatively low levels of exposure seen in dentists' offices. Arsenic is clearly carcinogenic, and cadmium is now being recognized as a contributor to osteoporosis. This article reviews these and other issues of concern in the practice of primary care.
Environmental Monitoring↗
Chlamydia pneumoniae infection significantly exacerbates aortic atherosclerosis in an LDLR-/- mouse model within six months.
We have previously shown that infection with the C. pneumoniae AR39 strain once monthly for 9 consecutive months significantly exacerbated atherosclerosis in mice with LDL receptor deficiency (LDLR-/-) in the presence of a high cholesterol diet. To further optimize the LDLR-/- mouse model for studying the mechanisms of C. pneumoniae atherogenesis, we have tested a different infection protocol with intranasal inoculation twice monthly for 6 consecutive months in the present study. We found that C. pneumoniae infection for 6 months was sufficient to produce a 130%, significantly greater exacerbation of aortic atherosclerosis in LDLR-/- mice in the presence of a high cholesterol diet. Mice receiving a high cholesterol diet alone displayed a lesion area index of 18.2 +/- 6.1 (S.D.) while mice treated with both the high cholesterol diet and C. pneumoniae infection had a lesion area index of 41.8 +/- 15.2 (S.D.). However, the chlamydial infection did not significantly alter the mouse serum total cholesterol or the LDL levels induced by the high cholesterol diet. This study not only confirms our previous findings that C. pneumoniae infection can exacerbate aortic atherosclerosis lesion in the LDLR-/- mice, but also further optimizes the LDLR-/- mouse model for future mechanism studies.
Animals↗
Validation of K x-ray fluorescence bone lead measurements by inductively coupled plasma mass spectrometry in cadaver legs.
K x-ray fluorescence (KXRF) systems are being used in a growing number of epidemiologic studies to measure bone lead levels as a biological marker of accumulated lead exposure. Although validation of the KXRF technique in lead-doped phantoms and bare bone specimens has been repeatedly demonstrated, few studies have compared KXRF to chemical measurements of actual intact cadaver limbs (with skin and soft tissues). In this study, lead levels in eight amputated human legs were measured by KXRF; after dissection, levels in the bare bones were again measured by KXRF and then by inductively coupled plasma mass spectrometry (ICP-MS). We observed close agreement between the KXRF and ICP-MS measurements with correlation coefficients for both the tibia and patella greater than 0.9. In this study we provide further support for the validity of KXRF measurements, particularly with respect to the patella.
Aged↗
A z gain nonuniformity correction for multislice volumetric CT scanners.
This paper presents a calibration and correction method for detector cell gain variations. A key functionality of current CT scanners is to offer variable slice thickness to the user. To provide this capability in multislice volumetric scanners, while minimizing costs, it is necessary to combine the signals of several detector cells in z, when the desired slice thickness is larger than the minimum provided by a single cell. These combined signals are then pre-amplified, digitized, and transmitted to the system for further processing. The process of combining the output of several detector cells with nonuniform gains can introduce numerical errors when the impinging x-ray signal presents a variation along z over the range of combined cells. These numerical errors, which by nature are scan dependent, can lead to artifacts in the reconstructed images, particularly when the numerical errors vary from channel-to-channel (as the filtered-backprojection filter includes a high-pass filtering along the channel direction, within a given slice). A projection data correction algorithm has been developed to subtract the associated numerical errors. It relies on the ability of calibrating the individual cell gains. For effectiveness and data flow reasons, the algorithm works on a single slice basis, without slice-to-slice exchange of information. An initial error vector is calculated by applying a high-pass filter to the projection data. The essence of the algorithm is to correlate that initial error vector, with a calibration vector obtained by applying the same high-pass filter to various z combinations of the cell gains (each combination representing a basis function for a z expansion). The solution of the least-square problem, obtained via singular value decomposition, gives the coefficients of a polynomial expansion of the signal z slope and curvature. From this information, and given the cell gains, the final error vector is calculated and subtracted from the projection data.
Algorithms↗
Determinants of bone and blood lead concentrations in the early postpartum period.
OBJECTIVE: This study investigated determinants of bone and blood lead concentrations in 430 lactating Mexican women during the early postpartum period and the contribution of bone lead to blood lead. METHODS: Maternal venous lead was measured at delivery and postpartum, and bone lead concentrations, measured with in vivo K-x ray fluorescence, were measured post partum. Data on environmental exposure, demographic characteristics, and maternal factors related to exposure to lead were collected by questionnaire. Linear regression was used to examine the relations between bone and blood lead, demographics, and environmental exposure variables. RESULTS: Mean (SD) blood, tibial, and patellar lead concentrations were 9.5 (4.5) microg/dl, 10.2 (10.1) microg Pb/g bone mineral, and 15.2 (15.1) microg Pb/g bone mineral respectively. These values are considerably higher than values for women in the United States. Older age, the cumulative use of lead glazed pottery, and higher proportion of life spent in Mexico City were powerful predictors of higher bone lead concentrations. Use of lead glazed ceramics to cook food in the past week and increased patellar lead concentrations were significant predictors of increased blood lead. Patellar lead concentrations explained one third of the variance accounted for by the final blood lead model. Women in the 90th percentile for patella lead had an untransformed predicted mean blood lead concentration 3.6 microg/dl higher than those in the 10th percentile. CONCLUSIONS: This study identified the use of lead glazed ceramics as a major source of cumulative exposure to lead, as reflected by bone lead concentrations, as well as current exposure, reflected by blood lead, in Mexico. A higher proportion of life spent in Mexico City, a proxy for exposure to leaded gasoline emissions, was identified as the other major source of cumulative lead exposure. The influence of bone lead on blood lead coupled with the long half life of lead in bone has implications for other populations and suggests that bone stores may pose a threat to women of reproductive age long after exposure has declined.
Adult↗
Vibration perception thresholds in workers with long term exposure to lead.
OBJECTIVES: To evaluate the impact of long term occupational exposure to lead on function of the peripheral nervous system as reflected by vibration perception threshold (VPT), measured with a portable vibrameter. METHODS: 217 Workers in a lead battery factory were required to have an annual blood lead measurement during each of the 5 years preceding this study. All were invited to take the VPT test. A total of 206 workers were studied. The associations were analysed between VPTs and current blood lead concentration, mean concentration of blood lead over the past 5 years, maximum blood lead concentration during the past 5 years, index of cumulative blood lead (ICL), time weighted index of cumulative blood lead (TWICL), and percentage of lifespan spent at work in the plant, as well as the other potential confounders. Ordinary multiple regressions, generalised additive models, and hockey stick regression analyses were used to explore the potential existence of a threshold effect of blood lead variables on VPT. RESULTS: VPT at a frequency of 220 Hz ranged from 6 to 100 (10(-2) g, or 0.098 m/s(2)) with a mean (SD) of 19.8 (14.2) for the feet and from 4 to 43 with a mean (SD) of 10.2 (6.1) for the hands. The five variables of exposure to lead were all significantly correlated with VPT of the feet but not the hands. In multiple linear regression analyses, the mean of the blood lead concentrations and the TWICL were significantly associated with VPT of the feet. The relation between VPT of the feet and mean blood lead was shown to be a J shaped curve with a generalised additive model and local smoothing technique. In the hockey stick regression, evidence was found of a threshold effect at a mean blood lead concentration of 31 microgram/dl. Above this threshold it was estimated that each increase of 1 microgram/dl mean blood lead over 5 years would increase VPT of the feet by 0.29 (10(-2) g) or 0.028 m/s(2) (at a frequency of 220 Hz) with other potential confounders held constant. CONCLUSION: This study suggests that measurement of vibration sensory threshold is a relatively effective tool for detecting lead neuropathy in field studies, and that lead might cause sensory neuropathy with an effect threshold corresponding to a 5 year mean blood lead concentration of 31 microgram/dl.
Adult↗
Four multidetector-row helical CT: image quality and volume coverage speed.
PURPOSE: To evaluate the imaging performance characteristics of four multidetector-row helical computed tomography (CT) and assess improvement in volume coverage speed over that with single multidetector-row helical CT. MATERIALS AND METHODS: The section-sensitivity profile and image noise of a four multidetector-row scanner were measured with phantom scans and compared with predictions from theoretic models. Nominal section thickness ranged from 1.25 to 10.00 mm, beam collimation from 1.25 to 5.00 mm, and table speed from 3.75 to 30.00 mm per rotation. Image artifacts with four and single multidetector-row helical CT were compared in both a phantom study and a subjective rating analysis of clinical images. RESULTS: Compared with single multidetector-row helical CT, the volume coverage speed of four multidetector-row helical CT (range, 3.75-30.00 mm per rotation) is at least twice as fast as that with single multidetector-row helical CT (1.0-10.0 mm per rotation) with fully comparable image quality or, in many cases, three times as fast with diagnostically comparable image quality. CONCLUSION: Compared with single multidetector-row helical CT, four multidetector-row helical CT provides a two- to threefold improvement in volume coverage speed with comparable diagnostic image quality.
Adult↗
Voltage-dependent facilitation of cardiac L-type Ca channels expressed in HEK-293 cells requires beta-subunit.
The activity of native L-type Ca channels can be facilitated by strong depolarizations. The cardiac Ca channel alpha(1C)-subunit was transiently expressed in human embryonic kidney (HEK-293) cells, but these channels did not exhibit voltage-dependent facilitation. Coexpression of the Ca channel beta(1a)- or beta(2a)-subunit with the alpha(1C)-subunit enabled voltage-dependent facilitation in 40% of cells tested. The onset of facilitation in alpha(1C) + beta(1a)-expressing HEK-293 cells was rapid after a depolarization to +100 mV (tau = 7.0 ms). The kinetic features of the facilitated currents were comparable to those observed for voltage-dependent relief of G protein inhibition demonstrated for many neuronal Ca channels; however, intracellular dialysis with guanosine 5'-O-(2-thiodiphosphate) and guanosine 5'-O-(3-thiotriphosphate) in the patch pipette had no effect on facilitation. Stimulation of G protein-coupled receptors, either endogenous (somatostatin receptors) or coexpressed (adenosine A(1) receptors), did not affect voltage-dependent facilitation. These results indicate that the cardiac Ca channel alpha(1C)-subunit can exhibit voltage-dependent facilitation in HEK-293 cells only when coexpressed with an auxiliary beta-subunit and that this facilitation is independent of G protein pathways.
Adenosine Diphosphate↗
Platelet-leukocyte cross talk in whole blood.
Thrombosis and inflammation involve complex platelet-leukocyte interaction, the details of which are not fully elucidated. Therefore, we investigated cross talk between platelets and leukocytes in whole blood, under the following physiological conditions: at 37 degrees C, with normal calcium concentrations, and with shear force. Platelet P-selectin and leukocyte CD11b expression were used to monitor platelet and leukocyte activation, respectively, and platelet-leukocyte aggregation (PLA) was analyzed. The leukocyte-specific agonist N:-formyl-methionyl-leucyl-phenylalanine (10(-6) mol/L) increased P-selectin-positive platelets from 2.5+/-0. 1% to 5.1+/-0.6% (P:<0.05). The increase was inhibited by either the platelet-activating factor (PAF) antagonist SR27417, the superoxide anion scavenger superoxide dismutase, the 5-lipoxygenase inhibitor Zileuton, or the 5-lipoxygenase-activating protein inhibitor MK-886, suggesting the involvement of PAF, superoxide anion, and 5-lipoxygenase products in leukocyte-induced platelet activation. The platelet-specific agonist collagen (1 microg/mL) increased leukocyte CD11b expression from 2.94+/-0.52 to 3.81+/-0.58 (P:<0. 05); this was not inhibited by the thromboxane A(2) receptor antagonist ICI 192.605 or the PAF antagonist SR27417. Platelet P-selectin expression induced by N:-formyl-methionyl-leucyl-phenylalanine and leukocyte CD11b expression induced by collagen could be suppressed by glycoprotein IIb/IIIa blockade or P-selectin blockade. This study documents platelet-leukocyte cross talk under conditions that mimic a physiological state and suggests that this involves multiple mediators and mechanisms. Furthermore, new evidence of integrin and selectin involvement in intracellular and intercellular signaling during platelet-leukocyte cross talk is provided.
Adult↗
Measurement variability associated with KXRF bone lead measurement in young adults.
In vivo bone lead measurement using K X-ray fluorescence (KXRF) has been used to estimate long-term lead exposure, especially in adults. Relatively few studies have been conducted on young subjects with this technique. To explore the measurement variability of KXRF bone lead measurements in young subjects, the tibiae of two male cadavers from Boston, Massachusetts, 17 and 20 years of age, were obtained for repeated bone lead measurements. Bone lead concentrations were measured using a grid of nine locations, 1 cm apart, centered at the midpoint of the tibia. Each location was sampled using five 60-min measurements. Measured concentrations ranged from < 0 to 11.8 microg Pb/g bone mineral across a tibia with mean concentrations for the midpoint locations of 0.8 microg Pb/g bone mineral SD = 2.5 and 2.0 microg Pb/g bone mineral (SD = 1.9) for the left and right legs of the younger subject and 3.6 microg Pb/g bone mineral (SD = 2.6) and 6.0 microg Pb/g bone mineral (SD = 3.3) for the left and right legs of the older subject. Although bone lead concentrations did not vary significantly by measurement location in an individual leg, reported measurement uncertainty increased significantly at locations that were 1 cm from the center of the tibia horizontally (p < 0.0001). Symmetry in bone lead concentration between legs was observed for the 17-year-old subject. Potential asymmetry between the left and right legs was suggested for the 20-year-old subject (p = 0.06). These data describe the degree of variability that may be associated with bone lead measurements of young subjects with low bone lead concentrations using a standard spot-source KXRF instrument. Because of the importance of conducting additional research on adolescent lead toxicity, further improvements to the precision of KXRF measurement are needed.
Adolescent↗
Effect of low level lead exposure on hyperuricemia and gout among middle aged and elderly men: the normative aging study.
OBJECTIVE: To determine whether longterm lead accumulation is associated with hyperuricemia and gouty arthritis among middle aged and elderly men. METHODS: In a retrospective cohort study, 777 male participants were evaluated between August 1991 and October 1996 in the Department of Veterans Affairs Normative Aging Study, a 35 year longitudinal study of aging. We examined the development of gout and an increased uric acid level in relation to lead, adjusting for other known risk factors. Lead levels were measured in blood and by K x-ray fluorescence (K-XRF) technique in tibial (cortical) and patellar (trabecular) bone. RESULTS: Blood lead levels in this mostly Caucasian (97%) population were low (mean 5.9 microg/dl, SD 3.5). Bone lead levels were comparable to those described in other general populations. In a multivariate analysis adjusting for the risk factors, age, body mass index, diastolic blood pressure, alcohol intake, and serum creatinine level, there was a positive association between patellar bone lead and uric acid levels (p = 0.02). Of 777 participants, 52 (6.7%) had developed gouty arthritis. In logistic regression of similar covariates, body mass index (p < 0.0001) and serum creatinine level (p = 0.005) were the strongest determinants of gout; neither bone nor blood lead levels predicted gout in this cohort. CONCLUSION: The longterm accumulation of lead is associated with an increased uric acid level in middle aged and elderly men. However, this study shows no association between lead and gouty arthritis at the levels arising from community exposure.
Age Factors↗
An experimental study of effect of zheng tai instant powder on grand mal epilepsy.
Zheng Tai Instant Powder [symbol: see text] is a complex prescription of traditional Chinese medicine indicated for grand mal epilepsy. Its effect on central nervous system, energy metabolism, neurotransmitters and hemorheology were studied in animal models. The results demonstrated that the effect of Zheng Tai Instant Powder is mild, long-lasting and effective in treatment and prevention of epilepsy without any side effects.
Animals↗