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Biomedical subjects

R D Lee

Publications and source records attributed to R D Lee.

At least 19 recordsLinked to original sources
PubMed2001

Should all infertile males undergo urologic evaluation before assisted reproductive technologies? Two cases of testicular cancer presenting with infertility.

OBJECTIVE: To report two cases of testicular cancer in patients presenting with infertility. DESIGN: Case reports. SETTING: University-affiliated urology practice. PATIENT(S): Two men presenting with infertility. INTERVENTION(S): Complete history and physical, hormonal assays, semen analysis, scrotal ultrasound, radical orchiectomy. MAIN OUTCOME MEASURE(S): Testicular pathology specimens. RESULT(S): Testicular cancer was diagnosed in two men sent to a urology clinic for infertility treatment. CONCLUSION(S): A thorough evaluation should be completed in all males in couples presenting with infertility.

Adult↗
PubMed2001

Mapping microbial biodiversity.

We report the development of a prototype database that "maps" microbial diversity in the context of the geochemical and geological environment and geographic location. When it is fully implemented, scientists will be able to conduct database searches, construct maps containing the information of interest, download files, and enter data over the Internet.

Databases, Factual↗
PubMed2000

Effects of ochratoxin A on cytotoxicity and cell differentiation in cultured rat embryonic cells.

In the present study, the effects of ochratoxin A (OTA) on cytotoxicity, cell differentiation, and other cell functions in the embryonic midbrain cells, which are dopaminergic, were compared to those in the limb bud cells, which are nondopaminergic, to assess the selectivity of OTA central action. Twelve-day rat embryo midbrain and limb bud cells were cultured in Dulbecco's modified Eagle's medium nutrient and Ham's F12 (1:1) mix ture containing 10% Nuserum for 96 h in the presence of various concentrations of OTA. OTA signicfiantly reduced the levels of protein, DNA and glutathione, and [H]thymidine incorporation into DNA in both embryonic midbrain and limb bud cells in a similar concentration-dependent manner. The IC50 values for cytotoxicity measured by neutral red uptake were 1.10 microM in the midbrain cells and 1.05 microM in the limb bud cells. The IC50 values of cell differentiation were 1.10 microM in the midbrain cells and 1.0 microM in the limb bud cells. The addition of exogenous glutathione (32.5 microM) did not change the OTA-induced fall in protein and DNA levels, or the IC50 values of cytotoxicity and differentiation in the midbrain and limb bud cells. Data show that OTA does not appear to exert a selective toxic dopaminergic cell action and that OTA-induced cytotoxicity and inhibition of cell differentiation were not prevented by exogenous glutathione.

Animals↗
PubMed1999

In vitro metabolism of the HIV-1 protease inhibitor ABT-378: species comparison and metabolite identification.

HIV protease inhibitor ABT-378 (ABT-378) was metabolized very extensively and rapidly by liver microsomes from mouse, rat, dog, monkey, and humans. The rates of NADPH-dependent metabolism of ABT-378 ranged from 2.39 to 9.80 nmol.mg microsomal protein-1.min-1, with monkey liver microsomes exhibiting the highest rates of metabolism. ABT-378 was metabolized to 12 metabolites (M-1 to M-12), which were characterized by mass and NMR spectroscopy. The metabolite profile of ABT-378 in liver microsomes from all five species was similar, except that the mouse liver microsomes did not form M-9, a minor secondary metabolite. The predominant site of metabolism was the cyclic urea moiety of ABT-378. In all five species, the major metabolites were M-1 (4-oxo-ABT-378) and M-3 and M-4 (4-hydroxy-ABT-378). Metabolite M-2 (6-hydroxy-ABT-378) was formed by rodents at a faster rate than by dog, monkey, and human liver microsomes. Metabolites M-5 to M-8 were identified as monohydroxylated derivatives of ABT-378. Metabolites M-9 and M-10 were identified as hydroxylated products of M-1. Metabolites M-11 and M-12 were identified as dihydroxylated derivatives of ABT-378. The metabolite profile in human hepatocytes and liver slices was similar to that of human liver microsomes. The results of the current study indicate that ABT-378 is highly susceptible to oxidative metabolism in vitro, and possibly in vivo, in humans.

Animals↗
PubMed1998

Effects of severe hypoxemia on mesenteric blood flow in neonatal piglets.

BACKGROUND: The purpose of this work was to determine the effects of hypoxemia on systemic hemodynamic variables and regional conduit arterial blood flows in neonatal piglets. MATERIALS AND METHODS: Using transit time blood flow probes, cardiac output and cranial mesenteric artery blood flow were monitored in groups of prematurely delivered (90% of term gestational age) and 2-week-old piglets prior to, during, and after exposure to a 30-min hypoxic (FIO2 = 0.12) challenge. RESULTS: The documented alterations in systemic mean arterial pressure and cardiac output pressure during hypoxia and reoxygenation were consistent with the maturational age of the animals. In response to hypoxia, all animals demonstrated significant reductions in mesenteric blood flow, with returns to baseline levels during the 30-min reoxygenation phase. In still other prematurely delivered piglets, nutrient mesenteric arterial blood flows were measured using in vivo videomicroscopy. The marked hypoxemia-induced decline in mucosal blood flow was reversed by reoxygenation. CONCLUSIONS: The physiologic mechanisms responsible for neonatal mesenteric vasoactive responsiveness are present in conduit and in nutrient vessels well prior to birth and can be activated by a significant perturbation. These observations are germane insofar as they provide a stable, age-matched acute animal model to study neonatal intestinal ischemic diseases, including necrotizing enterocolitis.

Animals↗
PubMed1998

Neither dopamine nor dobutamine corrects mesenteric blood flow depression caused by positive end-expiratory pressure in a rat model of acute lung injury.

OBJECTIVE: To determine if either dopamine or dobutamine would counteract the deleterious effect that positive end-expiratory pressure (PEEP) has on cardiac output and mesenteric blood flow in a rat model of acute lung injury. DESIGN: Prospective, randomized, controlled trial in a clinically relevant model of acute lung injury. SETTING: Microcirculation research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals were anesthetized with pentobarbital (30 mg/kg) by intraperitoneal injection. They underwent tracheostomy, jugular and femoral vein cannulation, femoral artery cannulation, carotid artery thermistor placement, and bowel preparation for in vivo video microscopy. Acute lung injury was created by administering 0.1 N hydrochloric acid (1 mL/kg) via the tracheostomy. Dopamine or dobutamine (2.5 or 12.5 microg/kg/min), followed by two intravenous fluid boluses, was administered to rats ventilated with 5, 10, 15, and 20 cm H2O of PEEP. MEASUREMENTS AND MAIN RESULTS: Mean arterial pressure, thermodilution cardiac output, mesenteric arteriolar diameter, and red blood cell velocity were measured and mesenteric blood flow was calculated. Cardiac output was depressed in rats exposed to 20 cm H2O of PEEP by 32+/-2%. The corresponding values for cardiac output depression at 20 cm H2O of PEEP in rats receiving 2.5 and 12.5 microg/kg/min of dopamine and 2.5 and 12.5 microg/kg/min of dobutamine were 31+/-1%, 21+/-1%, 29+/-0%, and 24+/-2%, respectively. Mesenteric blood flow was depressed in rats ventilated with 20 cm H2O of PEEP by 74+/-3%, while the corresponding values in rats exposed to 20 cm H2O of PEEP and receiving 2.5 or 12.5 microg/kg/min of dopamine or 2.5 or 12.5 microg/kg/min of dobutamine were 86+/-3%, 77+/-3%, 73+/-3%, and 66+/-3%, respectively. Fluid boluses did not correct the deficits in cardiac output or mesenteric blood flow caused by the combination of acute lung injury and PEEP. CONCLUSIONS: The higher doses of dopamine and dobutamine partially, but insignificantly, corrected the cardiac output depression caused by PEEP in a model of acute lung injury. Neither dose of dopamine nor dobutamine was able to improve PEEP-induced mesenteric blood flow depression.

Animals↗
PubMed1996

Vitamin A, visual pigments, and visual receptors in Drosophila.

The fly visual system has served for decades as a model for receptor spectral multiplicity and vitamin A utilization. A diverse armamentarium of structural techniques has dovetailed with convenient electrophysiology, photochemistry, genetics, and molecular biology in Drosophila to facilitate recent progress, which is reviewed here. New data are also presented. Ultrastructure of retinula cells of carotenoid-deprived flies shows that organelles associated with protein biosynthesis, i.e., rough endoplasmic reticulum and Golgi apparatus, are present, while organelles associated with rhabdomere turnover, i.e., multivesicular bodies (MVBs), are rare. Ultrastructure and morphometry suggest that retinoic acid-rearing stimulates membrane export and rhabdomere buildup, even though functional rhodopsin is missing. Confocal microscopy suggests that RH4, one of the ultraviolet rhodopsins, may reside in the previously-described pale fluorescent R7 cells with RH3 in the yellow fluorescent R7 cells.

Animals↗
PubMed1996

Control of Drosophila opsin gene expression by carotenoids and retinoic acid: northern and western analyses.

In the fly, thorough retinoid deprivation is possible, to optimize investigation of the effects of vitamin A metabolites and retinoic acid (RA) on visual development. Retinoids had been found to control fly opsin gene transcription, though this finding was contested. Northern blots on Drosophila heads showed that mRNA of Rh1 (the predominant rhodopsin) was high in vitamin A replete controls, very low in deprived flies, and increased upon feeding carrot juice to deprived flies as early as 1 hr. Expression of the ribosomal protein 49 [rp49] gene (the control) was equal both in deprivation and in replacement. Recovery of Rh1 protein upon such carotenoid replacement followed, barely detectable on Western blots at 4 hr but conspicuous by 8 hr. Alternative chromophore deprivation with yeast-glucose food yielded flies with opsin mRNA on Northerns but not rhodopsin, as demonstrated by Western blots, spectrophotometry and the electroretinogram (ERG). Rh1's mRNA but not Rh1 protein resulted from rearing flies from egg to adult on the otherwise deprivational medium supplemented with RA or beef brain-heart infusion. By comparing results from these different media it was concluded that: [1] deprivation and replacement affect opsin gene transcription; and [2] contradictory conclusions were from chromophore deprivation which does not eliminate all retinoid dependent factors which could affect the opsin promoter. Preliminary evidence shows that carotenoid deprivation decreases two proteins relevant to visual function: [1] phospholipase C (PLC); and [2] Drosophila retinoid binding protein (DRBP).

Animals↗
PubMed1996

Visualization of iontophoretic transport paths in cultured and animal skin models.

Physiological structures associated with iontophoretic paths in hairless mouse skin and two cultured skin models ("EpiDerm" by Mattek, Corp., and "SKIN2" by Advanced Tissue Sciences, Inc.) are reported. Visualization of ionic paths at current densities between 20 and 100 microA/ cm2 is accomplished by the counterdirectional transport of Fe(CN)6(4-) and Fe3+, resulting in the controlled precipitation of colloidal Prussian blue, Fe4[Fe(CN)6]3, at sites of high ionic conductivity. Examination of the Fe4[Fe(CN)6]3-stained tissues using optical microscopy allows unequivocal assignment of iontophoretic paths to physiological structures in the stratum corneum. Deposition of Fe4[Fe(CN)6]3 occurs exclusively at hair follicles in hairless mouse skin, indicating that these appendages provide highly conductive porous paths during iontophoresis. In contrast, the counterdirectional transport of Fe(CN)6(4-) and Fe3+ across cultured skin models, which lack appendages, results in the deposition of Fe4-[Fe(CN)6]3 along the boundaries of corneocytes. This observation suggests that paracellular iontophoretic transport through lipid bilayer regions is the predominant transport path in the absence of low-resistance pores.

Animals↗
PubMed1996

Hepatic uptake of choline in rat liver basolateral and canalicular membrane vesicle preparations.

Choline, an endogenous quaternary ammonium ion, is transported into the liver by both saturable and nonsaturable processes. The objective of the present investigation was to determine the driving force(s) for uptake of choline in rat liver basolateral membrane (blLPM) and canalicular membrane (cLPM) vesicles. Choline is transported into an osmotically sensitive intravesicular space in both blLPM and cLPM. Uptake of [3H]choline into both blLPM and cLPM exhibited temperature dependence (0 degree C vs. 37 degrees C). A valinomycin-induced inside-negative K+ diffusion potential significantly stimulated initial uptake of [3H]choline in both vesicles. Choline uptake in blLPM and cLPM was not stimulated in the presence of an inwardly directed sodium gradient or an outwardly directed H+ gradient, and ATP did not enhance choline uptake in cLPM. Choline itself and structurally similar derivatives, such as hemicholinium-3 and succinylcholine, inhibited [3H]choline uptake 11 to 92% (at 10-fold higher concentrations) in blLPM and cLPM. Other cations, including N1-methylnicotinamide, thiamine and d-tubocurarine, and cardioglycosides did not inhibit choline transport in either vesicle preparation. In addition, [3H]choline uptake into both blLPM and cLPM was enhanced when vesicles were preloaded with nonradiolabeled choline (trans-stimulation). Kinetic studies indicated that choline was transported into blLPM by both saturable and passive processes and into cLPM predominantly by a saturable process. These results suggest that the transport of choline is likely mediated by a potential-sensitive conductive pathway in both blLPM and cLPM. The electrogenic pathway in cLPM may play a role in the reabsorption of choline from bile.

Animals↗
PubMed1995

Comparison of eight microcomputer dietary analysis programs with the USDA Nutrient Data Base for Standard Reference.

OBJECTIVE: To compare the general operating features and nutrient databases of eight microcomputer dietary analysis programs. DESIGN: A 3-day food record with 73 food items was entered into each program by the authors. The general operating features of the program were summarized and evaluated. The nutrient database was evaluated by comparing the nutrient analysis output with the 1993 US Department of Agriculture (USDA) Nutrient Data Base for Standard Reference (NDB), full version, release 10, for microcomputers. RESULTS: The programs varied in cost, number of foods and nutrients in the database, use of non-USDA data, and inputting of data for missing values. We also found differences in the quality of user manuals and help screens, ease of food entry and averaging of 3-day nutrient intake, speed of analyzing and printing results, quality and number of print/export options, and overall ease of learning and using the program. All but one of the programs were within 15% of the USDA NDB for energy, protein, total fat, and total carbohydrates. However, there was some difference in the number of other nutrients and food components varying more than 15% from the USDA NDB. These differences occurred because of variations in the number of food items included in each programs' database and the number of missing nutrient values in the database. APPLICATIONS: Our results demonstrate the importance of carefully choosing a microcomputer dietary analysis program that is suitable to the user's specific and predetermined needs.

Databases, Factual↗
PubMed1995

Disaggregation in population forecasting: do we need it? And how to do it simply.

"We have described a method for reducing the dimensionality of the forecasting problem by parsimoniously modeling the evolution over time of the age schedules of vital rates. This method steers a middle course between forecasting aggregates and forecasting individual age specific rates: we reduce the problem to forecasting a single parameter for fertility and another one for mortality. We have described a number of refinements and extensions of those basic methods, which preserve their underlying structure and simplicity. In particular, we show how one can fit the model more simply, incorporate lower bounds to the forecasts of rates, disaggregate by sex or race, and prepare integrated forecasts of rates for a collection of regions. We also discuss alternate approaches to forecasting the estimated indices of fertility and mortality, including state-space methods. These many versions of the basic method have yielded remarkably similar results." (SUMMARY IN FRE)

Age Distribution↗
PubMed1995

In vitro metabolism of terfenadine by a purified recombinant fusion protein containing cytochrome P4503A4 and NADPH-P450 reductase. Comparison to human liver microsomes and precision-cut liver tissue slices.

The metabolism of terfenadine was studied with a cDNA-expressed/purified recombinant fusion protein containing human liver microsomal cytochrome P4503A4 (CYP3A4) linked to rat NADPH-P450 reductase (rF450[mHum3A4/mRatOR]L1) and was compared with that observed in the presence of human liver microsomes and precision-cut human liver tissue slices. In all three cases, [3H]terfenadine was metabolized to at least three major metabolites. LC/MS (electrospray) analysis confirmed that these metabolites were alpha, alpha-diphenyl-4-piperidinomethanol (M5), t-butyl hydroxy terfenadine (M4), and t-butyl carboxy terfenadine (M3), although the level of M5 detected in the presence of fusion protein was greater than that found with microsomes or tissue slices. Two additional metabolites, M1 (microsomes and tissue slices) and M2 (fusion protein), were also detected, but remain uncharacterized. Consumption of parent drug (microsomes: KM = 9.58 +/- 2.79 microM, Vmax = 801 +/- 78.3 pmol/min/nmol CYP; fusion protein: KM = 14.1 +/- 1.13 microM, Vmax = 1670 +/- 170 pmol/min/nmol CYP) and t-butyl hydroxylation to M4 (microsomes: KM = 12.9 +/-3.74 microM, Vmax = 643 +/- 62.5 pmol/min/nmol CYP, ; fusion protein: KM = 30.0 +/- 2.55 microM, Vmax = 1050 +/- 141 pmol/min/nmol CYP) obeyed Michaelis-Menten kinetics over the terfenadine concentration range of 1-200 microM. Ketoconazole, a well-documented CYP3A inhibitor, effectively inhibited terfenadine metabolism in all three models. The conversion of M4 to M3, studied with human liver microsomes and fusion protein, was NADPH-dependent and inhibited by ketoconazole. It is concluded that cDNA-expressed CYP3A4, in the form of a NADPH-P450 reductase-linked fusion protein, may also serve as a model for studying the metabolism of terfenadine in vitro and many other drugs.

Adult↗
PubMed1994

Famine, revolt, and the dynastic cycle: population dynamics in historic China.

"Historians have long noticed that population declines in ancient China often coincided with dynasty changes, and that most of these declines were the result of internecine wars which, in turn, were often initiated by famine or density pressure. Since the interactions between density pressure, internecine wars, and dynasty changes cannot be explained by the traditional age-specific density-dependent population structure, we propose to use a bandit/peasant/ruler occupation-specific population model to interpret the dynamic socio-economic transitions of ancient Chinese population, and provide econometric support to our model. We also highlight the rich dynamics of the composition of human population, a factor which was often neglected in previous research on general populations."

Asia↗
PubMed1994

Stochastic population forecasts for the United States: beyond high, medium, and low.

"This article presents and implements a new method for making stochastic population forecasts that provide consistent probability intervals. We blend mathematical demography and statistical time series methods to estimate stochastic models of fertility and mortality based on U.S. data back to 1900 and then use the theory of random-matrix products to forecast various demographic measures and their associated probability intervals to the year 2065. Our expected total population sizes agree quite closely with the Census medium projections, and our 95 percent probability intervals are close to the Census high and low scenarios. But Census intervals in 2065 for ages 65+ are nearly three times as broad as ours, and for 85+ are nearly twice as broad. In contrast, our intervals for the total dependency and youth dependency ratios are more than twice as broad as theirs, and our ratio for the elderly dependency ratio is 12 times as great as theirs. These items have major implications for policy, and these contrasting indications of uncertainty clearly show the limitations of the conventional scenario-based methods."

Age Factors↗