A case of VIPoma.

This case report addresses the management of a pregnant woman in the peripartum period with a VIPoma. This rare and highly malignant neuroendocrine tumour secretes vasoactive intestinal peptide (VIP), a substance that may cause potentially life-threatening disruption to physiology. A 36-year-old woman presented for induction of labour with a three-year history of chronic diarrhoea, hypophosphataemia, palpitations and skin flushing. Raised VIP levels indicated presence of a VIPoma, however despite extensive investigation prior to pregnancy by neuroendocrine specialists, the tumour location remained unidentified. The patient delivered a healthy boy with the aid of forceps in theatre following an epidural top-up. Key features of management were a multidisciplinary approach, avoidance of triggers for VIP secretion, strict management of electrolytes and avoidance of severe changes in sympathetic tone during labour with epidural analgesia.

Interfacial spin-orbit torques.

Spin-orbit torques offer a promising mechanism for electrically controlling magnetization dynamics in nanoscale heterostructures. While spin-orbit torques occur predominately at interfaces, the physical mechanisms underlying these torques can originate in both the bulk layers and at interfaces. Classifying spin-orbit torques based on the region that they originate in provides clues as to how to optimize the effect. While most bulk spin-orbit torque contributions are well studied, many of the interfacial contributions allowed by symmetry have yet to be fully explored theoretically and experimentally. To facilitate progress, we review interfacial spin-orbit torques from a semiclassical viewpoint and relate these contributions to recent experimental results. Within the same model, we show the relationship between different interface transport parameters. For charges and spins flowing perpendicular to the interface, interfacial spin-orbit coupling both modifies the mixing conductance of magnetoelectronic circuit theory and gives rise to spin memory loss. For in-plane electric fields, interfacial spin-orbit coupling gives rise to torques described by spin-orbit filtering, spin swapping and precession. In addition, these same interfacial processes generate spin currents that flow into the non-magnetic layer. For in-plane electric fields in trilayer structures, the spin currents generated at the interface between one ferromagnetic layer and the non-magnetic spacer layer can propagate through the non-magnetic layer to produce novel torques on the other ferromagnetic layer.

Interface-Generated Spin Currents.

Transport calculations based on ab initio band structures reveal large interface-generated spin currents at Co/Pt, Co/Cu, and Pt/Cu interfaces. These spin currents are driven by in-plane electric fields but flow out of plane and can have similar strengths to spin currents generated by the spin Hall effect in bulk Pt. Each interface generates spin currents with polarization along z[over ^]×E, where z[over ^] is the interface normal and E denotes the electric field. The Co/Cu and Co/Pt interfaces additionally generate spin currents with polarization along m[over ^]×(z[over ^]×E), where m[over ^] gives the magnetization direction of Co. The latter spin polarization is controlled by-but not aligned with-the magnetization, providing a novel mechanism for generating spin torques in magnetic trilayers.

Effects of dopamine receptor antagonist antipsychotic therapy on blood pressure.

WHAT IS KNOWN AND OBJECTIVE: Hypertension, a major risk factor for adverse cardiovascular events, such as stroke and myocardial infarction, affects 80 million American adults. The aetiology of hypertension is multifaceted and difficult to identify. Dopamine receptors, especially those in the kidneys, play a role in blood pressure regulation, and alterations in their function can cause hypertension. The objective of this review was to investigate the association between the use of dopamine antagonists with hypertension focusing especially on second-generation antipsychotics, like clozapine that is D4 receptor antagonist. METHODS: A literature review was conducted using MEDLINE, Ovid, Science Direct, Web of Science and Cochrane Database of Systematic Reviews databases with keywords:hypertension, hypotension, renin-angiotensin-aldosterone system, dopaminergic receptors, blood pressure, antipsychotics. Inclusion criteria were human or animal studies, systematic reviews, meta-analyses, randomized controlled trials, case report/series, published in selected for inclusion. RESULTS AND DISCUSSION: All 5 dopamine receptor subtypes (ie D1, D2, D3, D4 and D5) regulate sodium excretion and BP. The D1, D3 and D4 receptors interact directly with the renin-angiotensin-aldosterone system, whereas D2 and D5 receptors directly interact with the sympathetic nervous system to regulate BP. Use of dopaminergic agonists or antagonists could therefore disturb the regulation of BP by dopamine receptors. WHAT IS NEW AND CONCLUSION: Based upon this review, individuals on antipsychotic agents, particularly clozapine, should be routinely monitored for hypertension, and addition of antihypertensive agents such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) is indicated if hypertension occurs.

Anti-TNF therapy is not associated with an increased risk of post-colectomy complications, a population-based study.

AIM: Previous studies have raised concerns that the use of anti-tumour necrosis factor (anti-TNF) therapy in patients with ulcerative colitis (UC) undergoing surgery may increase the risk of postoperative complications. We have taken a population-based approach to investigate whether there is an association between anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. METHOD: Hospital Episode Statistics (HES) data and procedural coding were used to identify all patients in England between April 2006 and March 2015 undergoing subtotal colectomy for UC. Patients were grouped into those who received anti-TNF therapy within 12 or 4 weeks of surgery and those who did not. The incidence of postoperative complications was evaluated by HES coding and compared between groups. RESULTS: In all, 6225 UC patients underwent subtotal colectomy. 753 patients received anti-TNF therapy within 12 weeks prior to surgery (418 within 4 weeks). There was no difference in postoperative complications between groups although groups were not comparable for age and comorbidities. Logistic regression with complications as the outcome variable did not show any significant association between anti-TNF therapy and complications. Colectomy performed during an unplanned admission (vs planned admission) and smoking were associated with complications. CONCLUSION: This large population-based study does not demonstrate any association between preoperative anti-TNF therapy and postoperative complications in UC patients undergoing subtotal colectomy. The only variables associated with complications were colectomy performed during an unplanned admission and smoking.

Evaluation of FLT-PET-CT as an imaging biomarker of proliferation in primary breast cancer.

BACKGROUND: [(18)F]fluorothymidine (FLT) has been proposed as a positron emission tomography (PET)-imaging biomarker of proliferation for breast cancer. The aim of this prospective study was to assess the feasibility of FLT-PET-CT as a technique for predicting the response to neoadjuvant chemotherapy (NAC) in primary breast cancer and to compare baseline FLT with Ki-67. METHODS: Twenty women with primary breast cancer had a baseline FLT-PET-CT scan that was repeated before the second cycle of chemotherapy. Expression of Ki-67 in the diagnostic biopsy was quantified. From the FLT-PET-CT scans lesion maximum and mean standardised uptake values (SUVmax, SUVmean) were calculated. RESULTS: Mean baseline SUVmax was 7.3, and 4.62 post one cycle of NAC, representing a drop of 2.68 (36.3%). There was no significant association between baseline, post chemotherapy, or change in SUVmax and pathological response to NAC. There was a significant correlation between pre-chemotherapy Ki-67 and SUVmax of 0.604 (P=0.006). CONCLUSIONS: Baseline SUVmax measurements of FLT-PET-CT were significantly related to Ki-67 suggesting that it is a proliferation biomarker. However, in this series neither the baseline value nor the change in SUVmax after one cycle of NAC were able to predict response as most patients had a sizeable SUVmax reduction.

Experimental demonstration of scanned spin-precession microscopy.

We present a new tool for imaging spin properties. We show that a spatially averaged spin signal, measured as a function of a scanned magnetic probe's position, contains information about the local spin properties. In this first demonstration we map the injected spin density in GaAs by measuring spin photoluminescence with a resolution of 1.2 µm. The ultimate limit of the technique is set by the gradient of the probe's field, allowing for a resolution beyond the optical diffraction limit. Such probes can also be integrated with other detection methods. This generality allows the technique to be extended to buried interfaces and optically inactive materials.

Potential femoral head osteonecrosis model induced by high-intensity focused ultrasound.

Osteonecrosis of the femoral head is a common disease that can result in complex hip replacement. To evaluate potential treatments, a model that consistently creates osteonecrosis is needed. We studied and demonstrated the possibility of developing an osteonecrosis model using high-intensity focused ultrasound (HIFU) on canine femora in vitro. To achieve these goals, the temperature in the medullary cavity of the femoral head was measured. A phenomenological model was developed to fit the measured temperature variations with the HIFU parameters for similar HIFU experiments on femoral heads. The average temperature discrepancy between model and measured values was less than 0.83°C. Histology confirmed that the temperature in the medullary cavity can be elevated to a level at which an acute thermal injury is created. HIFU has the potential to be used in a non-invasive model of osteonecrosis.

Detection of electrically modulated inverse spin hall effect in an Fe/GaAs microdevice.

We report the detection of the inverse spin Hall effect (ISHE) in n-gallium arsenide (n-GaAs) combined with electrical injection and modulation of the spin current. We use epitaxial ultrathin-Fe/GaAs injection contacts with strong in-plane magnetic anisotropy. This allows us to simultaneously perform Hanle spin-precession measurements on an Fe detection electrode and ISHE measurements in an applied in-plane hard-axis magnetic field. In this geometry, we can experimentally separate the ordinary from the spin-Hall signals. Electrical spin injection and detection are combined in our microdevice with an applied electrical drift current to modulate the spin distribution and spin current in the channel. The magnitudes and external field dependencies of the signals are quantitatively modeled by solving drift-diffusion and Hall-cross response equations.

Allelic imbalance in Drosophila hybrid heads: exons, isoforms, and evolution.

Unraveling how regulatory divergence contributes to species differences and adaptation requires identifying functional variants from among millions of genetic differences. Analysis of allelic imbalance (AI) reveals functional genetic differences in cis regulation and has demonstrated differences in cis regulation within and between species. Regulatory mechanisms are often highly conserved, yet differences between species in gene expression are extensive. What evolutionary forces explain widespread divergence in cis regulation? AI was assessed in Drosophila melanogaster-Drosophila simulans hybrid female heads using RNA-seq technology. Mapping bias was virtually eliminated by using genotype-specific references. Allele representation in DNA sequencing was used as a prior in a novel Bayesian model for the estimation of AI in RNA. Cis regulatory divergence was common in the organs and tissues of the head with 41% of genes analyzed showing significant AI. Using existing population genomic data, the relationship between AI and patterns of sequence evolution was examined. Evidence of positive selection was found in 30% of cis regulatory divergent genes. Genes involved in defense, RNAi/RISC complex genes, and those that are sex regulated are enriched among adaptively evolving cis regulatory divergent genes. For genes in these groups, adaptive evolution may play a role in regulatory divergence between species. However, there is no evidence that adaptive evolution drives most of the cis regulatory divergence that is observed. The majority of genes showed patterns consistent with stabilizing selection and neutral evolutionary processes.

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study.

PURPOSE: We have previously found that ≤ 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. PATIENTS AND METHODS: Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. RESULTS: Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p<.0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p≤.0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p<.001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p≤.02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p<.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p≤.005), heart (p≤.003), and liver (p≤.04). CONCLUSIONS: Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution.

Size-fractionated heparins have differential effects on human neutrophil function in vitro.

BACKGROUND AND PURPOSE: Heparin is known to possess a range of activities, other than effects on blood coagulation, many of which are anti-inflammatory. Effects with potential anti-inflammatory applications include the inhibition of elastase release from neutrophils, as well as the adhesion of these cells to vascular endothelium. In the present study we aimed to investigate whether fractionation of heparin may yield molecules with enhanced or specific effects on human neutrophil function. EXPERIMENTAL APPROACH: Fractions of defined molecular size were obtained from heparin by different methods and assessed for their effects on elastase release induced by formyl Met-Leu-Phe (fMLP), from neutrophils, in some cases following the priming of these cells with tumour necrosis factor-alpha (TNF-alpha). Effects of the fractions on neutrophil adhesion to interleukin-1beta (IL-beta)-stimulated human umbilical vein endothelial cells (HUVECs) were also examined. KEY RESULTS: Elastase release was inhibited by very low molecular weight fractions of heparin, with an apparent minimum chain length of 10 saccharides required for full effect. In contrast, neutrophil-endothelial adhesion was unaffected by these fractionated heparins, suggesting that certain non-anticoagulant actions of heparin may be lost by such an approach. CONCLUSIONS AND IMPLICATIONS: These data suggest that an optimum chain length of heparin possibly exists for certain non-anticoagulant actions of heparin, which may prove to be useful in the design of novel drugs with specific anti-inflammatory actions.

[Anti-leukotoxin antibodies against Actinobacillus actinomycetemcomitans in serum and saliva samples from patients with localized juvenile periodontitis]. / Anticorpos antileucotoxina contra Actinobacillus actinomycetemcomitans em amostras de soro e saliva de pacientes com periodontite juvenil localizada.

The leukotoxin produced by Actinobacillus actinomycetemcomitans is considered the major virulence factor with potential to cause damage to the host defenses. The present work analyzed the serumal and salivary levels of antibodies against the leukotoxin produced by A. Actinomycetemcomitans, in patients with Localized Juvenile Periodontitis (LJP) and in healthy controls. Additionally, analysis of the immune complex (IC) was carried out in saliva samples. The classic ELISA method, with leukotoxin obtained through Sephadex G-200 gel filtration, and the capture ELISA method, using rabbit anti-A. Actinomycetemcomitans (leukotoxic, FDC Y4, IgG) adsorbed with a non-leukotoxic strain of A. actinomycetemcomitans, were used. The results obtained demonstrated significantly higher serumal levels of IgG in patients with LJP, when they were compared with the healthy controls, both for the classic and capture ELISA methods (p < 0.05). However, no significant differences were observed between the salivary levels of IgG, SIgA and IC in the examined individuals. These results suggest that even though A. actinomycetemcomitans presents virulence factors that affect the immune response, there is immune response to leukotoxin in LJP patients. This increase of IgG in the blood stream might contribute to host defense, limiting the lesion to the periodontal regions already colonized by A. actinomycetemcomitans.

Predicting percentage of intramuscular fat using two types of real-time ultrasound equipment.

In the present study, 500 steers were used to develop models for predicting the percentage of intramuscular fat (PIMF) in live beef cattle. Before slaughter, steers were scanned across the 11th and 13th ribs using Aloka 500V (AL-500) and Classic Scanner 200 (CS-200) machines. Four to five images were collected per individual steer using each machine. After slaughter, a cross-sectional slice of the longissimus muscle from the 12th rib facing was used for chemical extraction to determine actual carcass percentage of intramuscular fat (CPIMF). Texture analysis software was used by two interpreters to select a region for determination of image parameters, which included Fourier, gradient, histogram, and co-occurrence parameters. Four prediction models were developed separately for each of AL-500 and CS-200 based on images captured by the respective machines. These included models developed without transformation of CPIMF (Model I), models based on logarithmic transformation of CPIMF (Model II), ridge regression procedure (Model III), and principal component regression procedure (Model IV). Model R2 and root mean square error of AL-500 Models I, II, III, and IV were 0.72, 0.84%; 0.72, 0.85%; 0.69, 0.91%; and 0.71, 0.86%; respectively. The corresponding R2 and root mean square error values of CS-200 Models I, II, III, and IV were 0.68, 0.87%; 0.70, 0.85%; 0.64, 0.94%; and 0.65, 0.91%; respectively. Initially, AL-500 and CS-200 prediction models were validated separately on an independent data set from 71 feedlot steers. The overall mean bias, standard error of prediction, and rank correlation coefficient across the four AL-500 models were 0.42%, 0.84%, and 0.88, respectively. For the four CS-200 models, the corresponding overall mean values were 0.67%, 0.81%, and 0.91, respectively. In a second validation test, only Model II of AL-500 and CS-200 was evaluated separately based on data from 24 feedlot steers. The overall mean bias, absolute difference, and standard error of prediction of AL-500 Model II were 0.71, 0.92, and 0.98%. For CS-200 Model II, the corresponding values were 0.59, 0.97, and 1.03%. Both AL-500 and CS-200 equipment can be used to accurately predict PIMF in live cattle. Further improvement in the accuracy of prediction equations could be achieved through increasing the development data set and the variation in PIMF of cattle used.

Changes in myocardial protein expression in pacing-induced canine heart failure.

Canine rapid ventricular pacing produces a low output cardiomyopathic state which is similar to dilated cardiomyopathy. In this study dogs were paced at 245 beats per minute (bpm) for 3-4 weeks until signs of heart failure were apparent. Unpaced dogs were used as controls. A previous study identified myocardial protein changes in the pH region 4-7 following ventricular pacing by using two-dimensional electrophoresis (2-DE) (Heinke et al., Electrophoresis 1998 19, 2021-2030). Many of these proteins were associated with mitochondria, energy metabolism within the cardiomyocyte, the cytoskeleton and calcium cycling. The present study aimed to examine the proteins migrating in the more basic region of the 2-DE pattern using immobilised pH gradient 3-10 strips to separate myocardial proteins. The expression of 31 proteins was altered in the paced myocardium: 21 were decreased and 10 increased. Following the identification of 23 of these spots by either amino acid compositional analysis or peptide mass fingerprinting or a combination of both, we confirm that many of the proteins whose expression is altered following ventricular pacing are associated with the mitochondria and energy production within the cardiomyocyte, including creatine kinase M, triosephosphate isomerase, phosphoglycerate mutase, cytochrome c oxidase, cytochrome b5, hydroxymethyl glutaryl CoA synthase, myoglobin, and 3,2-trans-enoyl-CoA transferase. Additionally, the cytoskeletal protein actin was increased in the paced hearts. These results strongly support the notion that energy production is impaired and mitochondrial dysfunction is involved in the development of heart failure in the paced dog.

Repeatability of ultrasound-predicted percentage of intramuscular fat in feedlot cattle.

We used data from 144 bulls, heifers, and steers to determine the repeatability of ultrasound-predicted percentage of intramuscular fat and to study the effect of repeated measurements on the standard error of prediction. Animals were scanned at an average age of 433 d by a certified technician. Individual bulls, heifers, and steers were scanned five to six times each with two Aloka 500-V machines, and the percentage of intramuscular fat was predicted from two regions of interest within an image. Variance components and repeatability values were computed for the overall data and by machine, region of interest, and sex. Animals were broadly divided into two groups based on mean ultrasound-predicted percentage of intramuscular fat. Variance components and repeatability values were then estimated within each group. The overall repeatability of ultrasound-predicted percentage of intramuscular fat was .63 +/- .03. Differences in the repeatability values between machines and between regions of interest were not different from zero (P > .05). Bulls showed a lower within-animal SD of .82% as compared to .97 and 1.02% for steers and heifers, respectively. However, steer ultrasound-predicted percentage of intramuscular fat measures were more repeatable (P < .05) than those of bulls and heifers. The difference in repeatability between bull and heifer measures was not important (P > .05). Animals with mean ultrasound-predicted percentage of intramuscular fat less than 4.79% showed less repeatable measures (P < .05) than those with means above 4.79%. The image variance contributed to nearly 70% of the total variance of observations within an animal. Standard error of animal mean measures showed a 50% reduction when the number of images per animal increased to four. Therefore, we concluded that increasing the number of images per animal plays a more significant role in reducing the standard error of prediction than taking multiple measurements within a single image.

The myosin ATPase inhibitor 2,3-butanedione-2-monoxime (BDM) inhibits tip growth and cytokinesis in the fission yeast, Schizosaccharomyces pombe.

The growth of fission yeast cultures was reversibly inhibited by exposure to the myosin-ATPase inhibitor 2,3-butanedione-2-monoxime (BDM). Wild-type cells treated with 20 mM BDM for approximately two generation times were smaller than untreated controls and had a septation index approximately twice that seen in the absence of the inhibitor. The organization of actin at the cell poles was somewhat disorganized in the presence of BDM; however, cells formed a cytokinetic actin ring. When nitrogen-starved stationary-phase cells were reinoculated into fresh medium in the presence of BDM, the time taken to repolarize the actin cytoskeleton and to resume the characteristic vegetative cell shape before initiation of the first cell division were both substantially delayed. BDM significantly inhibited the increase in cell length of cdc25.22 cells arrested for cell cycle progress by incubation at the restrictive temperature and substantially delayed the initiation of both mitosis and cytokinesis in arrested cdc25.22 cells after release of the temperature block. These results suggest that tip growth and cytokinesis--processes in fission yeast that involve the actin cytoskeleton--also require myosin activity.

Antibodies to heat-shock protein 27 are associated with improved survival in patients with breast cancer.

The overexpression of the heat-shock proteins hsp90, hsp70 and hsp27 in human mammary carcinomas has previously been shown to correlate with reduced overall survival. Moreover, antibodies to hsp90 were detectable in the serum of a large proportion of breast cancer patients but they were not found in normal controls. High antibody levels also correlated with reduced survival. Here, we show that antibodies to hsp27 were also detectable in the sera from breast cancer patients but not from normal controls, whereas antibodies to hsp70 were detectable in approximately one-third of both groups. The presence of antibodies to hsp27 was correlated with an improved rather than a reduced survival, particularly beyond the first 5 years. Hence, the overexpression of hsps in breast cancer cells does not provoke a generalized immune response to all the hsps. Moreover, the presence of antibodies to different hsps has distinct associations with survival. These effects are discussed in terms of the mechanisms that provoke an immune response to the hsps and the protective/non-protective effects of such a response.

Ultrasound image texture analysis for characterizing intramuscular fat content of live beef cattle.

The primary factors in determining beef quality grades are the amount and distribution of intramuscular fat percentage (IMFAT). Texture analysis was applied to ultrasound B-mode images from ribeye muscle of live beef cattle to predict its IMFAT. We used wavelet transform (WT) for multiresolutional texture analysis and second-order statistics using a gray-level co-occurrence matrix (GLCM) technique. Sets of WT- and GLCM-based texture features were calculated from ultrasonic images from 207 animals and linear regression methods were used for IMFAT prediction. WT-based features included energy ratios, central moments of wavelet-decomposed subimages and wavelet edge density. The regression model using WT features provided a root mean square error (RMSE) of 1.44 for prediction of IMFAT using validation images, while that of GLCM features provided an RMSE of 1.90. The prediction models using the WT features showed potential for objective quality evaluation in the live animals.

Organic anion transporting polypeptide mediates organic anion/HCO3- exchange.

Organic anion transporting polypeptide (oatp) is an integral membrane protein cloned from rat liver that mediates Na+-independent transport of organic anions such as sulfobromophthalein and taurocholic acid. Previous studies in rat hepatocytes suggested that organic anion uptake is associated with base exchange. To better characterize the mechanism of oatp-mediated organic anion uptake, we examined transport of taurocholate in a HeLa cell line stably transfected with oatp under the regulation of a zinc-inducible promoter (Shi, X., Bai, S., Ford, A. C., Burk, R. D., Jacquemin, E., Hagenbuch, B., Meier, P. J., and Wolkoff, A. W. (1995) J. Biol. Chem. 270, 25591-25595). Whereas noninduced transfected cells showed virtually no uptake of [3H]taurocholate, taurocholate uptake by induced cells was Na+-independent and saturable (Km = 19.4 +/- 3.3 microM; Vmax = 62.2 +/- 1.4 pmol/min/mg protein; n = 3). To test whether organic anion transport is coupled to HCO3- extrusion, we compared the rates of taurocholate-dependent HCO3- efflux from alkali-loaded noninduced and induced cells. Monolayers grown on glass coverslips were loaded with the pH-sensitive dye 2', 7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; intracellular pH (pHi) was measured by excitation ratio fluorometry. Noninduced and induced cells were alkalinized to an equivalent pHi ( approximately 7.7) by transient exposure to a 50 mM HCO3-, Cl--free solution. In the absence of extracellular Cl- and taurocholate, isohydric reduction of superfusate HCO3- concentration from 50 to 25 mM resulted in an insignificant change in pHi over time (dpHi/dt) in both groups. Addition of 25 microM taurocholate to the superfusate led to a rapid fall in pHi in induced (-0.037 +/- 0.011 pH units/min to pHi of 7.41 +/- 0.14) but not in noninduced (0.003 +/- 0.006 pH units/min to pHi of 7.61 +/- 0.08) cells (p < 0.03). These data indicate that oatp-mediated taurocholate transport is Na+-independent, saturable, and accompanied by HCO3- exchange. We conclude that organic anion/base exchange is an important, potentially regulatable component of oatp function.