ST-segment analysis of the fetal electrocardiogram improves fetal heart rate tracing interpretation and clinical decision making.

INTRODUCTION: Since its introduction into clinical use, the efficacy of electronic fetal heart rate (FHR) monitoring (EFM) has been questionable. This has been due partly to the marked variation in interpretation of the FHR pattern and subsequent decisions for obstetric intervention, (e.g., the need for prompt delivery). Current application of EFM is limited to the assessment of FHR patterns and uterine contractions. Recent development of higher-order FHR analysis has yielded monitoring systems that can add automated fetal electrocardiographic ST segment analysis to the standard FHR and uterine contraction information. Our goal was to evaluate the effect of adding ST segment analysis to standard FHR information on observer agreement for clinical decision making. METHODS: Seven practitioners who were trained and experienced in combined FHR and ST monitoring reviewed 51 fetal monitor tracings, ranging from 2 to 4 h in length. Reviews were conducted in two sessions and at different times. The first session presented only the FHR and uterine contraction information, following which the participants determined the time at which intervention (decision for operative vaginal or Cesarean section delivery) was indicated. In the second session, the participants were provided with a randomized sequence of the same tracings with the addition of ST segment information, as produced by the STAN monitor system (Neoventa Medical, Gothenburg, Sweden). Observer agreement was based on the proportion of participants who agreed on the need for an intervention, and the per cent agreement on the timing of the intervention within 20 min before or after the median time of intervention. RESULTS: Of the 51 cases included in this study there were ten fetuses with umbilical artery (UA) pH between 7.05 and 7.14, and nine with UA pH of < 7.05. Observer agreement increased significantly for required intervention when the ST segment information was available for tracing analysis as compared with review of the standard tracing alone (0.96 vs. 0.80, p < 0.05) and the timing of intervention (0.92 vs. 0.66, respectively, p < 0.05). Similarly, correct identification for needed interventions on fetuses with abnormal outcomes increased from 86 to 93% while unneeded interventions on normal fetuses decreased from 43 to 6%. CONCLUSION: The addition of ST analysis to standard FHR monitoring improves observer consistency in both the decision for and timing of obstetric interventions. The incorporation of ST segment data with the standard FHR tracing may reduce the number of unneeded obstetric interventions when fetal compromise is absent.

Cloning and functional expression of ATA1, a subtype of amino acid transporter A, from human placenta.

This report describes the primary structure and functional characteristics of human ATA1, a subtype of the amino acid transport system A. The human ATA1 cDNA was isolated from a placental cDNA library. The cDNA codes for a protein of 487 amino acids with 11 putative transmembrane domains. The transporter mRNA ( approximately 9.0 kb) is expressed most prominently in the placenta and heart, but detectable level of expression is evident in other tissues including the brain. When expressed heterologously in mammalian cells, the cloned transporter mediates Na(+)-coupled transport of the system A-specific model substrate alpha-(methylamino)isobutyric acid. The transport process is saturable with a Michaelis-Menten constant of 0. 89 +/- 0.12 mM. The Na(+):amino acid stoichiometry is 1:1 as deduced from the Na(+)-activation kinetics. The transporter is specific for small short-chain neutral amino acids. The gene for the transporter is located on human chromosome 12.

Cesarean delivery for suspected fetal distress among preterm parturients.

OBJECTIVE: Among preterm parturients (< 37 weeks) who underwent cesarean delivery for suspected fetal distress, to determine the factors associated with decision-incision time (DIT) of < or = 30 minutes and to assess if umbilical arterial pH < 7.10 is more common with DIT < or = 30 or > 30 minutes. STUDY DESIGN: The peripartum course of all patients who had cesareans for suspected fetal distress over three years was reviewed. The inclusion criteria were reliable gestational age < 37 weeks and a single indication for cesarean delivery, suspected fetal distress. Twenty antepartum and intrapartum factors were used in a univariate analysis. RESULTS: The mean DIT among the 84 parturients was 30.5 +/- 21.2 minutes, and 63% of patients had surgery started within 30 minutes. The incidence of pH < 7.10 was 20%. Multivariate analysis indicated that the two factors significantly associated with prolonged time to surgery were tachycardia with decreased variability (odds ratio [OR] 5.9, 95% confidence interval [CI] 1.6-21.6) and use of spinal anesthesia (OR 6.2, 95% CI 1.1-35.0). Though none of the 20 variables had significant univariate associations with neonatal acidosis at alpha = .05, those with P < .20 were considered in multiple logistic regression analysis. None of the 20 factors were associated with pH < 7.10, including DIT of > or = 30 minutes (OR 0.26, 95% CI 0.06-1.03). CONCLUSION: DIT is likely to be > 30 minutes if cesarean delivery is due to decreased fetal heart variability or if spinal anesthesia is utilized; neonatal acidosis, however, is not significantly associated with a prolonged interval.

Differential influence of the 4F2 heavy chain and the protein related to b(0,+) amino acid transport on substrate affinity of the heteromeric b(0,+) amino acid transporter.

We provide evidence here that b(0,+) amino acid transporter (b(0, +)AT) interacts with 4F2 heavy chain (4F2hc) as well as with the protein related to b(0,+) amino acid transporter (rBAT) to constitute functionally competent b(0,+)-like amino acid transport systems. This evidence has been obtained by co-expression of b(0, +)AT and 4F2hc or b(0,+)AT and rBAT in human retinal pigment epithelial cells and in COS-1 cells. The ability to interact with 4F2hc and rBAT is demonstrable with mouse b(0,+)AT as well as with human b(0,+)AT. Even though both the 4F2hc x b(0,+)AT complex and the rBAT x b(0,+)AT complex exhibit substrate specificity that is characteristic of system b(0,+), these two complexes differ significantly in substrate affinity. The 4F2hc x b(0,+)AT complex has higher substrate affinity than the rBAT x b(0,+)AT complex. In situ hybridization studies demonstrate that the regional distribution pattern of mRNA in the kidney is identical for b(0,+)AT and 4F2hc. The pattern of rBAT mRNA expression is different from that of b(0,+)AT mRNA and 4F2hc mRNA, but there are regions in the kidney where b(0,+)AT mRNA expression overlaps with rBAT mRNA expression as well as with 4F2hc mRNA expression.

Structure, function, and genomic organization of human Na(+)-dependent high-affinity dicarboxylate transporter.

We have cloned and functionally characterized the human Na(+)-dependent high-affinity dicarboxylate transporter (hNaDC3) from placenta. The hNaDC3 cDNA codes for a protein of 602 amino acids with 12 transmembrane domains. When expressed in mammalian cells, the cloned transporter mediates the transport of succinate in the presence of Na(+) [concentration of substrate necessary for half-maximal transport (K(t)) for succinate = 20+/-1 microM]. Dimethylsuccinate also interacts with hNaDC3. The Na(+)-to-succinate stoichiometry is 3:1 and concentration of Na(+) necessary for half-maximal transport (K(Na(+))(0.5)) is 49+/-1 mM as determined by uptake studies with radiolabeled succinate. When expressed in Xenopus laevis oocytes, hNaDC3 induces Na(+)-dependent inward currents in the presence of succinate and dimethylsuccinate. At a membrane potential of -50 mV, K(Suc)(0.5) is 102+/-20 microM and K(Na(+))(0.5) is 22+/-4 mM as determined by the electrophysiological approach. Simultaneous measurements of succinate-evoked charge transfer and radiolabeled succinate uptake in hNaDC3-expressing oocytes indicate a charge-to-succinate ratio of 1:1 for the transport process, suggesting a Na(+)-to-succinate stoichiometry of 3:1. pH titration of citrate-induced currents shows that hNaDC3 accepts preferentially the divalent anionic form of citrate as a substrate. Li(+) inhibits succinate-induced currents in the presence of Na(+). Functional analysis of rat-human and human-rat NaDC3 chimeric transporters indicates that the catalytic domain of the transporter lies in the carboxy-terminal half of the protein. The human NaDC3 gene is located on chromosome 20q12-13.1, as evidenced by fluorescent in situ hybridization. The gene is >80 kbp long and consists of 13 exons and 12 introns.

Electrogenic nature of rat sodium-dependent multivitamin transport.

We report on the electrogenic nature of the transport process mediated by the rat sodium-dependent multivitamin transporter. In Cos-7 cells, the relationship of Na(+) concentration versus biotin and pantothenate uptake rate was sigmoidal with a Na(+):substrate stoichiometry of 2:1. In Cos-7 cells expressing rat SMVT biotin transport was significantly higher when the membrane was hyperpolarized and considerably reduced when the membrane was depolarized. Similarly, biotin uptake in X. laevis oocytes expressing rat SMVT was inhibited with depolarized oocyte membrane by altering the K(+) permeability across the membrane. It is concluded that the transport of biotin and pantothenate mediated by rat SMVT is electrogenic with a Na(+):substrate coupling ratio of 2:1 and that the transport process is associated with the transfer of one net positive charge across the membrane per transport cycle.

Sonographic measurements of fetal parts to predict pulmonary maturity among twins and singletons.

To determine if sonographic examination of fetus can be readily utilized to predict a mature lecithin/sphingomyelin (L/S) ratio among twins and singletons. Twins (n = 36) undergoing amniocentesis for assessment of pulmonary maturity were matched with singleton (1:2) for maternal demographics, gestational age (GA), and indications for procedure. At the time of amniocentesis, twins and singletons with mature L/S ratios differed significantly in mean GA (33.2 +/- 2.7 vs 34.5 +/- 4.6 wks, p = 0.01), biparietal diameter (BPD), abdominal circumference (AC), femur length (FL) and estimate of birth weight (EFW). Based on ten receiver operating characteristics curves constructed, the following diagnostic thresholds predicted a mature L/S ratio with a true positive rate of 100% among twins and singletons, respectively: 1) BPD $84 and $92 mm; 2) head circumference $315 and $320 mm; 3) AC $295 and $350 mm; or 4) FL $64 and $72 mm; or 5) EFW $2400 and $3200 g. Using any one of these five criteria correctly identified pulmonary maturity among 59% of twins and 28% of singletons (p = 0.001). Sonographic measurement of fetal parts or EFW may be a noninvasive method to predict a mature L/S ration among twins as well as singletons.

Cloning and functional characterization of a Na(+)-independent, broad-specific neutral amino acid transporter from mammalian intestine.

We have isolated a cDNA from a rabbit intestinal cDNA library which, when co-expressed with the heavy chain of the human 4F2 antigen (4F2hc) in mammalian cells, induces system L-like amino acid transport activity. This protein, called LAT2, consists of 535 amino acids and is distinct from LAT1 which also interacts with 4F2hc to induce system L-like amino acid transport activity. LAT2 does not interact with rBAT, a protein with a significant structural similarity to 4F2hc. The 4F2hc/LAT2-mediated transport process differs from the 4F2hc/LAT1-mediated transport in substrate specificity, substrate affinity, tissue distribution, interaction with D-amino acids, and pH-dependence. The 4F2hc/LAT2-associated transport process has a broad specificity towards neutral amino acids with K(t) values in the range of 100-1000 microM, does not interact with D-amino acids to any significant extent, and is stimulated by acidic pH. In contrast, the 4F2hc/LAT1-associated transport process has a narrower specificity towards neutral amino acids, but with comparatively higher affinity (K(t) values in the range of 10-20 microM), interacts with some D-amino acids with high affinity, and is not influenced by pH. LAT2 is expressed primarily in the small intestine and kidney, whereas LAT1 exhibits a much broader tissue distribution.

Managing nonreassuring fetal heart rate patterns before cesarean delivery. Compliance with ACOG recommendations.

OBJECTIVE: To determine the rate of compliance with current American College of Obstetricians and Gynecologists (ACOG) recommendations for management of parturients undergoing cesarean delivery for persistent nonreassuring fetal heart rate (FHR) tracings. STUDY DESIGN: We performed a retrospective chart review (July 1995-June 1998) of all parturients who underwent cesarean delivery for nonreassuring FHR tracings. Outcome measures included maneuvers for fetal assessment (scalp stimulation or scalp blood pH) and therapeutic interventions (tocolytic agents for reducing uterine activity or amnioinfusion). Patients with multiple gestations and cesarean delivery for other indications were excluded. Student's t test, chi 2 and Fisher's exact tests were used; odds ratio and 95% confidence interval were calculated. P < .05 was considered significant. RESULTS: Cesarean delivery for persistent nonreassuring FHR patterns included 134 (3.6%) of the 3,671 deliveries during three years. Thirty patients produced intrapartum FHR tracings containing persistent variable decelerations; 12 (40%) of these patients received amnioinfusion. In only 37% (50/134) of cases was there a documented attempt at scalp or acoustic stimulation prior to delivery. Scalp pH was obtained in 15% (15/98) of patients whose cervix was at least 3 cm dilated. Tocolytic agents were used for intrauterine resuscitation in 25% (34/134) of cases; their use varied significantly (P = .006) with the type of FHR abnormality. CONCLUSION: At our tertiary center, ACOG recommendations for management of nonreassuring intrapartum FHR tracings were used in a limited number of cases.

Nonstress testing and contraction stress testing.

Antepartum fetal heart rate (FHR) testing, including the nonstress test and contraction stress test, has evolved in clinical usage over the past 3 decades. Although the nonstress test has become a standard of care in high-risk pregnancy, it has been modified by the use of fetal stimulation (vibroacoustic stimulation) and the addition of automated fetal movement recording (actocardiotocography). In all of its formats, antepartum FHR testing has been associated with reduction of preventable fetal loss. More recently, there have been attempts to improve test efficacy by computer-enhanced approaches.

Perinatal outcome and amniotic fluid index in the antepartum and intrapartum periods: A meta-analysis.

OBJECTIVE: Our purpose was to perform a meta-analysis of studies on the risks of cesarean delivery for fetal distress, 5-minute Apgar score <7, and umbilical arterial pH <7.00 in patients with antepartum or intrapartum amniotic fluid index >5.0 or <5.0 cm. STUDY DESIGN: Using a MEDLINE search, we reviewed all studies published between 1987 and 1997 that correlated antepartum or intrapartum amniotic fluid index with adverse peripartum outcomes. The inclusion criteria were studies in English that associated at least one of the selected adverse outcomes with an amniotic fluid index of 5.0 cm. Contingency tables were constructed for each study, and relative risks and standard errors of their logs were calculated. Fixed-effects pooled relative risks were calculated for groups of studies that were homogeneous, whereas random-effects pooled relative risks were calculated for significantly heterogeneous groups of studies. RESULTS: Eighteen reports describing 10,551 patients met our inclusion criteria. An antepartum amniotic fluid index of 5.0 cm, is associated with an increased risk of cesarean delivery for fetal distress (pooled relative risk, 2.2; 95% confidence interval, 1.5-3.4) and an Apgar score of <7 at 5 minutes (pooled relative risk, 5.2; 95% confidence interval, 2.4-11.3). An intrapartum amniotic fluid index of

Human Na(+)-dependent vitamin C transporter 1 (hSVCT1): primary structure, functional characteristics and evidence for a non-functional splice variant.

We report here on the cloning and functional characterization of human Na(+)-dependent vitamin C transporter 1 (SVCT1). The human SVCT1 cDNA, obtained from a Caco2 cell cDNA library, encodes a protein of 598 amino acids with 12 putative transmembrane domains. The SVCT1-specific transcript, 2.4 kb in size, is expressed in kidney, liver, small intestine, thymus and prostate. When expressed heterologously in HRPE cells, SVCT1 mediates the transport of ascorbate, the reduced form of vitamin C, in a Na(+)-dependent manner. The transporter is specific for ascorbate with a K(t) of approximately 75 microM. The relationship between the cDNA-specific uptake rate of ascorbate and Na(+) concentration is sigmoidal with a Na(+):ascorbate stoichiometry of 2:1, indicating that the transport process is electrogenic. In Caco2 cells and in normal human intestine, SVCT1 also exists as a non-functional splice variant with a four amino acid sequence inserted between E-155 and V-156. The splice variant results from the use of a donor site 12 bp downstream of the normal donor site.

Cloning of the human thiamine transporter, a member of the folate transporter family.

We have isolated a cDNA from human placenta, which, when expressed heterologously in mammalian cells, mediates the transport of the water-soluble vitamin thiamine. The cDNA codes for a protein of 497 amino acids containing 12 putative transmembrane domains. Northern blot analysis indicates that this transporter is widely expressed in human tissues. When expressed in HeLa cells, the cDNA induces the transport of thiamine (K(t) = 2.5 +/- 0.6 microM) in a Na(+)-independent manner. The cDNA-mediated transport of thiamine is stimulated by an outwardly directed H(+) gradient. Substrate specificity assays indicate that the transporter is specific to thiamine. Even though thiamine is an organic cation, the cDNA-induced thiamine transport is not inhibited by other organic cations. Similarly, thiamine is not a substrate for the known members of mammalian organic cation transporter family. The thiamine transporter gene, located on human chromosome 1q24, consists of 6 exons and is most likely the gene defective in the metabolic disorder, thiamine-responsive megaloblastic anemia. At the level of amino acid sequence, the thiamine transporter is most closely related to the reduced-folate transporter and thus represents the second member of the folate transporter family.

Cloning and expression of a b(0,+)-like amino acid transporter functioning as a heterodimer with 4F2hc instead of rBAT. A new candidate gene for cystinuria.

We have cloned a transporter protein from rabbit small intestine, which, when coexpressed with the 4F2 heavy chain (4F2hc) in mammalian cells, induces a b(0,+)-like amino acid transport activity. This protein (4F2-lc6 for the sixth member of the 4F2 light chain family) consists of 487 amino acids and has 12 putative transmembrane domains. At the level of amino acid sequence, 4F2-lc6 shows significant homology (44% identity) to the other five known members of the 4F2 light chain family, namely LAT1 (4F2-lc1), y(+)LAT1 (4F2-lc2), y(+)LAT2 (4F2-lc3), xCT (4F2-lc4), and LAT2 (4F2-lc5). The 4F2hc/4F2-lc6 complex-mediated transport process is Na(+)-independent and exhibits high affinity for neutral and cationic amino acids and cystine. These characteristics are similar to those of the b(0,+)-like amino acid transport activity previously shown to be associated with rBAT (protein related to b(0,+) amino acid transport system). However, the newly cloned 4F2-lc6 does not interact with rBAT. This is the first report of the existence of a b(0,+)-like amino acid transport process that is independent of rBAT. 4F2-lc6 is expressed predominantly in the small intestine and kidney. Based on the characteristics of the transport process mediated by the 4F2hc/4F2-lc6 complex and the expression pattern of 4F2-lc6 in mammalian tissues, we suggest that 4F2-lc6 is a new candidate gene for cystinuria.

Fetal acoustic stimulation in early labor and pathological fetal acidemia: a preliminary report.

OBJECTIVE: To determine if a nonreactive response to fetal acoustic stimulation in early labor can predict a significantly higher risk of umbilical arterial pH <7.10 or <7.00. METHODS: Fetal acoustic stimulation was applied to the fetuses of term parturients (gestational age > or =37 weeks) with cervical dilation of < or =5 cm. The responses to stimulation were correlated with cesarean delivery for fetal distress and umbilical arterial pH. Student's t-test, Chi-square, and Fisher exact test were used; P < 0.05 was considered significant. Relative risks (RR) and 95% confidence intervals (CI) were calculated. RESULTS: The study population contained 271 subjects, of which 90% (244) had a reactive response following acoustic stimulation and 10% (27) a nonreactive response. The maternal demographics, time interval from stimulation to delivery (8.3 +/- 8.7 vs. 8.3 +/- 8.4 h; P = 1.00) were similar in the two groups. Compared to those with a reactive response, patients with a nonreactive response had a significantly greater risk for: 1) cesarean delivery for fetal distress (2.0% vs. 11.1%; P = 0.03, RR 4.1, 95% Cl 1.5, 60.5), 2) umbilical arterial pH <7.10 (2.0% vs. 14.8%; P = 0.007, RR 5.0, 95% CI 2.2, 11.6), and 3) umbilical arterial pH <7.00 (0.8% vs. 7%; P = 0.05, RR 5.0, 95% CI 1.8, 15.2). CONCLUSION: A nonreactive response to fetal acoustic stimulation in early labor is associated with a significantly increased risk for cesarean delivery for fetal distress and neonatal acidosis. This finding extends the potential value of acoustic stimulation as an intrapartum admission screening test.

Human placental sodium-dependent vitamin C transporter (SVCT2): molecular cloning and transport function.

We report here on the cloning and functional characterization of human SVCT2, a sodium-dependent vitamin C (ascorbate) transporter. The hSVCT2 cDNA obtained from a human placental choriocarcinoma cell cDNA library, codes for a protein of 650 amino acids with a predicted molecular mass of 70 kDa. At the level of amino acid sequence, the human SVCT2 exhibits 95% identity to its rat homolog. When functionally expressed in mammalian cells, hSVCT2 induces the transport of ascorbic acid. The transport process induced by hSVCT2 is Na(+)-dependent and is specific for ascorbate. The Michaelis-Menton constant (K(t)) for the transport of ascorbate in cDNA-transfected cells is 69 +/- 5 microM. The relationship between the cDNA-specific uptake rate of ascorbate and Na(+) concentration is sigmoidal with a Na(+):ascorbate stoichiometry of 2:1. Northern blot analysis shows that SVCT2-specific transcripts are present in heart, brain, placenta, and liver and is absent in lung and skeletal muscle. The size of the principal transcript is approximately 7.5 kb.

Cannabinoid receptors and their role in the regulation of the serotonin transporter in human placenta.

OBJECTIVE: We sought to investigate the expression of cannabinoid receptors in human placenta and BeWo choriocarcinoma cells and study their role in the regulation of the serotonin transporter. STUDY DESIGN: Expression of the 2 types of cannabinoid receptors (CB1 and CB2) in human placenta and BeWo cells was investigated by reverse transcriptase-polymerase chain reaction and Northern blot analysis. The involvement of the receptors in the regulation of the serotonin transporter expression was studied by using a cannabinoid receptor agonist (WIN 55212-2). BeWo cells were treated with the agonist in the presence or absence of forskolin, and the serotonin transporter activity was measured by assessing paroxetine-sensitive serotonin transport. Serotonin transporter density in cell membranes was monitored by measuring paroxetine-sensitive binding of RTI-55, a specific high-affinity ligand for the transporter. Agonist-induced changes in intracellular levels of cyclic adenosine monophosphate were also monitored. RESULTS: Reverse transcriptase-polymerase chain reaction and Northern blot analysis demonstrated unequivocally that human placenta and BeWo cells express both types of cannabinoid receptors. Treatment of BeWo cells with the receptor agonist blocked the activity of the constitutive, as well as the forskolin-induced, serotonin transporter without affecting the serotonin transporter density. This effect is not mediated by alterations in intracellular cyclic adenosine monophosphate levels. CONCLUSION: The results show that cannabinoid receptors are expressed in human placenta and BeWo cells and play a role in the regulation of the serotonin transporter activity. Human placenta is therefore a direct target for cannabinoids, and marijuana use during pregnancy is likely to affect the placental clearance of serotonin through the serotonin transporter.

Risk factors associated with blood transfusion in ectopic pregnancy.

OBJECTIVE: To determine the risk factors associated with blood transfusion in ectopic pregnancy. STUDY DESIGN: A retrospective chart review of the presentation and hospital course of ectopic pregnancies managed over five years at two hospitals was undertaken. Thirty-two variables, including demographics, presenting signs and symptoms, and intraoperative findings, were examined with univariate and multivariate logistic modeling. RESULTS: Among 185 patients with histologically confirmed ectopics who were managed surgically, 8.6% (16 women) required transfusion. Multivariate analysis of risk factors for blood transfusion demonstrated a statistically significant association with (1) initial hemoglobin < 10 g/dL (odds ratio [OR] 38.8, 95% confidence interval [CI] 6.0-356.8); (2) human chorionic gonadotropin levels > or = 6,500 mIU (OR 18.1, 95% CI 3.6-158.1); and (3) abnormal bleeding on presentation (OR 0.08, 95% CI 0.007-0.42). The presence of two of these factors had a sensitivity of 82% (95% CI 48-98%) and a positive predictive value of 33% (95% CI 16-54%). No case had all three factors. CONCLUSION: This study was, to our knowledge, the first regression analysis of risk factors for transfusion associated with ectopic pregnancy. It demonstrated that initial hemoglobin and human chorionic gonadotropin levels as well as abnormal bleeding on presentation are independent risk factors for blood transfusion in ectopic pregnancy.

Molecular and functional characterization of the intestinal Na+-dependent multivitamin transporter.

We have cloned a Na+-dependent multivitamin transporter from rabbit intestine (riSMVT). The cDNA codes for a protein of 636 amino acids with 12 putative transmembrane domains. When expressed in mammalian cells, the cDNA induces Na+-dependent uptake of the vitamins pantothenate and biotin. Lipoate is also a substrate for the cDNA-induced uptake process. The affinity constant for the cDNA-specific transport of pantothenate and biotin is approximately 2 and approximately 8 microM, respectively. The Na+:vitamin stoichiometry is greater than 1, indicating that the transport process is electrogenic. The SMVT-specific transcripts of 3.2 kbp are equally distributed throughout the small intestine. We have also cloned SMVT from the human intestinal cell line Caco-2. The Caco-2 SMVT cDNA codes for a protein of 635 amino acids which is homologous to riSMVT and is identical to the SMVT expressed in the human choriocarcinoma cell line JAR. Caco-2 SMVT also catalyzes Na+-dependent uptake of pantothenate, biotin, and lipoate. In oocytes expressing Caco-2 SMVT, all three vitamins evoke inward currents, confirming the electrogenicity of the transport process.