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Selenium (Se) is an essential element, but causes toxic effects in fish at a slightly elevated level beyond the threshold. However, the degree of Se toxicity differs depending on the chemical forms of Se (e.g., organic vs. inorganic) to which fish are exposed to. The mechanisms of Se metabolism and toxicity in fish, particularly at cellular level, are poorly understood. The present study was designed to examine the metabolic fate of different seleno-compounds, both inorganic and organic, in isolated hepatocytes of rainbow trout (Oncorhynchus mykiss) in primary culture using XANES spectroscopy. In cells exposed to 100 μM of selenate and selenite for 6-24 h, elemental Se was found to be the primary metabolite. Whereas, selenocystine appeared to be the major metabolite in cells exposed to 100 μM seleno-L-methionine for 6-24 h. Interestingly, we recorded L-methionine-γ-lyase activity in S9 fraction of cell lysate-an enzyme that directly catalyzes selenomethionine into methylselenol. We also found concurrent reduction of glutathione (GSH) concentration following reaction of seleno-L-methionine with cellular S9 fraction. Moreover, we observed a rapid increase in cellular reactive oxygen species (ROS) generation with increasing seleno-L-methionine exposure dose (100-1000 μM). These findings indicated the rapid cellular metabolism of seleno-L-methionine into methylselenol at higher exposure dose (≥100 μM), and the occurrence of GSH mediated redox cycling of methylselenol--a process that is known to produce reactive oxygen species (ROS). Overall, our results suggest that inorganic and organic selenium are metabolized through different metabolic pathways in rainbow trout hepatocytes. The findings of our study have important implications for understanding the chemical species-specific differences in Se toxicity to fish.

Stomatal responses to leaf temperature (T(l)) and to the mole fractions of water vapour in the ambient air (w(a)) and the leaf intercellular air spaces (w(i)) were determined in darkness to remove the potential effects of changes in photosynthesis and intercellular CO(2) concentration. Both the steady-state and kinetic responses of stomatal conductance (g(s)) to w(a) in darkness were found to be indistinguishable from those in the light. g(s) showed a steep response to the difference (Deltaw) between w(a) and w(i) when w(a) was varied. The response was much less steep when w(i) was varied. Although stomatal apertures responded steeply to T(l) when Deltaw was held constant at 17 mmol mol(-1), the response was much less steep when Deltaw was held constant at about zero. Similar results were obtained in the light for Deltaw = 15 mmol mol(-1) and Deltaw approximately 0 mmol mol(-1). These results are discussed in the context of mechanisms for the stomatal response to humidity.

Because spermatocyte meiotic error results in embryonic sex chromosomal aneuploidy, it is speculated that teratospermia correlates with increased embryonic sex chromosomal abnormalities. Our findings contradict this theory, suggesting that morphology does not correlate with sex chromosomal genotype., (Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Percent arsenic bioaccessibility is occasionally dependent upon arsenic concentration; however, the mechanism(s) of this relationship has not yet been defined. To evaluate the mechanism of this relationship, the arsenic bioaccessibility from freshly synthesized poorly crystalline scorodite was measured in the stomach, small intestine, and colon stages of the Simulator of the Human Intestinal Microbial Ecosystem (SHIME). The shape of the arsenic dissolution isotherms were different between stages (stomach: linear; small intestine: exponential rise to maxima; colon: sigmoidal). These results indicate that arsenic bioaccessibility may be limited by either in vitro GI fluid saturation or in vitro GI model residence time, depending upon the chemical/microbiological conditions of the model. Gastrointestinal microorganisms increased arsenic bioaccessibility of scorodite up to two-fold in the SHIME colon; however, this was dependent upon the sample arsenic concentration. Up to 40% of the bioaccessible arsenic was reduced to arsenite; however this process was neither mediated by GI microorganisms nor associated with increased arsenic bioaccessibility.

In this prospective, randomized study, waiting for the lead follicle to reach 14 mm before initiating GnRH antagonist administration effectively prevents an LH surge and ovulation during an IVF cycle. Furthermore, delaying GnRH start until the dominant follicle reaches 14 mm neither impacts the clinical pregnancy, implantation, or live birth rates nor increases the incidence of severe ovarian hyperstimulation syndrome.

In vitro gastrointestinal models, used to measure the metal(loid) bioaccessibility for site specific risk assessment, are typically operated under fasted conditions. We evaluated the hypothesis that fed conditions increase arsenic bioaccessibility on three reference soils (NIST 2711, NIST 2709, and BGS 102) and the bulk and <38 mum size fractions of a mine tailing. The three nutritional states included a fed state with a carbohydrate mixture, a second fed state with homogenized crowberries (Empetrum nigrum), and a fasted state. The carbohydrate mixture increased arsenic bioaccessibility from four of five samples in the simulator of the human intestinal microbial ecosystem (SHIME) stomach but only three of five samples in the SHIME small intestine and colon. In contrast, crowberries increased arsenic bioaccessibility from four of five samples in the SHIME small intestine but had variable affects in the SHIME stomach and colon. The effect of nutritional status on arsenic bioaccessibility was potentially mediated via ligand-promoted dissolution in the SHIME stomach and small intestine. The displacement of arsenic with phosphate was potentially present in the SHIME small intestine but not the SHIME stomach. Microbial activity increased arsenic bioaccessibility relative to sterile conditions from four of five samples under fasted conditions and three of the five samples under fed conditions, which may suggest that in vitro gastrointestinal (GI) models operated under fed conditions and with microbes provide a more conservative estimate of in vitro bioaccessibility. However, for some samples, the arsenic bioaccessibility in the SHIME colon (with microbial activity) was equivalent to values observed in a separate physiologically based extraction test under small intestinal conditions (without microbial activity). These results suggest that the incorporation of microbial activity into in vitro GI models does not necessarily make estimates of arsenic bioaccessibility more protective than those generated using in vitro models that do not include microbial activity.

Purpose: Intimate partner violence (IPV) frequently results in maxillofacial injuries. The purpose of this study is to compare 2 protocols to identify women who self-report IPV-related injuries., Materials and Methods: Using a cross-sectional study design, we enrolled a sample of injured women who presented to the emergency department (ED) for evaluation and treatment. The predictor variable was the protocol used to identify injury etiology, that is, an innovative diagnostic protocol (DP) or the ED's standard operating procedure (SOP). The outcome variable was self-reported injury etiology categorized as IPV or other. Descriptive and bivariate statistics were computed. Sensitivity, specificity, positive predictive value, negative predictive value, and odds ratios were computed (with P < or = .05 being considered statistically significant)., Results: The sample was composed of 286 women with a mean age of 45.8 years. The self-reported prevalence of IPV-related injuries was 11.5% and 5% for the DP and SOP, respectively (P = .03). The diagnostic statistics for the DP and SOP, respectively, were as follows: sensitivities, 94% and 50%; specificities, 76% and 95%; positive predictive values, 34% and 50%; and negative predictive values, 98% and 95%. In the adjusted model the women evaluated with the DP had a 38-fold increased likelihood of reporting IPV (P < .01) when compared with the SOP., Conclusions: These results suggest that the proposed DP is associated with an increased frequency of self-reported IPV-related injuries when compared with the ED's SOP.

Objective: To determine if ethnicity influences IVF birth outcome., Design: Retrospective cohort study., Setting: University-based IVF program., Patient(s): All African American women (n = 71) and Caucasian women (n = 180) who underwent initial fresh, nondonor IVF/embryo transfer (ET) cycles between January 1, 2004 and December 31, 2005., Intervention(s): None., Main Outcome Measure(s): Gonadotropin dose, duration of stimulation, peak estradiol levels, oocyte yield, implantation, clinical pregnancy, and live birth rates., Result(s): African American women generated significantly fewer embryos than Caucasian women (5.3 +/- 3.7 vs. 6.6 +/- 4.8) despite having similar ages, day 3 FSH, peak estradiol levels, length of stimulation, and number of oocytes retrieved. In addition, compared with Caucasian women, African American had significantly greater body mass indices (26.5 +/- 5.2 vs. 23.7 +/- 4.8) and required significantly more total gonadotropin (IU) (4,791 +/- 2,161 vs. 3,725 +/- 2,005) for ovarian stimulation. African American women were more likely to have uterine fibroids (21% vs. 3%) and tubal factor infertility (23% vs. 9%). Caucasian women were more likely to have unexplained infertility (53% vs. 32%). Differences in embryo yield between patient groups persisted after accounting for differences in infertility diagnosis and prevalence of fibroids. Biochemical, clinical pregnancy, and live birth rates as well as implantation rates (number of sacs visualized/number of embryos transferred) did not significantly differ between groups., Conclusion(s): Although African Americans yield fewer embryos than Caucasian women with IVF, these ethnic groups do not seem to differ with regard to IVF pregnancy outcomes.

Objective: To evaluate the impact on the rates of clinical pregnancy and live birth of polyploidy after intracytoplasmic sperm injection (ICSI)., Design: Retrospective cohort study., Setting: University-based IVF center., Patient(s): One hundred forty-three patients undergoing their first IVF-embryo transfer cycle requiring ICSI., Intervention(s): None., Main Outcome Measure(s): Patients were divided into two groups on the basis of the proportion of post-ICSI triploid fertilization that was observed at the time of fertilization assessment: group 1 included patients with 20% 3PN zygotes. The primary outcomes compared between groups were pregnancy and implantation rates; secondary outcome measures included clinical-pregnancy rate and live-birth rate per embryo transfer., Result(s): Pregnancy, implantation, clinical-pregnancy, and live-birth rates were significantly higher in the cohort of patients who had 20% of zygotes appearing triploid (relative risk [RR] for pregnancy, 2.4 [95% confidence interval {CI}, 1.22-4.77]; RR for implantation, 2.6 [95% CI, 1.17-5.56]; RR for clinical pregnancy, 2.8 [95% CI, 1.16-6.85]; and RR for live birth, 2.6 [95% CI, 1.06-6.38]). The proportion of 3PN zygotes after ICSI had a statistically significant inverse relationship to clinical-pregnancy rate., Conclusion(s): The proportion of triploid zygotes after ICSI serves as a negative prognostic indicator for IVF cycle outcome. This finding suggests that triploidy proportion is a surrogate marker of oocyte competence that represents the integrity of the oocytes in the entire recruited cohort. Such findings therefore may influence recommendations for embryo transfer number and freezing of supernumerary embryos.

The ability of guard cells to hydrate and dehydrate from the surrounding air was investigated using isolated epidermes of Tradescantia pallida and Vicia faba. Stomata were found to respond to the water vapour pressure on the outside and inside of the epidermis, but the response was more sensitive to the inside vapour pressure, and occurred in the presence or absence of living, turgid epidermal cells. Experiments using helium-oxygen air showed that guard cells hydrated and dehydrated entirely from water vapour, suggesting that there was no significant transfer of water from the epidermal tissue to the guard cells. The stomatal aperture achieved at any given vapour pressure was shown to be consistent with water potential equilibrium between the guard cells and the air near the bottom of the stomatal pore, and water vapour exchange through the external cuticle appeared to be unimportant for the responses. Although stomatal responses to humidity in isolated epidermes are the result of water potential equilibrium between the guard cells and the air near the bottom of the stomatal pore, stomatal responses to humidity in leaves are unlikely to be the result of a similar equilibrium.

Objective: To evaluate the impact of abnormal sperm morphology on the rates of aneuploidy, implantation, and clinical pregnancy., Design: Retrospective cohort study., Setting: University-based IVF center., Patient(s): Fifty-two patients undergoing their first IVF-preimplantation genetic diagnosis (PGD) cycle., Intervention(s): The PGD analysis of embryos., Main Outcome Measure(s): Patients were divided into two groups based on sperm morphology: teratospermic group (TSG) and normal sperm group (NSG). The primary outcome measures of rates of aneuploidy, implantation, clinical pregnancy rate (PR) per cycle, and clinical PR per embryo transfer were compared between TSG and NSG according to PGD analysis results., Results: A higher percentage of normal embryos was seen in the NSG (32%) versus the TSG (20%). Overall, 30% of IVF-PGD cycles had no normal embryos for transfer. The clinical PR per cycle was 44% in the NSG compared to 14% in the TSG (relative risk [RR] = 3.19; 95% confidence interval [CI] 1.1-9.0). A similar trend was noted with the clinical PR per embryo transfer with 57% patients becoming pregnant in the NSG versus 20% patients in the TSG (RR = 2.76; 95% CI 1.2-7.2). Implantation was twice as likely to occur in the NSG as compared to TSG (RR = 2.5; 95% CI 1.1-7.2)., Conclusion(s): Rates of euploidy, implantation, clinical PR per cycle, and clinical PR per embryo transfer were higher in the NSG compared to the TSG, suggesting that sperm morphology plays an important role in the outcome of IVF-PGD cycles.

Poor responders continue to be vexing in infertility therapy. By using GnRH antagonists before ovarian stimulation, we demonstrate an improvement in oocyte, embryo, and zygote yield in patients with a prior poor response.

The objective of this study was to assess the impact of assisted hatching (AH) on pregnancy rate (PR), clinical pregnancy rate (CPR), and implantation rate (IR) after a single failed, fresh, nondonor IVF cycle. Accordingly, we report that patients with one prior implantation failure benefit from AH with improved PR, CPR, and IR in a subsequent cycle.

The fate and mobility of boric acid in the environment is largely controlled by adsorption reactions with soil organic matter and soil minerals to form surface complexes (Soil Sci Soc. Am. J. 1991, 55, 1582; Geochim. Cosmochim. Acta 2002, 67, 2551; Soil Sci. Soc. Am. J. 1995, 59, 405; Environ. Sci. Technol. 1995, 29, 302). In this study, boric acid adsorption on pure am-Al(OH)3 and 5% (w/w) humic acid (HA) coated am-Al(OH)3 were investigated both as a function of pH (4.5-11) and initial boric acid concentration (0-4.5 mmol L(-1)). Batch adsorption isotherm experiments were also conducted with samples exposed to atmospheric CO2 and anaerobic (N2) conditions to examine the effects of dissolved CO2 on boric acid adsorption. Boron (B) K-edge X-ray absorption near-edge structure (XANES) spectroscopy was used to investigate the coordination of boric acid adsorbed at mineral/water interfaces. The XANES spectra of boric acid adsorption samples showed that both trigonally and tetrahedrally coordinated B complexes were present on the mineral surface. Both macroscopic and spectroscopic experiments revealed that the combination of HA coating on am-Al(OH)3 and dissolved CO2 decreased boric acid adsorption compared to adsorption on pure am-Al(OH)3.

Background: Patchy stomatal conductance is a poorly understood and little-studied phenomenon. It is relatively common, yet it appears to be detrimental to water-use efficiency under some conditions and has no immediately obvious physiological function of any kind. Much of the difficulty in studying patchy stomatal conductance is tied to its unpredictability, both in occurrence and in characteristics., Scope and Conclusions: Statistical analyses of the variability of stomatal patchiness reveal remarkable similarities to structures and behaviours found in locally connected networks of dynamic units that perform tasks. Such systems solve problems that reside at the level of the entire network despite the absence of a central processor or a mechanism for directly sharing information over the entire system. Frequently, task performance is emergent, in the sense that no unit independently performs the task. Because each unit in the network can communicate with only its immediate neighbours, problem solving is accomplished by the states of the individual units self-organizing into synchronized, collective patterns. In some cases, patches of states form and move coherently over the network, thus providing a means for distantly separated parts of the network to communicate. Often, exactly what form these patches take and how they move as the units synchronize is highly unpredictable. In analogy with such networks, it is suggested that stomatal patchiness may be a signature that plants optimize gas exchange in a more sophisticated and adaptive manner than if performed by their individual stomata independently.

Sorption processes at the mineral/water interface typically control the mobility and bioaccessibility of many inorganic contaminants such as oxyanions. Selenium is an important micronutrient for human and animal health, but at elevated concentrations selenium toxicity is a concern. The objective of this study was to determine the bonding mechanisms of selenate (SeO4(2-) and selenite (SeO3(2-) on hydrous aluminum oxide (HAO) over a wide range of reaction pH using extended X-ray absorption fine structure (EXAFS) spectroscopy. Additionally, selenate adsorption on corundum (alpha-Al2O3) was studied to determine if adsorption mechanisms change as the aluminum oxide surface structure changes. The overall findings were that selenite forms a mixture of outer-sphere and inner-sphere bidentate-binuclear (corner-sharing) surface complexes on HAO, selenate forms primarily outer-sphere surface complexes on HAO, and on corundum selenate forms outer-sphere surface complexes at pH 3.5 but inner-sphere monodentate surface complexes at pH 4.5 and above. It is possible that the lack of inner-sphere complex formation at pH 3.5 is caused by changes in the corundum surface at low pH or secondary precipitate formation. The results are consistent with a structure-based reactivity for metal oxides, wherein hydrous metal oxides form outer-sphere complexes with sulfate and selenate, but inner-sphere monodentate surface complexes are formed between sulfate and selenate and alpha-Me2O3.

It is well known that dissolved organic matter (DOM) increases in lakes associated with forestry activity but characterization of the DOM structure is incomplete. Twenty-three lakes with a wide range of forestry activities located in central Quebec, Canada were sampled and analyzed for dissolved organic carbon (DOC) concentration, DOC fluorescence, and ultra violet-visible (UV-VIS) absorption spectra. The results show that DOC increases (as does the associated DOC fluorescence) with increased logging (slope=0.122, r2=0.581, p<0.001; and slope=0.283, r2=0.308, p<0.01, respectively) in the 23 lakes sampled however, the aromaticity of the DOM does not change with changes in logging (as found by UV-VIS ratios, absorbance slope in the UV region, and DOC normalized fluorescence (slope=1.42x10(-2), r2=0.331, p<0.01). The DOM from four of these lakes was concentrated using reverse osmosis (RO) followed by freeze-drying. The structures of the concentrated dissolved organic matter (DOM) samples were analyzed using X-ray analysis of near edge structures (XANES), X-ray diffraction (XRD), and 13C solid-state nuclear magnetic resonance (13C NMR) analysis. XANES analysis of functional groups in the four concentrated samples shows that there are significant differences in reduced sulphur between the samples, however there was no clear relationship with forestry activity in the associated catchment. XRD data showed the presence of amorphous sulphide minerals associated with the DOM concentrate that may be important sites for mercury binding. The 13C NMR spectra of these samples show that the percentage of carbon present in carboxylic functional groups increases with increasing logging. Such structures are important for binding photo-reducible mercury and their presence may limit mercury photo-reduction and volatilization. We propose a mechanism by which increased logging leads to increased carboxylic groups in DOM and thereby increased weak binding of photo-reducible mercury. These results, in part, explain the decrease in dissolved gaseous mercury (DGM) production rates with increased logging found in our previous work.

It has been suggested that some biological processes are equivalent to computation, but quantitative evidence for that view is weak. Plants must solve the problem of adjusting stomatal apertures to allow sufficient CO(2) uptake for photosynthesis while preventing excessive water loss. Under some conditions, stomatal apertures become synchronized into patches that exhibit richly complicated dynamics, similar to behaviors found in cellular automata that perform computational tasks. Using sequences of chlorophyll fluorescence images from leaves of Xanthium strumarium L. (cocklebur), we quantified spatial and temporal correlations in stomatal dynamics. Our values are statistically indistinguishable from those of the same correlations found in the dynamics of automata that compute. These results are consistent with the proposition that a plant solves its optimal gas exchange problem through an emergent, distributed computation performed by its leaves.

While alum amendments have shown to be effective in lowering water-soluble phosphate levels in poultry litter, the mechanism by which this occurs is not fully known. To determine the solid-state speciation of phosphate in litter samples, experiments were conducted with X-ray absorption near edge structure (XANES) spectroscopy. XANES analysis reveals that, in unamended samples, phosphate is present as weakly bound inorganic as well as some organic phosphate, with some dicalcium phosphate-type calcium phosphates also present. When alum is applied in the houses, XANES results suggest that it precipitates out as amorphous Al(OH)3 and then reacts with phosphate via an adsorption mechanism. No evidence was found of aluminum phosphate precipitation in any samples.

Selenate (SeO4(2-)) is an oxyanion of environmental importance because of its toxicity to animals and its mobility in the soil environment. It is known that iron(III) oxides and hydroxides are important sorbents for SeO4(2-) in soils and sediments, but the mechanism of selenate adsorption on iron oxides has been the subject of intense debate. Our research employed Extended X-ray absorption fine structure and attenuated total reflectance-Fourier transform infrared spectroscopies to determine SeO4(2-) bonding mechanisms on hematite, goethite, and hydrous ferric oxide (HFO). It was learned that selenate forms only inner-sphere surface complexes on hematite but forms a mixture of outer- and inner-sphere surface complexes on goethite and HFO. This continuum of adsorption mechanisms is strongly affected by both pH and ionic strength. These results suggest that adsorption experiments should be conducted on several different iron oxides and over a wide range of reaction conditions to accurately assess the reactivity of oxyanions on iron oxides.

The mechanism of sulfate adsorption on goethite was investigated in situ using attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Sulfate adsorption was investigated at ionic strengths between 0.005 and 0.1 M, reactant concentrations between 5 and 500 µM, and pH values between 3.5 and 9.0. It was determined that sulfate forms both outer-sphere and inner-sphere surface complexes on goethite at pH less than 6. At pH values greater than 6, sulfate adsorbs on goethite only as an outer-sphere complex. The relative amount of outer-sphere sulfate surface complexation increased with decreasing ionic strength. The spectrum of sulfate adsorbed on goethite was also compared to the infrared spectrum of synthetic schwertmannite, an iron(III) oxy-hydroxy-sulfate. It was determined that in situ spectra of both schwertmannite and adsorbed sulfate are quite similar, suggesting that a continuum of outer- and inner-sphere sulfate occurs in both cases. Copyright 1999 Academic Press.

Women with recurrent abortion, primary unexplained infertility, and gestational trophoblastic neoplasia (GTN) manifest disordered human chorionic gonadotrophin (HCG) secretion. Mutations in the HCG beta/luteinizing hormone (LH) beta gene complex could cause aberrant HCG production in these disorders. The purpose of this study was to determine whether HCG beta gene deletions occur in women with recurrent abortion or primary unexplained infertility, and whether HCG beta gene duplications are present in women with GTN. DNA was extracted from 10 patients with unexplained recurrent abortion, 10 patients with unexplained primary infertility, 12 patients with GTN, three partners of women with GTN, and 30 controls. Southern blots were constructed and hybridized with DNA probes for HCG beta-5 and the LH beta gene. No gene deletions were identified in patients with recurrent abortion or primary unexplained infertility. Likewise, no gene duplications were identified in women with GTN. A previously described Mbol restriction fragment length polymorphism (RFLP) was identified in both patients and controls. A new Pstl RFLP was also characterized, but was present in patients and controls. Deletion/duplication mutations in the HCG beta/LH beta gene complex do not appear to be common causes of aberrant HCG production in humans with these disorders.

Objective: To examine the FSH receptor gene for detectable abnormalities in women with premature ovarian failure., Design: Study of genomic DNA from controls and from patients with 46,XX premature ovarian failure (POF)., Setting: Clinics and laboratories of university gynecology and obstetrics departments., Patients: Twenty-one women with 46,XX POF and 40 normal fertile controls., Interventions: Deoxyribonucleic acid was analyzed in patients and controls by Southern blot analysis, polymerase chain reaction (PCR), and denaturing gradient gel electrophoresis. Southern blots were hybridized with the FSH receptor complementary DNA and other smaller DNA probes. Exons 1, 5 to 6, and 10 were amplified by PCR and electrophoresed on agarose gels. Polymerase chain reaction products from exons 1 and 10 were electrophoresed on denaturing gradient gels., Main Outcome Measures: Fragments obtained by Southern blot analysis and PCR were compared in patients and controls. Polymerase chain reaction fragments electrophoresed on denaturing gels also were compared in patients and controls., Conclusions: No FSH receptor gene deletions or other mutations were identified in women with POF. Southern blots containing PstI- and HindIII-digested DNA revealed restriction fragment length polymorphisms in both patients and controls. Denaturing gradient gel electrophoresis analysis of PCR fragments of exon 10 also demonstrated DNA sequence polymorphisms in both patients and controls. Follicle-stimulating hormone receptor gene deletions are not common in women with POF, although the gene is polymorphic. We cannot exclude point mutations in other regions of the FSH receptor gene in some patients with POF.

Evidence had been provided that a disulfide-linked [125I]iodotyramine/poly(D-lysine) conjugate was reductively cleaved when bound nonspecifically to the surface of Chinese hamster ovary (CHO) cells and that this cleavage was abolished by membrane-impermeant sulfhydryl blockers. The same blockers were subsequently found to inhibit the cytotoxicity of diphtheria toxin, a disulfide-linked heterodimer that binds to a specific surface receptor and must undergo chain separation to exert its cytotoxicity. This suggested that the disulfides of both macromolecules might be cleaved by a thiol-disulfide interchange reaction, possibly mediated by protein disulfide-isomerase (PDI, EC 5.3.4.1). We tested whether inhibitors of PDI--in particular, bacitracin and anti-PDI antibodies--might mimic the two effects of sulfhydryl blockers. Both bacitracin and anti-PDI antibodies were effective in inhibiting both reductive processes. This strongly suggests that the disulfide cleavage in the two membrane-bound macromolecules is mediated by PDI and that this enzyme, besides its known retention in the endoplasmic reticulum, must also be exposed at the plasma membrane. This paper points to other potentially important disulfide reductions that might be catalyzed by surface-associated PDI. It thereby broadens the known functions of an enzyme already known for its multifunctional properties.