Abstract  BACKGROUND: The association between blood lead levels and mortality in patients on maintenance hemodialysis remains unclear. METHODS: A cross-sectional and 18-month prospective study included 927 patients on maintenance hemodialysis. Baseline variables and blood lead levels were measured before hemodialysis and categorized as 3 equal groups: high (>12.64 μg/dL), middle (8.51-12.64 μg/dL), and low (<8.51 μg/dL). Mortality and cause of death were recoded for longitudinal analyses. RESULTS: At baseline, after related variables were adjusted, logarithmic transformation of blood lead level was negatively related to log ferritin and positively related to the vintage of hemodialysis and the percentage of urban area patients. By the end of the follow-up, 59 patients had died. Kaplan-Meier survival analysis showed that the high blood lead level group had greater mortality than the low blood lead level group (log-rank test, P<.001). After adjustment for potential variables, Cox multivariate analysis demonstrated that by using the low blood lead level as the reference, high blood lead levels were associated with increased hazard ratios (HRs) for all-cause (HR 4.70; 95% confidence interval [CI], 1.92-11.49; P=.003), cardiovascular-cause (HR 9.71; 95% CI, 2.11-23.26; P=.005), and infection-cause (HR 5.35; 95% CI, 1.38-20.83; P=.046) 18-month mortality in patients on maintenance hemodialysis. Moreover, there was a significant trend (P=.032) of HRs for all-cause mortality among the 3 study groups. CONCLUSION: High blood lead level is associated with increased HRs for all-cause, cardiovascular-cause, and infection-cause 18-month mortality in patients on maintenance hemodialysis.

Abstract  In this mini review, we would like to challenge the well-established 'fact' that lead exposure causes chronic renal failure (CRF). Even though only scarce evidence exists of the relationship between lead and renal failure, a World Health Organization Environmental Health Criteria document summarizes that 'Lead has been a very common cause of acute or chronic renal failure'. It is also written and cited in textbooks and numerous publications that chronic lead nephropathy causes a slowly progressive interstitial nephritis manifested by a reduced glomerular filtration rate, and that there is a growing consensus that lead contributes to hypertension in the general population. We will argue that, when published reports are carefully scrutinized, such statements on lead and CRF are not evidence based but are rather founded on a few narrative reports on lead-exposed individuals and statistical associations between lead and serum creatinine (or urea) in a few population studies. We will, however, not argue that lead is not toxic and that lead does not cause other types of severe health effects where the evidence is unquestionable, but we do not believe that the kidneys are an early victim after lead exposure.

Abstract  The extractability of Cd, Pb, and Zn was investigated in contaminated agricultural topsoils located in an area highly affected by the past atmospheric emissions of two smelters in northern France in order to assess their mobility and human bioaccessibility. The determination of Cd, Pb, and Zn bioaccessibility (Unified Barge Method, in vitro test) was made to evaluate the absolute trace element (TE) bioavailability. The results highlighted differences in bioaccessibility between Cd, Pb, and Zn (Cd > Pb > Zn). The mean values of the bioaccessible fractions of Cd, Pb, and Zn during the gastric phase were 82, 55, and 33%, respectively, of the pseudototal concentrations, whereas during the gastrointestinal phase, the bioaccessible fractions of metals decreased to 45, 20, and 10%, respectively. Stepwise multiple regression analysis showed that human bioaccessibility was affected by various physicochemical parameters (i.e., sand, carbonates, organic matter, assimilated P, free Al oxides, and pseudototal Fe contents). Sequential extractions were performed as an indication of the TE availability in these soils. Cadmium occurred in the more available fractions, Pb was mostly present as bound by oxides, and a significant contribution to the pseudototal Zn concentration was defined as the unavailable residual form related to the crystalline structures of minerals. The concepts of bioavailability and bioaccessibility are important for quantifying the risks associated with exposure to environmental pollutants and providing more realistic information for human health.

Abstract  Present study investigates relationships between total and bioaccessibility of trace elements (Cd, Co, Cr, Cu, Mn, NI, Pb, V, and Zn) concentrations in sediment and their bioaccumulation in species in Shadegan wetland in southwest of Iran. Bioavailability factor (BAF) and translocation factor (TF) were calculated in plants and trophic transfer factor (TTF) was determined in bird species. For this purpose, sampling of sediments, aquatic plants including Phragmites australis, Typha australis, Scripus maritimus and two bird species encircling Porphyrio porphyrio and globally threatened Marmaronetta angustirostris were carried out during winter 2009. Result of chemical analysis show that bioaccessibility concentrations of Mn (8.31 mg/kg), V (1.33 mg/kg), and Pb (1.03 mg/kg) are higher than other metals. The uptake trend of trace elements in plant decreases as root > stem > leaf. Accumulation levels of trace elements in different tissues of P. porphyrio and M. angustirostris are almost identical and considerable. Accumulation and toxicity of Cd in birds is more than plants. In addition, BAF of V, Pb, and Cr indicates high accumulation by plants and great pollution rate in the area of study. In S. maritimus TF for Mn, Cu, Pb, and V are high whereas in T. australis, Cu and Pb posses the highest TF. Also Cr, Co, Mn, Ni, and Zn have higher TF from stem to leaf than root to stem in P. australis. Finally, TTFs were compared in various bird species.

Abstract  The aim of the study was to assess the effects of exposure to low doses of lead, cadmium and mercury dissolved in drinking water (at a concentration 200-fold of maximum allowable concentration) on selected serum proteins of 120 Wistar rats during three subsequent generations. Animals were divided into four groups in all observed generation-control (C) and three experimental groups exposed to low doses of heavy metals (lead acetate in concentration 100 μM; mercuric chloride in 1 μM; cadmium chloride in 20 μM of drinking water). We studied the biochemical parameters as well as total protein, albumin, transferrin and ferritin in the serum. Exposure to lead and mercury shortened life span, decreased body weight of the animals in each generation whereas cadmium had no such effect. Total protein increased after exposure to lead and mercury (P<0.001), albumin increased after exposure to lead and mercury in 1st filial and 2nd filial generation (P<0.05) and insignificantly decreased after exposure to cadmium in parental and 1st filial generation. Transferrin and ferritin increased in all exposed groups and generations (P<0.05). Transferrin and ferritin are good markers for intoxication of rats with heavy metals. For the results evaluation, not only data at the end of experiment should be taken into account, but entire duration of trials (i.e., more time steps), which makes results more objective.

Abstract  Manganese (Mn) and lead (Pb) exposures during developmental period can impair development by direct neurotoxicity or through interaction with iron metabolism. Therefore, we examined the effects of maternal ingestion of Mn or Pb in drinking water during gestation and lactation on iron metabolism as well as behavior in their offspring. Pregnant dams were given distilled water, 4.79mg/ml Mn, or 2.84mg/ml Pb in drinking water during gestation and lactation. Pups were studied at time of weaning for (59)Fe absorption from the gut, duodenal divalent metal transporter 1 (DMT1) expression, hematological parameters, and anxiety-related behavior using an Elevated Plus Maze (EPM) test. Metal-exposed pups had lower body weights and elevated blood and brain concentrations of the respective metal. Pb-exposed pups had lower hematocrits and higher blood Zn protoporphyrin levels. In contrast, Mn exposed pups had normal hematological parameters but significantly reduced Zn protoporphyrin. Pharmacokinetic studies using (59)Fe showed that intestinal absorption in metal-exposed pups was not different from controls, nor was it correlated with duodenal DMT1 expression. However, intravenously injected (59)Fe was cleared more slowly in Pb-exposed pups resulting in higher plasma levels. The overall tissue uptake of (59)Fe was lower in Mn-exposed and lower in the brain in Pb-exposed pups. The EPM test demonstrated that Mn-exposed, but not Pb-exposed, pups had lower anxiety-related behavior compared to controls. We conclude that gestational and lactational exposures to Mn or Pb differentially alter Fe metabolism and anxiety-related behavior. The data suggest that perturbation in Fe metabolism may contribute to the pathophysiologic consequences of Mn and Pb exposure during early development.

Abstract  Many metals are essential elements and necessary for proper biological function at low intake levels. However, exposure to high intake levels of these metals may result in adverse effects. In addition, exposures to mixtures of metals may produce interactions that result in synergistic or antagonistic effects. This chapter focuses on metals that affect the hematological system and how exposures to mixtures of metals may contribute to their hematotoxicity. Exposure to arsenic, cadmium, copper, lead, mercury, tin or zinc has been shown to produce some effect on the hematological system. Binary interactions resulting from exposure to combinations of metals may increase or decrease the hematotoxicity induced by individual metals. For example, copper, iron, and zinc have been shown to have a protective effect on the hematotoxicity of lead. In contrast, co-exposure to manganese may increase the hematotoxicity of lead.

Abstract  The objectives of this study were to evaluate the efficiency in treatment of lead-induced intoxication in mice with γ-PGA as chelating agent and compare with the drug (meso-2,3-dimercaptosuccinic acid). The results showed the incorporation of γ-PGA at 200 and 400 mg/kg could reduce the accumulation of lead in the liver, heart, and testis; however, the latter was more effective in decreasing the lead content in the kidney and spleen. Nevertheless, both doses failed to inhibit the lead accumulation in the lung and brain. Additionally, both doses of γ-PGA could reduce TBARs in the kidney and brain, as well as elevate δ-aminolevulinic acid dehydrase (δ-ALAD) activity in blood and decrease glutamic pyruvic transaminase (GPT) and lactic dehydrogenase (LDH) activities in the serum. For hematological parameters, both white blood cells (WBCs) and hematocrite (HCT) were raised by 400 mg/kg of γ-PGA, while for both doses of γ-PGA, a slight decline in hemoglobin (HGB), mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) was observed, with the red blood cells (RBCs) being unaffected.

Abstract  The septal and temporal poles of the hippocampus differ markedly in their anatomical organization, but whether these distinct regions exhibit differential neurochemical profiles underlying lead (Pb(2+)) neurotoxicity remains to be determined. In the present study, we examined changes in the expression of Ca(2+)/calmodulin-dependent enzymes, including calpain, calcineurin, phospho-CaMKII (Thr286) and neuronal nitric oxide synthase (nNOS), in the rat dorsal and ventral hippocampus (DH and VH) after acute Pb(2+) exposure. Five days after Pb(2+) exposure, we observed constitutively active forms of calcineurin (45kDa and 48kDa) in ventral portions of the hippocampus, a result consistent with the observed calpain activation that is indicated by the breakdown of spectrin in this region. Our data demonstrate that nNOS expression is significantly higher in the ventral region of the hippocampus when compared to the dorsal region, whereas phosphorylation of CaMKII (Thr286) is less pronounced in the ventral portion of the hippocampus and more pronounced in dorsal regions after acute Pb(2+) exposure. Thus, it appears likely that the ventral region of hippocampus is more vulnerable to the neurotoxic effects of Pb(2+) than the dorsal region. Taken together, the present data suggest that acute lead exposure leads to differential expression patterns of Ca(2+)/calmodulin-dependent enzymes along the dorsoventral axis of the hippocampus.

Abstract  This work aimed at comparing the ability of two plants in accumulating atmospheric trace elements. Samples of Parmelia sulcata (lichen) were transplanted and covered with a net into an exposed location on the trunk of Jacaranda mimosifolia (bark) at different sites impacted by urban - industrial emissions for a period of 3 months. Lichen samples were harvested along with bark samples for trace element analysis with the use of ICP-MS. The results indicated that concentrations in bark and lichen transplants correlated significantly with atmospheric deposition for all the elements. There was a consistent pattern of accumulation in both biomonitors with the bark outperforming the lichen. Significant differences were observed in the accumulation efficiency for both biomonitors at different sites (p <0.01). Both plants studied showed Pb to be related to vehicular emission and Cr to the mining industries within the study site. Both plants could serve as alternative biomonitors, however and wherever possible both plants should not be used interchangeably in areas with trace elements deposits.

Abstract  The composition of tree rings and soils was studied at several locations affected by smelting and transportation in the vicinity of Kitwe (Copperbelt, Zambia). The contents of cobalt (Co), copper (Cu), manganese (Mn), and lead (Pb) and the Pb-206/Pb-207 isotope ratios in the tree rings were interpreted in relation to potential sources of contamination such as smelter production, acidification of the environment, soil composition, raw material processing, and atmospheric suspended particulate matter (SPM). The highest Co contents in the tree rings correspond to maximum ore production in the mid-1970s. Acidification through SO2 emissions is documented in the increased Mn contents from the mid-1980s. The isotopic composition of the tree rings of the studied tree species varies in the interval 1.16-1.34 and the youngest parts of all the studied trees exhibit a low Pb-206/Pb-207 ratio (< 1.17). The soil isotope composition varies in the range Pb-206/Pb-207 = 1.18-1.35. The Pb isotope composition in the soils and tree rings was formed by a combination of lithogenic Pb (Pb-206/Pb-207 similar to aEuro parts per thousand 1.3), Pb in processed ores (Pb-206/Pb-207 similar to aEuro parts per thousand 1.2), and SPM (automobile) Pb (Pb-206/Pb-207 similar to 1.1). As the soils in the distant region have high Pb-206/Pb-207 ratios (> 1.3) in the whole profile and simultaneously the youngest parts of the tree rings of tree species growing in this soil have a low Pb-206/Pb-207 ratio (< 1.17), it can be assumed that the Pb in the youngest parts of the tree species is derived from absorption of SPM Pb through the bark rather than root uptake. The absence of Pb with a low Pb-206/Pb-207 ratio in soils in the distant area is probably affected by fires in the herbaceous and bush undergrowth and plant litter, which prevents Pb from biomass from entering the soil and mobilize it back into the atmosphere.

Abstract  The problematic of the stable development is very wide. Recognition of ecological aspects of stable development composes a guarantee of health in ecosystems and especially for the community. The monitoring of the air that is carried out in Tirana shows that the most important polluters continue to be the total dust LGS and respiratory dust PM 10. The average quantity of lead in the monitored air drops has been increased from 0.19 mu gm(-3) to 0.29 mu gm(-3), i.e., an amount of 50 Pb that is constantly increasing in the content of urban air almost in all monitored places of the country. Many sources of air pollution have always existed.

Abstract  This paper presents the key findings of an Environment Agency's project aimed to ascertain what types of in vitro bioaccessibility methods are currently being used in the United Kingdom, what information is being reported and how they compare. Three samples of soil with elevated levels of arsenic, lead and nickel were collected from contaminated sites. The prepared and homogenised soils were sent as blind triplicate samples to 11 participating laboratories, of which 2 were from outside the UK. Analysis for total arsenic, lead and nickel content and the in vitro bioaccessible fraction was requested. An aqua regia extract was also prepared and sent with the soil samples for analysis. Whilst laboratory identification remains anonymous, codes A, B, C, D, E, F, G, H, J, K and L were assigned to individual laboratories. Three different types of in vitro methods were identified in the project producing bioaccessibility data. Each laboratory used the same bioaccessibility method for all three contaminants, irrespective of concentration or matrix. The results varied between laboratories and the variability is largely attributed to the difference in the in vitro methods used.

Abstract  The first step in modeling lead kinetics during pregnancy includes a description of sequential maternal blood lead (PbB) during pregnancy and the factors controlling it. We analyzed PbB of 105 women living in the Valley of Mexico from week 12 to week 36 of pregnancy and again at parturition. We also used data from all women contributing blood at any stage of pregnancy to determine antecedents of PbB. Pregnancies were uneventful, and offspring were normal. Although geometric mean PbB level averaged around 7.0 micrograms/dl (0.34 mumol/l), with a range of 1.0-35.5 micrograms/dl throughout pregnancy, analysis of variance revealed a significant decrease in mean PbB from week 12 to week 20 (1.1 micrograms/dl) and various significant increases in mean PbB from week 20 to parturition (1.6 micrograms/dl). Regression analyses confirmed the positive linear PbB trend from 20 weeks to parturition and additional contributions of dietary calcium, reproductive history, lifetime residence of Mexico City, coffee drinking, and use of indigenous lead-glazed pottery. Although decreasing hematocrit has been suggested to explain first-half pregnancy PbB decrease, the time course of hematocrit decrease in the present study did not match the sequential changes in PbB. While hemodilution and organ growth in the first half of pregnancy may account for much of the PbB decrease seen between 12 and 20 weeks, the remaining hemodilution and accelerated organ growth of the last half of pregnancy do not predict the trend toward increasing maternal PbB concentration from 20 weeks to delivery. Mobilization of bone lead, increased gut absorption, and increased retention of lead may explain part of the upward PbB trend in the second half of pregnancy. Reduction of lifetime lead exposure may be required to decrease risk of fetal exposure.

Abstract  Reviews the empirical literature concerning prediction of childhood and adult IQ scores from infant test scores, emphasizing size of the correlations, age of assessment, reliability of the tests, sex differences, socioeconomic status, and specific items and abilities. Since most of these studies were conducted under the assumption of an immutable, pervasive, general coception of intelligence, an alternative orientation is offered which emphasizes short-term correlational transitions between specific item clusters and behaviors during infancy. 1 type of analysis illustrating this approach indicates a major developmental trend characterized by manipulative exploration and the investigation of sensorimotor contingencies at 6 mo., motor and verbal imitation at 12 and 18 mo., and vocabulary and grammatical fluency at 18 and 24 mo. The similarity of these results to Piagetian theory is noted.

Abstract  To determine the influences of maternal diet and nutrition during pregnancy on the blood lead level of neonates, we conducted a study of mother-infant pairs from lower socioeconomic circumstances living in Albany County, New York. Maternal blood lead (MBPb), anthropometry, and diet were assessed in each trimester. Neonates' blood lead (NBPb) levels were low (geometric mean = 1.58 Ág/dL), and none had elevated blood lead. More than 50% of the mothers had intakes below the recommended dietary allowances for zinc, calcium, iron, vitamin D, and kilocalories. As expected, MBPb was strongly and positively related to NBPb. Among the anthropometric measures of maternal nutritional status, variables measuring gain in weight and arm circumference were negatively related to NBPb. In multivariable models reflecting different analytic strageties and including MBPb, anthropometry, and sociodemographic characteristics, dietary intakes of iron and vitamin D were negatively related to NBPb. The effect of zinc varied substantially depending on model covariates. Effects of dietary constituents are difficult to distinguish, given the intercorrelated nature of nutrients in the diet. Nevertheless, the influences of maternal anthropometric variables, iron, and vitamin D on neonatal lead levels are clear in our analyses.

Abstract  The absorption of lead from loops of small intestinein situ was investigated in rats in which iron absorption was increased by stimuli varying in type, intensity, or duration. Lead absorption was increased by a short period of severe iron restriction before any change in hematological indices became apparent. A period of hypoxia, which markedly increased iron absorption, did not influence absorption of lead. An extended period of moderate iron restriction resulted in a marked reduction in liver iron stores and increased iron absorption throughout the 17-wk experiment. Under these conditions lead absorption was initially also increased, but after 12 wk, when iron intake had become adequate to meet essential requirements, lead absorption was similar to that in iron-supplemented rats. These results are discussed in the light of evidence for a receptor-mediated absorption process for iron.

Abstract  In evaluating the accuracy and reliability of blood lead (PbB) measurements with the Environmental Science Associates Model 3010A Trace Metal Analyzer, intralaboratory comparison demonstrated that use of the operating conditions recommended by the manufacturer resulted in consistently underestimated PbB concentrations less than 400 micrograms/L and overestimated PbB values greater than 400 micrograms/L. At PbB concentrations less than 50 micrograms/L, measured concentrations were often registered as negative results. However, these negative values could be replicated to within +/- 10 micrograms/L, indicating good precision of the method, but obviously not good accuracy. In addition, lower-than-expected lead (Pb) values were measured in samples containing increased concentrations of copper (Cu), such as may occur in pregnant women. We modified the procedure to eliminate these inaccuracies by substituting manual peak-height measurements for reliance on the integrator and digital display of the instrument. We established the accuracy of the modified procedure by using calibration standards previously quantified by isotope dilution-mass spectroscopy. A quality-control program for monitoring PbB analysis is also described.

Abstract  Cynomolgus monkeys (Macaca fascicularis) were dosed continuously from birth onward with 100, 50, or 0 micrograms/kg/day of lead. This resulted in blood lead concentrations of 25, 15, or 3 micrograms/dl respectively before withdrawal of infant formula at 200 days of age. Blood lead concentrations declined thereafter over the next 100-150 days to steady-state concentrations of 13, 11, or 3 micrograms/dl. At seven to eight years of age, monkeys were tested on a delayed alternation task. The task required the monkey to alternate responses between two pushbuttons; each alternation was rewarded with a small amount of apple juice. After each monkey learned the task, a delay was instituted between trials. The initial delay was 100 msec, and was increased in steps to 15 sec by the end of the experiment. Treated monkeys were impaired in their ability to learn the alternation task, but were not different from controls at short delay values (1 and 3 sec). At longer delay values (5 and 15 sec), treated monkeys again exhibited impairment. At the 15 sec delay value, some individuals in both treated groups exhibited marked perseveration, responding on the same button in some instances for hours at a time. Treated monkeys were also more variable in their performance across sessions than were controls. The data are interpreted as indicative of spatial learning and short-term memory deficits in the lead-exposed monkeys.

Abstract  This report presents detailed information on age- and gender-related differences in the anatomical and physiological characteristics of reference individuals. These reference values provide needed input to prospective dosimetry calculations for radiation protection purposes for both workers and members of the general public. The purpose of this report is to consolidate and unify in one publication, important new information on reference anatomical and physiological values that has become available since Publication 23 was published by the ICRP in 1975. There are two aspects of this work. The first is to revise and extend the information in Publication 23 as appropriate. The second is to provide additional information on individual variation among grossly normal individuals resulting from differences in age, gender, race, or other factors. This publication collects, unifies, and expands the updated ICRP reference values for the purpose of providing a comprehensive and consistent set of age- and gender-specific reference values for anatomical and physiological features of the human body pertinent to radiation dosimetry. The reference values given in this report are based on: (a) anatomical and physiological information not published before by the ICRP; (b) recent ICRP publications containing reference value information; and (c) information in Publication 23 that is still considered valid and appropriate for radiation-protection purposes. Moving from the past emphasis on 'Reference Man', the new report presents a series of reference values for both male and female subjects of six different ages: newborn, 1 year, 5 years, 10 years, 15 years, and adult. In selecting reference values, the Commission has used data on Western Europeans and North Americans because these populations have been well studied with respect to antomy, body composition, and physiology. When appropriate, comparisons are made between the chosen reference values and data from several Asian populations. The first section of the report provides summary tables of all the anatomical and physiological parameters given as reference values in this publication. These results give a comprehensive view of reference values for an individual as influenced by age and gender. The second section describes characteristics of dosimetric importance for the embryo and fetus. Information is provided on the development of the total body and the timing of appearance and development of the various organ systems. Reference values are provided on the mass of the total body and selected organs and tissues, as well as a number of physiological parameters. The third section deals with reference values of important anatomical and physiological characteristics of reference individuals from birth to adulthood. This section begins with details on the growth and composition of the total body in males and females. It then describes and quantifies anatomical and physiological characteristics of various organ systems and changes in these characteristics during growth, maturity, and pregnancy. Reference values are specified for characteristics of dosimetric importance. The final section gives a brief summary of the elemental composition of individuals. Focusing on the elements of dosimetric importance, information is presented on the body content of 13 elements: calcium, carbon, chloride, hydrogen, iodine, iron, magnesium, nitrogen, oxygen, potassium, sodium, sulphur, and phosphorus.

Abstract  We examined data recorded for 3 545 subjects aged 6-19 y who participated in the Hispanic Health and Nutrition Survey. We sought to confirm a relationship between blood lead levels and elevated hearing thresholds that we previously reported in a similar study in which data from the Second National Health and Nutrition Examination Survey was used. Lead was associated with an increased risk of hearing thresholds that were elevated above the standard reference level at all four frequencies (i.e., 500 Hz, 1 000 Hz, 2 000 Hz, and 4 000 Hz). Lead was also associated with hearing thresholds when they were treated as a continuous outcome. The relationships appeared to continue at blood lead levels less than 10 μg/dl. An increase in blood lead, from 6 μg/dl to 18 μg/dl, was associated with a 2-dB loss in hearing at all frequencies, and an additional 15% of children had hearing thresholds that were below the standard at 2 000 Hz.

Abstract  Studies were undertaken to address the necessity of B-T cell contact for the enhancement of B cell differentiation caused by the heavy metal lead (Pb). Membrane segregated cultures were used so that the influences of direct B-T cell contact and T cell factors on B cell differentiation could be independently evaluated. B-T cell contact was not absolutely required for Pb's enhancement of B cell maturation to antibody forming cells (AFCs); however, enhancement of the AFC response by Pb was optimal when B-T cell interactions were allowed. These results were corroborated by use of anti-L3T4 (mouse CD4) to block CD4+ T cell-B cell interaction. Blockade of B-T cell contact with anti-L3T4 did not inhibit the enhancement of the AFC response by Pb. Additional experimentation showed that Pb enhanced the AFC response and Ig production in the presence of antigen-specific T cell help, suggesting that Pb enhances B cell differentiation by augmenting cognate help rather than by inducing a response to Pb-altered-self. In studies employing antigen-specific T cell clones, Pb was found to differentially modulate antigen presentation to TH1 versus TH2 T cell clones, in that TH1 activation was inhibited and TH2 activation was enhanced by Pb.