Biomedical subjects

D A Fox

Publications and source records attributed to D A Fox.

At least 73 records · Page 4Linked to original sources

PubMed1992

Cell cycle progression is associated with distinct patterns of phosphorylation of Op18.

Op18 is a highly conserved major cytosolic phosphoprotein which has been implicated in signal transduction in a wide variety of cell types. Freshly isolated peripheral blood lymphocytes (PBL) constitutively express low levels of mostly unphosphorylated Op18. Following mitogenic stimulation of PBL, Op18 synthesis is induced at a time when cells are entering S-phase. In this study we have characterized Op18 phosphorylation during progression of freshly isolated PBL through the cell cycle. Transition from G0 to G1 following activation with OKT3 was associated with an increase in a phosphorylated form designated Op18c. Progression of cells through G1 into S resulted in an increase in phosphorylated Op18 forms, designated Op18a and Op18b, which paralleled new Op18 synthesis. Transition of cells into G2 + M resulted in the appearance of the more acidic phosphorylated forms Op18d and Op18e. Calphostin C, a specific inhibitor of protein kinase C, dramatically decreased all forms of phosphorylated Op18 in OKT3 treated Jurkat cells. Our results suggest that Op18 phosphorylation is mediated in part by PKC activation as well as by other kinases yielding different phosphorylated forms at specific stages of the cell cycle.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1992

Fine mapping of monoclonal antibody epitopes on human von Willebrand factor using a recombinant peptide library.

A recombinant human von Willebrand factor (vWF) cDNA fragment library was constructed in lambda gt11 for the localization of anti-vWF monoclonal antibody epitopes. Twelve of 21 monoclonal antibodies screened identified epitopes expressed in lambda gt11 as beta-galactosidase fusion proteins. By sequence analysis, these antigenic determinants were localized to segments ranging from 17 to 105 amino acids in length. Four epitopes apparently shared by more than one antibody were identified, suggesting the presence of immuno-dominant epitopes within vWF. Monoclonal antibody C3, which blocks factor VIII (FVIII) binding to vWF, bound to the same epitope previously identified by a second monoclonal antibody which also blocks this function, suggesting that this region may be at or near the vWF/FVIII binding domain. Three antibodies recognize the same region within the vWF A2 repeat. Mutations near this region appear to be responsible for Type IIA von Willebrand's disease. The co-localization of these antibodies suggests that this domain might be exposed on the surface of vWF, consistent with its apparent increased sensitivity to plasma proteases.

Antibodies, Monoclonal↗

PubMed1992

Developmental lead exposure selectively alters the scotopic ERG component of dark and light adaptation and increases rod calcium content.

Electrophysiological studies have established that lead exposure produces selective rod deficits. The present electroretinographic (ERG) and correlated calcium experiments examined whether low-level or moderate-level developmental lead exposure (peak blood lead of 19 and 59 micrograms/dl, respectively) altered dark adaptation and/or light adaptation. Developmental lead exposure produced long-term dose-response (1) decreases in the slope of the increment threshold function only at scotopic adapting backgrounds, (2) decreases only in the sensitivity of the rod phase of dark adaptation and (3) increases in the calcium content of rod outer segments which may partially mediate the ERG results. The relevance and applicability of these data to lead-exposed children have yet to be established.

Adaptation, Ocular↗

PubMed1991

S100-positive, T-cell chronic lymphoproliferative disease: an aggressive disorder of an uncommon T-cell subset.

S100-positive T lymphocytes account for less than 3% of peripheral blood T cells. Rare cases of S100-positive T-cell lymphoma have been previously described. We report four such cases of S100-positive T-cell chronic lymphoproliferative disease. In all cases, hepatosplenomegaly was observed, without prominent lymphadenopathy. Central nervous system (CNS) involvement by the leukemic cells was suggested in three cases by physical symptoms and confirmed in two cases by cerebrospinal fluid studies. Despite treatment, three patients died at 3, 6, and 8 months after diagnosis. Although there was a leukemic presentation, only minimal bone marrow infiltration was evident. Splenectomy showed red pulp infiltration. Liver and lymph node biopsies showed sinusoidal leukemic involvement. In all cases, the leukemic cells expressed mature T-cell- and natural killer cell-associated antigens. Cytoplasmic S100 was detected in the leukemic cells in the blood, spleen, liver, and lymph node. Southern blot studies in two cases showed T-beta, T-gamma, and T-delta gene rearrangements. RNA Northern blots showed T-alpha and T-beta chain transcripts with no T-gamma or T-delta RNA identified. Southern blot analysis showed no hybridization to probes specific for Epstein-Barr virus, cytomegalovirus, human immunodeficiency virus-1, or human T-cell lymphotropic virus type-1. These findings show that S100-positive T-cell chronic lymphoproliferative disorder is an aggressive, extramedullary-based disease frequently associated with CNS involvement and characterized by short survivals.

Adult↗

PubMed1991

Defective CD2 pathway T cell activation in systemic lupus erythematosus.

CD2 (T11; sheep erythrocyte receptor) is the surface component of an alternative, antigen-independent pathway of human T cell activation. The response to certain anti-CD2 antibodies is relatively independent of accessory cell signals and therefore provides a direct measurement of T cell function. The CD2 pathway may be important in the differentiation of thymocytes, on which the expression of CD2 precedes the appearance of the CD3-T cell receptor complex. In view of the impaired T cell regulation of immune responses in patients with systemic lupus erythematosus (SLE), we examined the activation of peripheral blood lymphocytes by anti-CD2 antibodies in 57 SLE patients and 32 normal control subjects. The CD2 pathway response was lower in the SLE patients (P less than 0.0001); 18 of the 57 SLE patients had a lower response than any of the control subjects. The SLE low-responder patients did not differ from the normal-responder patients in terms of disease activity or use of antiinflammatory and immunosuppressive medications. Low responses to anti-CD2 were corrected to normal by the coaddition of a submitogenic amount of phorbol myristate acetate (1 ng/ml). In some low-responder patients, the responses were normalized by the removal of non-T cells. The data indicate that some SLE patients have impaired responses to CD2 pathway activation and that this may reflect intrinsic T cell defects and/or regulatory influences of non-T cells.

Adult↗

PubMed1991

Developmental lead exposure inhibits adult rat retinal, but not kidney, Na+,K(+)-ATPase.

Neonatal lead exposure produces selective rod degeneration and functional deficits in adult hooded rats. Similar alterations occur following retinal exposure to ouabain. This study determined whether there were long-term effects of neonatal lead exposure on rat retinal or renal Na+,K(+)-ATPase (Na,K-ATPase) activity and employed in vitro studies to examine the mechanism of ionic lead (Pb2+)-induced inhibition of retinal Na,K-ATPase. Pups, exposed to lead only via the milk of dams consuming 0, 0.02, or 0.2% lead solutions, had mean blood lead concentrations of 1.2, 18.8, and 59.4 micrograms/dl at weaning, respectively, and 5-7 micrograms/dl as adults. Prior lead exposure produced significant dose-dependent decreases in isolated retinal Na,K-ATPase activity (-11%; -26%) whereas activity in the kidney was unchanged. In contrast, Na,K-ATPase from both isolated control tissues was inhibited by Pb2+. The half-maximal inhibitory dose (I50) of Pb2+ for retinal and renal Na,K-ATPase was 5.21 x 10(-7) and 1.25 x 10(-5) M, respectively. The Hill coefficient of the retina was 0.42 whereas it was 0.88 in the kidney. With MgATP as a substrate, the Pb(2+)-induced inhibition of retinal Na,K-ATPase was competitive and reversible with a Ki of 2.1 x 10(-7) M. Retinal and renal Na,K-ATPase were 20-fold and 1.1-fold more sensitive to inhibition by Pb2+ than by Ca2+, respectively. The Pb(2+)-induced inhibition of retinal Na,K-ATPase was antagonized by Na+, potentiated by Mg2+, not altered by K+ or Ca2+, and prevented by ATP. Kinetic and competition studies with the retinal Na,K-ATPase establish that the Pb(2+)-induced inhibition is complex. The increased sensitivity of retinal, compared to renal, Na,K-ATPase to inhibition following in vivo or in vitro lead exposure may relate to their different alpha subunit composition. This is speculated to play a fundamental role in the target organ toxicity of lead.

Administration, Oral↗

PubMed1991

Refractive-error changes in kitten eyes produced by chronic on-channel blockade.

The dependence of the emmetropization process on retinal ON-channel activity was examined in developing kittens by making regular intravitreal injections of D,L-2-amino-4-phosphonobutyric acid (APB). In comparison to sham-injected control eyes, the APB-treated eyes had shorter axial lengths and were more hyperopic. Since chronic atropinization did not alter the development of the APB-induced hyperopia, these anomalous refractive errors are not the result of altered accommodative function. The axial hyperopia observed in the APB-treated eyes indicates that the mechanisms responsible for normal axial elongation are dependent to some extent on ON-channel activity and that, even in the presence of a clear retinal image, OFF-channel activity, by itself, is not sufficient to regulate the normal emmetropization process.

Aminobutyrates↗

PubMed1991

Low level developmental lead exposure decreases the sensitivity, amplitude and temporal resolution of rods.

Electroretinographic (ERG), morphometric and biochemical studies on retinas from monkeys or rats reveal that moderate level developmental lead (Pb) exposure produces long-term selective rod deficits and degeneration. The present studies determined whether similar alterations occur following low level developmental Pb exposure. Long-Evans rats, exposed to Pb only via dam's milk from parturition to weaning, had mean blood Pb of 18.8 micrograms/dl at weaning and 6.6 micrograms/dl at 90 days of age. Morphometric and ultrastructural studies revealed no signs of rod loss or degeneration although the presence of glycogen in some rod mitochondria suggests the occurrence of a metabolic dysfunction. Retinal sensitivity and rhodopsin content per eye were decreased in a manner such that, they followed the established log-linear relationship. A- and b-wave voltage- and latency-log intensity functions, generated from single-flash ERGs in fully dark-adapted rats, revealed that low level Pb exposure caused a 25% and 15% decrease in mean amplitude, a 0.5 and a 0.5 log unit decrease in absolute sensitivity, and a 23% and 16% increase in mean latency, respectively. Scotopic (rod-mediated) and photopic (cone-mediated) flicker fusion frequency measures revealed selective rod deficits. Adult rats had a 15% inhibition of retinal cGMP-phosphodiesterase resulting in a 19% and 12% increase in cGMP in dark- and light-adapted states, respectively. The above data confirm and extend our previous studies conducted in rats with blood lead levels of 59 micrograms/dl during development. The rhodopsin and cyclic nucleotide metabolism data, as well as our recent data showing an inhibition of retinal Na+, K(+)-ATPase, are entirely consistent with the observed ERG changes. The fact that rat rods are similar to monkey and human rods suggests the relevance and applicability of these data to low level pediatric Pb poisoning. Thus, these data suggest that alterations in rod sensitivity and temporal processing may occur in children exposed to low levels of lead during perinatal development.

Animals↗

PubMed1991

Prenatal ethanol exposure alters scotopic and photopic components of adult rat electroretinograms.

Ocular malformations and visual deficits are pathognomic of fetal alcohol syndrome (FAS). However, there are no reports on retinal visual function. To determine if prenatal (human second-trimester equivalent) or prenatal plus 10 days of postnatal (human third-trimester equivalent) ethanol exposure produced scotopic and/or photopic deficits in adult hooded rats, electroretinography (ERG) was used to examine rod and cone, increment threshold, dark adaptation, and paired-flash amplitude recovery functions. The rhodopsin content per eye also was determined. Five main results were found. First, voltage-log intensity and latency-log intensity functions, generated from single-flash ERGs in fully dark-adapted rats, showed increases in absolute threshold and latency and decreases in response amplitude. Second, cone ERGs had latency increases. Third, there were decreases in the scotopic and photopic critical flicker-fusion frequencies, increment threshold functions, and absolute and relative refractory periods. Fourth, rod sensitivity, range, and rate of dark adaptation were decreased. Fifth, rhodopsin content per eye was decreased. These data showed that prenatal ethanol exposure produces long-term deficits in retinal sensitivity, amplitude, light and dark adaptation, temporal processing, and excitability. Larger deficits occurred in the scotopic than photopic system and were produced with an additional 10 days of postnatal ethanol exposure. Alterations in photoreceptors and other cells of the distal retina probably contributed to these deficits. The relevance and applicability of these data to FAS and subclinical alcohol embryopathy have yet to be demonstrated; however, they suggest that similar retinal alterations may occur in human FAS.

Animals↗

PubMed1990

In vivo ultraviolet-exposed human epidermal cells activate T suppressor cell pathways that involve CD4+CD45RA+ suppressor-inducer T cells.

In vivo UV exposure of human epidermis abrogates the function of CD1+DR+ Langerhans cells and induces the appearance of CD1-DR+ Ag-presenting macrophages. Epidermal cells from UV-exposed skin, in contrast to epidermal cells from normal skin, potently activate autologous CD4+ T cells, and, in particular, the CD45RA+ (2H4+) (suppressor-inducer) subset. We therefore determined whether UV-exposure in humans leads to a T cell response in which suppression dominates. Autologous blood T cells were incubated with epidermal cell suspensions from in vivo UV-irradiated skin. After activation, repurified T cells were transferred in graded numbers to autologous mononuclear cells (MNC) stimulated with PWM and the resultant IgG production analyzed by ELISA. Relative to T cells activated by unirradiated control epidermal cells, T cells activated by UV-exposed epidermal cells demonstrated enhanced capacity to suppress IgG production (n = 6; p less than or equal to 0.03). Within the T cell population, CD8+ cells stimulated by UV-exposed epidermal cells could be directly activated to suppress PWM-stimulated MNC Ig production if IL-2 was provided in the reaction mixture. The suppressive activity was also transferable with purified CD4+ T cells stimulated by UV-exposed epidermal cells (n = 10; p less than or equal to 0.01), and was radiosensitive. Suppression was decreased when PWM-stimulated MNC were depleted of CD8+ T cells before mixing with CD4+ T cells activated by UV-exposed epidermal cells, suggesting indirect induction of CD8+ Ts cells contained within the responding MNC populations. Indeed, physical depletion of CD45RA+ cells resulted in total abrogation of the suppressor function contained in the CD4+ T cells. Activation of suppressor function was critically dependent on DR+ APC contained in UV-exposed epidermis. The data suggest that UV-exposure modulates cutaneous APC activity in humans, as in mice, such that the dominant immune response is tilted toward suppression. These mechanisms in normal individuals may function to dampen responses to UV-induced endogenous Ag that are pathogenic in autoimmune disorders. However, these mechanisms might also facilitate the growth of UV-induced skin cancers.

Antibody Formation↗

PubMed1990

Activation of human T cell clones through the UM4D4/CDw60 surface antigen.

UM4D4 is a recently defined antigen that is expressed on approximately 25% of peripheral blood T cells, but on the majority of T cells in inflammatory synovial fluid. Anti-UM4D4 activates peripheral blood T cells in the presence of accessory cells and/or phorbol ester. UM4D4 has been assigned to a new antigen cluster termed CDw60. The present study examined the ability of anti-UM4D4 to activate T cell clones derived from the synovial fluid of patients with rheumatoid arthritis. UM4D4 was expressed at varying levels on both lectin-generated and antigen-specific clones, including clones of CD4+, CD8+, and CD4-CD8- phenotypes. Anti-UM4D4 used in soluble form as a single stimulus was typically mitogenic for the CD4+ and some of the CD8+ clones, but not for the CD4-CD8- clones. Phorbol ester boosted the response to anti-UM4D4 in some clones, had no effect in others, and diminished the responses in some cases. In contrast to anti-UM4D4, anti-CD3 was generally not mitogenic in soluble form, although it was mitogenic when conjugated to beads. The data show that T cell clones derived from an inflammatory T cell infiltrate can be readily activated through the UM4D4/CDw60 antigen.

Antibodies, Monoclonal↗

PubMed1990

UM4D4+ (CDw60) T cells are compartmentalized into psoriatic skin and release lymphokines that induce a keratinocyte phenotype expressed in psoriatic lesions.

UM4D4 (CDw60), the surface molecule of a novel antigen-independent T-cell activation pathway, was found to be highly expressed on lesional psoriatic T cells. To examine whether UM4D4 represents a T-cell activation pathway for psoriatic T cells, a T-cell line was initiated from an acute skin lesion and cloned by limiting dilution. Clonality was verified by analysis of T-cell receptor gene rearrangement. All T-cell clones tested, whether CD4+2H4+CD8-, CD4+2H4-CD8-, or CD4-CD8+CD11b-, expressed UM4D4 and were activated by the monoclonal antibody anti-UM4D4. Lesional psoriatic T-cell clones were heterogeneous in the degree of anti-UM4D4-induced proliferation and in their production of IL-2 and gamma-interferon. Lymphokines released by anti-UM4D4 activation were capable of inducing ICAM-1 and HLA-DR expression on cultured normal keratinocytes. Thus, the high expression of UM4D4 on T-cells in psoriatic skin provides an alternative mechanism for T-cell activation that may be operative in the psoriatic lesional milieu. Indeed, activation of lesional T-cells through the UM4D4 molecule resulted in release of lymphokines that directly induced keratinocytes to express a phenotype displayed in psoriatic skin lesions.

Antigens, CD↗

PubMed1990

Identification of two related markers for common acute lymphoblastic leukemia as heat shock proteins.

By direct analysis of the polypeptide constituents of leukemic cells, we have previously detected several polypeptides that are restricted in their expression to acute lymphoblastic leukemia (ALL). In this study, we provide evidence that two polypeptides designated L2 and L4 are structurally related and represent novel markers for common ALL. Partial amino acid sequence analysis did not uncover differences between L2 and L4. The sequences obtained correspond to a previously cloned human gene designated hsp 27 that is expressed, following heat shock treatment, in a variety of cells. 32Pi incorporation studies indicate that L4 is an unphosphorylated form and L2 is a phosphorylated form of hsp27. The two forms were inducible by heat shock in leukemic and nonleukemic lymphoid cells. Thus, in acute leukemia, the common ALL subtype is uniquely characterized by the constitutive expression of a polypeptide that represents a major cellular phosphoprotein.

Amino Acid Sequence↗

PubMed1990

Activation pathways of synovial T lymphocytes. Expression and function of the UM4D4/CDw60 antigen.

Accumulating evidence implicates a central role for synovial T cells in the pathogenesis of rheumatoid arthritis, but the activation pathways that drive proliferation and effector function of these cells are not known. We have recently generated a novel monoclonal antibody against a rheumatoid synovial T cell line that recognizes an antigen termed UM4D4 (CDw60). This antigen is expressed on a minority of peripheral blood T cells, and represents the surface component of a distinct pathway of human T cell activation. The current studies were performed to examine the expression and function of UM4D4 on T cells obtained from synovial fluid and synovial membranes of patients with rheumatoid arthritis and other forms of inflammatory joint disease. The UM4D4 antigen is expressed at high surface density on about three-fourths of synovial fluid T cells and on a small subset of synovial fluid natural killer cells; in synovial tissue it is present on more than 90% of T cells in lymphoid aggregates, and on approximately 50% of T cells in stromal infiltrates In addition, UM4D4 is expressed in synovial tissue on a previously undescribed population of HLA-DR/DP-negative non-T cells with a dendritic morphology. Anti-UM4D4 was co-mitogenic for both RA and non-RA synovial fluid mononuclear cells, and induced IL-2 receptor expression. The UM4D4/CDw60 antigen may represent a functional activation pathway for synovial compartment T cells, which could play an important role in the pathogenesis of inflammatory arthritis.

Adult↗

PubMed1989

Time- and frequency-dependent effects of potassium channel blockers on large and medium diameter optic tract axons.

Compound action potential recording techniques were used to investigate the time- and frequency-dependent effects of 4-aminopyridine (4-AP) and tetraethylammonium (TEA) on large diameter, fast conducting (t1) and medium diameter, middle conducting (t2) optic tract axons in anesthetized hooded rats. Single-pulse studies show 4-AP causes a rapid decrease in t1 and t2 response amplitude with larger decreases and longer lasting effects in t2 axons. In both axons, 4-AP leads to waveform broadening which is accounted for by increases in fall time since rise time and conduction velocity are unaffected by 4-AP. Strength-duration curves reveal 4-AP increases rheobase and decreases chronaxie in both axons with larger increases occurring in t1. T1, but not t2, axons also display some TEA-sensitivity. The absolute and relative refractory periods, determined with paired-pulse recovery functions, are increased by 4-AP to a greater degree in t1 than t2 axons. These axons, however, display equal sensitivity to TEA. In contrast, 4-AP and TEA decrease frequency following in both axons with larger effects observed in t2. Based on our data, and that of others, we speculate that t1 axons exhibit 4-AP and TEA sensitivity at nodal/paranodal regions and not at internodal regions, while t2 axons exhibit 4-AP sensitivity at nodal/paranodal and internodal regions and TEA sensitivity only at internodal regions of the axolemma. The possible relevance of these findings to the distribution of 4-AP- and TEA-sensitive potassium channels on t1 and t2 axons and the coding of visual spatial and temporal information remains to be determined.

4-Aminopyridine↗

PubMed1989

Expression and function of the UM4D4 antigen in human thymus.

UM4D4 is a newly identified T cell surface molecule, distinct from the Ag receptor and CD2, which is expressed on 25% of peripheral blood T cells, resting or activated. Monoclonal anti-UM4D4 is mitogenic for T cells and T cell clones. Since alternative activation pathways independent of Ag/MHC recognition may be important in thymic differentiation, the expression and function of UM4D4 was examined in human thymus. UM4D4 was found on the surface of 6% of thymocytes. All thymocyte subsets contained UM4D4+ cells but expression was greatest on thymocytes that were CD1- (12%), CD3+ (11%) and especially CD4-CD8- (18%). CD3+CD4- CD8- cells, most of which bear the gamma delta-receptor, were greater than or equal to 50% + for UM4D4. Moreover, anti-UM4D4 was comitogenic for thymocytes together with PMA or IL-2. Anti-UM4D4 also reacted strongly with a subset of thymic epithelial cells in both cortex and medulla. Dual color fluorescence microscopy, with anti-UM4D4 and antibodies to other thymic epithelial Ag, showed UM4D4 expression on neuroendocrine thymic epithelium but not on thymic fibrous stroma. Thus, UM4D4 is expressed on, and represents an activation pathway for, a subset of thymic T cells. In addition, this determinant, initially identified as a novel T cell activating molecule, is broadly expressed by neuroendocrine thymic epithelium. Although the function of UM4D4 on the thymic epithelial cells is not yet clear, it is possible that UM4D4 represents a pathway for the functional activation of a subset of the thymic epithelium as well as a subset of thymocytes, thus playing a dual role in T cell differentiation.

Antibodies, Monoclonal↗

PubMed1989

Molecular cloning of a novel human leukemia-associated gene. Evidence of conservation in animal species.

We have recently described an 18-kilodalton polypeptide (p18) that is present in much greater abundance in acute leukemic blast cells (myeloid and lymphoid) than in resting or proliferating nonleukemic lymphoid cells or chronic lymphoid and myeloid leukemic cells. In this report we describe the cloning of two different sized full-length cDNAs that code for p18. The two cDNAs differ in their 3'-noncoding regions as a result of alternative polyadenylation. Analysis of the complete nucleotide sequence and the corresponding amino acid sequence did not reveal significant homology to any previously described sequences. We show evidence that this gene is highly conserved in several animal species and low stringency hybridization studies suggest that the p18 gene may be a member of a family of partially homologous genes in the human genome.

Amino Acid Sequence↗

PubMed1989

Age-related changes in retinal sensitivity, rhodopsin content and rod outer segment length in hooded rats following low-level lead exposure during development.

Electroretinographic, morphometric and cyclic nucleotide metabolism studies in adult hooded rats have established that low-level lead exposure during early postnatal development (postnatal days 0-21) causes long-term selective rod deficits and degeneration. To determine if this same low-level lead exposure during early postnatal development produces immediate and/or long-term alterations in retinal sensitivity we examined ERG b-wave threshold responses in dark-adapted control and lead-exposed rats at 1-, 3- and 12 months of age. In addition, to determine possible sites and mechanisms of action responsible for the observed decreases in retinal sensitivity we analyzed the rhodopsin content per eye, the lambda max of rhodopsin and rod outer segment (ROS) length in superior and inferior posterior retina at 1-, 3- and 12 months of age. Relative to adult (3-month-old) controls whose log threshold was arbitrarily set at 0 log units, the mean log relative threshold in control rats was 0.4 log units at 1 month of age and 0.2 log units at 1 yr of age. In contrast, the mean log relative threshold in lead-exposed rats was 1.3 log units at 1 month of age and 1.1-1.2 log units at 3- and 12 months of age. Thus, compared with controls, retinal sensitivity in lead-exposed rats was decreased approx. 1 log unit at all ages examined. The rhodopsin content per eye in control rats increased 13% between 1- and 3 months of age, reaching an adult value of 1.99 nmol per eye, and then decreased 8% by 1 yr of age. In contrast, the eyes from lead-exposed rats contained 30-34% less rhodopsin at all ages examined. No change in the lambda max of rhodopsin was observed in the retinas from the lead-exposed rats. In both controls and lead-exposed rats, the developmental changes in log b-wave relative threshold were paralleled by linear increases and decreases in rhodopsin content per eye such that a log-linear relation between retinal sensitivity and rhodopsin content per eye existed between 1- and 12 months of age. The developmental changes in the superior and inferior retinal ROS length were similar in control and lead-exposed rats: ROSs were at their adult length at 1 month of age and then slightly decreased by 1 yr of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗