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J D Erickson

Publications and source records attributed to J D Erickson.

At least 73 records · Page 4Linked to original sources
PubMed1995

Molecular biology of the vesicular ACh transporter.

The cholinergic synapse has long been a model for biochemical studies of neurotransmission. The molecules that are responsible for synaptic transmission are being identified rapidly. The vesicular transporter for ACh, which is responsible for the concentration of ACh within synaptic vesicles, has been characterized recently, both at the molecular and functional level. Definitive identification of the cloned gene involved genetics of Caenorhabditis elegans, the specialized Torpedo electromotor system, and expression in mammalian tissue culture. Comparison of the vesicular transporter for ACh with the vesicular transporters for monoamines demonstrates a new gene family. Gene mapping has demonstrated a unique relationship between the genes for the vesicular ACh transporter and for choline acetyltransferase.

Acetylcholine↗
PubMed1995

Paternal occupation and risk of birth defects in offspring.

Several epidemiologic studies indicate that some paternal occupations are associated with an increased risk of birth defects in offspring. We evaluated this relation using data from a population-based case-control study. Cases are infants with a major birth defect registered with the Metropolitan Atlanta Congenital Defects Program between 1968 and 1980. We selected controls from livebirths in the Atlanta area using frequency matching for race, year, and hospital of birth. Case and control parents were interviewed to solicit information on several factors, including occupation. We classified paternal occupation according to the job held during the time from 6 months before until 1 month after the estimated date of conception. We compared fathers in one occupational category with fathers in all other categories combined. We identified a number of associations including: firemen with cleft lip [odds ratio (OR) = 13.3; 95% confidence interval (CI) = 4.0-44.4]; painters with atrial septal defect (OR = 2.7; 95% CI = 1.0-7.4); and farmers with cleft lip and palate (OR = 3.3; 95% CI = 0.9-11.9). This study, however, did not corroborate several associations found in previous studies, such as painters and neural tube defects. We identified several additional occupations as potential risk factors for some defects, including printers, electronic equipment operators, and vehicle manufacturers.

Adult↗
PubMed1995

Pregnancy experience after delivery of a child with a major birth defect: a population study.

OBJECTIVE: Data from a large population-based, case-control study were analyzed to determine whether women giving birth to children with major birth defects have different subsequent pregnancy patterns than those giving birth to live-born babies without defects. Other studies examining this phenomenon have been smaller, have not been population-based, or have not addressed the different effects that a wide range of major defects might have on mothers' subsequent pregnancy rates. METHODS: Mothers of 4918 infants with major birth defects born from 1968 through 1980 in metropolitan Atlanta were compared with mothers of 3029 control infants, frequency-matched on birth year, birth hospital, and race. RESULTS: The pregnancy rate in the first 3 years after the index birth was higher among case mothers (36%) than among control mothers (30%, P < .0001). This excess was seen for mothers of stillborn case infants (64%) and mothers of case infants who survived the first year of life (31%). Pregnancy rates varied by birth defect type. Maternal and infant factors varied among case and control subjects and influenced subsequent pregnancy rates. CONCLUSION: The reproductive behavior observed in this study supports the theory that mothers of nonsurviving children with birth defects compensate by acting to "replace" the lost child. Reproductive behavior was also strongly associated with having completed a previous pregnancy and by the type of birth defect.

Case-Control Studies↗
PubMed1994

Functional identification of a vesicular acetylcholine transporter and its expression from a "cholinergic" gene locus.

The vesicular acetylcholine transporter (VAChT) has been identified and characterized based on the acquisition of high affinity vesamicol binding and proton-dependent, vesamicol-sensitive acetylcholine accumulation by a fibroblast cell line transfected with a clone from a rat pheochromocytoma cDNA library encoding this protein. The distribution of VAChT mRNA coincides with that reported for choline acetyltransferase (ChAT), the enzyme required for acetylcholine biosynthesis, in the peripheral and central cholinergic nervous systems. A human VAChT cDNA was used to localize the VAChT gene to chromosome 10q11.2, which is also the location of the ChAT gene. The entire sequence of the human VAChT cDNA is contained uninterrupted within the first intron of the ChAT gene locus. Transcription of VAChT and ChAT mRNA from the same or contiguous promoters within a single regulatory locus provides a previously undescribed genetic mechanism for coordinate regulation of two proteins whose expression is required to establish a mammalian neuronal phenotype.

Acetylcholine↗
PubMed1994

Cloning and expression of the vesamicol binding protein from the marine ray Torpedo. Homology with the putative vesicular acetylcholine transporter UNC-17 from Caenorhabditis elegans.

Complementary DNA clones corresponding to a messenger RNA encoding a 56 kDa polypeptide have been obtained from Torpedo marmorata and Torpedo ocellata electric lobe libraries, by homology screening with a probe obtained from the putative acetylcholine transporter from the nematode Caenorhabditis elegans. The Torpedo proteins display approximately 50% overall identity to the C. elegans unc-17 protein and 43% identity to the two vesicle monoamine transporters (VMAT1 and VMAT2). This family of proteins is highly conserved within 12 domains which potentially span the vesicle membrane, with little similarity within the putative intraluminal glycosylated loop and at the N- and C-termini. The approximately 3.0 kb mRNA species is specifically expressed in the brain and highly enriched in the electric lobe of Torpedo. The Torpedo protein, expressed in CV-1 fibroblast cells, possesses a high-affinity binding site for vesamicol (Kd = 6 nM), a drug which blocks in vitro and in vivo acetylcholine accumulation in cholinergic vesicles.

Amino Acid Sequence↗
PubMed1994

Prevention of folic acid-preventable spina bifida and anencephaly.

The results of the British Medical Research Council's randomized controlled trial proved that folic acid can prevent spina bifida and anencephaly. The trial provided critical scientific data upon which to base public health policy for preventing folic acid-preventable spina bifida and anencephaly. Within weeks of publication of the results, the Centers for Disease Control and Prevention in the US developed and issued guidelines for women who had had a pregnancy affected by spina bifida or anencephaly. A year later, the US Public Health Service issued the recommendation that all women of child-bearing age who are capable of becoming pregnant should consume 0.4 mg of folic acid per day. The Public Health Service needed a year to make inferential judgements about dose, target groups, safety, timing of ingestion, and existing and proposed vitamin and drug policies and regulations. Current policy discussions concern whether to permit manufacturers of vitamins or food products to claim that folic acid will prevent folic acid-preventable spina bifida and anencephaly and whether to allow a food staple to be fortified with folic acid.

Anencephaly↗
PubMed1994

On the use of affected controls to address recall bias in case-control studies of birth defects.

Inferences regarding causes of birth defects in humans are often based on results of case-control studies conducted after birth. To address bias in these studies caused by potential differential recall of past exposures between case and control mothers, many investigators have advocated the use of affected controls (babies with birth defects other than the one of interest). To evaluate whether the use of affected controls is warranted for a wide range of scenarios, we analyzed data from a population-based case-control study of birth defects in Atlanta, in which there were 4,918 babies with serious defects ascertained in the first year of life and 3,029 babies without defects. We compared the magnitude of the odds ratios for 10 specific defects--risk factor associations between normal and affected controls. These associations included demographic factors (e.g., advanced maternal age and Down syndrome), chronic maternal illnesses (e.g., diabetes and cardiac defects), chronic exposures (e.g., multivitamins and neural tube defects), and acute exposures (e.g., flu and neural tube defects). In all instances, the use of affected controls did not change etiologic inferences derived from using normal controls and there were only moderate changes in odds ratios. On the basis of theoretical considerations, we show that recall bias can lead to spurious inferences only under extreme conditions. We conclude that concerns about recall bias are overrated in birth defects studies and that the use of normal controls is acceptable unless evidence of substantial recall bias exists.

Case-Control Studies↗
PubMed1994

Distribution of the vesicular acetylcholine transporter (VAChT) in the central and peripheral nervous systems of the rat.

Expression of the acetylcholine biosynthetic enzyme choline acetyltransferase (ChAT), the vesicular acetylcholine transporter (VAChT), and the high-affinity plasma membrane choline transporter uniquely defines the cholinergic phenotype in the mammalian central (CNS) and peripheral (PNS) nervous systems. The distribution of cells expressing the messenger RNA encoding the recently cloned VAChT in the rat CNS and PNS is described here. The pattern of expression of VAChT mRNA is consistent with anatomical, pharmacological, and histochemical information on the distribution of functional cholinergic neurons in the brain and peripheral tissues of the rat. VAChT mRNA-containing cells are present in brain areas, including neocortex and hypothalamus, in which the existence of cholinergic neurons has been the subject of debate. The demonstration that VAChT is a completely adequate marker for cholinergic neurons should allow the systematic delineation of cholinergic synapses in the rat nervous system when antibodies directed to this protein are available.

Animals↗
PubMed1994

Localization of vesicular monoamine transporter isoforms (VMAT1 and VMAT2) to endocrine cells and neurons in rat.

Polyclonal antipeptide antibodies have been raised against each of the two isoforms of the rat vesicular monoamine transporter, VMAT1 and VMAT2. Antibody specificity was determined by isoform-specific staining of monkey fibroblasts programmed to express either VMAT1 or VMAT2. The expression of VMAT1 and VMAT2 in the diffuse neuroendocrine system of the rat has been examined using these polyclonal antibodies specific for either VMAT1 or VMAT2. VMAT1 is expressed exclusively in endocrine/paracrine cells associated with the intestine, stomach, and sympathetic nervous system. VMAT2 is expressed in neurons of the sympathetic nervous system, and aminergic neurons in the enteric and central nervous systems. VMAT2 is expressed in at least two endocrine cell populations in addition to its expression in neurons. A subpopulation of chromogranin A (CGA)-expressing chromaffin cells of the adrenal medulla also express VMAT2, and the oxyntic mucosa of the stomach contains a prominent population of CGA- and VMAT2-positive endocrine cells. The expression of VMAT2 in neurons, and the mutually exclusive expression of VMAT1 and VMAT2 in endocrine/paracrine cell populations of stomach, intestine, and sympathetic nervous system may provide a marker for, and insight into, the ontogeny and monoamine-secreting capabilities of multiple neuroendocrine sublineages in the diffuse neuroendocrine system.

Adrenal Medulla↗
PubMed1994

First-trimester anesthesia exposure and the risk of central nervous system defects: a population-based case-control study.

OBJECTIVES: Although up to 2% of women undergo surgery during pregnancy, teratogenic effects of general anesthesia have not been adequately studied. Recently, an association between first-trimester operations and central nervous system defects has been described. This issue was explored in a population-based case-control study. METHODS: Case patients included live-born and stillborn infants with central nervous system defects born to residents of metropolitan Atlanta, Ga, between 1968 and 1980. Control patients included normal babies frequency matched to case patients by race, birth hospital, and period of birth. Conditional logistic regression analysis was used to adjust for potential confounding factors. RESULTS: Of 694 mothers of infants with central nervous system defects, 12 reported first-trimester anesthesia exposure; 34 of 2984 control mothers reported such exposure (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 0.8, 3.3). A striking association was observed between reported anesthesia exposure and hydrocephalus with another major defect (OR = 9.6, 95% CI = 3.8, 24.6). The strongest association was that of anesthesia exposure with hydrocephalus and eye defects (OR = 39.6, 95% CI = 7.5, 209.2). CONCLUSIONS: An increased risk of hydrocephalus with other defects was found among offspring of mothers with reported first-trimester anesthesia. Further studies are needed to explore the possible teratogenic effects of general anesthesia.

Abnormalities, Drug-Induced↗
PubMed1993

Monitoring for new multiple congenital anomalies in the search for human teratogens.

The ability of birth defects monitoring to detect new human teratogenic and mutagenic agents may be limited if only isolated defects are monitored. Surveillance for "new" multiple congenital anomalies (MCA) may improve the detection of environmental agents associated with new defect patterns. To evaluate the feasibility of such monitoring, we examined data from two programs: 1) the Metropolitan Atlanta Congenital Defects Program (MACDP), which ascertains infants with serious defects diagnosed in the first year of life, and, 2) the Italian Multicenter Register for Congenital Malformations (IPIMC), which ascertains newborn infants with birth defects from many hospitals in Italy. We focused on 24 relatively serious defects and defect groups. For a baseline period (MACDP: 1968-1988, 581,000 births; IPIMC: 1986-1989, 448,000 births), we identified all possible combinations of defects occurring in the same baby. For a test period (MACDP: 1989-1990, 77,000 births; IPIMC: 1990, 91,500 births), we identified babies with "new" MCA (i.e., combinations of defects not observed before in the system). During this period in MACDP, of the 85 babies with two or more defects, 9 babies had new MCAs. In IPIMC, of the 54 babies with two or more defects, 10 babies had new MCAs. A review of the records of infants with new MCAs in MACDP and IPIMC did not identify commonalities in maternal characteristics. This analysis illustrates the feasibility of monitoring for new MCAs in surveillance systems. This approach, complemented by an evaluation of exposures, may be a powerful additional tool in searching for human teratogens and mutagens.

Abnormalities, Multiple↗
PubMed1993

Case-control study of congenital defects and parental employment in health care.

Health care workers may be occupationally exposed to known and suspected teratogens including viruses, anesthetic gases, sterilants, mercury, and x-radiation. To assess the risk of congenital defects among offspring of health care workers, we analyzed parental occupational histories for 4,915 case babies with congenital defects, registered during the years 1968-1980 by the Metropolitan Atlanta Congenital Defects Program (MACDP) registry, and for 3,027 control babies born without defects during the same period. Offspring of mothers employed in a nursing occupation during the periconceptional period had a modest excess risk of having at least one congenital defect (relative risk [RR] = 1.42; 95% confidence interval [CI] 1.06-1.88); the offspring were at statistically significant increased risk of having anencephaly or spina bifida (RR = 2.00; 95% CI 1.01-4.30), coarctation of the aorta (RR = 2.06; 95% CI 1.10-3.82), genital system defects (RR = 1.61; 95% CI 1.03-2.53), and urinary system defects (RR = 3.43; 95% CI 1.41-8.34). These associations were not confounded by maternal age, education, or alcohol consumption. Offspring of mothers employed in administrative or clerical jobs in the health care industry also had a modest excess risk of defects (RR = 1.35; 95% CI 0.96-1.90), including a statistically significant excess risk of limb defects. We also found associations between neural tube defects and potential exposure to anesthetic gases and to x-radiation, but each association was based on only three case babies of potentially exposed parents. We found no associations between defects and paternal health care employment, except for a few individual defects, and these were based on small numbers of exposed subjects. Only one of five previous studies reviewed found an increased risk of congenital defects among offspring of nurses, but three of the four negative studies had substantially smaller sample sizes than the present study. Detection bias may be a possible explanation for the apparent excess risk of certain defects among offspring of nurses.

Abnormalities, Drug-Induced↗
PubMed1993

Recurrent pregnancy loss as an indicator for increased risk of birth defects: a population-based case-control study.

Stillbirths and spontaneous abortuses have higher rates of birth defects than liveborn infants. The relationship between a woman's previous pregnancy loss and the risk of birth defects in the offspring has not been adequately examined, however. Using data from a population-based case-control study, we assessed whether one or more previous pregnancy loss was associated with increased birth defect risks. Case subjects were 4918 infants with serious births defects diagnosed in the first year of life and ascertained by the Metropolitan Atlanta Congenital Defects Program from 1968 to 1980. Control subjects were 3028 normal liveborn infants frequency-matched to case infants by race, hospital and period of birth. Among case and control infants whose mothers had already had at least one previous pregnancy, reported pregnancy losses (stillbirths and miscarriages) were associated with elevated risks of birth defects (odds ratios for one pregnancy loss of 1.24, two pregnancy losses of 1.49, and three or more pregnancy losses of 1.62, P < 0.0001 for trend). This association held after considering several potential confounders using logistic regression analysis. When specific defects were examined, many exhibited this association, notably hydrocephalus, and some cardiovascular, genital and limb defects. We estimate that the risk of serious birth defects increases from 2.5% for infants of women with no prior pregnancy loss to 4.2% for infants of women with three or more pregnancy losses. This finding has both clinical implications for pregnancy counselling and pathogenetic implications related to birth defect aetiology.

Abortion, Habitual↗
PubMed1993

Functional identification and molecular cloning of a human brain vesicle monoamine transporter.

A vesicle monoamine transporter was functionally identified, molecularly cloned, and characterized from a human substantia nigra cDNA library. The ATP-dependent transport of 5-[3H]hydroxytryptamine ([3H]5-HT) by digitonin-permeabilized fibroblasts expressing the vesicle monoamine/H+ antiporter in culture exhibited a Km of 0.55 microM. Reserpine and tetrabenazine, inhibitors of two monoamine binding sites, effectively blocked [3H]5-HT accumulation with Ki values of 34 and 78 nM, respectively. Pretreatment of cells with as little as 10 nM reserpine in the presence of ATP abolished uptake. The rank order for substrate inhibition of [3H]5-HT uptake for both the previously reported rat vMAT1 and the human transporter clone followed the order 5-HT > dopamine > epinephrine > norepinephrine > 1-methyl-4-phenylpyridinium > 2-phenylethylamine > histamine. The virtually identical transport characteristics of rvMAT1 and hvMAT1 confirm the relevance of neuropharmacological studies of rat brain biogenic amine uptake and storage to human brain neurochemistry.

Adenosine Triphosphate↗
PubMed1993

Glycoprotein III (clusterin, sulfated glycoprotein 2) in endocrine, nervous, and other tissues: immunochemical characterization, subcellular localization, and regulation of biosynthesis.

Specific antisera were raised against the A and B chains of glycoprotein III. Immunoblotting revealed that in adrenal medulla both chains migrate very closely together in two-dimensional electrophoresis. Both chains with slightly differing molecular sizes are found in several endocrine tissues and in brain, kidney, liver, and serum. The mRNA has an analogous widespread distribution. In primary cultures of chromaffin cells the level of message becomes significantly increased by treatment with histamine or 12-O-tetradecanoylphorbol 13-acetate/forskolin. However, the increase is small when compared with that of secretogranin II. The subcellular localization of glycoprotein III in endocrine organs and in the posterior pituitary was investigated by subcellular fractionation and immunoelectron microscopy. Glycoprotein III was found to be confined to the large dense-core vesicles of these organs. For a discussion of the function of glycoprotein III, its localization in these organelles has to be taken into account.

Animals↗
PubMed1992

Improved ascertainment of cardiovascular malformations in infants with Down's syndrome, Atlanta, 1968 through 1989. Implications for the interpretation of increasing rates of cardiovascular malformations in surveillance systems.

Several birth defects surveillance systems have shown an upward trend in the birth prevalence of several congenital cardiovascular malformations. Improvements in clinical ascertainment have been suggested as an explanation for this increase. For several decades, 40-50% of infants with Down's syndrome have been reported to have cardiac defects associated with the unbalanced genotype. Therefore, secular changes in the frequency of ascertained cardiovascular malformations among infants with Down's syndrome in surveillance systems could shed light on improvements in the ascertainment of these defects. The authors examined changes in the frequency of ascertained cardiovascular malformations among 532 cases of Down's syndrome recorded in the Metropolitan Atlanta Congenital Defects Program from 1968 through 1989. Overall, 33% of the cases have reported cardiovascular malformations. However, the frequency of these defects in Down's syndrome infants increased dramatically from about 20% in the early 1970s to more than 50% in the late 1980s (p = 0.0001). This upward trend was seen for all major categories of cardiac defects and persisted after the cases were stratified by race, sex, maternal age, hospital of birth, birth weight, and gestational age. These results show improvement in the ascertainment of cardiovascular malformations among Down's syndrome infants in a surveillance population. They are also consistent with the hypothesis that the increasing rates of cardiac defects are related, at least in part, to improved ascertainment of these defects in the population.

Down Syndrome↗
PubMed1992

Expression cloning of a reserpine-sensitive vesicular monoamine transporter.

A cDNA for a rat vesicular monoamine transporter, designated MAT, was isolated by expression cloning in a mammalian cell line (CV-1). The cDNA sequence predicts a protein of 515 amino acids with 12 putative membrane-spanning domains. The characteristics of [3H]serotonin accumulation by CV-1 cells expressing the cDNA clone suggested sequestration by an intracellular compartment. In cells permeabilized with digitonin, uptake was ATP dependent with an apparent Km of 1.3 microM. Uptake was abolished by the proton-translocating ionophore carbonylcyanide p-trifluoromethoxyphenylhydrazone and with tri-(n-butyl)tin, an inhibitor of the vacuolar H(+)-ATPase. The rank order of potency to inhibit uptake was reserpine > tetrabenazine > serotonin > dopamine > norepinephrine > epinephrine. Direct comparison of [3H]monoamine uptake indicated that serotonin was the preferred substrate. Photolabeling of membranes prepared from CV-1 cells expressing MAT with 7-azido-8-[125I]iodoketanserin revealed a predominant tetrabenazine-sensitive photolabeled glycoprotein with an apparent molecular mass of approximately 75 kDa. The mRNA that encodes MAT was present specifically in monoamine-containing cells of the locus coeruleus, substantia nigra, and raphe nucleus of rat brain, each of which expresses a unique plasma membrane reuptake transporter. The MAT cDNA clone defines a vesicular monoamine transporter representing a distinct class of neurotransmitter transport molecules.

Affinity Labels↗