Search PubMed⌕ Search

Biomedical subjects

J D Erickson

Publications and source records attributed to J D Erickson.

At least 55 records · Page 3Linked to original sources
PubMed1997

The return of thalidomide: are birth defects surveillance systems ready?

In the 1960s, thalidomide caused limb deficiencies in thousands of infants worldwide. The limb deficiencies were frequently of the intercalary type. As a result, numerous countries started birth defect surveillance programs. In 1967, the Centers for Disease Control (CDC) started the Metropolitan Atlanta Congenital Defects Program (MACDP), a population-based surveillance system, to provide early warning against new teratogens. Recent studies have shown that thalidomide may be beneficial for a range of conditions, including cancer and AIDS, and it may once again become widely available. Here, we examine the ability of MACDP to detect an increase in the birth prevalence of limb deficiency as an early warning of fetal exposure to thalidomide. We calculated base rates for all limb deficiencies, for bilateral nonsyndromic intercalary or preaxial deficiencies, and for all nonsyndromic intercalary limb deficiencies among Atlanta infants born from 1968 through 1993. We used relative risk estimates from previous studies and a range of pregnancy exposure rates for thalidomide. We tested the statistical power of MACDP to detect subtle changes in the birth prevalence of these defects using Poisson and cumulative sum (CUSUM) techniques. The base rates for all limb deficiencies, for bilateral intercalary or preaxial deficiencies, and for all intercalary limb deficiencies, were 0.53, 0.035, and 0.022/1,000, and the estimated relative risks were 175, 4,570, and 8,180, respectively. We varied the assumed rate of exposure to thalidomide from 1/10,000 to 5/100. With a 1/1,000 exposure rate, both Poisson and CUSUM techniques will detect a rate change in intercalary limb deficiency in about 6 months of monitoring, and a rate change in bilateral intercalary or preaxial deficiencies in about 12 months of monitoring. When monitoring all limb deficiencies, a pregnancy exposure rate of 3.5% or less would go unnoticed by the Poisson method and would take more than 50 years for the CUSUM method to signal an alarm with a 1/1,000 exposure rate. However, for rates of exposure less than 1/1,000, a progressively longer period of time or larger sample are needed to detect a rate change by both methods. Our findings highlight the importance of enlarging the monitored population and correct case classification in birth defects surveillance.

Abnormalities, Drug-Induced↗
PubMed1997

Elevated rates of severe neural tube defects in a high-prevalence area in northern China.

In the northern provinces of China, the birth prevalence rate of neural tube defects (NTDs) is among the highest in the world-at about 6 per 1,000 births in rural areas. A unique population-based birth defects surveillance system in which photographs are taken of infants with selected external birth defects was implemented in two provinces in northern China and two provinces in southern China where NTD rates approximate those in the United States. In the period from March 1992 through December 1993, 660 infants with NTDs were identified by the surveillance project from a birth cohort of 251,567. We compared data from the two surveillance areas in China with data from a low-prevalence area in the United States to determine if the pattern of NTD types differs. Based on birth prevalence rates of NTDs from the Metropolitan Atlanta Congenital Defects Program, the observed to expected ratios for two types of NTDs are markedly increased at 80.8 for craniorachischisis and 25.0 for iniencephaly. Rates of these two NTDs in the southern provinces are increased to a lesser degree with observed to expected ratios of 7.1 for craniorachischisis and 2.7 for iniencephaly. The pattern of NTDs in northern China shows an increase in types that are rare in low-prevalence areas such as metropolitan Atlanta. Increased awareness of varying patterns of NTDs in different populations may have important implications for identifying etiologic and pathogenetic mechanisms of NTDs.

China↗
PubMed1997

Multivitamin supplementation and multiple births.

It is well established that maternal multivitamin supplementation reduces the risk of neural tube defects and evidence suggests that it may be associated with other reproductive outcomes. The present study was prompted by a report from a randomized trial in Hungary which showed a 40% increase in multiple births among periconceptional vitamin users. Retrospectively collected data on multivitamin supplementation were obtained on multiple and singleton births from three separate studies: Atlanta Birth Defects Case-Control Study (ABDCCS) malformed and nonmalformed infants born 1968-1980, California Birth Defects Monitoring Program (CBDMP) malformed and nonmalformed infants born 1987-1989, and Boston University Slone Epidemiology Unit Birth Defects Study (SEU-BDS) malformed infants born 1987-1994. Supplementation was divided into three mutually exclusive categories based on timing: "periconceptional" use--before through at least the third month after conception; "early" use--beginning in the first month and continuing through at least the third month after conception; and "later" use--beginning in the second or third month after conception. For periconceptional use, four of five datasets showed a 30 to 60% greater prevalence of supplementation among mothers of multiple births. In contrast, this pattern was not evident for "early" and "later" use. Overall, the study findings are tentative, due to a lack of consistency across all five datasets and they should not alter recent recommendations related to folate supplementation for the prevention of neural tube defects.

Congenital Abnormalities↗
PubMed1997

Vesicular neurotransmitter transporters. Potential sites for the regulation of synaptic function.

Neurotransmission depends on the regulated release of chemical transmitter molecules. This requires the packaging of these substances into the specialized secretory vesicles of neurons and neuroendocrine cells, a process mediated by specific vesicular transporters. The family of genes encoding the vesicular transporters for biogenic amines and acetylcholine have recently been cloned. Direct comparison of their transport characteristics and pharmacology provides information about vesicular transport bioenergetics, substrate feature recognition by each transporter, and the role of vesicular amine storage in the mechanism of action of psychopharmacologic and neurotoxic agents. Regulation of vesicular transport activity may affect levels of neurotransmitter available for neurosecretion and be an important site for the regulation of synaptic function. Gene knockout studies have determined vesicular transport function is critical for survival and have enabled further evaluation of the role of vesicular neurotransmitter transporters in behavior and neurotoxicity. Molecular analysis is beginning to reveal the sites involved in vesicular transporter function and the sites that determine substrate specificity. In addition, the molecular basis for the selective targeting of these transporters to specific vesicle populations and the biogenesis of monoaminergic and cholinergic synaptic vesicles are areas of research that are currently being explored. This information provides new insights into the pharmacology and physiology of biogenic amine and acetylcholine vesicular storage in cardiovascular, endocrine, and central nervous system function and has important implications for neurodegenerative disease.

Amino Acid Sequence↗
PubMed1997

Hypospadias trends in two US surveillance systems.

OBJECTIVE: Hypospadias is a common congenital anomaly, the cause of which is unknown. Unexplained increases in the rates of hypospadias occurred in five European countries in the 1970s and 1980s. We examined data from two birth defects surveillance systems in the United States for evidence of similar trends. METHODOLOGY: The Metropolitan Atlanta Congenital Defects Program (MACDP) provided birth prevalence rates from 1968 to 1993. The nationwide Birth Defects Monitoring Program (BDMP) provided rates from 1970 to 1993. MACDP data are population-based and could be categorized by the severity of the hypospadias. BDMP data allowed analysis of rate trends for the four census regions of the United States. RESULTS: Data from both surveillance systems showed an approximate doubling of hypospadias rates in the 1970s and 1980s. MACDP data showed that the rate of severe cases increased while the ratio of mild to severe cases decreased. BDMP data showed that hypospadias rates increased markedly in all four regions of the United States. CONCLUSIONS: The observed increases are unlikely to be attributable to increased sensitivity of the surveillance systems or the identification of more mild cases by physicians over time, because either trend would have increased rather than decreased the ratio of mild to severe cases. If real, these trends represent the largest number of cases and the first report of an increase in hypospadias rates outside of Europe. Additional investigation of a possible increase in hypospadias rates is warranted.

Humans↗
PubMed1996

Active transport of acetylcholine by the human vesicular acetylcholine transporter.

The characteristics of ATP-dependent transport of acetylcholine (ACh) in homogenates of pheochromocytoma (PC-12) cells stably transfected with the human vesicular acetylcholine transporter (VAChT) cDNA are described. The human VAChT protein was abundantly expressed in this line and appeared as a diffuse band with a molecular mass of approximately 75 kDa on Western blots. Vesicular [3H]ACh accumulation increased approximately 20 times over levels attained by the endogenous rat VAChT, expressed at low levels in control PC-12 cells. The transport of [3H]ACh by human VAChT was dependent upon the addition of exogenous ATP at 37 degrees C. Uptake was abolished by low temperature (4 degrees C), the proton ionophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone (2.5 microM) and bafilomycin A1 (1 microM), a specific inhibitor of the vesicular H+-ATPase. The kinetics of [3H]ACh uptake by human VAChT were saturable, exhibiting an apparent Km of 0.97 +/- 0.1 mM and Vmax of 0.58 +/- 0.04 nmol/min/mg. Maximal steady-state levels of vesicular [3H]ACh accumulation were directly proportional to the concentration of substrate present in the medium with saturation occurring at approximately 4 mM. Uptake was stereospecifically inhibited by L-vesamicol with an IC50 of 14.7 +/- 1.5 nM. The apparent affinity (Kd) of [3H]vesamicol for human VAChT was 4.1 +/- 0.5 nM, and the Bmax was 8.9 +/- 0.6 pmol/mg. The turnover (Vmax/Bmax) of the human VAChT was approximately 65/min. This expression system should prove useful for the structure/function analysis of VAChT.

Acetylcholine↗
PubMed1996

Distinct pharmacological properties and distribution in neurons and endocrine cells of two isoforms of the human vesicular monoamine transporter.

A second isoform of the human vesicular monoamine transporter (hVMAT) has been cloned from a pheochromocytoma cDNA library. The contribution of the two transporter isoforms to monoamine storage in human neuroendocrine tissues was examined with isoform-specific polyclonal antibodies against hVMAT1 and hVMAT2. Central, peripheral, and enteric neurons express only VMAT2. VMAT1 is expressed exclusively in neuroendocrine, including chromaffin and enterochromaffin, cells. VMAT1 and VMAT2 are coexpressed in all chromaffin cells of the adrenal medulla. VMAT2 alone is expressed in histamine-storing enterochromaffin-like cells of the oxyntic mucosa of the stomach. The transport characteristics and pharmacology of each VMAT isoform have been directly compared after expression in digitonin-permeabilized fibroblastic (CV-1) cells, providing information about substrate feature recognition by each transporter and the role of vesicular monoamine storage in the mechanism of action of psychopharmacologic and neurotoxic agents in human. Serotonin has a similar affinity for both transporters. Catecholamines exhibit a 3-fold higher affinity, and histamine exhibits a 30-fold higher affinity, for VMAT2. Reserpine and ketanserin are slightly more potent inhibitors of VMAT2-mediated transport than of VMAT1-mediated transport, whereas tetrabenazine binds to and inhibits only VMAT2. N-methyl-4-phenylpyridinium, phenylethylamine, amphetamine, and methylenedioxymethamphetamine are all more potent inhibitors of VMAT2 than of VMAT1, whereas fenfluramine is a more potent inhibitor of VMAT1-mediated monamine transport than of VMAT2-mediated monoamine transport. The unique distributions of hVMAT1 and hVMAT2 provide new markers for multiple neuroendocrine lineages, and examination of their transport properties provides mechanistic insights into the pharmacology and physiology of amine storage in cardiovascular, endocrine, and central nervous system function.

Amino Acid Sequence↗
PubMed1996

Visualization of the vesicular acetylcholine transporter in cholinergic nerve terminals and its targeting to a specific population of small synaptic vesicles.

Immunohistochemical visualization of the rat vesicular acetylcholine transporter (VAChT) in cholinergic neurons and nerve terminals has been compared to that for choline acetyltransferase (ChAT), heretofore the most specific marker for cholinergic neurons. VAChT-positive cell bodies were visualized in cerebral cortex, basal forebrain, medial habenula, striatum, brain stem, and spinal cord by using a polyclonal anti-VAChT antiserum. VAChT-immuno-reactive fibers and terminals were also visualized in these regions and in hippocampus, at neuromuscular junctions within skeletal muscle, and in sympathetic and parasympathetic autonomic ganglia and target tissues. Cholinergic nerve terminals contain more VAChT than ChAT immunoreactivity after routine fixation, consistent with a concentration of VAChT within terminal neuronal arborizations in which secretory vesicles are clustered. These include VAChT-positive terminals of the median eminence or the hypothalamus, not observed with ChAT antiserum after routine fixation. Subcellular localization of VAChT in specific organelles in neuronal cells was examined by immunoelectron microscopy in a rat neuronal cell line (PC 12-c4) expressing VAChT as well as the endocrine and neuronal forms of the vesicular monoamine transporters (VMAT1 and VMAT2). VAChT is targeted to small synaptic vesicles, while VMAT1 is found mainly but not exclusively on large dense-core vesicles. VMAT2 is found on large dense-core vesicles but not on the small synaptic vesicles that contain VAChT in PC12-c4 cells, despite the presence of VMAT2 immunoreactivity in central and peripheral nerve terminals known to contain monoamines in small synaptic vesicles. Thus, VAChT and VMAT2 may be specific markers for "cholinergic" and "adrenergic" small synaptic vesicles, with the latter not expressed in nonstimulated neuronally differentiated PC12-c4 cells.

Acetylcholine↗
PubMed1996

Cloning and expression of a neuronal rat brain glutamate transporter.

Glutamate is the major excitatory transmitter in the mammalian central nervous system. Glutamate transporters, which keep the extracellular glutamate concentration low, are required both for normal brain function and for protecting neurons against harmful glutamatergic overstimulation. We have isolated the cDNA for a rat brain glutamate transporter (REAAC1) which has 90% amino acid and 86% nucleotide identity to the rabbit EAAC1. When REAAC1 was expressed in HeLa cells using a recombinant vaccinia-T7 virus expression system, a sodium dependent glutamate uptake was observed. The affinity of the carrier to various substrates was typical of brain "high affinity' glutamate uptake: threo-3-hydroxyaspartate, (R)-aspartate, (S)-glutamate and (S)-trans-pyrrolidine-2,4-dicarboxylic acid were strong inhibitors, but not (R)-glutamate or gamma-aminobutyrate. High resolution, non-radioactive in situ hybridization histochemistry in rat brain revealed the mRNA in several types of glutamatergic as well as non-glutamatergic neurons, but not in glial cells.

ATP-Binding Cassette Transporters↗
PubMed1996

Mission simulation as an approach to develop requirements for automation in Advanced Life Support Systems.

This paper examines mission simulation as an approach to develop requirements for automation and robotics for Advanced Life Support Systems (ALSS). The focus is on requirements and applications for command and control, control and monitoring, situation assessment and response, diagnosis and recovery, adaptive planning and scheduling, and other automation applications in addition to mechanized equipment and robotics applications to reduce the excessive human labor requirements to operate and maintain an ALSS. Based on principles of systems engineering, an approach is proposed to assess requirements for automation and robotics using mission simulation tools. First, the story of a simulated mission is defined in terms of processes with attendant types of resources needed, including options for use of automation and robotic systems. Next, systems dynamics models are used in simulation to reveal the implications for selected resource allocation schemes in terms of resources required to complete operational tasks. The simulations not only help establish ALSS design criteria, but also may offer guidance to ALSS research efforts by identifying gaps in knowledge about procedures and/or biophysical processes. Simulations of a planned one-year mission with 4 crewmembers in a Human Rated Test Facility are presented as an approach to evaluation of mission feasibility and definition of automation and robotics requirements.

Automation↗
PubMed1996

Periconceptional multivitamin use and the occurrence of conotruncal heart defects: results from a population-based, case-control study.

OBJECTIVE: The preventive efficacy of the periconceptional use of multivitamins is well established for neural tube defects, much less so for other birth defects. We conducted a population-based, case-control study to assess the effects of multivitamin use on the risk for conotruncal defects, a group of severe heart defects that includes transposition of the great arteries, tetralogy of Fallot, and truncus arteriosus. METHODS: From the population-based Atlanta Birth Defects Case-Control Study, we identified 158 case infants with conotruncal defects and 3026 unaffected, randomly chosen control infants, born from 1968 through 1980 to mothers residing in metropolitan Atlanta. Periconceptional multivitamin use was defined as reported regular use from 3 months before conception through the third month of pregnancy. We present the results of the crude analysis, because the multivariate model yielded essentially identical results. RESULTS: Mothers who reported periconceptional multivitamin use had a 43% lower risk of having infants with conotruncal defects (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.33 to 1.00) than did mothers who reported no use. The estimated relative risk was lowest for isolated conotruncal defects (OR, 0.41; 95% CI, 0.20 to 0.84) compared with those associated with noncardiac defects (OR, 0.91; 95% CI, 0.33 to 2.52) or a recognized syndrome (OR, 1.82; 95% CI, 0.31 to 10.67). Among anatomic subgroups of defects, transposition of the great arteries showed the greatest reduction in risk (OR, 0.36; 95% CI, 0.15 to 0.89). CONCLUSIONS: Periconceptional multivitamin use is associated with a reduced risk for conotruncal defects. These findings could have major implications for the prevention of these birth defects.

Adolescent↗
PubMed1995

Validity of mother's report of father's occupation in a study of paternal occupation and congenital malformations.

Agreement between the mother's and father's report of the father's occupation was assessed in a case-control study of paternal occupation and birth defects. Cases were identified from births registered with the Metropolitan Atlanta Congenital Defects Program between 1968 and 1980; controls were selected from liveborn infants without defects. Both parents were sought for interview, and each parent was asked about the father's job history for 2 years prior to the infant's death. This concordance analysis is based on 3,739 case infants and 2,279 control infants for whom both parents were interviewed. The authors considered the father's report of his occupation as correct, and they assessed the ability of the mother to report the same occupation(s) during a 7-month period around conception. The exact agreement between mother's and father's report of the father's occupation was 59%. Agreement improved slightly with increasing family income and when fathers were college graduates. Female partners were not accurate proxy respondents in this study of paternal occupation and birth defects, which suggests that investigators should interview both parents in studies of paternal exposures and reproductive outcomes, i.e., mothers for pregnancy history and maternal confounders and fathers for occupational history and paternal confounders.

Case-Control Studies↗
PubMed1995

Human and monkey cholinergic neurons visualized in paraffin-embedded tissues by immunoreactivity for VAChT, the vesicular acetylcholine transporter.

The predicted C-terminal dodecapeptide of the human vesicular acetylcholine transporter (VAChT), deduced from the unique open reading frame of the recently cloned human VAChT cDNA, was conjugated through an N-terminal cysteine to keyhole limpet hemocyanin and used as an immunogen to generate polyclonal antihuman VAChT antibodies in rabbits. The distribution of the VAChT antigen in representative regions of the cholinergic nervous system was examined and compared to that of the acetylcholine biosynthetic enzyme choline acetyltransferase (ChAT), a specific marker for cholinergic neurons. VAChT immunoreactivity was localized in cell bodies of neurons in the basal forebrain and ventral horn of the spinal cord, regions in which major cholinergic projection systems to the cerebral cortex and to skeletal muscle, respectively, originate. The primate caudate nucleus contained numerous VAChT-positive interneurons. VAChT immunoreactivity was visualized in both cell bodies and extensive terminals in striatal interneurons, in contrast to formalin-fixed, deparaffinized sections stained for ChAT, in which cell bodies and fibers were stained but nerve terminals were less well visualized than with the VAChT antiserum. VAChT-positive nerve fibers were visualized in routinely immersion-fixed, paraffin-embedded human cerebral cortex, comparable to the density of fibers observed in perfusion-fixed Bouin's-postfixed monkey cerebral cortex. Extensive investment of virtually all principal ganglion cells of thoracic sympathetic ganglia of monkey and human with VAChT-positive nerve terminals was observed. VAChT-positive cell bodies, presumably corresponding to cholinergic sympathetic sudomotor neurons, were a significant fraction of the total principal cell population in monkey and human thoracic sympathetic ganglia.

Acetylcholine↗
PubMed1995

Reserpine- and tetrabenazine-sensitive transport of (3)H-histamine by the neuronal isoform of the vesicular monoamine transporter.

The transport of (3)H-histamine by the endocrine-specific (VMAT1) and neuronal (VMAT2) isoforms of the vesicular monoamine transporter has been evaluated in digitonin-permeabilized fibroblasts transfected with either VMAT1 or VMAT2. Transport of (3)H-histamine by both VMAT1 and VMAT2 was reserpine-sensitive but only transport by VMAT2 was inhibited by tetrabenazine. Maximal equilibrated levels of (3)H-histamine accumulation by VMAT2 (K(m) 300 mu M) were approximately three times greater than that mediated by VMAT1 when using a subsaturating concentration of exogenous (3)H-histamine (50 mu M). The expression of VMAT2 in histaminergic neurons in the rat brain was examined with polyclonal antipeptide antibodies specific for VMAT1 or VMAT2. VMAT2-positive and tyrosine hydroxylase-negative immunoreactive cell bodies were localized to the ventral part of the posterior hypothalamus in the region of the mamillary nuclei. The transport properties of VMAT2 and the distribution of VMAT2 in cell bodies in the tuberomammillary nucleus of the posterior hypothalamus reported here and the apparent absence of VMAT1 and VMAT2 in tissue mast cells support previous findings of reserpine-sensitive and reserpine-resistant pools of histamine in brain and peripheral tissues.

Adrenergic Uptake Inhibitors↗