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Biomedical subjects

D A Beckman

Publications and source records attributed to D A Beckman.

At least 37 records · Page 2Linked to original sources
PubMed1991

Medical sonography: reproductive effects and risks.

While it is clear that the levels and types of medical sonography that have been used in the past have no measurable risks, it would be inaccurate to label the modality of ultrasound as totally safe regardless of exposure. Most agents have reproductive risks and even teratogenic risks if the exposure is raised sufficiently. Thus the prudent use of sonography means that clinicians and designers of equipment have to maintain exposures far below the risks that have been demonstrated in animal studies and from the knowledge obtained about the physical changes that can be produced in humans as the absorbed dose is elevated. The reproductive risks were evaluated using five criteria: 1) human epidemiology, 2) secular trend data, 3) animal experiments, 4) dose response relationships, and 5) biologic plausibility. The analysis reveals that the human epidemiology does not indicate that diagnostic ultrasound presents a measurable risk to the developing embryo or fetus. Animal studies also indicate that diagnostic levels of ultrasound are safe and do not elevate the fetal temperature into the region where deleterious embryonic and fetal effects will occur. Because higher exposures of ultrasound can elevate the temperature of the embryo, the use of diagnostic procedures and the design of sonographic equipment should take into consideration the hyperthermic potential of higher exposures of ultrasound and the hypothetical additional risk of performing sonography on pregnant patients who are febrile. It would appear that if the embryonic temperature never exceeds 39 degrees C, then there is no measurable risk. We suggest that sonography (the field) and sonogram (the procedure) are the most appropriate and least anxiety provoking terms.

Animals↗
PubMed1991

Ultrastructure and function of the rat yolk sac: damage caused by teratogenic anti-VYS serum and recovery.

It was hypothesized that heterologous anti-rat visceral yolk sac serum (AVYS) exerts its teratogenic effect by reducing the endocytosis of serum proteins by the visceral yolk sac (VYS), thus reducing the supply of amino acids to the embryo and VYS. To evaluate this hypothesis, we studied the effect of teratogenic AVYS on the endocytic function of the VYS and the ultrastructure of the VYS and parietal yolk sac (PYS). Rat conceptuses were exposed to a teratogenic dose of AVYS on the 10th day of gestation in vivo or in vitro. Control and AVYS-exposed specimens were collected 24-192 hr later and prepared for scanning and transmission electron microscopy (SEM and TEM, respectively) utilizing standard procedures. The Endocytic Index was calculated for the VYS utilizing standard procedures. Approximately 97% of the in vivo exposed and 94% of the in vitro exposed embryos were morphologically abnormal. Ultrastructural observations showed that exposure to AVYS in vivo or in vitro caused severe damage to the VYS endodermal epithelial cells with loss of cellular borders, reduction in the number and length of microvilli, and increased cellular inclusions; and some damage to PYS endodermal cells with increased blebbling and decreased cell number. Recovery was evident at 72 hr and complete by 96 hr. The Endocytic Index was significantly reduced in the VYS 24 and 48 hr after injecting AVYS into the pregnant rat but was not significantly different at 96 and 192 hr. Our results show that the AVYS antiserum damaged visceral endodermal epithelium experienced ultrastructural recovery with parallel functional recovery. These studies suggest that transient yolk sac placental ultrastructural damage and dysfunction was probably sufficient to cause irreversible damage to the developing embryo during early organogenesis. We conclude that the proximate effect of the AVYS was on the plasma membrane of the visceral endoderm and that decreased pinocytosis is a consequence of this effect.

Animals↗
PubMed1990

Experimental manipulation of the rodent visceral yolk sac.

The visceral yolk sac (VYS) is an especially important placental organ in the rodent because it is the primary source of exchange between the embryo and mother during early organogenesis before the chorioallantoic placenta circulation is established. The VYS is involved with nutritional, endocrine, metabolic, immunologic, secretory, excretory, and hematopoietic functions. The VYS also plays a role in steroid metabolism and interacts with a variety of blood-borne factors: parathyroid hormone, glucocorticoids, insulin, and vitamin D metabolites. The importance of the VYS during development is emphasized by the embryotoxicity resulting from exposure to agents which cause VYS dysfunction when administered to the pregnant animal during organogenesis. Several experimental procedures have provided useful information concerning a variety of VYS functions from early organogenesis to term: Culture of the Embryo, Fetal Incubation, Culture of the Fetus, Giant Yolk Sac, Short- and Long-Term Culture of the Yolk Sac, Modified Ussing's Chamber, Single or Double Diffusion Chamber, and the use of Heterologous Rodent Visceral Yolk Sac Antibodies. Since human yolk sac pathology has been associated with developmental toxicity and spontaneous abortion, it is important to discover whether there are some common functional roles among different mammalian species and to determine if other experimental animal models can be used to study the possible contribution of human yolk sac dysfunction to some human reproductive problems.

Animals↗
PubMed1990

Experimental yolk sac dysfunction as a model for studying nutritional disturbances in the embryo during early organogenesis.

Our investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti-rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti-rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our laboratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutritional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal development during mammalian organogenesis.

Animals↗
PubMed1989

Preparation and developmental toxicity of monoclonal antibodies against rat visceral yolk sac antigens.

Thirty clones producing monoclonal antibodies (MCAs) to rat visceral yolk sac (VYS) antigens have been prepared. These MCAs localized by immunofluorescence in the VYS endoderm in vitro and were tested for developmental toxicity by intraperitioneal injection of ascites fluid into pregnant rats on day 9 of gestation. Five of the hybridomas produced MCAs that induced embryonic death, malformation, and growth retardation; the other MCAs had no developmental toxicity. Five MCAs, three teratogenic and two nonteratogenic, were tested for their ability to inhibit pinocytosis in the isolated day 17-VYS. Only the teratogenic MCAs were inhibitory, providing further evidence for the hypothesis that teratogenic antibodies interfere with the nutritional supply to the embryo.

Animals↗
PubMed1986

In vitro studies on the effect of yolk sac antisera on functions of the visceral yolk sac: I. Pinocytosis and transport of small molecules.

The production of congenital malformations by the administration of teratogenic antisera to pregnant animals has been reported from many laboratories. This work has focused our attention on the importance of the yolk sac placenta in supporting the rat embryo during early organogenesis and the significance of yolk sac dysfunction in rodent teratogenesis. The studies reported in this article deal with the effect of teratogenic antisera on the process of yolk sac transport; specifically pinocytosis (as measured by 14C-sucrose uptake) and small-molecule transport utilizing 14C-alpha-aminoisobutyric acid (AIB) and 3H-2-deoxyglucose (DOG). We sought to determine whether several different yolk sac localizing antibodies interfere with these transport processes, and, if so, which transport processes were most affected. The results of the experiments indicated that teratogenic antisera interfered with the process of pinocytosis in the yolk sac and that pinocytosis can be reduced as much as 40%. Nonteratogenic antisera, even when they localized in the yolk sac, did not interfere with the process of pinocytosis. Furthermore, the teratogenic antisera did not interfere with the transport of small molecules (either AIB or DOG) in the yolk sac. These results indicated that while fluorescent localization of an antiserum in the yolk sac did not invariably indicate the potential for teratogenicity, it is likely that the reduction in pinocytosis may directly correlate with the teratologic and embryopathic events. This work reaffirms the view that the yolk sac in important during rodent organogenesis and that yolk sac dysfunction can play an important role in the development of congenital malformations.(ABSTRACT TRUNCATED AT 250 WORDS)

Aminoisobutyric Acids↗
PubMed1986

Mechanism of known environmental teratogens: drugs and chemicals.

Basic principles of teratology and mechanisms of teratogenesis applicable to human exposures to environmental drugs and chemicals are discussed. The available clinical and experimental animal literature on environmental agents alleged or known to cause human malformations is critically reviewed and summarized.

Abnormalities, Drug-Induced↗
PubMed1983

A noninvasive acoustic method using frequency perturbations and computer-generated vocal-tract shapes.

This study investigated improved processing of acoustic data with two adult Down's syndrome subjects. Sustained vowel samples were processed through a fast-Fourier-transform spectrum analyzer, and digital waveform data were used to obtain period-by-period measurements of the fundamental frequencies. Unusual frequency perturbation (jitter), later identified as diplophonia, was found for one of the Down's subjects. In addition, the first three formant frequencies of the vowels were determined and, utilizing an algorithm described by Ladefoged and his colleagues, computer-generated vocal-tract shapes were plotted. Differences in vocal-tract shapes, especially for the back vowels, were observed between the Down's female and the normal shape. Correlations between vocal-tract shapes of the Down's subjects and those for a normal man or woman were computed. A partial three-way factor analysis was carried out to determine those load factors or coefficients for each subject that were due to individual differences. These procedures, offering synthesized techniques portraying the interpharyngeal/oral functioning of the speech structures, may eventually have direct noninvasive diagnostic and therapeutic benefit for voice/resonance-disordered clients.

Adult↗
PubMed1979

RBC-51Cr half-life and albumin turnover in growing beagle dogs during chronic radial acceleration.

The effects of chronic centrifugation on growing Beagle dogs exposed to -2 or -2.6 Gx on albumin and RBC turnover rates, albumin concentration and space, and total blood volume were determined and compared with caged and run control animals. Albumin-125I and autologous RBC-51Cr preparations were injected into all dogs at day 82 of the centrifugation period and the disappearance curves were determined by successive bleedings of the animals over the next 35 d, during which the centrifugation was continued. There were no differences in albumin turnover rates or space. Two populations of RBCs were found in both centrifuged groups, one with a normal half-life of 27 +/- 1 S.E.M. d, and one with a significantly ( less than 0.01) shorter half-life of 15 +/- 2 S.E.M. d. An absolute polycythemia was also observed in both centrifuged groups. The results suggest that chronic centrifugation acts through some as yet unknown mechanism to affect RBC population kinetics.

Acceleration↗
PubMed1978

Studies on the erythron and the ferrokinetic responses in beagles adapted to hypergravity.

Red cell survival, ferrokinetics, and hematologic parameters were investigated in Beagle dogs exposed to chronic hypergravity (2.6 Gx). Ineffective erythropoiesis, red cell mass, plasma volume, and 51 Cr elution were significantly increased; maximum 59Fe incorporation was decreased; and there was no change in the mean erythrocyte life span following autologous injection of 51Cr-labeled red cells and 59Fe-labeled transferrin. Red cell count, Fcells, total body hemoglobin (Hb), susceptability to osmotic lysis, and differential reticulocyte count were increased. White blood cell count, venous blood %Hb, mean cell volume, mean cell Hb, mean cell Hb concentration, and serum iron were decreased. No changes were observed for body mass, mg Fe per g Hb, iron binding capacity, percent saturation of iron carrying capacity, or the electrophoretic mobility of purified Hb. This study indicated that chronic exposure to hypergravity induced changes in red cell size, volume, total mass, and membrane permeability.

Adaptation, Physiological↗
PubMedDate not supplied

Evaluation of the reproductive and developmental safety of cysteamine in the rat: effects on female reproduction and early embryonic development.

Cystinosis is an autosomal recessive metabolic disease in which the amino acid cystine accumulates in lysosomes due to a defect in lysosomal cystine transport. Cystinosis in infancy is associated with poor growth, muscle wastage, and death at about age 10 due to kidney failure. Treatment with cysteamine and kidney transplantation enables cystinotic girls to reach reproductive age and to be healthy enough to permit pregnancy. It is not known whether exposure to cysteamine will have adverse effects on reproduction in the human. It is also possible that some of the complications seen in cystinotic children could be avoided if a pregnant woman carrying a cystinotic fetus were given cysteamine. However, this treatment is not likely to occur until therapeutic exposures to cysteamine are judged to present no increased risk to the human fetus. As part of a larger investigation assessing the reproductive and developmental safety of cysteamine (as phosphocysteamine) using the rat, the two studies reported herein were performed. The first, a dose-finding study, led to the selection of 150 mg/kg/day as the highest dose of cysteamine used for the second and primary focus of this report. The second study involved the exposure of female rats to cysteamine from premating through day 6.5 postconception and assessment of female fertility and early embryonic development. Cysteamine was administered orally in doses of 0, 37.5, 75, 100, or 150 mg/kg/day. There were no clinical signs of maternal toxicity during the exposures of 2 to 5 weeks before successful mating. Animals in the 150 mg/kg/day group experienced a nonsignificant decrease in body weight gain during pregnancy to day 6.5 postconception, a significant increase in liver and spleen weights, and a significant increase in days to coitus--suggesting that a low level of toxicity was manifested. However, there were no adverse effects on reproductive performance with respect to conception and early embryonic development.

Animals↗
PubMedDate not supplied

Developmental toxicity of cysteamine in the rat: effects on embryo-fetal development.

The reproductive and developmental safety of cysteamine has become an important issue to children with cystinosis because renal transplants and treatment with cysteamine reduce the complications associated with cystinosis and increase the lifespan of the affected children. In addition, there is the potential to decrease the severity or the incidence of renal Fanconi syndrome with administration of cysteamine to pregnant women carrying fetuses with cystinosis, and to ease significantly the burden of this disease throughout their lives. If cysteamine increases significantly the risk of fetal death, growth retardation or birth defects at doses used to treat women with cystinosis, treatment of the affected female should cease during pregnancy and would not be considered for fetal treatment. The goal of this study was to assess the developmental safety of exposure in utero to cysteamine in the rat. Pregnant rats were given cysteamine (as phosphocysteamine) from day 6.5 through day 18.5 postconception and fetuses were assessed for survival, growth, and structural abnormalities on day 20.5. Cysteamine was administered orally in doses of 0, 37.5, 75, 100, or 150 mg/kg/day. Cysteamine produced dose-dependent developmental toxicity with an apparent no adverse effect observed level of 75 mg/kg/day. Specific malformations were associated with this effect (cleft palate, kyphosis), as well as intrauterine growth retardation and fetal death at 100-150 mg/kg/day, without signs of maternal toxicity. Investigations continue into the mechanism for the developmental toxicity of cysteamine.

Administration, Oral↗
PubMedDate not supplied

Sources of amino acids for protein synthesis during early organogenesis in the rat. 2. Exchange with amino acid and protein pools in embryo and yolk sac.

Tenth-day rat conceptuses were cultured in whole rat serum containing [3H]leucine and harvested after 24 or 48 h. Hydrolysates of the acid-precipitable fraction of embryo or yolk-sac homogenates were prepared and subjected to paper chromatography. Liquid scintillation counting of the separated amino acids showed that leucine was the only amino acid with above-background radioactivity. This established that radiolabel was not transferred from leucine to other amino acids in the cultured rat conceptus. Tenth-day rat conceptuses were cultured in whole rat serum containing [3H]leucine, as above. After 19 h, some conceptuses were harvested; other conceptuses were rinsed, transferred to culture medium without [3H]leucine, and after a further 24 h of culture the embryos and yolk sacs were harvested. A comparison of the protein-associated radioactivity of embryo and yolk sac before and after culturing for the further 24-h period showed that these structures quantitatively conserve radiolabelled leucine incorporated into their proteins. Further experiments involved culturing the rat conceptus for 24 h as above but in the presence of either [3H]leucine or [3H]leucine-labelled serum proteins. After harvesting the conceptuses, the specific radioactivity of [3H]leucine was determined in the acid-soluble and acid-precipitable fractions prepared from embryo and yolk-sac homogenates. The specific radioactivity of [3H]leucine in the acid-soluble fraction of embryos or yolk sacs from conceptuses grown in the presence of radiolabelled protein was about 120 per cent of that in the culture medium, while that in the acid-precipitable fractions was about 70 per cent of that in the culture medium. By comparison, the specific radioactivity of [3H]leucine in the acid-soluble fraction of embryos and yolk sacs from conceptuses grown in the presence of free [3H]leucine was only 3-4 per cent of that in the culture medium, while that in the acid-precipitable fraction was about 1 per cent of that in the culture medium. If our data on the fate of leucine incorporated into newly synthesized proteins of the early post-implantation rat embryo can be extrapolated to the other amino acids, they suggest that once amino acids have been incorporated into newly synthesized protein in embryo or yolk sac, they are not exchanged to any detectable extent with amino acid pools outside the conceptus. The results also provide independent confirmation of our earlier conclusion that the only significant source of amino acids utilized by the 10th-day embryo is protein taken up by the yolk sac and digested intracellularly.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMedDate not supplied

Reproductive and teratologic effects of electromagnetic fields.

The reproductive risks of electromagnetic fields (EMF) were evaluated based on an extensive review of the scientific literature pertaining to human epidemiologic studies, secular trend data, in vivo animal studies and in vitro studies, and biologic plausibility. The epidemiologic studies involving the reproductive effects of EMF exposures to human populations have included populations exposed to: (1) video display terminals (VDTs), and (2) power lines and household appliances. The clinical use of diagnostic MRI (magnetic resonance imaging) has been increasing, but there are few reports or studies of pregnant women or individuals of reproductive age who have been exposed to MRI, and whose reproductive performance has been evaluated. The population that has been studied most frequently are women exposed to VDTs, but their EMF exposures are extremely low and frequently are at the level of the ambient EMF in a house or office. The results of epidemiologic studies involving VDTs are generally negative for the reproductive effects that have been studied. Based on the number of studies, the exposure levels, and the fairly consistent results, it can be argued that VDT epidemiologic studies should no longer be given priority. There have been fewer studies concerned with the reproductive risks of power lines, electric substations, and home appliances. In some publications, positive findings for reproductive risks were reported, but the more consistent findings indicate that EMF, even at these higher exposures, do not generate a measurable increase in reproductive failures in the human population. When compared to other fields of human epidemiology, it is obvious that these studies have many difficulties. Exposures are rarely determined. Studies frequently involve small sample sizes and the investigators rarely have a combined expertise in EMF physics, engineering, and reproductive biology. Because of the allegation that there may be particular windows of frequency, wave shape, and intensity that may be deleterious, it is impossible to disregard low frequency EMF exposures as having no deleterious reproductive effects. Yet the epidemiologic data that are available would point in that direction. Secular trend data analysis of birth defect incidence data indicate that increasing generation of electric power during this century is not associated with a concomitant rise in the incidence of birth defects. There are over 70 EMF research projects dealing with animal and in vitro studies that are concerned with some aspect of reproduction and growth. Unfortunately, a large proportion of the embryology studies utilized the chick embryo and evaluated the presence or absence of teratogenesis after 48 to 52 hours of development.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗