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Biomedical subjects

M R Meyer

Publications and source records attributed to M R Meyer.

At least 37 records · Page 2Linked to original sources

Absence of a direct effect of recombinant tumor necrosis factor-alpha on human sperm function and murine preimplantation development.

OBJECTIVE: This study was designed to test the in vitro effects of human recombinant tumor necrosis factor (rTNF) on sperm motility, fertilization, and preimplantation development. DESIGN: A sensitive enzyme immunoassay was used to determine half-lives of rTNF and confirm concentrations of cytokine throughout experimental conditions. Effect of rTNF on human sperm survival was measured by computer-assisted methodology, and effect on human sperm penetration was assessed by hamster ova penetration. Cytokine effect on murine gamete interaction was determined by in vitro fertilization (IVF). Murine preimplantation development was assessed by in vitro development of cryopreserved-thawed one-cell zygotes. RESULTS: The half-life of rTNF was reduced by the addition of sperm to culture media (P less than 0.001). Sperm motility (P = 0.245) and hamster ova penetration (P = 0.62) were not altered by incubations in the presence of concentrations of rTNF up to 10,000 U/mL. Mouse IVF (P = 0.60) and preimplantation development (P = 0.56) were not altered by rTNF in concentrations up to 5,000 U/mL. CONCLUSIONS: These results demonstrate rTNF by itself does not interfere with gamete function or early embryo development.

Analysis of Variance↗

Conservation of antigen 3G6: a crystalline cone constituent in the compound eye of arthropods.

A monoclonal antibody (MAb), 3G6, highly selective for neuropil glia in the CNS of the house cricket Acheta domesticus, also demonstrates remarkable selectivity for the nonneuronal crystalline cone cells of the compound eye. MAb 3G6 labels cone cells in eucone eyes throughout Insecta, from ancestral forms such as the bristle tail to the more recent honeybee; eucone structures are also recognized in Crustacea. Analogous nonneural structures found in pseudocone or acone eyes also express detectable 3G6 immunoreactivity. Immunoblot analysis demonstrates that MAb 3G6 binds to similar Mr85 kDa glycoproteins in the cricket CNS and retina, corresponding to the glial and crystalline cone forms of the antigen. Further, polypeptides of similar relative mass are also recognized in the eucone eye of the butterfly Pieris and the pseudocone eye of the fly Calliphora. The properties and function of glycoprotein 3G6 in the CNS and retina are yet to be explored. However, the finding that a unique antigen is highly conserved within the crystalline cone or analogous regions of the retina throughout the Arthropoda lends support at the molecular level to the notion that the arthropod compound eye has a monophyletic origin.

Animals↗

Evaluation of recruitment strategies for prospective studies of spontaneous abortion.

The examination of spontaneous abortions may offer a sensitive index to potential adverse health effects due to environmental exposures. However, difficulties in ascertaining spontaneous abortions on a population basis, as well as problems in recruiting unselected women into studies of this nature, have severely limited the use of this end point in environmental epidemiology studies. The current research assesses the feasibility of recruiting a representative sample of women into a prospective pregnancy study. Four protocols varying in intensity of data collection were offered to the participants. Fifty-two percent of the eligible women agreed to participate. Seventy-four percent chose the most intensive protocol level. Overall compliance for urine collection and questionnaire completion were 80% and 81%, respectively. Four pregnancies were observed, which was the expected number for the study area during this time frame, suggesting that the majority of pregnancies occurring within a population could be ascertained with this approach.

Abortion, Spontaneous↗

Developmental modulation of a glial cell-associated glycoprotein, 5B12, in an insect, Acheta domesticus.

The expression of an insect (Acheta domesticus) adult glial cell-specific antigen, 5B12 undergoes major changes during development. The 5B12 antigen is detected as early as 20-25% of embryonic development, when immunoreactivity is distributed throughout the periphery, present at the luminal surface of epithelial cells which compose developing limb buds, sensory appendages, and the body cavity. The antigen is also localized on the cell surface of neural elements within commissural tracts in the embryonic CNS. 5B12 is secreted extracellularly in the periphery, where it is associated with the embryonic basal lamina in developing cercal sensory appendages. Luminal surface expression is transient, and disappears by 95% of embryonic development. As development proceeds, 5B12 distribution becomes more restricted, so that in the adult the antigen is predominantly associated with specific glial elements within the nervous system where it occurs as a specialized component of the extracellular matrix. The 5B12 antigen is also associated with discrete central and peripheral fiber tracts. Antigen 5B12 is present in whole embryos and in the adult CNS as a Mr 185-kDa glycoprotein. Distinct carbohydrate moieties with chondroitin sulfate-like properties are situated on the 5B12 epitope. Thus the glia-associated 5B12 macromolecule has the characteristics of a small proteoglycan. Based upon features of its distribution, pattern of spatiotemporal expression, and biochemical properties, it is speculated that 5B12 participates in events related sequentially to the development and the function of the insect nervous system.

Age Factors↗

Evaluation of methods for the prospective identification of early fetal losses in environmental epidemiology studies.

A major problem in the epidemiologic investigation of early fetal losses has been incomplete or biased ascertainment. In order to assess early fetal losses more accurately, one must first develop a simple method to identify early pregnancy. This study, conducted at the University of Pittsburgh from October 1985 through October 1986, has developed such a method through the use of monoclonal antibody urine pregnancy testing kits. A total of 88 volunteers collected urine samples beginning on the seventh postovulatory day and continued until either menses occurred or a serum radioimmunoassay pregnancy test was performed on day 16. If pregnancy was diagnosed, all of the participants' urine specimens from that menstrual cycle were analyzed by five monoclonal antibody tests. A total of 34 pregnancies were diagnosed, six (18%) of which resulted in early fetal losses. Pregnancy was first detectable between eight and 18 days postovulation. The mean time to the first positive test was 14 days for all five kits. The results indicate that it is possible to diagnose early pregnancy with urine testing and that this method is likely to prove acceptable for use in large-scale prospective studies.

Abortion, Spontaneous↗

Immunological probes reveal spatial and developmental diversity in insect neuroglia.

A set of monoclonal antibodies (MAbs) has been generated that recognizes distinct classes of neuroglia in the adult nervous system of the cricket Acheta domesticus corresponding to glial types distinguished by morphological criteria. These include antibodies that bind to the neuroglia of the ganglionic cortex, perineurium, neuropil, and glia associated with the glial lacunar system (interface) and fiber tracts. Another MAb specifically labels components of the neural lamella, a complex extracellular matrix secreted by underlying perineurial cells. Selected adult glial-specific MAbs recognize particular glial antigens expressed during embryonic development of Acheta. Immunohistochemical staining of frozen sections of late- (90-95%) and intermediate- (50-55%) stage whole embryos reveals that the spatial distribution, degree of tissue restriction, or level of expression of some glial determinants changes as development proceeds. Labeling of certain neuroblasts in the embryonic CNS at 50-55% development by an antibody (MAb 3G6) that binds to neuropil glia in the adult CNS implies that at least 1 class of insect glia may be generated by these cells.

Animals↗

Metabolic changes in deafferented central neurons of an insect, Acheta domesticus. II. Effects on cholinergic binding sites and acetylcholinesterase.

Following the finding that cercal deafferentation of developing giant interneurons in the terminal abdominal ganglion (TG) of the cricket Acheta domesticus reduces TG protein metabolism within target interneuron dendrites and somata (Meyer and Edwards, 1982), it is now shown that deafferentation alters the turnover of three macromolecules associated with cholinergic transmission in the cercal sensory-giant interneuron pathway. The labeled specific ligands 3H-quinuclidinyl benzilate and 125I-alpha-bungarotoxin were used to assay populations of putative TG muscarinic and nicotinic cholinergic receptors, respectively, in control and deafferented groups of ganglia. The AChE activity of TG was also determined by assay and histochemical methods. Long-term deafferentation sustained throughout postembryonic development markedly reduces the densities of both muscarinic and nicotinic binding sites in the TG; short-term deafferentation of adult TG also leads to characteristic alterations in the properties of all three cholinergic markers within several days. Rapid changes seen in adults thus correlate with ultrastructural data demonstrating loss of afferent terminals within hours of sensory appendage removal. We propose that peripheral innervation-dependent regulatory mechanisms operate in both the developing and adult insect nervous system. Such mechanisms may influence transsynaptically the synthesis and turnover of specific macromolecules, some of which may reside on the cell surface of insect central neurons that are part of the cercal sensory-giant interneuron system.

Acetylcholinesterase↗

Muscarinic and nicotinic cholinergic binding sites in the terminal abdominal ganglion of the cricket (Acheta domesticus).

Cricket (Acheta domesticus) terminal abdominal ganglia (TG) contain high concentrations (approximately 2 pmol/mg protein) of muscarinic and nicotinic cholinergic binding sites, based on the capacity of TG to bind specifically the labelled ligands L-[3H]quinuclidinyl benzilate ([3H]QNB) and [125I]alpha-bungarotoxin ([125I]alpha-BGT) with high affinity. For both ligands, binding is saturable and reversible. Competitive displacement experiments indicate that the [3H]QNB and [125I]alpha-BGT binding sites probably represent pharmacologically distinct classes of putative TG acetylcholine receptors (AChRs). Results from physiological recording and autoradiographic localization experiments demonstrate that a portion of the putative nicotinic AChRs is localized in synaptic regions of the well-characterized cercal sensory-giant interneuron pathway in the TG, where they are likely to serve as functional synaptic AChRs. Unlike nicotinic ligands, muscarinic agents do not appear to be pharmacologically active in this pathway. Therefore, in the insect CNS, putative muscarinic and nicotinic AChRs coexist at high density, but can be pharmacologically distinguished from one another on the basis of criteria derived from both ligand binding and physiological methods.

Animals↗

In vivo regulation of muscarinic cholinergic receptors in embryonic chick brain.

Prolonged treatment of chick embryos in vivo with the muscarinic agonists oxotremorine or carbachol leads to dose- and time-dependent decreases in the number of brain muscarinic acetylcholine receptors (mAChR) as measured by the specific binding of the potent muscarinic ligand L-[3H]quinuclidinyl benzilate to brain membranes. Maximal doses of agonists reduced the number of mAChR as much as 44%. Maximal loss of mAChR occurs 4 hr after treatment, but can be prevented or totally reversed within 24 hr by blockade of agonist-receptor interactions with muscarinic antagonists. After sustained in vivo oxotremorine treatment, brain mAChR show a decreased apparent affinity for agonists owing to a decrease in the affinities of both the high- and low-affinity agonist binding sites.

Animals↗

Metabolic changes in deafferented central neurons of an insect, Acheta domesticus. I. Effects upon amino acid uptake and incorporation.

Chronic cercal deafferentation of the terminal ganglion in developing crickets (Acheta domesticus), which is known to suppress normal development of giant interneuron dendritic arborizations is shown here to reduce [3H]leucine uptake and incorporation into ganglion proteins. Short term deafferentation of adult crickets, in contrast, does not depress amino acid uptake and incorporation significantly. Following unilateral long term deafferentation of the terminal ganglion, a comparison was made of the [3H]leucine incorporation into primary dendritic processes and somata of deafferented and normally innervated medial giant interneurons (MGIs) within the same ganglion by means of quantitative autoradiography. Grain densities within dendrites of deafferented MGIs were significantly lower than in paired control MGIs' grain densities within somata of deafferented MGIs also were reduced, although the effects of deafferentation were less pronounced in somata than in target dendrites. These results imply a specific influence of afferent innervation on protein metabolism during growth and development of target postsynaptic elements.

Afferent Pathways↗

Muscarinic cholinergic binding sites in an orthopteran central nervous system.

Homogenates of cricket (Acheta domesticus) central nervous system (CNS) specifically bind to potent muscarinic ligand [3H]-QNB. Binding assay and pharmacologic data indicate that the cricket CNS contains a high density of muscarinic cholinergic binding sites. These sites appear to be a unique class of invertebrate cholinergic receptor with properties distinct from those of previously described nicotinic receptors.

Animals↗

Juvenile detention: another boundary issue for physicians.

It is estimated that there are 500,000 youngsters in detention in the United States per year. Detention facilities offer a unique environment in which adolescents at high risk for medical problems can be identified and treated. A health care program within the secure juvenile detention facility for New York is described in order to demonstrate how an academic medical center can effect improvement in the health status of underserved, incarcerated youth while meeting professional educational objectives for health trainees. Results of medical services are given for the past 11 years. Medical problems were diagnosed in 46% of the 47,288 adolescents examined. The conditions were grouped into those related to the legal status of the youngsters, socioeconomic background, and/or the institutional setting. The interrelationship of medical conditions with legal, ethical, and youth advocacy issues were demonstrated. The setting affords on opportunity to train primary care physicians with special emphasis on issues such as the nature of the doctor-patient relationship, confidentiality, and patient advocacy, while providing a necessary service to medically disadvantaged adolescents.

Academic Medical Centers↗

Histological studies of trophic dependencies in crayfish giant axons.

Medial giant (MGA) and lateral giant (LGA) axons of crayfish were doubly cut in order to selectively isolate axonal segments from perikaryal and transsynaptic sources of trophic input. Isolated MGA segments remained morphologically intact for over 43 days, whereas isolated LGA segments usually degenerated within one week. The glial sheaths around isolated MGA segments had significantly increased in thickness within one week, but severed LGA segments showed no increase in sheath thickness at any time after lesioning. These data suggest that cells of the surrounding glial sheath can provide trophic support to isolated MGA segments but not to isolated LGA segments. Extent of glial hypertrophy seems dependent upon specific spatiotemporal parameters. The diameters of isolated MGA segments decreased more rapidly than the diameters of singly cut MGA segments. These data suggest that the MGA also receives some trophic support from pre- or postsynaptic sources. Conversely, some singly cut LGA segments completely degenerated within one week, whereas other singly cut LGA segments remained intact for at least 43 days after lesioning. Such results suggest that the LGA receives a significant trophic input from pre- or postsynaptic structures.

Animals↗

Biochemical studies of trophic dependences in crayfish giant axons.

Data from previous histological studies indicate that long-term survival of crayfish medial giant axons might be due in part to trophic support from cells of the surrounding glial sheath which often hypertrophy in response to transection of the medial giants. The biochemical studies reported herein show that segments from transected ventral nerve cords (VNC) always incorporate more [3H]leucine into protein than do corresponding segments from intact VNCs. Furthermore, the relative amount of [3H]leucine incorporation in severed segments seems to be influenced by distance and direction from the lesion site as well as time after lesioning. Similar spatiotemporal parameters were previously shown to be correlated with extent of glial hypertrophy around severed medial giant axons. Quantitative autoradiography of medial giant axons after incubation in [3H]leucine revealed that the grain density of label in glial sheaths surrounding severed medial giants was over two-fold greater than in sheaths around corresponding control axons. Moreover, the grain density in the axoplasm of severed medial giants was nearly four-fold greater than the grain density in the axoplasm of control axons. Data from experiments using short or long labeling intervals suggests that labeling in the medial giant axoplasm may be due more to transfer from glial sheath cells than from inherent axonal synthetic mechanisms. In light of this and other data, we concluded that long-term survival of severed medial giant axons is probably due to the direct transfer of trophic substances from cells of the glial sheath into the axon.

Animals↗

Herpesvirus infection in the newborn. Its treatment by exchange transfusion and adenosine arabinoside.

A case is reported of herpesvirus infection in the newborn following maternal genital herpesvirus infection. The rationale for treating a newborn infant with signs of disseminated herpesvirus infection by exchange transfusion in addition to adenosine arabinoside is discussed. Because of the lack of data concerning therapy for a disease with a 50 to 100% mortality rate, it is important to present material such as this in order to provide information about possible new therapeutic modalities.

Adult↗