Search PubMed⌕ Search

Biomedical subjects

D J Anderson

Publications and source records attributed to D J Anderson.

At least 271 records · Page 15Linked to original sources

Ten-year follow-up of patients with secondary amenorrhea and normal prolactin.

A group of 46 patients with secondary amenorrhea without galactorrhea or hyperprolactinemia were studied retrospectively after being clinically categorized into four groups with the use of progesterone-induced uterine bleeding and measurement of serum gonadotropins and prolactin levels. The ability to have regular spontaneous menstrual cycles and to conceive was assessed after a follow-up period of 10 years. Patients who had been classified as having hypothalamic pituitary "failure" (hypoestrogenic amenorrhea) with low levels of circulating estradiol had a greater rate of recovery of spontaneous ovulation and menses when compared with patients who had been classified as having only hypothalamic pituitary dysfunction (euestrogenic amenorrhea). The patients with diagnosis of hyperandrogenic chronic anovulation or polycystic ovary syndrome generally required clomiphene citrate for induction of ovulation and almost all the patients with premature ovarian failure (hypergonadotropic amenorrhea) remained estrogen-deficient and unable to ovulate. Hyperprolactinemia or an identifiable pituitary adenoma has not developed in any of the patients to date.

Adolescent↗

V-myc immortalization of early rat neural crest cells yields a clonal cell line which generates both glial and adrenergic progenitor cells.

We describe the isolation and characterization of an immortal cell line derived by infection of rat neural crest cells with a v-myc-containing replication-defective retrovirus. This clonal cell line, called NCM-1, contains a majority cell population with antigenic and morphologic properties that suggest it may represent a peripheral glial progenitor. In conditioned or in serum-free medium, these NGF receptor-positive cells differentiate to an elongated, bipolar morphology resembling that of primary Schwann cells. This morphologic differentiation is prevented by TGF-beta 1, which also acts as a mitogen for the cells. The NCM-1 line is also able to generate clonal derivatives which have extinguished expression of most or all glial markers. Once generated, such cells are stable and do not revert to the glial phenotype. At least some of these cells have acquired sympathoadrenal progenitor-like properties, as shown by their capacity to coexpress tyrosine hydroxylase (TH) and neurofilament (NF) in response to basic FGF and dexamethasone. These data imply that the NCM-1 line contains self-renewing cells with the potential to generate precursors in at least two of the sublineages that normally develop from the neural crest. This in turn suggests that the process of immortalization may preserve at least some of the developmental properties characteristic of multipotential neural crest cells. NCM-1 cells may prove useful for the study of neural crest cell lineage segregation, Schwann cell differentiation, and the mechanisms controlling the initial induction of TH and NF gene expression.

Animals↗

Evidence that enteric neurons may derive from the sympathoadrenal lineage.

The first neurons that differentiate in the embryonic foregut of mammals transiently express catecholamine biosynthetic enzymes and accumulate catecholamine. Since this transmitter is found predominantly in cells of the sympatho-adrenal (SA) lineage, it has been suggested that enteric and sympathetic neurons may derive from the same progenitor. Enteric neurons would then lose the catecholamine phenotype during further development, as the two lineages diverge. We have further investigated this possibility using the SA1 monoclonal antibody that binds selectively to SA progenitor cells in the embryonic rat. We find that SA1 binds to the tyrosine hydroxylase+, neurofilament+, and SCG10+ cells of the Embryonic Day 14.5 (E14.5) rat foregut. We also find that a marker for later neuronal differentiation in the SA lineage, B2, also appears in the myenteric plexus concomitant with the loss of SA1 staining. Thus, at least some enteric neuronal precursors may exhibit the SA1----B2 antigenic switch previously observed in developing sympathetic neurons at E14.5. SA1 staining in the foregut partially overlaps with staining for neuropeptide Y, vasoactive intestinal polypeptide, and serotonin. These results support the hypothesis that enteric and sympathetic neurons derive from a common progenitor and that as the markers for the SA lineage are down-regulated, the many types of enteric neurons begin to differentiate.

Animals↗

Co-expression of multiple neurotransmitter enzyme genes in normal and immortalized sympathoadrenal progenitor cells.

We have examined the expression of mRNAs encoding five major neurotransmitter-synthesizing enzymes in MAH cells, a clonal cell line derived by retroviral immortalization of a rat embryonic sympathoadrenal progenitor cell. These mRNAs include tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), tryptophan hydroxylase (TpH), and glutamic acid decarboxylases (GADs) 1 and 2. We find that MAH cells express high levels of TH mRNA and low levels of ChAT and TpH mRNAs. Neither GAD1 nor GAD2 mRNAs are detectable using an RNase protection assay with a detection limit of less than one transcript per cell. A similar pattern of mRNA expression is observed in postnatal superior cervical ganglia, adrenal medulla, and in PC12 cells. Transmitter synthesis and accumulation assays indicate that MAH cells can synthesize both catecholamines and acetylcholine. Thus the TH and ChAT mRNAs detected in these cells are likely to be translated into active enzyme. To corroborate these data obtained using MAH cells, we performed similar transmitter synthesis and accumulation assays on sympathoadrenal progenitors directly isolated from E14.5 fetal adrenal glands by fluorescence-activated cell sorting. These progenitor cells also synthesize and accumulate both catecholamines and acetylcholine, albeit to different extents than MAH cells. Both MAH cells and their nonimmortal counterparts are able to increase slightly their cholinergic function upon short-term exposure to CDF/LIF, a factor known to induce acetylcholine synthesis in postmitotic sympathetic neurons. Taken together, these data suggest that progenitor cells in the sympathoadrenal lineage acquire the ability to simultaneously transcribe several different neurotransmitter enzyme genes early in development, prior to their choice of final cell fate. At the same time, the progenitors possess receptors which regulate expression of these genes in response to environmental factors. This ability may permit the cells to choose from several different transmitter phenotypes in response to different environments, as they migrate through the embryo. The persistent transcription of these genes in adult cells, moreover, may in part account for the phenotypic plasticity of cells in this lineage.

Acetylcholine↗

Use of sperm viability and acrosomal status assays in combination with immunofluorescence technique to ascertain surface expression of sperm antigens.

Sperm antigens are being sought for the development of prototype contraceptive vaccines. For vaccine-induced antisperm antibodies to inhibit the function of viable sperm, target antigens must be expressed on the sperm surface before, during or after the acrosome reaction. The purpose of this study was to develop an approach to detect accurately surface binding of antibodies to viable acrosome-intact or acrosome-reacted sperm, and to confirm sperm surface binding characteristics of a panel of antisperm monoclonal antibodies submitted to the World Health Organization Antifertility Vaccines Task Force. Monoclonal antibodies were tested using a combination of carboxyl-fluorescein diacetate (CoFDA) sperm viability, and rhodamine immunofluorescence assays to ascertain surface binding to viable membrane-intact human sperm, and, in parallel studies, with a combination of fluorescein isothiocyanate (FITC) conjugated Pisum sativum agglutinin (PSA) and rhodamine immunofluorescence assays to ascertain the acrosomal status of antibody-positive sperm. Only 14 out of 32 antibodies that were previously considered to be surface-reactive were confirmed to be positive with these methods. Five were positive on unfixed viable (CoFDA-labelled) fresh sperm in this study, and 9 different antibodies were positive on unfixed acrosome-reacted sperm. We conclude that this multifaceted approach is more accurate and informative than previous techniques used for detection of sperm surface antigens such as radioimmunoassay, standard immunofluorescence, sperm agglutination assays and enzyme-linked immunosorbent assays, which can give false positive results due to the presence of contaminating non-sperm cells, insoluble seminal plasma material, or permeabilized non-viable sperm. Furthermore, the combination of assays employed in this study does not depend on sperm motility, as do the immunobead and sperm immobilization assays, and provides information about the acrosomal status of antibody-positive cells.

Acrosome↗

Shared-stimulus driving and connectivity in groups of neurons in the dorsal cochlear nucleus.

Extracellular spike discharges were recorded from ensembles of up to five neurons simultaneously in the DCN of guinea pig using solid-state, thin-film, multichannel electrodes having up to five recording sites spanning up to 600 microns. Responses from 73 unit pairs were collected of which 54 had both units responding to pseudorandom wideband noise stimulation. Shared-stimulus driving was present in 78% (42/54) of the unit pairs and could be attributed to an overlap in their spectral sensitivities. Effective connectivity was indicated for 87% (47/54) of the unit pairs. Wideband noise proved more useful than tonebursts for investigating shared-stimulus driving and connectivity because it evoked widespread, but not overly synchronous, responses in the ensembles.

Acoustic Stimulation↗

The effects of soluble products of activated lymphocytes and macrophages on blastocyst implantation events in vitro.

The purpose of this study was to investigate the effects of soluble products of activated lymphocytes and macrophages on mouse blastocyst attachment and trophoblast outgrowth in vitro. Hatched blastocysts were incubated with medium alone, supernatant fluids from mixed lymphocyte cultures (MLC), and with individual human and murine lymphokines and monokines in fibronectin-coated wells. Cultures were assessed at 24, 48, and 72 h for blastocyst attachment and trophoblast outgrowth. Both human and murine MLC supernatant fluids significantly enhanced trophoblast outgrowth in vitro. The cytokine, interleukin-1 beta (Il-1 beta), at a concentration of 10(3) U/ml, inhibited blastocyst attachment but significantly enhanced trophoblast outgrowth of attached blastocysts. Granulocyte, macrophage-colony-stimulating factor (GM-CSF) at a concentration of 250 U/ml significantly inhibited blastocyst attachment, while gamma interferon (gamma-IFN) at a concentration of 2.5 x 10(3) U/ml significantly inhibited trophoblast outgrowth and caused degenerative morphological changes in these cells. The results of this study indicate that products of activated immune cells may either facilitate or impede implantation events depending on the types of predominant cytokines present, their concentration(s), and the timing of their secretion relative to embryonic development.

Animals↗

Mammalian achaete-scute homolog 1 is transiently expressed by spatially restricted subsets of early neuroepithelial and neural crest cells.

Using monoclonal antibodies, we have examined the expression pattern of MASH1, a basic helix-loop-helix protein that is a mammalian homolog of the Drosophila achaete-scute proteins. In Drosophila, achaete-scute genes are required for the determination of a subset of neurons. In the rat embryo, MASH1 expression is confined to subpopulations of neural precursor cells. The induction of MASH1 precedes, but is extinguished upon, overt neuronal differentiation. MASH1 is expressed in the forebrain by spatially restricted domains of neuroepithelium and in the peripheral nervous system exclusively by precursors of sympathetic and enteric neurons. The features of early and transient expression, in spatially restricted subpopulations of neural precursors, are similar to those observed for achaete-scute. Thus, the amino acid sequence conservation between MASH1 and achaete-scute is reflected in a parallel conservation of cell type specificity of expression, similar to the case of mammalian MyoD and Drosophila nautilus. These data support the idea that helix-loop-helix proteins may represent an evolutionarily conserved family of cell-type determination genes, of which MASH1 is the first neural-specific member identified in vertebrates.

Animals↗

DNA fingerprinting by pulsed field gel electrophoresis and ribotyping to distinguish Pseudomonas cepacia isolates from a nosocomial outbreak.

We typed 40 isolates of Pseudomonas cepacia obtained from patients involved in a single outbreak using pulsed field gel electrophoresis and ribotyping. All isolates from the majority of the patients, 16 of 18 (89%), were included in a single group. These typing methods should aid in the clarification of the epidemiology of infection with P. cepacia.

Bacterial Typing Techniques↗

Anatomy of the major fissure: evaluation with standard and thin-section CT.

The major fissures of the right and left lungs were studied with standard computed tomography (CT) (10-mm-thick sections) and thin-section CT (2-mm-thick sections) in 50 patients. On standard CT scans, the major fissures were seen in 90%-100% of cases at each of three selected levels. They usually appeared as hypoattenuating bands and less often as lines or hyperattenuating bands. Although in most cases the major fissure was seen as a line on thin-section CT scans, this appearance was more common in the upper portion of the left major fissure than in the upper portion of the right major fissure. A "double-fissure sign" was most frequently seen at the base of the left lung; however, the sign was also seen at higher levels, with approximately equal frequency in the right and left lungs. An incomplete major fissure was noted in the right lung in 32 cases (64%) and in the left lung in 26 cases (52%). The upper and middle portions of the left major fissure were less frequently incomplete than were the comparable portions of the right major fissure. Thin-section CT provided better delineation of the major interlobar fissures than did standard CT.

Aged↗

Artifacts in computed radiography.

Storage-phosphor digital radiographic systems are becoming widely used in a variety of diagnostic procedures. The equipment is reliable and produces images of consistently high quality. However, the images may contain artifacts directly related to the digital techniques used, to the phosphor imaging plate, or to radiography in general. This article illustrates many of the artifacts encountered that are specific to computed radiography, some of which can simulate pathologic lesions. Their causes and remedies are discussed briefly.

Algorithms↗

Pharmacological profiles for rat cortical M1 and M2 muscarinic receptors using selective antagonists: comparison with N1E-115 muscarinic receptors.

We previously showed that M1 and M2 muscarinic receptors in dissociated cells of the adult rat cortex couple to phosphoinositide (Pl) and cyclic AMP (cAMP) metabolism, respectively. To further classify these receptors according to probable subtype, we have employed a group of selective muscarinic antagonists to obtain pharmacological profiles of the cortical M1 and M2 receptors, and to compare them with the muscarinic receptors in N1E-115 cells, which contain M1 receptors mediating cyclic GMP elevation and M4 receptors inhibiting cAMP levels. The M2-mediated inhibition of cAMP levels in cortex was blocked by 4-diphenylacetoxy-N-methyl piperidine methiodide (4-DAMP) with higher potency (0.29 nM) than for reported potency in cardiac tissue (approximately 10 nM), indicating that this cortical response is probably not mediated by the m2 gene product. Similarly, the potency of hexahydrosiladiphenidol (HSD) at the cortical M2 receptor (159 nM) was somewhat greater than the reported potency in cardiac tissue (295 nM). The cardioselective drugs AF-DX 116 and methoctramine blocked the cortical M2 response less potently (135 nM and 229 nM, respectively) than would be expected for involvement of the m2 gene product. Thus, the potencies of AF-DX 116, methoctramine, 4-DAMP and HSD suggest that the cortical M2 response, like the striatal M2 receptor, is mediated by a noncardiac M2 receptor, perhaps by the m4 gene product. This postulate was supported by the significant correlations between cortical and striatal M2 receptors as compared to the M4 receptor in N1E-115 cells (r = 0.92 and 0.99, respectively, P less than .025).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Programs and services received by older persons with mental retardation.

Findings from a study of the programs and services received by a national sample of older persons with mental retardation were reviewed. Individuals were selected from a national sample of all facilities owned, operated, or licensed by developmental disabilities agencies having one or more persons 63 years of age or older with mental retardation. Facilities included foster care, small group homes, large private facilities, and state-operated facilities. One or two residents per facility were studied. A total of 370 individuals in 235 facilities were surveyed (10% of all eligible facilities). Comprehensive information on resident characteristics, day program participation, and services received was gathered through extensive questionnaire and telephone interviews of primary careproviders and directors of the day programs attended by individuals in the resident sample. Differences in programs and services received were presented by facility type.

Aged↗

Antibody markers identify a common progenitor to sympathetic neurons and chromaffin cells in vivo and reveal the timing of commitment to neuronal differentiation in the sympathoadrenal lineage.

Using specific antibody markers and double-label immunofluorescence microscopy, we have followed the fate of progenitor cells in the sympathoadrenal (SA) sublineage of the neural crest in developing rat embryos. Such progenitors are first recognizable in the primordial sympathetic ganglia at embryonic day 11.5 (E11.5), when they express tyrosine hydroxylase. At this stage, the progenitors also coexpress neuronal markers such as SCG 10 and neurofilament, together with a series of chromaffin cell markers called SA 1-5 (Carnhan and Patterson, 1991 a). The observation of such doubly labeled cells is consistent with the hypothesis that these cells represent a common progenitor to sympathetic neurons and adrenal chromaffin cells. Subsequent to E 11.5, expression of the chromaffin markers is extinguished in the sympathetic ganglia but retained by cells within the adrenal gland. Concomitant with the loss of the SA 1-5 immunoreactivity in sympathetic ganglia, a later sympathetic neuron-specific marker, B2, appears. In dissociated cell suspensions, some B2+ cells that coexpress SA 1 are seen. This implies a switch in the antigenic phenotype of developing sympathetic neurons, rather than a replacement of one cell population by another. The SA 1----B2 transition does not occur for the majority of cells within the adrenal primordium. In vitro, most B2+ cells fail to differentiate into chromaffin cells in response to glucocorticoid. Instead, they continue to extend neurites and then die. Taken together, these data imply that the SA 1----B2 transition correlates with a loss of competence to respond to an inducer of chromaffin differentiation. Thus, the development of SA derivatives is controlled both by environmental signals and by changes in the ability of differentiating cells to respond to such signals.

Adrenal Glands↗

Detection of human immunodeficiency virus type 1 in semen from seropositive men using culture and polymerase chain reaction deoxyribonucleic acid amplification techniques.

We have demonstrated that the polymerase chain reaction is a valid and sensitive technique for the detection of human immunodeficiency virus type 1 (HIV-1) proviral deoxyribonucleic acid (DNA) in human semen. The combination of extraction, polymerase chain reaction, and liquid hybridization techniques used in this study was sensitive to a level of detection of one HIV-1 infected cell in 100,000 (or 3 infected cells/test sample). In a series of matched peripheral blood mononuclear cells (PBMC) and semen cells from 25 HIV-1 seropositive homosexual men, HIV-1 DNA was detected by polymerase chain reaction in 23 of 25 PBMC samples and 1 of 25 semen samples. By coculture on mitogen-activated peripheral blood leukocyte target cells, 19 of 24 PBMC and 4 of 24 semen samples were positive for infectious HIV-1. Of the four culture-positive semen samples, three were negative for the proviral form of the virus in the polymerase chain reaction assay. These data indicate that HIV-1 infected cells are not as prevalent in semen as in the peripheral blood. Furthermore, they indicate that the classical polymerase chain reaction approach, which only detects HIV-1 proviral DNA (infected cells), is not sufficient for clinical screening programs whose goal is the detection of HIV-1-infected semen samples. Accurate semen analysis by polymerase chain reaction may require enrichment of the infected cell population and/or a reverse transcriptase step to enable detection of the infectious ribonucleic acid form of the virus.

DNA↗

Persons with mental retardation in nursing homes in 1977 and 1985.

Findings from the 1977 and 1985 National Nursing Home Surveys with respect to residents with mental retardation were compared. The single most notable finding was that very little changed over the 8-year period. The size of the mentally retarded population changed little (remaining at an estimated 40,500), the characteristics of the population remained essentially the same, and the services received by residents with mental retardation in 1985 remained at essentially the same low levels as those found in 1977. Implications of the findings as they relate to the initiative begun with the passage of P.L. 100-203 in 1987 and the forthcoming regulations to guide its implementation were discussed.

Activities of Daily Living↗

Two rat homologues of Drosophila achaete-scute specifically expressed in neuronal precursors.

In vertebrates, the peripheral nervous system is embryologically derived from the neural crest. Although the earliest neural crest cells seem to be multipotent, the molecular mechanisms responsible for the restriction of these cells to different sublineages are not understood. We therefore searched for developmental control genes expressed in crest cells or their derivatives. One important class of regulatory molecules comprises proteins with common DNA-binding and dimerization domains, the basic helix-loop-helix (B-HLH) region. Members of this family include MyoD, a mammalian myogenic determination molecule, and proteins encoded by genes of the achaete-scute complex of Drosophila, which have an important role in neuronal determination. From a sympathetic neuronal precursor cell line derived from the neural crest we have now isolated two different mammalian genes that are homologous to genes of the achaete-scute complex. The sequence of the B-HLH-encoding region of these genes is more similar to that of the genes of the achaete-scute complex than it is to that of other, mammalian members of the B-HLH family. At least one of these genes is transiently expressed in the embryonic rat nervous system, is not detected in non-neuronal tissues or cell lines, and is induced by nerve growth factor in PC12 cells.

Adrenal Glands↗