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D J Anderson

Publications and source records attributed to D J Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Isolation of a stem cell for neurons and glia from the mammalian neural crest.

We have isolated mammalian neural crest cells using a monoclonal antibody to the low affinity NGF receptor, and established conditions for the serial propagation of these cells in clonal culture to assess their developmental potential. This analysis indicates that, first, single mammalian neural crest cells are multipotent, able to generate at least neurons and Schwann cells like their avian counterparts. Second, multipotent neural crest cells generate multipotent progeny, indicating that they are capable of self-renewal and therefore are stem cells. Third, multipotent neural crest cells also generate some clonal progeny that form only neurons or glia, suggesting the production of committed neuroblasts and glioblasts. Manipulation of the substrate alters the fate of the multipotent cells. These findings have implications for models of neural crest development in vivo, and establish a system for studying the generation of cellular diversity by a multipotent stem cell in vitro.

Animals↗
PubMed1992

Membrane depolarization induces p140trk and NGF responsiveness, but not p75LNGFR, in MAH cells.

Nerve growth factor (NGF) is required for the maturation and survival of sympathetic neurons, but the mechanisms controlling expression of the NGF receptor in developing neuroblasts have not been defined. MAH cells, an immortalized sympathoadrenal progenitor cell line, did not respond to NGF and expressed neither low-affinity NGF receptor (p75) nor p140trk messenger RNAs. Depolarizing concentrations of potassium chloride, but none of a variety of growth factors, induced expression of p140trk but not p75 messenger RNA. A functional response to NGF was acquired by MAH cells under these conditions, suggesting that expression of p75 is not essential for this response. Depolarization also permitted a relatively high proportion of MAH cells to develop and survive as neurons in fibroblast growth factor and NGF. These data establish a relation between electrical activity and neurotrophic factor responsiveness in developing neurons, which may operate in the functioning of the mature nervous system as well.

Blotting, Northern↗
PubMed1992

Mild and moderate dyskaryosis: can women be selected for colposcopy on the basis of social criteria?

OBJECTIVE: To describe the distribution of cervical intraepithelial neoplasia grades among women with mild and moderate dyskaryosis after a single cervical smear and to determine whether social criteria could help identify women who are at increased risk of grade II or III disease. DESIGN: Cross sectional analysis within a randomised prospective study. Subjects had a repeat smear, a colposcopic examination, and an excision biopsy of the transformation zone. In addition, women were asked to complete a social questionnaire. SETTING: Colposcopy clinic, Aberdeen. SUBJECTS: 228 women with a single smear test showing mild or moderate dyskaryosis. MAIN OUTCOME MEASURES: Histology, age, sexual and contraceptive history, cigarette smoking. RESULTS: 159 (70%) women had cervical intraepithelial neoplasia grades II or III. Among current smokers the prevalence of grade II and III disease was higher in women who smoked greater than or equal to 20 cigarettes a day (84%) than among those who smoked less (66%; p less than 0.04). Women with more than one sexual partner also had a higher prevalence (75%) than women with only one partner (50%; p = 0.0028). Use of oral contraceptives and younger age were not significantly associated. The prevalence of grade II or III disease was up to 66% in the lower risk groups. CONCLUSIONS: Because of the high prevalence of cervical intraepithelial neoplasia grades II and III in both the high and the low risk groups social factors are not useful for selecting women with mild or moderate dyskaryosis for either early referral to colposcopy or cytological surveillance.

Adult↗
PubMed1992

CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130.

Ciliary neurotrophic factor (CNTF) has a variety of actions within the nervous system. While some of the actions of leukemia inhibitory factor (LIF) on neurons resemble those of CNTF, LIF also has broad actions outside of the nervous system that in many cases mimic those of interleukin-6 (IL-6). Comparison of the tyrosine phosphorylations and gene activations induced by CNTF and LIF in neuron cell lines reveals that they are indistinguishable and also very similar to signaling events that characterize LIF and IL-6 responses in hematopoietic cells. We provide a basis for the overlapping actions of these three factors by demonstrating that the shared CNTF and LIF signaling pathways involve the IL-6 signal transducing receptor component gp130. Thus, the receptor system for CNTF is surprisingly unlike those used by the nerve growth factor family of neurotrophic factors, but is instead related to those used by a subclass of hematopoietic cytokines.

Animals↗
PubMed1992

Effects of disease stage and zidovudine therapy on the detection of human immunodeficiency virus type 1 in semen.

OBJECTIVE: To determine the prevalence and temporal expression of infectious human immunodeficiency virus type 1 (HIV-1) in the semen of HIV-1 seropositive men and to determine whether the detection of HIV-1 in semen is associated with disease stage, zidovudine treatment status, or other clinical factors. DESIGN: A microculture technique was used to detect infectious HIV-1 in semen from a cohort of 95 seropositive men. In addition, semen cultures were performed monthly for at least 6 months for 14 of the men. Information was obtained by interview and extracted from medical records to identify clinical variables associated with HIV-1 in semen. PATIENTS: Sixty HIV-1 seropositive homosexual men participating in clinical studies at the Fenway Community Health Center, Boston, Mass, and 35 HIV seropositive bisexual or heterosexual men participating in the California Partner Study of the University of California, San Francisco. MAIN OUTCOME MEASURES: Semen HIV-1 culture results, seminal leukocyte counts, Centers for Disease Control (CDC) disease stage, peripheral CD4+ cell counts, zidovudine therapy, HIV risk category. RESULTS: In the cross-sectional study, HIV-1 was cultured from the semen of nine (9%) of 95 men. Factors associated with detection of HIV-1 in semen were peripheral CD4+ cell counts of 0.20 x 10(9)/L (200/microL) or less (adjusted odds ratio [OR], 23.33; 95% confidence interval [Cl], 2.89 to 175.63); symptomatic (CDC class IV) disease (adjusted OR, 6.56; 95% Cl, 1.02 to 66.76); and seminal leukocytosis (greater than 1 x 10(9) white blood cells per liter of semen) (adjusted OR, 7.02; 95% Cl, 1.28 to 39.29). Zidovudine therapy was associated with decreased detection of HIV-1 in semen (adjusted OR, 0.04; 95% Cl, 0.00 to 0.63). In the longitudinal study of 14 men who had neither peripheral CD4+ cells counts of 0.20 x 10(9)/L or less nor seminal leukocytosis, seminal HIV-1 was detected in at least one sample from six men (43%). CONCLUSION: HIV-1 is more commonly found in semen from men with advanced HIV-1 infection and seminal leukocytosis but can also be cultured from semen of men with neither of these conditions. Zidovudine therapy may decrease the prevalence and/or titer of seminal HIV-1. However, all HIV-1-infected persons should continue to assume that they are potentially infectious through sexual contact.

CD4-Positive T-Lymphocytes↗
PubMed1992

DNA binding and transcriptional regulatory activity of mammalian achaete-scute homologous (MASH) proteins revealed by interaction with a muscle-specific enhancer.

The MASH genes are vertebrate homologues of achaete-scute, genes required for neuronal determination in Drosophila. The sequence of MASH1 and MASH2 contains a basic helix-loop-helix (bHLH) motif that is present in other transcriptional regulators such as MyoD and E12. In the absence of an authentic target for the MASH proteins, we examined their DNA binding and transcriptional regulatory activity by using a binding site (the E box) from the muscle creatine kinase (MCK) gene, a target of MyoD. Like myogenic bHLH proteins, the MASH proteins form heterooligomers with E12 that bind the MCK E box with high affinity in vitro. Unexpectedly, however, MASH1 and MASH2 also activate transcription of both exogenous and endogenous MCK in transfected C3H/10T1/2 fibroblasts. However, they do not induce myogenesis. Myogenic activity is not exclusively a property of the MyoD basic region, as substitution of this domain fails to confer myogenic activity on MASH1. These data suggest that different bHLH proteins may activate overlapping but distinct sets of target genes in the same cell type.

Amino Acid Sequence↗
PubMed1992

Effects of nicotine on spatial memory deficits in rats with septal lesions.

Impaired septohippocampal function has been implicated in the memory deficits associated with Alzheimer's disease (AD), and septal lesions have been used to model the cognitive deficits associated with AD. In this study, we assessed the effects of systemic administration of nicotine on lesion-induced deficits in the acquisition of a spatial discrimination version of the Morris water maze. Rats with radiofrequency lesions of the medial septum were required to learn which of two visible platforms in a pool of water provided a means of escape. On each of the first 4 days of training, the rats received an injection of (-)nicotine (0, 0.1 or 0.3 mg/kg, i.p.) before training. Nicotine markedly improved the performance of septal rats. This enhanced performance was maintained in rats subsequently tested 1 and 15 days later without additional drug treatment. Septal rats initially trained under nicotine were impaired, however, when the platform locations were reversed and training was conducted under saline. Our findings suggest that nicotinic receptor stimulation might be useful in the treatment of cognitive deficits.

Alzheimer Disease↗
PubMed1992

Human vaginal leukocytes and the effects of vaginal fluid on lymphocyte and macrophage defense functions.

OBJECTIVES: The purpose of this study was to quantify, characterize, and further define the role of vaginal white blood cells in defense mechanisms and human immunodeficiency virus infection. STUDY DESIGN: Vaginal lavages were obtained from five healthy women throughout three menstrual cycles. Lymphocyte subpopulations, macrophages, and granulocytes were characterized and quantified by an immunohistologic technique. Vaginal lavage fluid was added to peripheral blood mononuclear cells, and effects on cell viability, lymphocyte proliferation, macrophage phagocytosis, and expression of various cell surface molecules critical to immunologic functions were assessed. Data were analyzed by Student's t test. RESULTS: Few lymphocytes were found at any stage of the menstrual cycle; however, granulocytes and macrophages were abundant at menstruation and present at low levels through the proliferative phase. Vaginal lavage fluid collected during menses, at midcycle, and after coitus suppressed mitogen-induced lymphocyte proliferation but had no effect on surface expression of human leukocyte antigen or CD4 antigens, or on macrophage function. Likewise, low pH (less than 5.0) medium significantly inhibited lymphocyte proliferation but had no effect on macrophage phagocytosis. The spermicide nonoxynol 9 was toxic to both lymphocytes and macrophages. CONCLUSION: White blood cells, including lymphocytes and macrophages, are infrequently present in cervicovaginal secretions of healthy women except during menses; the vaginal environment may effect their function.

Adult↗
PubMed1992

Molar villous fluid suppresses mononuclear cell cytotoxicity.

Complete molar pregnancy tissue is an allograft to the mother because all molar chromosomes are of paternal origin. Interactions between molar tissue and the maternal immune system may be important in the natural history of complete molar pregnancy. Molar villous fluid (MVF) has previously been demonstrated to suppress both mitogen and interleukin-2-induced T lymphocyte proliferation. The current study was undertaken to evaluate the potential effect of MVF on the cytotoxic activity of mononuclear cells (MNC) and lymphokine-activated mononuclear cells (LA-MNC). Sera and molar villous fluid were obtained from four women at the time of molar evacuation. K-562 erythroblastoid cells were used as target cells for MNC-mediated lysis, and JEG-3 choriocarcinoma cells were used as targets for LA-MNC-mediated lysis in a 51Cr release assay. Relative to patient sera, all MVF tested significantly inhibited both MNC and LA-MNC lysis of target cells (48.3 and 91% mean inhibition, respectively; P < 0.05). This study provides additional evidence that molar gestational tissue produces factor(s) that suppress maternal immunologic responses. Potential therapies may become available to reduce or eliminate the immunosuppressive effects of molar gestations resulting in a more favorable clinical outcome in patients with complete molar pregnancy and postmolar gestational trophoblastic tumors.

Choriocarcinoma↗
PubMed1992

Antifertility effects of antisperm cell-mediated immunity in mice.

C57BL/6 female mice were immunized with allogeneic (DBA/2) sperm in Freund's adjuvant either subcutaneously (s.c.), transcervically into the uterine lumen (i.u.), or with a combination of s.c. and i.u. immunization approaches. Control mice received DBA/2 lymphocytes, human erythrocytes or saline in adjuvant using the same immunization protocols. Immunization with sperm or control cells in adjuvant exclusively by s.c. or i.u. approaches did not affect subsequent fertility, although sperm-injected mice from both protocols had high titers of circulating antisperm antibodies. In contrast, mice that were immunized with sperm in adjuvant by a combination of s.c. and i.u. injections demonstrated significant reductions in fertilization rate and number of viable fetuses and an increased rate of fetal resorption when compared with non-immunized and control-immunized mice. Mice receiving sperm by the s.c./i.u. protocol had high titers of antisperm antibodies and a marked infiltration of T lymphocytes and macrophages into the uterine endometrium. To determine whether cellular immune mechanisms contributed to the infertility effect, T lymphocytes from spleens and pelvic lymph nodes of s.c./i.u. sperm-immunized mice and non-immunized mice were passively transferred to naive syngeneic female recipients which were subsequently mated. The total number of fetuses on day 15 of pregnancy was significantly reduced in mice receiving T-lymphocytes from sperm-immunized mice and a significant increase in fetal resorption sites was also observed. These mice did not have detectable titers of circulating antisperm antibodies, but had a significant infiltration of CD4+ T lymphocytes and macrophages in the uterine epithelium and endometrium. These data indicate that intrauterine antisperm cell-mediated immunity can be induced in mice by a combination of systemic and intrauterine immunizations and provide evidence for the existence of reproductive tract mucosal antisperm cellular immune responses that adversely affect fertility and pregnancy.

Animals↗
PubMed1992

A common silencer element in the SCG10 and type II Na+ channel genes binds a factor present in nonneuronal cells but not in neuronal cells.

We have localized a cell type-specific silencer element in the SCG10 gene by deletion analysis. This neural-restrictive silencer element (NRSE) selectively represses SCG10 expression in nonneuronal cells and tissues. The NRSE contains a 21 bp region with striking homology to a sequence present in a silencer domain of the rat type II sodium channel (NaII), another neuron-specific gene. We have identified a sequence-specific protein(s) that binds the SCG10 NRSE, as well as the homologous element in the NaII gene. A point mutation in the NRSE that abolishes binding of this neural-restrictive silencer-binding factor (NRSBF) in vitro also eliminates silencing activity in vivo. NRSBF is present in nuclear extracts from nonneuronal cells but not in extracts from neuronal cells, suggesting that the neuron-specific expression of SCG10 reflects, at least in part, the absence or inactivity of this protein. These data identify the NRSE as a potentially general DNA element for the control of neuron-specific gene expression in vertebrates.

Base Sequence↗
PubMed1992

Changes in competence determine the timing of two sequential glucocorticoid effects on sympathoadrenal progenitors.

We have studied the control of adrenal chromaffin cell development by glucocorticoids (GCs), in a reconstituted in vitro system. The development of the chromaffin phenotype involves two sequential, GC-dependent events: the decision not to become a sympathetic neuron, and the decision to express the epinephrine-synthesizing enzyme, phenylethanolamine-N-methyltransferase (PNMT). Both decisions appear to be mediated by the type II GC receptor. Competence to express PNMT develops on a schedule in vitro which parallels that seen in vivo, but only in progenitors that have first failed to undergo neuronal differentiation. The schedule of PNMT induction is thus controlled by the time of appearance of neither the inducing signal nor its receptor, as previously suggested, but rather by a cell-intrinsic timed process in chromaffin precursors. The two effects of GCs are pharmacologically distinct, suggesting that the GC receptor may interact differently with different genes in the same cell, in a manner that changes with development.

Adrenal Medulla↗
PubMed1992

Evidence of embryo- and trophoblast-toxic cellular immune response(s) in women with recurrent spontaneous abortion.

OBJECTIVE: The purpose of this study was to determine whether reproductive antigens stimulate lymphocytes and macrophages from women with recurrent abortion to secrete factors that are toxic to preimplantation embryos or trophoblast cells in vitro. STUDY DESIGN: Mononuclear cells were isolated from 30 fertile controls and 300 nonpregnant women being evaluated for recurrent abortion. Supernatants generated from these cells after separate culture with sperm and trophoblast antigen extracts were added to two-cell mouse embryo cultures and trophoblast proliferation assays. Toxicity was assumed when the median percentage of embryos developing to blastocysts or trophoblast proliferation was less than or equal to 50% of control values. Both parametric and nonparametric statistical methods were used where appropriate. RESULTS: Mouse embryo development and/or trophoblast proliferation were significantly inhibited by supernatants from trophoblast and/or sperm antigen-activated peripheral blood leukocyte cultures from a majority of 300 women with recurrent abortion but not from 30 women with normal reproductive histories. The mouse blastocyst development assay was more sensitive than the trophoblast proliferation assay in determining toxic factor production. Embryo-toxic factors were produced by activated leukocyte cultures from 90% of 180 women with a history of recurrent abortion of unexplained etiology, whereas trophoblast-inhibitory factors were detected in 50% of women from the same group. The embryo-toxic factor(s) was heat labile, had a molecular weight(s) between 10 and 30 kd, and was absorbed out by passage through affinity columns containing anti-interferon gamma beads. CONCLUSION: We conclude that recurrent abortion in some women is associated with embryo- and/or trophoblast-toxic factor production in response to stimulation by sperm or trophoblast antigens and that the principal factor may involve the 18 kd, heat-labile, T-lymphocyte cytokine interferon gamma. This study suggests a new cause of recurrent abortion.

Abortion, Habitual↗
PubMed1992

Interferon-gamma receptors on human gestational choriocarcinoma cell lines: quantitative and functional studies.

OBJECTIVES: This study was performed to further define the effects of interferon-gamma on choriocarcinoma cell lines and to determine whether variations in response among cell lines are attributable to quantitative differences in interferon-gamma receptors. STUDY DESIGN: Interferon-gamma receptors were quantified on BeWo, JEG-3 and Jar choriocarcinoma cell lines by a radiolabeled interferon-gamma ligand binding assay. The response of these cell lines to interferon-gamma was measured in two functional assays: a cell proliferation assay and a cell lysis assay after exposure to interferon-gamma with and without actinomycin-D. RESULTS: The number of interferon-gamma receptors on BeWo, Jar, and JEG-3 cells did not differ significantly (650, 560, and 420 interferon-gamma receptors per cell, respectively). Proliferation of all three choriocarcinoma cell lines was significantly inhibited to a similar extent by interferon-gamma. After treatment with interferon-gamma actinomycin-D, each choriocarcinoma cell line exhibited dose-dependent cell lysis; lysis of Jar was significantly less than that of either BeWo or JEG-3. CONCLUSION: These data further document variations in the response of choriocarcinoma cell lines to interferon-gamma and indicate that these differences are not the result of interferon-gamma receptor number but of postreceptor mechanisms.

Binding Sites↗
PubMed1992

Cryptococcal disease presenting as cellulitis.

Three immunocompromised patients presented with cellulitis as the primary manifestation of cryptococcal disease. Two were recipients of cadaveric renal transplants who were receiving immunosuppressive drug therapy. The other patient had profound lymphopenia and severe hypoalbuminemia due to intestinal lymphangiectasia. All had failed to respond to empiric therapy for presumed bacterial cellulitis before results of skin biopsy or aspiration were available for the correct diagnosis to be made. With administration of systemic antifungal therapy, two patients survived. Although other forms of cryptococcal involvement of the skin are not rare, cellulitis is seldom considered to be a cutaneous manifestation of the disease. Our cases and a review of the English-language literature indicate that Cryptococcus neoformans must be included in the differential diagnosis of cellulitis in immunocompromised patients and that the presence of cryptococcal cellulitis suggests disseminated cryptococcal disease. Prompt diagnosis and treatment may dramatically reduce mortality.

Adult↗
PubMed1992

Generalized anxiety disorder vs. panic disorder. Distinguishing characteristics and patterns of comorbidity.

In order to examine the validity of the distinction between generalized anxiety disorder (GAD) and panic disorder (PD) we compared 41 subjects with GAD and 71 subjects with PD. The GAD subjects had never had panic attacks. In contrast to the symptom profile in PD subjects suggestive of autonomic hyperactivity, GAD subjects had a symptom pattern indicative of central nervous system hyperarousal. Also, subjects with GAD had an earlier, more gradual onset of illness. In terms of coexisting syndromes, GAD subjects more often had simple phobias, whereas PD subjects more commonly reported depersonalization and agoraphobia. GAD subjects more frequently had first-degree relatives with GAD, whereas PD subjects more frequently had relatives with PD. A variety of measures indicated that our GAD subjects had a milder illness than those with PD. Also, fewer GAD subjects gave histories of major depression than did PD subjects. Among GAD subjects, coexisting major depression was associated with simple phobia and thyroid disorders and among PD subjects, comorbid depression was associated with social phobia and hypertension. Our findings indicate that the separation of GAD from PD is a valid one. They also indicate that, within disorders, unique patterns of comorbidity may exist that are important both clinically and theoretically.

Adult↗