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Biomedical subjects

K Reid

Publications and source records attributed to K Reid.

At least 73 records · Page 4Linked to original sources
PubMed1994

FGF2 regulates proliferation of neural crest cells, with subsequent neuronal differentiation regulated by LIF or related factors.

Two of the key early events in the development of the peripheral nervous system are the proliferation of neural crest precursor cells and their subsequent differentiation into different neural cell types. We present evidence that members of the fibroblast growth factor family, (FGF1 or FGF2) act directly on the neural crest cells in vitro to stimulate proliferation in the presence of serum. These findings correlate with in situ hybridisation analysis, which shows FGF2 mRNA is expressed in cells both in the neural tube and within newly formed sensory ganglia (dorsal root ganglia, DRG) at embryonic day 10 in the mouse, when neural crest precursors are proliferating within the DRG. This data infers an autocrine/paracrine loop for FGF regulation of proliferation. Evidence supporting this notion is provided by the finding that part of the endogenous proliferative activity in the NC cultures is related to FGF. It was also found, in early neural crest cultures, that exogenous FGF completely inhibited neuronal differentiation, probably as a direct consequence of its mitogenic activity. In order to stimulate neuronal differentiation significantly, it was necessary to remove the FGF and replace it with leukemia inhibitory factor (LIF) or related factors. Under these conditions, 50% of the cells differentiated into neurons, which developed a sensory neuron morphology and were immunoreactive for the sensory markers CGRP and substance P. These data support a model of neural crest development, whereby multipotential neural crest precursor cells are stimulated to divide by FGF and subsequent development into sensory neurons is regulated by LIF or other cytokines with a similar signalling mechanism.

Animals↗
PubMed1993

Inactivation of viruses during ultraviolet light treatment of human intravenous immunoglobulin and albumin.

A comparison of ultraviolet (UV) irradiation of two wavelength ranges UVB (280-320 nm) and UVC (lower than 280 nm) showed that UVC in particular could very effectively inactivate, in intravenous immunoglobulin (IVIG) and albumin preparations, non-enveloped and non-acid labile model viruses (i.e., Polio 2 and T4 phage) and dry heat-resistant viruses (vaccinia and T4 phage). This effective virucidal treatment (5 min, 5,000 J/m2 dose) was achieved before an unacceptable level of IVIG aggregates occurred. The use of UV irradiation to inactivate infectious agents could add safety and supplement current methods, e.g. solvent/detergent, low pH, which do not inactivate non-enveloped, non-acid labile or dry-heat-resistant viruses at present.

Antibodies, Viral↗
PubMed1993

Involvement of leukemia inhibitory factor and nerve growth factor in the development of dorsal root ganglion neurons.

Leukemia inhibitory factor (LIF) was recently shown to stimulate the generation of sensory neurons from the murine neural crest in vitro. Here, we examine the respective activities of LIF and nerve growth factor (NGF) throughout the embryonic development of sensory neurons in dorsal root ganglia (DRG) and neural crest. In cultures of embryonic day 12 (E12) DRG, which contain sensory neuron precursor cells, a combination of both LIF and NGF are required for the differentiation of mature sensory neurons from their neurofilament negative (NF-) precursors. The primary differentiation step from NF- cell to NF+ immature neuron is promoted by LIF, whereas the survival and further maturation of the newly differentiated neurons depends on NGF. In cultures of sensory neurons isolated at the time of target innervation (E14 and E15 DRG), the survival of the majority of the neurons is dependent on NGF. However, LIF acts as a survival agent for a discrete population of NGF non-responsive neurons. From E16, the number of neurons maintained by LIF increases to > 90% by birth. Consistent with the in vitro observations, LIF mRNA could be detected at early developmental stages (E12-E13), within the spinal column and DRG as well as the limbs and, later (after E15), in areas of sensory innervation (skin, limbs, feet and gut). This supports the idea that LIF, as well as NGF, may regulate sensory development in vivo.

Animals↗
PubMed1992

Steel factor is required for maintenance, but not differentiation, of melanocyte precursors in the neural crest.

Skin melanocytes are derived from neural crest cells that migrate into the dermis during embryogenesis. Two mouse mutants, Steel and White dominant-spotting, which have defects in melanocyte production, have recently been shown to have deletions in the genes that code for a new growth factor, steel factor (SLF), and its receptor, respectively. Here, we have investigated the role that SLF plays in melanogenesis using cultures of mouse neural crest and found that its primary action is the maintenance of melanocyte precursors. It has no effect on the final stage of melanocyte differentiation, the production of melanin, which appears to require an additional factor whose action is mimicked by the phorbol ester TPA (12-O-tetradecanoyl-phorbol-13-acetate).

Animals↗
PubMed1992

Pertussis toxin-mediated ribosylation of G proteins blocks the hypnotic response to an alpha 2-agonist in the locus coeruleus of the rat.

Biologic responses mediated by adrenoceptors are transduced by a receptor-effector mechanism that involves a guanine nucleotide binding protein (G protein). Recently, we determined that the transduction mechanism for the hypnotic response to dexmedetomidine, a highly selective alpha 2-agonist, is located in the locus coeruleus (LC) of the rat. In this study, we examined the role of pertussis toxin-sensitive (PTX) G proteins in the LC for the hypnotic response to dexmedetomidine. The LC of rats were stereotactically cannulated and treated with PTX, 0.34 micrograms, or vehicle. Five days later, the hypnotic response to dexmedetomidine, 7 micrograms into the LC or 50 micrograms.kg-1 IP, was tested. On the following day, the LC was harvested and assayed to determine whether the G proteins had been ribosylated by pretreatment with PTX in vivo. Quantitative immunoblotting of G0 alpha, Gi alpha 1,2, and Gi alpha 3, the alpha-subunit of three PTX-sensitive proteins, was also performed. In vivo treatment with PTX into the LC blocked the hypnotic response to LC-administered dexmedetomidine and, to a lesser extent, IP-administered dexmedetomidine. The in vivo PTX treatment effectively ribosylated the G proteins. No alteration in the amount of the different species of PTX-sensitive alpha-subunit was produced by in vivo PTX treatment. These data suggest a pivotal role for PTX-sensitive G proteins in the LC in the hypnotic response to alpha 2-agonists in the rat.

Adenosine Diphosphate↗
PubMed1992

Synergistic interaction between alpha 2-adrenergic agonists and benzodiazepines in rats.

Both alpha 2-adrenergic agonists and benzodiazepines exert anxiolytic and sedative effects when administered as preoperative medications. Clinical effects achieved with a combination of drugs, representative of these classes of compounds, is greater than that which could be expected from a simple additive response. Therefore, we investigated the nature of the interaction between dexmedetomidine, the highly-selective alpha 2-adrenergic agonist, and midazolam in a series of in vivo and in vitro studies in rats. Rats were administered midazolam, dexmedetomidine, or a combination of midazolam and dexmedetomidine intravenously to derive three dose-response curves for loss of righting reflex (LRR). LRR was determined in rats in a rotating cage (4 rotations/min) by observing whether the rat failed to maintain its upright posture for greater than or equal to 15 s exactly 2.5 min after drug administration. The effect of either flumazenil (benzodiazepine receptor antagonist) or atipamezole (the alpha 2-adrenergic antagonist) on the LRR was also determined. A probit analysis was performed and an isobologram for the ED50 was derived to assess the nature of the interaction. Rat brain membranes were prepared for receptor binding assays using [3H]-flumazenil and [3H]-rauwolscine to characterize the benzodiazepine and alpha 2-adrenergic receptors, respectively. The ability of either midazolam or dexmedetomidine to displace the radiolabeled ligand from the alternative receptor was assessed. To detect a possible kinetic interaction between the two drugs, separate cohorts of rats were administered the two drugs individually or in combination at the combination ED50 doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1992

Inhibition of adenylate cyclase in the locus coeruleus mediates the hypnotic response to an alpha 2 agonist in the rat.

Recently, we determined that the transduction mechanism for the hypnotic response to dexmedetomidine, a highly selective alpha 2 agonist, resides in the locus coeruleus (LC) of the rat. Candidates for the effector mechanism of this alpha 2 adrenoceptor-mediated hypnotic response include inhibition of adenylate cyclase, which has been shown to be pivotal to the cellular response of alpha 2 agonists in some, but not in all, cases. The LC of rats were stereotaxically cannulated with an indwelling catheter, and after the 2nd day, the hypnotic response to 7 micrograms of dexmedetomidine into the LC (an effective hypnotic dose for 95% of animals) was tested. Other groups of rats were pretreated with the permeable nonhydrolyzable cyclic AMP (cAMP) analog, dibutyryl cAMP (dB cAMP), at a dose of 0.2 to 1.2 ng into the LC, or 2.75 to 275 micrograms.kg-1 i.p. rolipram, a cAMP-specific phosphodiesterase inhibitor, and the hypnotic response to 7 micrograms of dexmedetomidine into the LC was tested. Both dB cAMP and rolipram reversed the hypnotic response to dexmedetomidine. To test for the specificity of these hypnotic-reversing perturbations, rats were pretreated with Rp-adenosine-3',5'-cyclic phosphorothioate, a cAMP-dependent protein kinase inhibitor, and the experiments were repeated. The hypnotic-reversing property of either dB cAMP or rolipram could be prevented by blocking cAMP-dependent protein kinase ("A" kinase) activity with Rp-adenosine-3',5'-cyclic phosphorothioate.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclase Inhibitors↗
PubMed1991

Generation of sensory neurons is stimulated by leukemia inhibitory factor.

The processes that regulate the development of peripheral neurons from their precursors in the embryonic neural crest are essentially unknown. In this report, we show that leukemia inhibitory factor stimulates the generation of neurons in cultures of mouse neural crest. These neurons have the morphology of sensory neurons and contain neuropeptides found in mammalian sensory neurons. Consistent with these neurons being of the sensory lineage is the finding that they arise from nondividing precursors within the neural crest. In addition, we show that leukemia inhibitory factor supports the generation and/or maturation of sensory neurons in cultures of cells obtained from embryonic dorsal root ganglia. In cultures of postnatal dorsal root ganglia, which contain mature sensory neurons, leukemia inhibitory factor acts directly as a survival molecule on the majority of neurons.

Animals↗
PubMed1991

Cell lines derived from mouse neural crest are representative of cells at various stages of differentiation.

In order to study mammalian neural crest differentiation in vitro, a series of clonal neural crest (NC) cell lines have been generated by infection of migrating mouse neural crest cells with two recombinant retroviruses containing either the c-myc or N-myc proto-oncogenes. Many cell lines were generated which could be subdivided into three groups based on their appearance in culture. Eleven of these cell lines representative of each of the morphological groups were characterized for the expression of six antigenic markers expressed by neural cells. In addition, mRNA was prepared from these cell lines and analyzed for the expression of a number of neural specific genes. These analyses show that the cell lines are representative of the following cell types: (1) neural crest-like cell lines that do not differentiate in 10% serum; (2) progenitor cell lines, some of which can partially differentiate in culture; and (3) mature neuronal cell lines or bipotential cell lines. Southern blot analysis of DNA from these lines indicated that they have multiple integration sites for the provirus and suggest that phenotypically different cell types have arisen from a single cell. None of the cell lines showed any proliferative or morphological response to nerve growth factor (NGF), whereas over two-thirds of the lines showed both marked proliferative and morphological responses to fibroblast growth factor (FGF). These data indicate that we have generated a range of cell lines representative of a spectrum of mouse neural crest derivatives.

Animals↗
PubMed1991

Humoral (immunological) responses in female albino rats during rotating magnetic field exposures.

Experiments were designed to evaluate the primary and secondary humoral responses to a rotating magnetic field configuration, which is known to evoke significant biobehavioral changes. Ten days after inoculation with human serum albumin and 10 days before a booster, female rats were exposed to either a 0.5 Hz rotating magnetic field (RMF) or to room conditions (control). The lighting schedule was either continuous or involved a light-dark cycle (LD) of 12:12 h. A third group of rats served as colony room controls. Group differences of low statistical significance were found when females were exposed to continuous lighting rather than the LD 12:12 light-dark cycle. However, the effects were considered trivial and not sufficient to explain the previously reported biobehavioral changes evoked by this field configuration.

Animals↗
PubMed1991

Sex differences in primary humoral responses of albino rats to human serum albumin.

Primary humoral responses to human serum albumin, with or without concomitant Freund's adjuvant, were determined for over 300 male and female Wistar albino rats. Groups of female rats always displayed significantly more antibody production than males. Without adjuvant only 70% of the males responded compared to 99% of the females. When the antigen was accompanied by adjuvant, more than 95% of both sexes responded. Whereas without adjuvant the female response was only twice that of the males, adjuvant facilitated the response to a factor of 10 greater than the males. Both the gender and adjuvant effect each accounted for about 16% of the variance in the measurements of antigen binding capacity. Post-weaning castration did not stimulate the gender differences; there were no group differences in ABC at the extremes of estrus-related ambulatory cycles.

Adjuvants, Immunologic↗
PubMed1991

Corneal biopsy in microbial keratitis.

Presumed microbial keratitis in the absence of a specific microbiological diagnosis is a particularly difficult clinical problem. Corneal biopsy may provide the diagnosis when corneal scrapings have been negative. We present two cases in which corneal biopsy was helpful and discuss the role of corneal biopsy in the management of chronic keratitis.

Acanthamoeba Keratitis↗
PubMed1991

Hotter than a pepper sprout.

This year's federal budget contains a five-year deficit reduction plan that requires Medicare Part A and Part B be cut by $44.1 billion through fiscal 1995. One idea to help ease the transition would be to extend the prospective payment system to ever-growing outpatient charges under Part B through a system called Ambulatory Patient Groups.

Ambulatory Care↗
PubMed1991

Trans-thoracic fluid shifts and endocrine responses to 6 degrees head-down tilt.

A tomographic method of measuring electrical impedance known as Applied Potential Tomography (APT) has been used to image the impedance changes within the thoraxes of 8 healthy volunteers (4 male, 4 female) during 4-h periods of 6 degrees head-down tilt (HDT). A large decrease in impedance, reflecting an increase in thoracic fluid, was apparent within 1 min of tilting, peaked after 45 min, and was maintained throughout, although during the 4 h there was an 8% return towards baseline resistivity. Resistivity changes were most obvious in the region of the lungs. Simultaneous measurements of the key fluid regulating hormones revealed a significant increase in atrial natriuretic peptide (ANP) and a significant decrease in angiotensin II (AII) and aldosterone. There was no significant difference in plasma antidiuretic hormone level. These results illustrate the dynamic nature of fluid shifts during HDT, the spatial distribution of the fluid within the thorax and the associated endocrine responses.

Adult↗
PubMed1989

Topical nitroglycerin: a potential treatment for impotence.

The effect of 2 per cent nitroglycerin paste applied to the penile shaft of impotent subjects was evaluated in a placebo controlled double-blind study under laboratory conditions. After application of nitroglycerin paste or a placebo ointment base, penile tumescence was recorded through a strain gauge transducer while subjects viewed an erotic video presentation. Relative to the placebo paste the number of subjects demonstrating an increase in penile circumference after nitroglycerin (18 of 26) was significantly different than all other outcome possibilities (p less than 0.05). Noninvasive vascular assessment by ultrasonography demonstrated an increase in diameter and blood flow in the cavernous arteries after application of nitroglycerin paste. Nitroglycerin paste increases blood flow in the cavernous arteries and improves tumescence after erotic stimulation. This agent may represent a new therapy for impotence.

Administration, Topical↗