Biomedical subjects
S Marsh
Publications and source records attributed to S Marsh.
You can say no. Teenagers--don't be pressured into sex.
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We simply cannot afford to economise any further in nursing manpower.
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Helping the employee victim of violence in hospitals.
Violent behavior of patients is an occupational health hazard of health care professionals that the authors believe has not been fully recognized. Hospitals have developed a wide variety of techniques to manage patients who assault staff but have consistently ignored the plight of the victimized employee. Although professional staff who have been assaulted resist seeing themselves as victims, the authors believe they experience the feelings and reactions typical of other victims and therefore may need help in dealing with emotional trauma. The authors describe a victims' assistance program adopted by Royal Victoria Hospital in Montreal and discuss problems associated with implementing programs like it.
Children with spina bifida: the role of the health visitor in tertiary prevention.
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Mental handicap. Fears unfounded.
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DNA synthesis by erythroid precursors in a completely defined medium: a rapid, sensitive, and convenient bioassay for erythropoietin.
We detail a novel, sensitive, and reproducible in vitro bioassay for erythropoietin that can be performed conveniently in any laboratory and is well suited for analysis of large numbers of samples. The assay measures DNA synthesis by a cohort of highly erythropoietin-responsive red cell precursors appearing in bone marrow of anemic rabbits after treatment with a single dose of actinomycin D. The assay is conducted in a completely defined culture medium that totally dispenses not only with serum but also with serum-replacing factors. Under well-defined conditions, incorporation of [3H]thymidine by the cells depends specifically on erythropoietin. A stimulation index of up to 40-fold is obtained at 50 mU/ml of the hormone. The assay is linear in the range 0-50 mU/ml and not saturated before 1 U/ml of erythropoietin. Sample volumes of 1-30 microliter suffice for assay. Assay cells can be frozen in aliquots that retain their viability and ability to respond to erythropoietin over extended periods. Using microtiter-plate techniques, cells from one rabbit suffice for over 5000 triplicate erythropoietin determinations. Concentrations of 0.1-0.2 mU/well of erythropoietin can be detected. Erythropoietin values determined in sera from a variety of patients correlate extremely well with values obtained by the colony formation method. The ability to follow erythropoietin-dependent DNA synthesis and multiple cell divisions by a cohort of erythroid precursors in completely defined culture conditions may find application in controlled studies of red cell development.
gamma-Aminobutyric acid efflux from sympathetic glial cells: effect of 'depolarizing' agents.
1. Isolated desheathed rat superior cervical ganglia were incubated in [3H]2,3,-gamma-aminobutyric acid ([3H]GABA) solution (1--10 microM for 2--3 hr) in the presence of 10 microM-amino-oxyacetic acid (AOAA). The subsequent efflux of tritium into a stream of superfused non-radioactive GABA-free Krebs solution at 25 degrees C was measured. 2. In the presence of 10 micrometer-AOAA the mean basal efflux rate coefficient (k0) for exit of tritium into the superfusion fluid was 0.7 x 10(-3) min-1. More than 98% of effluent tritium comprised unchanged [3H]GABA. The rate coefficient showed no correlation with the amount of [3H]GABA previously accumulated by the ganglion. 3. Elevation of [K+]o to greater than 50 mM increased the rate coefficient for [3H]GABA release by up to four times. Changes in efflux rate were not correlated with osmotic changes, and persisted after re-accumulation of effluent [3H]GABA by the inward carrier was inhibited. The effect of alkali metal cations diminished in the order Rb+ greater than K+ greater than Cs+Li+. Effects of K+ solutions were not reduced by omitting Ca2+ ions, with or without the addition of Mg2+. 4. Application of electrical pulses (0.1--1 msec duration, 1--10 Hz, 4 min trains) to the ganglion soma or to the preganglionic nerve trunk also raised k0. This effect declined with repeated stimulus trains, without an accompanying diminution in the response to K+. Responses to electrical stimulation were not reduced by amethocaine (300 microM), tetrodotoxin (3 microM) or raised [Mg2+i1 (0 mM-[Ca2+]/30 mM-[Mg3+]). Separate local superfusion of the pre- and post-ganglionic nerve trunks and of the ganglion soma showed that the response to electrical stimulation was localized to the vicinity of the stimulus and was not propagated along the nerve trunks or across the synapses. 5. Electrical recording from impaled 'inexcitable' cells (presumed to be neuroglial cells (Appendix)) indicated that the quantities of K+ ion accumulating during repetitive nerve stimulation are insufficient to stimulate the release of GABA from the glial cells. No physiological role for the release process in modulating neuronal excitability could be adduced.
Distribution of gaba-receptors and gaba-carriers in the mammalian nervous system.
1. Extrasynaptic GABA-receptors occur on both neurone somata and unmyelinated axons in the mammalian peripheral nervous system. Activation of these receptors leads to depolarization, reduced spike amplitude and slowed conduction, probably mediated through increased Cl- conductance. 2. GABA also depolarizeds preganglionic nerve terminals in the rat superior cervical ganglion and reduces the release of acetylcholine by preganglionic nerve impulses. 3. The Schwann and satellite neuroglial cells surrounding peripheral unmyelinated axons and neurones possess a GABA-carrier promoting net uptake of GABA at external concentrations greater than or equal to 1 microM. 4. The possible significance of extrasynaptic receptors and carriers for GABA is discussed.
Axonal GABA-receptors in mammalian peripheral nerve trunks.
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Carcinogenicity and metabolic profiles of 6-substituted benzo[a]pyrene derivatives on mouse skin.
The ability was tested of appropriate substituents of benzo[a]pyrene (BP) at C-6 to decrease or suppress the carcinogenic activity for these BP derivatives relative to the parent compound. 8-week-old female Swiss mice in 9 groups of 30 were treated on the back with 0.2 mumol of compound in acetone 4 times weekly for 20 weeks. The following compounds were administered: BP, 6-methylbenzo[a]pyrene (BP-6-CH3), 6-hydroxymethylbenzo[a]pyrene (BP-6-CH2OH), benzo[a]pyrene-6-carboxaldehyde (BP-6-CHO), benzo[a]pyrene-6-carboxylic acid, 6-methoxybenzo[a]pyrene, 6-acetoxybenzo[a]pyrene, 6-bromobenzo[a]pyrene, and 6-iodobenzo[a]pyrene. Two additional groups received BP or BP-6-CH3 twice weekly for 20 weeks at a total dose 25% of that above. In addition, the metabolism of selected 6-substituted BP derivatives was studied, using mouse skin homogenates in vitro and mouse skin in vivo. Only four compounds were carcinogenic; the order of potency was BP greater than BP-6-CH3 greater than BP-6-CH2OH and BP-6-CHO. The difference in carcinogenicity between BP-6-CH2OH and BP-6-CHO could not be assessed by this experiment. In a further tumorigenesis experiment the carcinogenicity of BP-6-CH2OH was compared to that of BP-6 CHO, BP-6-CH3 and 6-hydroxymethylbenzo[a]pyrere sulfate ester (BP-6-CH2OSO3Na) on mouse skin. 9-week-old female Swiss mice in groups of 28 were treated at three dose levels with 0.8, 0.2 and 0.05 mumol of compounds in dioxane--dimethyl sulfoxide (75 : 25) twice weekly for 40 weeks. After 40 experimental weeks BP-6-CH2OSO3Na proved to be a more potent carcinogen than BP-6-CH2OH, which, in turn was more active than BP-6-CHO. The greater carcinogenicity of BP-6-CH3 relative to BP-6-CH2OH and BP-6-CHO is confirmed, suggesting that BP-6-CH2OH is not a proximate carcinogenic metabolite for BP-6-CH3. Since BP-6-CHO is a weaker carcinogen than BP-6-CH2OH and is efficiently reduced metabolically to BP-6-CH2OH, the latter compound may be a common proximal carcinogenic metabolite. The stronger potency of BP-6-CH2OSO3Na, compared to its alcohol, suggests that an ester of BP-6-CH2OH might be the ultimate alkylating compound reacting with cellular nucleophiles.
Carcinogenicity and metabolic profiles of 3-methylcholanthrene oxygenated derivatives at the 1 and 2 positions.
Trapping of 3-methylcholanthrene (MC) radical cation by nucleophilic compounds occurs specifically at the 1-carbon atom. With the purpose of providing more evidence for the hypothesis that the critical mechanism of activation of MC is one-electron oxidation, the carcinogenicity of MC was compared to that of 1-hydroxy-3-methylcholanthrene (MC-1-OH), 3-methylcholanthrene-1-one (MC-1-one), 2-hydroxy-3-methylcholanthrene (MC-2-OH), 3-methylcholanthrene-2-one (MC-2-one) and 3-methylcholanthrylene (MCL) by repeated application on mouse skin. Seven-week-old female Swiss mice in 6 groups of 30 were treated on the back with 0.2 mumol of compound in acetone twice weekly for 20 weeks. In addition, the metabolism of MC and its derivatives was studied using mouse skin homogenates. The compounds tested were classified according to carcinogenicity in 4 groups: MC and MC-2-OH, the strongest carcinogens; MC-2-one and MCL, weaker than MC and MC-2-OH; MC-1-OH, the weakest carcinogen; and MC-1-one, non-carcinogenic. These results support the hypothesis that one-electron oxidation for MC, MC-2-OH and MC-1-one might be the critical mechanism of carcinogenic activation, with C-1 the binding site to cellular nucleophiles. The carcinogenic effect of MC-1-OH is speculated to be the formation of an ester bearing a good leaving group, which might be the ultimate alkylating compound in the in vivo reaction. The lack of carcinogenic activity for MC-1-one may be attributed to absence of nucleophilic trapping at C-1 via the radical cation pathway as well as the inability of mouse skin to reduce MC-1-one to the carcinogenic MC-1-OH.
Action of GABA on mammalian peripheral nerves [proceedings].
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Transplacental effects of nitrosamines in Syrian hamsters. II. Nitrosopiperidine.
Nitrosopiperidine (NP) was found in Syrian hamsters quantitatively in the maternal blood for more than 8 h after subcutaneous injection, whereas it disappeared from placenta, fetus and amniotic fluid within the same time period. For N6MI, only traces were seen after 2 h in the same tissues. The long-term transplacental effect of a single dose of NP was weak, as demonstrated by a low respiratory tract tumor incidence (P-generation: 54%, F1- generation: 4%). Some tumors occurring in the digestive tract of exposed young were not found in their mothers and not commonly observed in controls. These tumors were considered a borderline transplacental effect. Tumors of other sites (i.e., the urogenital and genital tracts, reticuloendothelial system, endocrine organs and other tissues) corresponded in incidences to the overall fluctuations observed in this hamster colony.
Transplacental effects of nitrosamines in Syrian hamsters. III. Dimethyl- and dipropylnitrosamine.
The aliphatic nitrosamines dimethylnitrosamine (DMN), diethylnitrosamine (DEN), dipropylnitrosamine (DPN), and dibutylnitrosamine (DBN) reached fetal tissue in quantitatively measurable amounts after subcutaneous administration to pregnant Syrian hamsters. The compounds were present for at least 2 h in maternal blood, placenta, fetus, and amniotic fluid; DBN was still measurable after 6 h. Only a weak or borderline transplacental effect was seen when incidences and latencies of neoplasms in the respiratory and digestive tracts of the F1-generation were compared with those of the P-generation after exposure to a single dose of DMN or DPN. However, some tumor types occurred at relatively high rates in the young, but were seen only occcasionally in their mothers or in this hamster colony in general.
Indirect effects of amino-acids on sympathetic ganglion cells mediated through the release of gamma-aminobutyric acid from glial cells.
1 All experiments were performed on rat isolated desheathed superior cervical ganglia maintained in Krebs solution containing amino-oxyacetic acid (10 muM) at 25 degrees C. 2 Influx rates of gamma-amino-n-butyric acid (GABA) were measured by incubating ganglia in 0.5 muM [3H]-GABA for 30 minutes. Influx was inhibited by 50% on adding 14.3 muM unlabelled GABA, 59.2 muM beta-alanine (BALA) or 424 muM beta-amino-n-butyric acid (BABA). 3 Efflux of [3H]-GABA into non-radioactive solution superfused over ganglia previously incubated for 60 min in 1 muM [3H]-GABA was measured. The mean resting efflux rate coefficient (k) was 0.64 +/- 0.05 X 10(-3) min-1. Addition of high concentrations of unlabelled GABA, BABA or BALA to the superfusing solution increased k by (maximally) 3.6-4.3 times; half-maximal increases occurred at the following concentrations: GABA, 16 muM; BALA, 85 muM; BABA, 606 muM. Replacement of external Na+ with Li+ or TRIS increased the resting value of k and inhibited acceleration by external amino acids. Prior incubation in 1 muM [3H]-GABA with 1 mM unlabelled GABA increased resting k 1.5 times, but did not alter the peak rate coefficient produced by external amino acids. 4 Neuronal depolarization produced by the amino acids was measured with surface electrodes. Pre-incubation in 1 mM GABA for 60 min potentiated low-amplitude responses to BALA or BABA but not those to GABA or 3-aminopropanesulphonic acid (a potent agonist with low affinity for the GABA carrier). Omission of external Na+ reduced responses to BABA but increased those to GABA. 5 Incubation in 1 mM GABA for 60 min (as required to potentiate BABA or BALA actions) increased the amount of GABA in the tissue from 0.21 to 0.73 mmol/kg wet weight. Autoradiographs in which labelled GABA was used indicated that uptake into neuroglial cells was responsible for this accumulation. 6 It is suggested that: (i) BALA and BABA are substrates for the inward GABA carrier responsible for GABA entry into ganglionic glial cells; (ii) they accelerate efflux by inhibiting carrier-mediated reaccumulation of effluent GABA by the glial cells; (iii) interstitial GABA concentrations are thereby increased to a level capable of depolarizing adjacent neurones; and (iv) this, rather than direct GABA-receptor activation, accounts for the depolarization produced by low concentrations of BALA and BABA. Potentiation of their depolarizing action after pre-incubation in 1 mM GABA is suggested to result from the increased amount of intracellular GABA available for release, and is quantitatively compatible with this increase; inhibition in Na+-free solution is due to their inability to inhibit reaccumulation of GABA under these conditions. 7 A model for the action of carrier substrates is described in an Appendix. Calculations based thereon yield increments in interstitial GABA concentration in the presence of carrier substrates compatible with those determined experimentally (up to 1 muM at rest or 3.4 muM after pre-incubation in GABA).
A very simple method for recording ganglion depolarization.
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Depolarization of sympathetic ganglion cells mediated through the release of gamma-aminobutyric acid (GABA) from adjacent glial cells.
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