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Biomedical subjects

G White

Publications and source records attributed to G White.

At least 145 records · Page 8Linked to original sources
PubMed1990

Ethanol inhibition of neuronal glutamate receptor function.

Acute ethanol intoxication is associated with changes in the activity of neurons in the central nervous system. However, the cellular and molecular mechanisms underlying these changes are poorly understood. We have examined the acute effects of ethanol on excitatory synaptic mechanisms in neurons from mammalian central nervous system, and observed that intoxicating concentrations of ethanol can inhibit the ion current activated by the glutamate receptor agonist N-methyl-D-aspartate in cultured neurons from mouse hippocampus, cortex and spinal cord. This inhibition is seen under a variety of experimental recording conditions. On the other hand, ethanol is less effective in inhibiting ion current produced by activation of non-N-methyl-D-aspartate glutamate receptors. Intoxicating concentrations of ethanol also inhibit excitatory synaptic transmission mediated by N-methyl-D-aspartate receptors in hippocampal slices from adult rodents. These observations support the hypothesis that the N-methyl-D-aspartate receptor/ionophore complex is a target for the neural actions of ethanol, and that inhibition of N-methyl-D-aspartate receptor-mediated responses might contribute to acute ethanol intoxication. The possibility that other receptor-gated ion channels may also be sensitive to ethanol is discussed.

Action Potentials↗
PubMed1990

NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat.

The effect of ethanol (EtOH) on synaptic transmission mediated by N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors was investigated in slices from adult rat hippocampus. Synaptic responses were elicited by stimulation of stratum radiatum and were recorded in CA1 stratum radiatum or stratum pyramidale. Population EPSPs (pEPSPs) mediated by NMDA receptor activation were isolated by application of a solution containing the kainate/quisqualate receptor antagonist 6,7-dinitroquinoxaline-2,3-dione and either low (0.1 mM) Mg2+ or 100 microM bicuculline. Increasing concentrations of EtOH produced increasing inhibition of NMDA receptor-mediated pEPSPs with EtOH concentrations between 1 and 50 mM. At a concentration of 50 mM, EtOH inhibited NMDA receptor-mediated pEPSPS by 43%; the inhibition by 100 mM EtOH was not significantly different from that produced by 50 mM. Methanol and 1-butanol also inhibited the NMDA receptor-mediated pEPSPs; the potency of the alcohols for inhibition of NMDA receptor-mediated pEPSPs was 1-butanol greater than ethanol greater than methanol. pEPSPs mediated by non-NMDA glutamate receptors were isolated by the application of the NMDA receptor antagonist d,1-2-amino-5-phosphonovaleric acid in the presence of 1.5 mM Mg2+. These pEPSPs were not significantly affected by 50 mM EtOH, whereas 100 mM EtOH reduced the amplitude of these pEPSPs by 9%. The observations indicate that synaptic excitation mediated by NMDA receptors in tissue from adult rat is inhibited by intoxicating concentrations of EtOH. The data are consistent with the hypothesis that EtOH-induced inhibition of EPSPs mediated NMDA receptors may contribute to the intoxicating effects of EtOH.

Animals↗
PubMed1989

Post-natal development of burst firing behavior and the low-threshold transient calcium current examined using freshly isolated neurons from rat dorsal root ganglia.

Burst firing was triggered by an afterdepolarizing potential (ADP) in whole-cell recordings from neurons recently isolated from dorsal root ganglia (DRG) of adult rats, less frequently in neurons from 12-day-old rats, and not at all in neurons from 1-day-old rats. Both the ADP and voltage-activated transient (T-type) Ca2+ current which generates the ADP were present in neurons at all postnatal ages; however, the amplitude of the ADP and of the T-type current were greatest in neurons from adults, smaller in neurons from 12-day animals, and smallest in neurons from 1-day animals. These observations suggest that the increase in amplitude of the T-type current with age leads to the generation of an ADP of increased amplitude and those properties of the ADP which develop with age may contribute to or generate burst firing behavior.

Action Potentials↗
PubMed1989

Ethanol inhibits NMDA-activated ion current in hippocampal neurons.

The ion current induced by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) in voltage-clamped hippocampal neurons was inhibited by ethanol (EtOH). Inhibition increased in a concentration-dependent manner over the range 5 to 50 mM, a range that also produces intoxication. The amplitude of the NMDA-activated current was reduced 61 percent by 50 mM EtOH; in contrast, this concentration of EtOH reduced the amplitude of current activated by the glutamate receptor agonists kainate and quisqualate by only 18 and 15 percent, respectively. The potency for inhibition of the NMDA-activated current by several alcohols is linearly related to their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication.

1-Butanol↗
PubMed1989

The effects of gepirone and 1-(2-pyrimidinyl)-piperazine on levels of corticosterone in rat plasma.

It was found that gepirone and 1-(2-pyrimidinyl)-piperazine (1-PP) increased levels of corticosterone in plasma in the intact rat. Gepirone was more potent and more efficacious than its metabolite, 1-PP. The ED50 was 6.4 mumol/kg for gepirone and 65.4 mumol/kg for 1-PP. Forty-five min after intraperitoneal administration, gepirone and 1-PP produced maximum increases in corticosterone of 283% and 211%, respectively, above control values. The amplitude and duration of the effects of the drugs were dependent on the ongoing activity in the hypothalamic-pituitary-adrenal axis. Consequently, the greatest absolute increases in corticosterone were produced during the afternoon when the activity in the hypothalamic-pituitary-adrenal axis was greatest. A single 10 mg/kg dose of gepirone significantly elevated levels of corticosterone in plasma (313% after 1 hr) above control values for 2 hr during afternoon trials and for 1 hr (244%) during morning trials. In addition, it was found that the effects of the administration of gepirone and of stress on the levels of corticosterone in plasma were additive. In the light of other work on the hypothalamic-pituitary-adrenal axis, these results suggest that the increased levels of corticosterone, elicited by gepirone, were mediated through a serotonergic action rather than through noradrenergic activity.

Animals↗
PubMed1989

Heartrate variation of umbilical artery Doppler waveforms.

Umbilical artery Doppler waveforms from 20 patients were used to investigate the dependence of resistance index and pulsatility index on beat to beat pulse length over short time periods for individual patients, and on the usefulness of a common normalisation formula. For individual patients the resistance index and pulsatility index were only partially correlated with pulse length. Changes in both indices occurred independently of pulse length. Use of a common normalisation formula resulted in no significant reduction of the coefficient of variation of the resistance index (p greater than 0.1), and a reduction in the coefficient of variation of the pulsatility index of 10% (p greater than 0.001). It is concluded that short term changes in resistance index and pulsatility index cannot be corrected by a common normalisation formula.

Female↗
PubMed1989

Transient low-threshold Ca2+ current triggers burst firing through an afterdepolarizing potential in an adult mammalian neuron.

In a variety of mammalian neurons, a brief depolarization generates an afterdepolarizing potential that triggers the firing of a short series or burst of action potentials. Although such burst firing is thought to contribute to the processing of neural information, the ionic currents that underlie this phenomenon have not been established. In whole-cell patch-clamp experiments on dorsal root ganglion neurons, we have found that the current that underlies this type of burst firing is a transient low-threshold (T-type) Ca2+ current. The data suggest that the T-type Ca2+ current may play an important role in the processing of information in the nervous system by virtue of its ability to elicit burst firing in neurons.

Action Potentials↗
PubMed1989

High frequency edge enhancement in the detection of fine pulmonary lines. Parity between storage phosphor digital images and conventional chest radiography.

Fine linear structures represent a severe test of the minimum spatial resolution that is needed for digital chest imaging. We studied the comparative observer performance of storage phosphor digital imaging (1760 X 2140 pixel matrix, 10 bits deep), and conventional radiography (Lanex medium screen, Ortho C film) in the detection of simulated fine pulmonary lines superimposed on the normal chest when exposure factors were identical (20mR skin entrance dose at 141 kVp). Receiver operating characteristics analysis of 2160 observations by six readers found that high frequency edge-enhanced digital images (ROC area: 0.78 +/- 0.06) performed better than unenhanced digital images (ROC area: 0.70 +/- 0.07) (P less than 0.01 for paired t-test), and that edge enhanced digital images performed on a par with conventional radiography (ROC area: 0.78 +/- 0.09). We conclude that for the detection of fine linear structures, storage phosphor digital images can perform on a par with higher resolution conventional chest radiographs when a high frequency edge-enhancement algorithm is employed.

Adult↗
PubMed1989

In vivo efficacy of zidovudine (3'-azido-3'-deoxythymidine) in experimental gram-negative-bacterial infections.

The therapeutic efficacy of orally administered zidovuldine (3'-azido-3'-deoxythymidine) was determined in animals infected with Escherichia coli and Salmonella dublin. The 50% effective dose (ED50) of zidovudine (9.6 to 11.8 mg/kg of body weight) compared favorably with that of trimethoprim (19.4 to 22.2 mg/kg) in mice with systemic E. coli infection. At 50 mg/kg, both zidovudine and ampicillin reduced the number of bacteria in the kidneys of mice and prevented lethal infection in mice with ascending pyelonephritis caused by E. coli. Zidovudine prevented a lethal S. dublin infection in calves over a wide dose range (8.0 to 31.0 mg/kg per day). Zidovudine levels in plasma of uninfected mice were 28.2 +/- 4.5 and 7.9 +/- 2.2 micrograms/ml at 30 and 60 min, respectively, exceeding the MICs for the bacteria used in the infections. Few zidovudine-resistant strains were observed. The in vivo data raise the possibility that zidovudine may have an antibacterial effect in patients receiving this therapy.

Ampicillin↗
PubMed1989

Asymmetric breast tissue.

A prospective study was undertaken to evaluate the significance of asymmetric breast tissue (asymmetric volume of breast tissue, asymmetrically dense breast tissue with preserved architecture, or asymmetrically prominent ducts) on mammograms. Of 8,408 mammograms obtained in 1985, 221 (3%) demonstrated asymmetric breast tissue. Follow-up was 36-42 months after the initial mammographic study. During this time none of the patients underwent biopsy on the basis of mammographic findings, although 20 underwent excisional biopsy because of clinical findings. Breast cancer was diagnosed in two patients and breast lymphoma in one patient. Biopsy specimens from the remaining 17 patients were benign. At mammography, all three malignant lesions had a palpable abnormality associated with the asymmetric tissue. Breast cancer was not found in any of the remaining 201 patients. Therefore, an asymmetric volume of breast tissue, asymmetrically dense breast tissue, or asymmetrically prominent ducts that do not form a mass, do not contain microcalcifications, or do not produce architectural distortion should be viewed with concern only when associated with a palpable asymmetry and are otherwise normal variations.

Adult↗
PubMed1988

A comparison of the effects of buspirone and diazepam on plasma corticosterone levels in rat.

The effect of the anxiolytic agents, buspirone and diazepam, on the hypothalamic-pituitary-adrenal axis (HPAA), indicated by changes in the concentration of corticosterone (CS) in plasma, were studied 1/2, 1, 2, 4, 6, 8 and 24 hr after administration of the drug (i.p.). Samples of plasma were collected in the mid-morning (0930-1130 hr) when activity in the hypothalamic-pituitary-adrenal axis in the rat and control levels of corticosterone were low and were repeated in the afternoon (1400-1600 hr) when activity in the hypothalamic-pituitary-arenal axis and levels of corticosterone were higher. At small doses (1 mg/kg) buspirone had a greater facilitating effect on the hypothalamic-pituitary-adrenal axis than did diazepam. In addition, buspirone had a greater maximum facilitatory effect (477%) on levels of corticosterone than diazepam (345%). However, buspirone (ED50 = 8.6 mumol/kg) and diazepam (ED50 = 8.7 mumol/kg) were equipotent. Administration of 1 mg/kg of buspirone in the morning increased the combined 1/2 and 1 hr circulating levels of corticosterone 75% above control levels. Diazepam, at 1 mg/kg, did not produce any significant changes in levels of corticosterone. Large doses (10 mg/kg) of buspirone increased morning levels of corticosterone by 328% and diazepam increased levels of corticosterone by 265%. During the afternoon small doses of buspirone or diazepam did not significantly alter levels of corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Determination of the presence of fetal apnoea using umbilical artery and umbilical vein Doppler waveforms.

Fetal breathing movements were observed using real-time ultrasound imaging. Simultaneous Doppler recordings of the flow velocity waveform from the umbilical artery and umbilical vein were obtained. Twenty patients were studied. The Doppler traces obtained during fetal apnoea and fetal breathing for each patient were analysed using a BBC microcomputer. A combination of venous variation index (VVI) and the coefficient of variation of arterial pulsatility index (CVPI) gave complete separation between breathing and apnoeic groups (lower values of VVI and CVPI being associated with the apnoeic group). Hence, when stand alone continuous wave Doppler units are used to acquire umbilical artery Doppler waveforms during fetal apnoea, the presence of apnoea can be determined using the variability of the arterial and venous trace without the need for visualisation of the fetus using imaging equipment.

Apnea↗
PubMed1988

Evidence that associative interactions between synapses during the induction of long-term potentiation occur within local dendritic domains.

The present study evaluates whether the associative interactions between synapses that lead to long-term potentiation and depression (LTP and LTD) can occur between spatially segregated synapses of the medial and lateral temporodentate pathway of the rat. Coconditioning of crossed and ipsilateral pathways resulted in LTP of the crossed system only when the current sinks of the two conditioned pathways overlapped sufficiently. Likewise, conditioning of an ipsilateral pathway alone resulted in LTD of the crossed pathway only when those current sinks overlapped sufficiently. These observations support the idea that associative events that lead to LTP or LTD can be restricted to a local dendritic domain. The postsynaptic cell can therefore serve as more than one unit of integration for synaptic modification.

Animals↗
PubMed1988

Does preoperative needle localization lead to an increase in local breast cancer recurrence?

Between 1978 and 1981, 74 women with nonpalpable breast cancer underwent surgery after localization guides were placed. In 72 patients, guides were introduced parallel to the chest wall; in two the needle was positioned anteroposteriorly under computed tomographic guidance. Fifty-six cases (76%) were infiltrating cancer; 13 (17%), intraductal cancers; two (3%), inflammatory; and three (4%), lobular carcinoma in situ. Surgery was not used to treat the latter five patients. In the remaining 69 women, 42 (61%) were treated by means of modified radical mastectomy; six (9%), total mastectomy; 12 (17%), local excision and radiation therapy; and seven (10%), local excision alone; exact therapy for two women (3%) was unknown. At a minimum follow-up of 5 years, none of the 67 women in whom the parallel approach was used had a local recurrence. The authors conclude that preoperative placement of guides parallel to the chest wall does not appear to increase the risk of local breast cancer recurrence.

Breast Neoplasms↗
PubMed1988

Comparison of two screen-film combinations in contact and magnification mammography: detectability of microcalcifications.

A new dual-screen, dual-emulsion-film combination that allows a decrease in radiation dose of approximately 66% was compared with a widely used single-screen, single-emulsion-film system in contact and magnification mammography. Clustered microcalcifications randomly superimposed on a breast phantom were detected, and the location and number of individual calcifications were determined by four observers. The detectability of calcifications, determined with a receiver operating characteristic (ROC) analysis area, was 0.92 for magnification and 0.82 for contact mammography with the single-emulsion-film system, compared with 0.84 and 0.72, respectively, with the dual-emulsion-film system. More clusters were correctly located and more individual calcifications were counted with magnification than with contact mammography. The dual-emulsion-film system with the magnification technique performs as well as the single-emulsion-film system with the contact technique, while retaining a decrease in required dose of approximately 40%.

Breast Diseases↗