Biomedical subjects

J Church

Publications and source records attributed to J Church.

At least 55 records · Page 3Linked to original sources

PubMed1995

The effects of (-)- and (+)-beta-cyclazocine on NMDA-evoked responses and NMDA-mediated cell damage in cultured rat hippocampal neurons.

Microspectrofluorimetric measurements of excitatory amino acid-evoked rises in intracellular free calcium concentration ([Ca2+]i), electrophysiological measurements of currents through single NMDA receptor-operated ion channels and estimates of cellular viability following NMDA challenge were employed to examine the interactions of (-)- and (+)-beta-cyclazocine with the NMDA receptor-channel complex in cultured rat hippocampal neurons. Rises in [Ca2+]i evoked by NMDA, but not those evoked by kainate, AMPA or 50 mM K+, were reduced by (-)-beta-cyclazocine in a concentration- and use-dependent manner with an estimated IC50 value of 272 nM. In outside-out patches, (-)-beta-cyclazocine did not change the magnitudes of unitary NMDA-evoked currents but diminished both the frequency of channel openings and their mean open time. The IC50 for (-)-beta-cyclazocine against NMDA channel open state probability was estimated at 84 nM. The actions of (-)-beta-cyclazocine were consistent with a voltage-dependent open channel block of the NMDA channel with a blocking rate constant of 7.03.10(7) M-1.s-1 at -40 mV. Neurons exposed to a high concentration of NMDA in vitro were protected from death by 1 and 10 microM (-)-beta-cyclazocine. In all of the above assays, (+)-beta-cyclazocine was considerably less potent an NMDA antagonist and neuroprotective agent than (-)-beta-cyclazocine; the IC50 for (+)-beta-cyclazocine against channel open state probability was estimated at 14 microM. The results demonstrate that (-)-beta-cyclazocine is a potent and selective inhibitor of NMDA-evoked responses in cultured rat hippocampal neurons and an effective neuroprotective agent in vitro.

Animals↗

PubMed1995

(-)-beta-cyclazocine is an antagonist of NMDA receptor-mediated responses and a potent neuroprotectant in rat cortical neurons.

Microspectrofluorimetry and excitotoxicity experiments were performed to study the NMDA receptor-blocking and neuroprotective actions of (-)- and (+)-beta-cyclazocine in cultured rat cortical neurons. (-)-beta-Cyclazocine potently antagonized NMDA-induced[Ca2+]i increases (IC50 = 220 nM) in neurons loaded with the Ca2+ fluorophore, fura-2. (-)-beta-Cyclazocine was specific for NMDA receptor-mediated responses versus those mediated through non-NMDA receptors or voltage-activated Ca2+ channels. The agent was active against NMDA-induced neurotoxicity, even at 1 microM. In all experiments, the (+)-enantiomer was found to be considerably less potent than the (-)-enantiomer. These results indicate that (-)-beta-cyclazocine is a specific NMDA receptor antagonist with potent neuroprotective properties in rat cortical neurons.

Animals↗

PubMed1995

Blockade by sigma site ligands of N-methyl-D-aspartate-evoked responses in rat and mouse cultured hippocampal pyramidal neurones.

1. The effects of a range of structurally-dissimilar compounds which possess affinity for sigma binding sites were examined on the responses of cultured hippocampal pyramidal neurones to the excitatory amino acid analogues N-methyl-D-aspartate (NMDA), kainate and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA). 2. In mouse hippocampal neurones under whole-cell voltage-clamp, the compounds tested reversibly attenuated NMDA-, but not kainate- or AMPA-, evoked currents with a rank order potency (IC50 values in microM): ifenprodil (0.8) > (+)-N-allylnormetazocine (1.1) > dextromethorphan (1.8) = haloperidol (1.9) > (+)-pentazocine (7.2) > 1S,2R-(-)-cis-N-methyl-N-[2-(3, 4-dichlorophenyl) ethyl]-2-(1-pyrrolidinyl)cyclohexylamine (17) = rimcazole (18) > 1,3-di(2-tolyl)guanidine (37) > opipramol (96) > caramiphen (110) = carbetapentane (112) > > (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine (485). 3. The attenuation of NMDA-evoked responses was not mediated through interactions with the agonist, glycine (except haloperidol) or polyamine (except ifenprodil) binding sites on the NMDA receptor-channel complex but, in the light of the voltage- and, in some cases, use-dependent nature of their antagonism, an interaction with the ion channel appears to be a likely mechanism of action for many of the compounds. 4. Micromolar concentrations of selected sigma site ligands also reduced NMDA-evoked rises in intracellular free calcium concentration in Fura-2-loaded cultured hippocampal neurones of the rat with the same rank order potency as observed in the electrophysiological studies. 5. The data indicate that, at micromolar concentrations, the sigma site ligands tested act as NMDA receptor antagonists, an action which does not appear to be mediated by high-affinity sigma binding site(s). The functional effects of micromolar concentrations of sigma site ligands cannot, therefore, be attributed exclusively to interactions with high-affinity sigma binding sites.

Animals↗

PubMed1995

Blockade by sigma site ligands of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones.

1. The effects of a series of structurally-dissimilar sigma site ligands were examined on high voltage-activated Ca2+ channel activity in two preparations of cultured hippocampal pyramidal neurones. 2. In mouse hippocampal neurones under whole-cell voltage-clamp, voltage-activated Ca2+ channel currents carried by barium ions (IBa) were reduced with the rank order (IC50 values in microM): 1S,2R-(-)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]- 2-(1-pyrrolidinyl)cyclohexylamine (7.8) > rimcazole (13) > haloperidol (16) > ifenprodil (18) > opipramol (32) > carbetapentane (40) = 1-benzylspiro[1,2,3,4-tetrahydronaphthalene-1,4-piperidine] (42) > caramiphen (47) > dextromethorphan (73). At the highest concentrations tested, the compounds almost abolished IBa in the absence of any other pharmacological agent. 3. The current-voltage characteristics of the whole-cell IBa were unaffected by the test compounds. The drug-induced block was rapid in onset and offset, with the exceptions of carbetapentane and caramiphen where full block was achieved only after two to three voltage-activated currents and was associated with an apparent increase in the rate of inactivation of IBa. 4. In rat hippocampal neurones loaded with the Ca(2+)-sensitive dye Fura-2, rises in intracellular free Ca2+ concentration evoked by transient exposure to 50 mM K(+)-containing medium, either in the absence or in the presence of 10 microM nifedipine (to block L-type high voltage-activated Ca2+ channels), were also reversibly attenuated by the sigma ligands. The rank order potencies for the compounds in these experimental paradigms were similar to that observed for blockade of IBa in the electrophysiological studies. 5. These results indicate that, at micromolar concentrations, the compounds tested block multiple subtypes of high voltage-activated Ca2+ channels. These actions, which do not appear to be mediated by high-affinity sigma binding sites, may play a role in some of the functional effects previously described for the compounds.

Animals↗

PubMed1994

Interactions of dextromethorphan with the N-methyl-D-aspartate receptor-channel complex: single channel recordings.

The actions of dextromethorphan (DXM) on the 50 pS conductance state of the N-methyl-D-aspartate (NMDA) receptor-operated channel were studied using outside-out patches obtained from cultured rat hippocampal pyramidal neurons. DXM (5-50 microM) had no effect on the amplitudes of unitary currents but caused concentration-dependent reductions in channel mean open times and the frequency of channel openings. Channel open probability was reduced in a concentration-dependent manner by DXM and was one-half of the control value at a DXM concentration of 6 microM, with the patch potential held at -60 mV. An IC50 value of 4 microM was obtained for the reduction by DXM of NMDA-evoked rises in [Ca2+]i in cultured rat hippocampal pyramidal neurons loaded with Fura-2. The results were consistent with drug block of the open NMDA channel with an onward (blocking) rate constant of 7.7 x 10(6) M-1.s-1 (at -60 mV). The estimated unblocking rate constant was about 10 s-1, a value considerably higher compared to the off-rate constant found for dizocilpine block of the NMDA channel.

Animals↗

PubMed1994

The actions of L-687,384, a sigma receptor ligand, on NMDA-induced currents in cultured rat hippocampal pyramidal neurons.

The actions of the sigma receptor ligand L-687,384 were studied on N-methyl-D-aspartate (NMDA)-induced currents recorded from outside-out patches obtained from cultured rat hippocampal pyramidal neurons and on NMDA-evoked rises in [Ca2+]i in the same preparation. L-687,384 did not change the magnitudes of unitary NMDA currents or frequency of channel-openings but diminished channel-open probability by decreasing mean open time. This action was consistent with a voltage-dependent open-channel block of the NMDA channel by L-687,384 with a blocking rate constant of 5.9 x 10(6) M-1 s-1 at -80 mV. L-687,384 also reduced NMDA-evoked rises in [Ca2+]i in Fura-2-loaded neurons with an apparent IC50 value of 49 +/- 8 microM. The results demonstrate that L-687,384 acts as an antagonist at the NMDA receptor-channel complex.

Animals↗

PubMed1994

Haloperidol blocks voltage-activated Ca2+ channels in hippocampal neurones.

The Ca2+ channel antagonist action of the antipsychotic haloperidol was investigated using two functional assays of Ca2+ channel activity. Haloperidol dose dependently attenuated the rise in intracellular free Ca2+ ([Ca2+]i) evoked by 50 mM extracellular K+ in Fura-2 loaded cultured rat hippocampal neurones with an IC50 (+/- S.E.M.) of 7.8 +/- 0.5 microM and similarly reduced whole-cell Ba2+ currents (IBa) in voltage-clamped mouse hippocampal neurones with an IC50 value of 15.6 +/- 1.1 microM. Block of whole-cell IBa by haloperidol was rapid, fully reversible, and was greater at more depolarized membrane potentials. Our data indicate that haloperidol non-selectively blocks neuronal voltage-gated Ca2+ channels at micromolar concentrations.

Animals↗

PubMed1994

Blockade by ifenprodil of high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones: comparison with N-methyl-D-aspartate receptor antagonist actions.

1. The block by ifenprodil of voltage-activated Ca2+ channels was investigated in intracellular free calcium concentration ([Ca2+]i) evoked by 50 mM K+ (high-[K+]o) in Fura-2-loaded rat hippocampal pyramidal neurones in culture and on currents carried by Ba2+ ions (IBa) through Ca2+ channels in mouse cultured hippocampal neurones under whole-cell voltage-clamp. The effects of ifenprodil on voltage-activated Ca2+ channels were compared with its antagonist actions on N-methyl-D-aspartate- (NMDA) evoked responses in the same neuronal preparations. 2. Rises in [Ca2+]i evoked by transient exposure to high-[K+]o in our preparation of rat cultured hippocampal pyramidal neurones are mediated predominantly by Ca2+ flux through nifedipine-sensitive Ca2+ channels, with smaller contributions from nifedipine-resistant, omega-conotoxin GVIA-sensitive Ca2+ channels and Ca2+ channels sensitive to crude funnel-web spider venom (Church et al., 1994). Ifenprodil (0.1-200 microM) reversibly attenuated high-[K+]o-evoked rises in [Ca2+]i with an IC50 value of 17 +/- 3 microM, compared with an IC50 value of 0.7 +/- 0.1 microM for the reduction of rises in [Ca2+]i evoked by 20 microM NMDA. Tested in the presence of nifedipine 10 microM, ifenprodil (1-50 microM) produced a concentration-dependent reduction of the dihydropyridine-resistant high-[K+]o-evoked rise in [Ca2+]i with an IC50 value of 13 +/- 4 microM. The results suggest that ifenprodil blocks Ca2+ flux through multiple subtypes of high voltage-activated Ca2+ channels. 3. Application of the polyamine, spermine (0.25-5 mM), produced a concentration-dependent reduction of rises in [Ca2+]i evoked by high-[K+]o. The antagonist effects of ifenprodil 20 micro M on high-[K+]0-evoked rises in [Ca2+]. were attenuated by spermine 0.25 mM but not by putrescine 1 or 5 mM. In contrast,spermine 0.1 mM increased rises in [Ca2+]i evoked by NMDA and enhanced the ifenprodil (5 micro M) block of NMDA-evoked rises in [Ca2+]i.4. Similar results were obtained in mouse cultured hippocampal pyramidal neurones under whole-cell voltage-clamp. Ifenprodil attenuated both the peak and delayed whole-cell IB. with an IC% value of 18 +/- 2 micro M, whilst it attenuated steady-state NMDA-evoked currents with an IC50 of 0.8 +/- 0.2 micro M. Block of IBa by ifenprodil 10 JaM was rapid in onset, fully reversible and occurred without change in thecurrent-voltage characteristics of Ba. The ifenprodil block of IBa was enhanced on membrane depolarization and was weakly dependent on the frequency of current activation. Spermine 0.1 mM potentiated control NMDA-evoked currents but attenuated IB,. In agreement with the microspectrofluorimetric studies, co-application of spermine produced a small enhancement of the inhibitory effect of ifenprodil 10 micro M on NMDA-evoked responses whereas the reduction of I4 by ifenprodil 10 micro M in the presence of spermine was less than expected if the inhibitory effects of ifenprodil and spermine on IBa were simply additive.5. The results indicate that ifenprodil blocks high voltage-activated Ca2+ channels in rat and mouse cultured hippocampal pyramidal neurones. Although the Ca2+ channel blocking actions of ifenprodil are observed at higher concentrations than those associated with NMDA antagonist activity, Ca2+ channel blockade may contribute, at least in part, to the established neuroprotective and anticonvulsant properties of the compound.

Animals↗

PubMed1994

Loperamide blocks high-voltage-activated calcium channels and N-methyl-D-aspartate-evoked responses in rat and mouse cultured hippocampal pyramidal neurons.

The effects of the antidiarrheal agent loperamide on high-voltage-activated (HVA) calcium channel activity and excitatory amino acid-evoked responses in two preparations of cultured hippocampal pyramidal neurons were examined. In rat hippocampal neurons loaded with the calcium-sensitive dye fura-2, rises in intracellular free calcium concentration ([Ca2+]i) evoked by transient exposure to 50 mM K(+)-containing medium [high extracellular potassium concentration ([K+]o)] were mediated by Ca2+ flux largely through nifedipine-sensitive Ca2+ channels, with smaller contributions from omega-conotoxin GVIA (omega-CgTx)-sensitive Ca2+ channels and channels insensitive to both nifedipine and omega-CgTx. Loperamide reversibly blocked rises in [Ca2+]i evoked by high [K+]o in a concentration-dependent manner, with an IC50 of 0.9 +/- 0.2 microM. At the highest concentration tested (50 microM), loperamide eliminated rises in [Ca2+]i evoked by high [K+]o, a result otherwise achieved only in Ca(2+)-free medium or by the combined application of nifedipine, omega-CgTx, and funnel web spider venom to Ca(2+)-containing medium. The action of loperamide was neither naloxone sensitive nor mimicked by morphine and was seen at concentrations substantially less than those required to block influx of Ca2+ through the N-methyl-D-aspartate (NMDA) receptor-operated ionophore. Similar results were obtained in cultured mouse hippocampal pyramidal neurons under whole-cell voltage clamp. Voltage-activated Ca2+ channel currents carried by barium ions (IBa) could be discriminated pharmacologically into nifedipine-sensitive (L-type) and nifedipine-resistant, omega-CgTx-sensitive (N-type) components. Loperamide (0.1-50 microM) produced a concentration-dependent reduction of the peak IBa with an IC50 value of 2.5 +/- 0.4 microM and, at the highest concentration tested, could fully block IBa in the absence of any other pharmacological agent. The loperamide-induced block was rapid in onset and offset, was fully reversible, and did not appear to be related to the known calmodulin antagonist actions of loperamide. The current-voltage characteristics of the whole-cell IBa were unaffected by loperamide and the block was not voltage dependent. Loperamide also attenuated NMDA-evoked currents recorded at a membrane potential of -60 mV, with an IC50 of 73 +/- 7 microM. The block of NMDA-evoked currents was not competitive in nature, was not reversed by elevation of the extracellular glycine or spermine concentration, and was not affected by changes in the membrane holding potential. Steady state currents evoked by kainate and DL-alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid were, in contrast, relatively unaffected by 100 microM loperamide.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Evaluation of families wherein a single male manifests a phenotype of X-linked lymphoproliferative disease (XLP).

The Epstein-Barr virus (EBV)-induced diseases of males with X-linked lymphoproliferative disease (XLP) include fatal infectious mononucleosis (IM), non-Hodgkin lymphoma (ML), agammaglobulinemia, and aplastic anemia. These phenotypes also occur as sporadic cases in families, and EBV seronegative males in these families must be considered at risk for XLP until they seroconvert normally to EBV. Given that 50% of males inheriting the defective XLP gene die following primary EBV infection, it is vital that they be identified pre-EBV infection. Here we report results using molecular genetic techniques to provide information as to the relative risks of EBV negative males and potential carrier females in ten families wherein a single male had died of IM.

Adolescent↗

PubMed1993

Electrogalvanic stimulation for levator syndrome: how effective is it in the long-term?

Levator syndrome is a symptom complex of severe pain and pressure in the anorectal area. Electrogalvanic stimulation (EGS) has been proposed as a treatment for this condition. Several reports have described EGS as up to 90 percent "effective" in treating levator syndrome, but the length of follow-up was uncertain or short-term in these studies. The purpose of this study was to examine the long-term benefits of EGS in levator syndrome patients treated at one institution. All patients undergoing EGS for levator syndrome between 1985 and 1991 were studied. Initial complaints, physical examination, number of treatments, procedure tolerance, and long-term benefit were determined through personal interviews and chart reviews. There were 52 patients (63 percent females and 37 percent males) with a median age of 54 years (range, 24-84 years). All patients presented with anorectal pain. Tenderness was localized by examination to the left in 43 percent, to the right in 23 percent, and bilateral in 8.6 percent and was not localized in 2.6 percent. Fifty percent received fewer than four one-hour treatments, 33 percent received four to six treatments, and 17 percent received more than six treatments. Seventy-seven percent felt that the treatment was painless. Follow-up results were as follow: number, 52; percent follow-up, 88; mean follow-up, 28 months (range, 0-71 months); symptoms relieved, 19 percent; partial relief, 24 percent; no relief, 57 percent. Of four patients with a wrong diagnosis, three were ultimately diagnosed with recurrent pelvic cancer and one had an anal fissure. At our institution, EGS was a tolerable treatment, but a substantial number of patients received no benefit. An organic etiology of anorectal pain must always be excluded.

Adult↗

PubMed1993

Investigation of motivational and behavioural factors influencing men who have sex with other men in public toilets (cottaging).

One-hundred-and-thirty-four individuals engaging in cottaging returned postal questionnaires. The sample was mainly urban and gay identified. Cottagers reported that cottaging was one way of meeting partners amongst a range of others they used. Most enjoyed it and felt in control of their cottaging. The majority of cottagers engaged in safer sexual activity, but there were a significant number who engaged in unsafe sexual activity last time they cottaged. Of those who had been voluntarily tested in the past and reported their serostatus, 23% were seropositive. Unsafe sexual activity was unrelated to whether tested or not, known serostatus or knowledge of the risks of transmission.

Adult↗

PubMed1993

Selective reduction of N-methyl-D-aspartate-evoked responses by 1,3-di(2-tolyl)guanidine in mouse and rat cultured hippocampal pyramidal neurones.

1. The effects of 1,3-di(2-tolyl)guanidine (DTG) were examined on the responses of cultured hippocampal neurones to the excitatory amino acid analogues N-methyl-D-aspartate (NMDA), kainate, quisqualate and (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). 2. In rat hippocampal neurones loaded with the Ca(2+)-sensitive dye Fura-2, DTG (10-100 microM) produced a concentration-dependent depression of the NMDA-evoked rises in intracellular free calcium ([Ca2+]i), an effect that was not modified by changes in the extracellular glycine concentration. DTG (at 50 and 100 microM) also attenuated, although to a lesser extent, the rises in [Ca2+]i evoked by naturally-derived quisqualate. In contrast, 50 and 100 microM DTG did not depress responses evoked by kainate, AMPA and synthetic, glutamate-free (+)-quisqualate although on occasions DTG enhanced kainate- and AMPA-evoked rises in [Ca2+]i. 3. DTG attenuated NMDA-evoked currents recorded from mouse hippocampal neurones under whole-cell voltage-clamp with an IC50 (mean +/- s.e. mean) of 37 +/- 5 microM at a holding potential of -60 mV. The DTG block of NMDA-evoked responses was not competitive in nature and was not dependent on the extracellular glycine or spermine concentration. The block did, however, exhibit both voltage-, and use-, dependency. The steady-state current evoked by naturally-derived quisqualate was also attenuated by DTG whereas those evoked by kainate and AMPA were not. 4. We conclude that DTG, applied at micromolar concentrations, is a selective NMDA antagonist in cultured hippocampal neurones, the block exhibiting both Mg(2+)- and phencyclidine-like characteristics. Given the nanomolar affinity of DTG for sigma binding sites it is unlikely that the antagonism observed here is mediated by sigma-receptors, but the data emphasize the potential danger of ascribing the functional consequences of DTG administration solely to sigma receptor-mediated events.

Amino Acids↗

PubMed1993

Cytosolic free Ca2+ in human syncytiotrophoblast cells increased by gonadotropin-releasing hormone.

Effects of GnRH on free cytosolic Ca2+ concentrations ([Ca2+]i) were examined in individual first trimester human cytotrophoblast and syncytiotrophoblast cells by fura-2 microspectrofluorimetry. GnRH (10(-6) M) did not affect [Ca2+]i in cytotrophoblasts on days 2-9 of culture, with 50 cells tested each day. GnRH (10(-6) M) did not affect [Ca2+]i on days 2-3, but increased [Ca2+]i in 15% of culture-derived syncytiotrophoblasts on day 4 (8 of 52 cells) and in 48% on days 5-9 of culture (158 of 332 cells). Culture-derived syncytiotrophoblasts originated from four first trimester placentae. GnRH increased [Ca2+]i in a preliminary trial using syncytiotrophoblasts derived directly from a single first trimester placenta and cultured for 3 days (13 of 33 cells). Culture-derived first trimester syncytiotrophoblast cells that responded to 10(-6) M GnRH (28 of 63 cells) on day 6 also responded to GnRH at 10(-7) M (26 of 28 of the above cells), 10(-8) M (24 of 28 cells, 10(-9) M (22 of 28 cells), and 10(-10) M (3 of 28 cells). No cells responded to GnRH below a concentration of 10(-10) M. Desensitization of syncytiotrophoblasts by continuous GnRH perifusion (10(-6) M) and blockade of GnRH by competitive antagonism with Nal-Glu-GnRH (10(-6) M) suggested that effects of GnRH were receptor specific. The results provide direct evidence supporting the contention that the intracellular signaling resultant from GnRH receptor-ligand interactions in syncytiotrophoblasts may be at least partially mediated by transient increases in [Ca2+]i.

Calcimycin↗

PubMed1992

Endoluminal ultrasound defines anatomy of the anal canal and pelvic floor.

The aims of this study were to determine whether endoluminal ultrasound (ELUS) could identify various layers of the normal anal canal and to evaluate whether a 10-MHz probe provided better image resolution than a 7-MHz probe. Sonographic anatomy of the anal canal on ELUS was directly correlated with anatomic dissection of various layers (mucosa-submucosa, internal anal sphincter, and external anal sphincter) in cadavers. Sonographic appearance of the anal sphincters was further evaluated in patients by "tagging" various layers using sonodense needles. A higher frequency 10-MHz ultrasound probe (focal length, 1-4 cm) provides improved sonographic images of the anal canal, compared with the 7-MHz probe (focal length, 2-5 cm). ELUS can also successfully identify various structures of the pelvic floor including the puborectalis, urethral sphincter, vagina, and outlines of the pelvis and ischiorectal fossae. Its role in the evaluation of anorectal disorders appears promising.

Anal Canal↗

PubMed1992

Comparison of cytobrush with Cervex-Brush for endocervical cytologic sampling.

This study was designed to compare the quality of the Papanicolaou (Pap) smear and side effects associated with the Ayres spatula/cytobrush combination and the Cervex-Brush. We evaluated 165 Pap smears, of which 84 (51%) were cytobrush/spatula specimens, and 81 (49%) were from Cervex-Brush specimens. The cytobrush/Ayres spatula combination and the Cervex-Brush alone were equally successful in detecting squamous cells, however, the cytobrush/Ayres spatula combination was significantly better in picking up endocervical cells than the Cervex-Brush (p less than 0.01). There were no significant differences between the two techniques in degree of bleeding and pain in adolescents. The combination of the cytobrush and spatula appears to be superior to the Cervex-Brush alone in producing adequate Pap smears.

Adolescent↗

PubMed1992

Correction of antigen-specific T-lymphocyte function by recombinant cytokines in children infected with human immunodeficiency virus type 1.

To determine the role of cytokines in the immunodeficiency of children infected with human immunodeficiency virus type 1 (HIV-1), we compared the antigen-specific (tetanus toxoid-induced) T-lymphocyte blastogenesis of HIV-1-infected patients with and without the addition of exogenous interleukin-1 and interleukin-2. Acquisition of in vitro antigen-specific immunologic function was seen in some patients after the addition of exogenous cytokines. The antigen-specific immunodeficiency in some HIV-1-infected children is due to defects in cytokine production rather than to an absence of antigen-specific T lymphocytes.

Acquired Immunodeficiency Syndrome↗

PubMed1992

A change from HCO3(-)-CO2- to hepes-buffered medium modifies membrane properties of rat CA1 pyramidal neurones in vitro.

1. Intracellular recordings were obtained from CA1 pyramidal neurones in rat hippocampal slices. Perfusion with a HCO3(-)-CO2-free, HEPES-buffered medium at pH 7.4 produced a wide variety of reversible effects on neuronal excitability, compared to responses obtained under standard (21 mM-HCO3-, 5% CO2, pH 7.4) conditions. 2. Introduction of HCO3(-)-CO2-free medium most commonly elicited, within 5-20 min, a fall in resting membrane potential (Vm), a rise in threshold for Na(+)-dependent action potential generation, and a reduction in input resistance. Anomalous inward rectification in the hyperpolarizing direction and subthreshold inward rectification were commonly reduced in HEPES-buffered medium. More prolonged exposure (> or = 25 min) to HCO3(-)-CO2-free medium produced, on occasion, Na+ spike inactivation. 3. The amplitudes of the fast and medium after-hyperpolarizations (AHPs) following a single depolarizing current-evoked action potential were attenuated during perfusion with HEPES-buffered medium at pH 7.4, as was the composite AHP following a train of action potentials. 4. Perfusion with HEPES-buffered medium at pH 7.4 reduced the degree of spike frequency adaptation and abolished depolarizing current-evoked burst-firing behaviour when this was present under standard conditions. 5. In tetrodotoxin (TTX)- and tetraethylammonium (TEA)-poisoned neurones, perfusion with HCO3(-)-CO2-free medium at pH 7.4 slightly raised the threshold for activation of Ca(2+)-dependent potentials and slightly reduced their duration, compared to responses obtained in HCO3(-)-CO2-buffered medium at the same pH. The AHP following the Ca2+ spike was, however, markedly attenuated. 6. Perfusion with a low-pH HCO3(-)-CO2-buffered medium (7 mM-HCO3-, 5% CO2, pH 6.9) produced changes qualitatively similar to those observed during perfusion with HEPES-buffered medium at pH 7.4. Raising the pH of the HEPES-buffered medium to 7.8 or 7.9 reversed inconsistently and then only in part the changes noted on the transition from a HCO3(-)-CO2- to a HEPES-buffered medium at the same pH (7.4). 7. The effects noted are unlikely to be due to a direct action of HEPES itself on neuronal membrane conductances. Rather, I suggest that they are likely to be caused by intracellular acidosis consequent upon the omission of HCO3- and CO2 from the extracellular medium.

Action Potentials↗