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J Church

Publications and source records attributed to J Church.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1991

CD4 T-lymphocyte counts and Pneumocystis carinii pneumonia in pediatric HIV infection.

The relationship between CD4 T-lymphocyte counts and infection with the human immunodeficiency virus (HIV) is retrospectively investigated for 266 HIV-infected and uninfected children who were born to infected women, including 39 with Pneumocystis carinii pneumonia (PCP), in a population-based surveillance study. Of 21 perinatally HIV-infected children with PCP only 10 (48%) had CD4 T-lymphocyte counts that were less than 500 x 10(6) cells/L (500 cells/mm3), compared with all 18 who were infected via blood transfusions or clotting factors. Among 68 children who were 1 year or younger, 18 (90%) of 20 PCP cases had CD4 T-lymphocyte counts that were less than 1500 x 10(6) cells/L (1500 cells/mm3) compared with only five (10%) of 48 children who did not have the acquired immunodeficiency syndrome (odds ratio, 77.4; 95% confidence interval, 19.7 to 313.4). The mean CD4 T-lymphocyte count was lower for the 39 PCP cases when compared with the 188 children who were at different stages of HIV infection and did not have the acquired immunodeficiency syndrome (AIDS) independent of age. The majority of perinatally HIV-infected children with PCP were 6 months or younger and 50% were previously unknown to be infected. Thus, HIV-positive children should be identified early and followed closely. CD4 T-lymphocyte counts may be useful in monitoring HIV-positive children and determining when to begin PCP prophylaxis.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Dextromethorphan and phencyclidine receptor ligands: differential effects on K(+)- and NMDA-evoked increases in cytosolic free Ca2+ concentration.

The ability of dextromethorphan (DXM) and phencyclidine (PCP) receptor ligands to attenuate increases in cytosolic free Ca2+ concentration ([Ca2+]i) evoked by N-methyl-D-aspartate (NMDA) and high extracellular [K+] was examined using the fluorescent dye Fura 2 in cultured rat hippocampal pyramidal neurons. The DXM receptor ligand caramiphen (40 microM) reduced K(+)-evoked rises in [Ca2+]i to a greater extent than NMDA-evoked rises; the reverse was true for the PCP receptor ligands ketamine (10-40 microM) and dextrorphan (10 microM). DXM itself, which has affinity for both DXM and PCP receptors, reduced both K(+)- and NMDA-evoked increases in [Ca2+]i in a concentration-dependent manner. The results suggest that DXM receptor ligands may at least in part exert their known anticonvulsant and neuroprotective effects by reducing Ca2+ influx through voltage-activated Ca2+ channels.

Animals↗
PubMed1991

Ketamine promotes hippocampal CA1 pyramidal neuron loss after a short-duration ischemic insult in rats.

The neuroprotective activity of the N-methyl-D-aspartate (NMDA) antagonist ketamine was examined in two groups of rats subjected to forebrain ischemia of differing durations. Ketamine provided a limited degree of protection against hippocampal CA1 pyramidal cell loss following a 10 min ischemic insult. In contrast after 6 min ischemia, which in non-treated control animals resulted in less CA1 neuron loss than was seen after 10 min ischemia, ketamine at the same dose worsened outcome. The data indicate that the possession by a drug of NMDA antagonist activity does not alone determine its neuroprotective activity in vivo.

Animals↗
PubMed1991

NMDA receptor antagonist effects of the stereoisomers of beta-cyclazocine in rats, in vivo and in vitro.

(+)- and (-)-beta-cyclazocine were examined as NMDA receptor antagonists following bath application to rat cortical wedges in vitro and i.v. administration to rat spinal cord neurones in vivo. Both isomers were found to be selective NMDA antagonists with little effect on excitations evoked by quisqualate. In vitro, IC50 values for (-)- and (+)-beta-cyclazocine against responses to 40 microM NMDA were estimated at 0.51 and greater than 100 microM, respectively. In vivo, (-)-beta-cyclazocine 0.25 mg.kg-1 reduced NMDA-evoked excitations by 70%, an effect substantially greater than that produced by (+)-beta-cyclazocine 2.5 mg.kg-1. (-)-beta-cyclazocine is the most potent NMDA antagonist benzomorphan tested to date, being about twice as potent as (-)-alpha-cyclazocine in this respect. In addition, the separation in potency exhibited by the beta-cyclazocine enantiomers as NMDA antagonists is much greater than that reported previously for the stereoisomers of the alpha-series.

Animals↗
PubMed1991

Bursting response to current-evoked depolarization in rat CA1 pyramidal neurons is correlated with lucifer yellow dye coupling but not with the presence of calbindin-D28k.

Calbindin-D28k (CaBP) immunohistochemistry has been combined with electrophysiological recording and Lucifer Yellow (LY) cell identification in the CA1 region of the rat hippocampal formation. CaBP is shown to be contained within a distinct sub-population of CA1 pyramidal cells which is equivalent to the superficial layer described by Lorente de Nó (1934). The neurogenesis of these CaBP-positive neurons occurs 1-2 days later than the CaBP-negative neurons in the deep pyramidal cell layer, as shown by 3H-thymidine autoradiography. No correlation could be found between the presence or absence of CaBP and the type of electrophysiological response to current-evoked depolarizing pulses. The latter could be separated into bursting or non-bursting types, and the bursting-type response was nearly always found to be associated with the presence of LY dye coupling. Furthermore, when dye coupling involved three neurons, a characteristic pattern was observed which may represent the coupling of phenotypically identical neurons into distinct functional units within the CA1 pyramidal cell layer. In this particular case the three neurons were all likely to be CaBP-positive.

Animals↗
PubMed1991

Manometric and functional comparison of ileal pouch anal anastomosis with and without anal manipulation.

We report the results of postoperative physiologic and functional evaluation of 153 patients with ileal pouch anal-anastomosis (IPAA). Ninety-nine patients had anal manipulation for either mucosal proctectomy, transanal placement pursestring suture with stapled IPAA, or handsewn IPAA (manipulation). Fifty-four patients had stapled IPAA with anal pursestrings placed transabdominally without mucosectomy (no manipulation). Patients with transabdominal anal pursestring placement and stapled IPAA without mucosectomy had a higher mean maximum anal resting pressure than patients who had endoanal manipulation. This correlates with improved continence and a reduced need to wear a pad. Avoidance of anal manipulation preserves anal canal resting tone and improves the functional result after IPAA.

Adult↗
PubMed1991

Exposure to high-pH medium increases the incidence and extent of dye coupling between rat hippocampal CA1 pyramidal neurons in vitro.

Previous studies have demonstrated that dye coupling between neurons can be reduced by maneuvers that reduce intracellular pH. However, it is apparent that marked extracellular alkaline- as well as acid-going pH shifts can occur in the mammalian CNS. In light of the fact that an applied change in extracellular pH may produce a damped change in intracellular pH in the same direction, in this study we have examined the effects of exposure to high extracellular pH (achieved by raising [HCO3-] at a constant PCO2) on the incidence of Lucifer yellow dye coupling between CA1 pyramidal neurons in the rat hippocampal slice. Under standard conditions (pH 7.4), 44% of CA1 pyramidal neurons were dye-coupled, and the mean number of neurons stained per injection was 1.62. A marked increase in the incidence (88%) and extent (mean number of neurons stained per injection, 3.25) of dye coupling was observed during exposure to high-pH medium (pH 7.9). Under both standard and high-pH conditions, dye coupling was associated with the ability of CA1 pyramidal neurons to generate bursts of action potentials in response to intracellularly applied depolarizing current pulses. The results provide additional evidence that dye coupling between hippocampal pyramidal neurons may be modulated dynamically and may have implications for the genesis of synchronized epileptiform activity under alkalotic conditions.

Animals↗
PubMed1990

Anticonvulsant actions of phencyclidine receptor ligands: correlation with N-methylaspartate antagonism in vivo.

1. Drugs with phencyclidine (PCP)-like activity in behavioural discrimination and [3H]PCP binding studies share anticonvulsant properties. 2. We have compared the rank order potency of a series of PCP-like compounds as N-methylaspartate (NMA) antagonists, determined from previously published studies from our laboratory, with their rank order anticonvulsant potencies as determined by two independent research groups in three different in vivo models of experimentally-induced epilepsy. 3. Rank order potency for NMA antagonism correlated well with rank order anticonvulsant potency. Furthermore, the systemic doses required for an effective blockade of NMA-evoked excitations were, in most cases, similar to those which produced anticonvulsant activity. 4. The results suggest that functional NMA antagonism may underlie the shared anticonvulsant properties of structurally dissimilar compounds with PCP-like activity.

Animals↗
PubMed1990

Failure of sigma-receptor ligands to reduce the excitatory actions of N-methyl-DL-aspartate on rat spinal neurons in-vivo.

Haloperidol and (+)-3-PPP, compounds with known affinity for the sigma-receptor, have been examined for their ability to reduce the excitatory actions of N-methyl-DL-aspartate (NMDLA), quisqualate and kainate on rat spinal neurons in-vivo. The actions of (-)-3-PPP were also tested. Haloperidol was injected intravenously whereas the 3-PPP enantiomers were administered by microelectrophoresis. Haloperidol had little effect on excitations evoked by NMDLA, quisqualate or kainate whereas both (+)- and (-)-3-PPP usually enhanced, non-selectively, responses to all three excitatory amino acid analogues. The results support suggestions that phencyclidine (PCP)-like compounds with affinity for both PCP and sigma-receptors reduce neuronal excitations mediated by the N-methyl-D-aspartate (NMDA) receptor via a selective effect at the PCP site.

Animals↗