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Biomedical subjects

J Church

Publications and source records attributed to J Church.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1990

Cyclazocine and pentazocine as N-methylaspartate antagonists on cat and rat spinal neurons in vivo.

The effects of the racemic mixtures and separated enantiomers of cyclazocine and pentazocine were examined on the responses of spinal neurons to excitatory amino acid analogs and acetylcholine in pentobarbital-anesthetized cats and rats. Each compound was administered both by microelectrophoresis and by i.v. injection. The racemic mixture and separated optical isomers of cyclazocine reduced selectively neuronal excitations evoked by N-methylaspartate (NMA), with only small and variable effects on responses to quisqualate and kainate. (+/-), (+)- and (-)-pentazocine also antagonized NMA actions, although they were less potent and somewhat less selective than the corresponding cyclazocine compounds in this respect. Overall, in both microelectrophoretic and i.v. tests, (+/-)-cyclazocine was about 7 times more potent an NMA antagonist than (+/-)-pentazocine. The (-)-isomers of both drugs were about 2 times more potent than the (+)-isomers, although the weak NMA antagonist effects of (+)-pentazocine were rather variable. Neither naloxone nor haloperidol affected the NMA antagonist activity of the drugs tested. Examination of the relative NMA antagonist potencies of the compounds suggests that the effect is mediated via an interaction with the phencyclidine receptor. The results are discussed with particular reference to those behavioral effects of cyclazocine and pentazocine which might reflect functional NMA antagonism in vivo.

Animals↗
PubMed1989

Clonogenic cell assay for anchorage-dependent squamous carcinoma cell lines using limiting dilution.

Clonogenic assays under either anchorage-dependent or -independent conditions are very useful for testing the sensitivity of tumor cells to cytotoxic drugs and radiation. These assays have not been widely used with squamous-cell carcinomas (SCC) because of poor tumor-cell viability and poor cloning efficiency, especially in semi-solid media. To find a clonogenic assay suitable for use with human squamous cancers we tested SCC lines, derived in our laboratory from patients with head and neck cancer, for the capacity to form colonies in soft agar and in 96-well plates. Of 13 UM-SCC lines tested for colony formation in agarose, only UM-SCC-11A was capable of growth in conventional semi-solid media. One other line, UM-SCC-14C, produced colonies in agarose only in the presence of epidermal growth factor. In contrast, all 17 of the SCC lines tested exhibited colony formation in adherent cell culture using limiting dilution in 96-well plates. The plating efficiencies of the SCC lines in the 96-well plate assay ranged from 0.02 to 0.52 colonies (wells)/cell whereas the PE values in soft agar were lower, ranging from 0.0055 to 0.0086 colonies/cell. The 96-well plate assay is not affected by cell migration, a problem encountered with some cell lines when clonogenic assays are performed in Petri dishes. UM-SCC-11A was tested for radiation sensitivity both in soft agar and in the 96-well plate assay. Comparable results were obtained. In summary, the majority of SCC cell lines did not form viable colonies in soft agar but the 96-well plate assay was applicable to a broad spectrum of anchorage-dependent human SCC cell lines and provides an efficient method for evaluating clonogenic cell survival.

Agar↗
PubMed1989

Lymphocyte phenotype does not predict immune function in pediatric patients infected with human immunodeficiency virus type 1.

To determine whether assays of lymphocyte phenotype were predictive of antigen-specific immunologic function in children infected with human immunodeficiency virus type 1 (HIV-1), we compared the antigen-specific cellular and humoral functions (tetanus toxoid-induced T lymphocyte blastogenesis and anti-tetanus toxoid antibody) with the patients' T lymphocyte phenotype, determined at the same time. Although both HIV-1-infected patient populations studied (pediatric hemophilia patients and other pediatric patients) had decreases in the values determined by their functional and phenotypic assays, no association between the functional and phenotypic assays was demonstrated. Thus some HIV-1-infected patients with a normal phenotype had no antigen-specific function, whereas other patients with a markedly abnormal T lymphocyte phenotype had normal antigen specific T lymphocyte function. These results indicate that the assessment of HIV-1-infected patients should include assays of antigen-specific immune function in addition to assays of T lymphocyte phenotype.

Acquired Immunodeficiency Syndrome↗