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Biomedical subjects

N Moran

Publications and source records attributed to N Moran.

At least 37 records · Page 2Linked to original sources
PubMed1997

Correlation of widespread preoperative magnetic resonance imaging changes with unsuccessful surgery for hippocampal sclerosis.

Despite meticulous preoperative assessment, about 30% of patients with refractory partial epilepsy due to hippocampal sclerosis fail to become seizure free after appropriate temporal lobe surgery. Perioperative complications, hippocampal remnants, and bitemporal disease do not account for all failures; extrahippocampal epileptogenic tissue must persist in some patients. Such dual pathology is detected on routine visual inspection of magnetic resonance images in about 15% of patients with hippocampal sclerosis, but most such patients are excluded from surgery. We postulated that some patients have occult extrahippocampal cerebral structural abnormalities (i.e., subtle dual pathology) and that the presence of these abnormalities would be associated with a poor surgical outcome. Quantitative postprocessing of preoperative magnetic resonance images from 27 patients subsequently proved to have hippocampal sclerosis demonstrated extrahippocampal structural abnormalities in 14, 10 of whom did not become seizure free, while 11 of 13 patients without such changes did become seizure free (chi2, p < 0.005). Such structural information may supplement clinical decision making in some patients being evaluated for epilepsy surgery and help to explain the biological basis of poor outcome from such surgery.

Adolescent↗
PubMed1997

Periventricular nodular heterotopia and intractable temporal lobe epilepsy: poor outcome after temporal lobe resection.

We describe 5 women and 5 men with periventricular nodular heterotopia and electroclinical features suggestive of temporal lobe epilepsy, who were surgically treated for control of medically refractory seizures. Magnetic resonance imaging revealed bilateral periventricular nodular heterotopia in 7 of the 10 patients. Because of the lack of clear localization, 6 patients were studied with intracranial depth electrode recordings. Seizures were of hippocampal onset (3 patients), regional temporal lobe onset (2 patients), or occipital-temporal onset (1 patient). Anterior temporal lobectomy was performed in 6 patients; selective amygdalohippocampectomy, in 1; and anterior temporal lobectomy plus resection of the heterotopic tissue, in 3. None of the 9 patients followed for more than 12 months postoperatively were seizure free. Two patients were initially seizure free for approximately 18 months, but then seizures recurred. One patient had a major reduction in seizure frequency at a 39-month follow-up after most of the unilateral heterotopic tissue was included in the temporal resection. Temporal resection did not lead to a long-term favorable outcome in this group of patients with periventricular nodular heterotopia and epileptogenic discharges involving the temporal lobe. This suggests a more widespread disorder with epileptogenic activity possibly originating in or near the heterotopic tissue. The clinical and electrographic features of periventricular nodular heterotopia pointing to temporal lobe origin are misleading and temporal resection does not result in long-term cessation of seizures.

Adult↗
PubMed1997

Continued thromboxane A2 formation despite administration of a platelet glycoprotein IIb/IIIa antagonist in patients undergoing coronary angioplasty.

Experimental data suggest that formation of thromboxane A2 may be suppressed during administration of a glycoprotein IIb/IIIa antagonist. We determined the dose of one such compound, fradafiban, required to provide > 80% occupancy of the platelet glycoprotein IIb/IIIa and examined its effects on thromboxane A2 formation in patients undergoing PTCA. The dose response to fradafiban and additional effects of aspirin were explored initially in patients with stable coronary artery disease. Fradafiban induced a dose-dependent inhibition of platelet aggregation that correlated with fibrinogen receptor occupancy and plasma drug concentration. Addition of aspirin 300 mg had no effect on these parameters. At the highest dose, mean fibrinogen receptor occupancy was 89.7 +/- 1.2% (n = 3) at 4 hours and platelet aggregation had decreased by 93.4 +/- 2.7%. Eighteen patients undergoing coronary angioplasty were randomized to receive either aspirin 330 mg or that dose of fradafiban producing > 80% fibrinogen receptor occupancy. Platelet aggregation was suppressed throughout the infusion of fradafiban to a greater extent than with aspirin. However, there was a marked increase in urinary excretion of 11-dehydrothromboxane B2 in patients treated with fradafiban: from 1973 +/- 889 to a peak of 9760 +/- 3509 pg/mg creatinine (P = .0046). Despite this evidence of continued platelet activation in vivo, there were no cases of coronary thrombosis. In conclusion, fradafiban suppresses platelet aggregation and may be a useful alternative to aspirin in the prevention of thrombotic events in patients undergoing PTCA. However, there is continued formation of thromboxane A2, which may continue to exert its effects as a potent vasoconstrictor and vascular smooth muscle mitogen.

Administration, Oral↗
PubMed1997

Red cell ferritin, a marker of iron deficiency in hemodialysis patients.

Estimation of red cell ferritin (RCFer) may give a good indication of iron supply to the erythron and it may therefore be clinically useful for the detection of functional iron deficiency. In a cross-sectional study of hemodialysis patients on erythropoietin (EPO) therapy and regular oral iron we have compared the RCFer levels with conventional indicators of iron status. The patients studied, 19 female, 48 male, mean age 62 +/- 3.6 years (range 20-83 years) were characterized by the following mean parameters: aluminum 1.24 +/- 0.12 mumol/L, PTH 115.7 +/- 39 pg/mL, vitamin B12 626 +/- 71.2 ng/L, serum folate 18.8 +/- 2.2 micrograms/L, and hemoglobin 9.8 +/- 0.3 g/dL (range 7.3-12.4). The median serum ferritin (SF), RCFer, total iron binding capacity (TIBC), transferrin saturation (TS), and serum iron were 68 micrograms/L, 14.1 ag ferritin/red cell, 57 mumol/L, 20% and 11.5 mumol/L, respectively. Eleven patients had a reduced RCFer (< 7 ag ferritin/red cell), 5 had a SF of < 15 micrograms/L and 22 a TS of < 16%. The occurrence of functional iron deficiency was suggested by the presence of 10 subjects with reduced RCFer despite normal SF levels (15-240 micrograms/L). Four patients with reduced SF showed acceptable levels of RCFer, suggesting that some patients may maintain an adequate iron supply despite diminished iron stores. Despite oral iron therapy, a significant number of patients (63%) on regular hemodialysis remain relatively iron deficient with a serum ferritin of less than 100 micrograms/L. It has previously been proposed that oral iron provides adequate supplementation during increased demand caused by EPO stimulation. The present study has demonstrated overt iron deficiency in five subjects and suggests functional iron deficiency in a further seven (22% of total patients). We therefore conclude that oral iron therapy cannot maximize the response to EPO.

Administration, Oral↗
PubMed1997

Pattern of injecting drug uses and HIV-1 infection: analysis from needle exchange program.

Contents of exchanged needles/syringes were analyzed to examine: i) the prevalence of HIV-1 infection among injecting drug users (IDU's), and ii) the classes of drugs injected by the population. A needle exchange program in Puerto Rico (PR) was initiated under the auspices of the PR Department of Health and is currently being administered by the Community Research Initiative of Puerto Rico, Inc. Serological tests for human immunodeficiency virus type 1 (HIV-1) were performed with 387 samples with clearly visible amounts of blood, which were chosen randomly from the needle exchange program of the San Juan Metropolitan area on the north coast, and also of the Mayaguez area on the west coast of the island. In addition, 200 syringes without visible amount of blood were also randomly chosen, their contents were extracted with acidified methanol and analyzed by gas chromatography-mass spectrometry (GC/MS) for drug content. One hundred and ninety four of the samples (58%) were confirmed to be positive for HIV-1. Four samples contained heroin alone, 190 were positive for cocaine and 2 indicated simultaneous use of both heroin and cocaine. In contrast to existing literature, based mostly on self-description, which indicates widespread use of heroin and cocaine mixture ("speedball") among IDU's, our physical evidence suggests that a large majority of IDU's in PR currently inject cocaine but not heroin; and also that mixed drug use is rather rare. Reliability of self-described information may need to be re-evaluated.

Gas Chromatography-Mass Spectrometry↗
PubMed1996

External protons enhance the activity of the hyperpolarization-activated K channels in guard cell protoplasts of Vicia faba.

Hyperpolarization-activated K channels (KH channels) in the plasmalemma of guard cells operate at apoplastic pH range of 5 to over 7. Using patch clamp in a whole-cell mode, we characterized the effect of varying the external pH between 4.4-8.1 on the activity of the KH channels in isolated guard cell protoplasts from Vicia faba leaves. Acidification from pH 5.5 to 4.4 increased the macroscopic conductance of the KH channels by 30-150% while alkalinization from pH 5.5 to 8.1 decreased it only by roughly 15%. The voltage-independent maximum cell conductance, increased by -60% between pH 8.1 and 4.4 with an apparent pKa of 5.3, most likely owing to the increased availability of channels. Voltage-dependent gating was affected only between pH 5.5 and 4.4. Acidification in this range shifted the voltage-dependent open probability by over 10 mV. We interpret this shift as an increase of the electrical field sensed by the gating subunits caused by the protonation of external negative surface charges. Within the framework of a surface charge model the mean spacing of these charges was approximately 30 A and their apparent dissociation constant was 10(-4.6). The overall voltage sensitivity of gating was not altered by pH changes. In a subgroup of protoplasts analyzed within the framework of a Closed-Closed-Open model, the effect of protons on gating was limited to shifting of the voltage-dependence of all four transition rate constants.

Fabaceae↗
PubMed1996

The endosymbiont (Buchnera sp.) of the aphid Diuraphis noxia contains plasmids consisting of trpEG and tandem repeats of trpEG pseudogenes.

Most aphids are dependent for their survival on prokaryotic endosymbionts assigned to the genus Buchnera. Among the functions of Buchnera species is the synthesis of tryptophan, which is required by the aphid host. In Buchnera species from the aphid Diuraphis noxia, the genes for anthranilate synthase (trpEG) were found on a plasmid which consisted of seven tandem repeats of a 3.2-kb unit and one 2.6-kb unit which differed in containing a 0.6-kb deletion. One of the 3.2-kb units contained open reading frames corresponding to trpEG; the remaining units contained trpEG pseudogenes (psi). The nucleotide sequence upstream of trpE contained a region that has characteristics of an origin of replication (ori). Relative to trpB (a chromosomal gene), there were about two copies of the trpEG-containing plasmid. Comparisons of the nucleotide sequences of the 3.2-kb units containing trpEG and psi trpEG indicated that most changes occurred in a 700-nucleotide segment that included the region upstream of trpE and the portion of this gene coding for the N terminus. The consequence of these changes was the silencing of trpEG by inactivation of the putative promoter region and premature termination of the TrpE peptide. In contrast, the nucleotide sequence of the segment corresponding to ori was conserved in the units containing trpEG and psi trpEG. We offer a number of speculations on the evolutionary pressure in this lineage which resulted in the silencing of most of trpEG while still retaining the regions resembling ori.

Animals↗
PubMed1996

Lesbian health care needs.

OBJECTIVE: To define the special health care needs of Canadian lesbians. DESIGN: A questionnaire containing 61 yes-or-no and multiple-choice questions sought information on six areas: demographics; health care use; habits, diet, and exercise; preventive care; mental health; and physical health. SETTING: The organizational meeting of a lesbian softball league in Toronto. PARTICIPANTS: Of 360 women eligible for the meeting, 205 attended and 195 completed the survey. Questionnaires used for analysis were those of the 186 women who answered yes to the question, "Are you a lesbian?" MAIN OUTCOME MEASURES: How lesbian health care needs differ from those of women in general. Results of the survey were compared with results of the 1991 Canadian General Health Survey and the 1986 Health Promotion Survey (for comparable sex and age groups). RESULTS: The lesbians were young, white, and middle class. They visited the same health care professionals as other Canadian women but for different reasons. They smoked, drank alcohol, used caffeine, and exercised somewhat more than other women, but they were not very knowledgeable about healthy diets. The lesbians got Pap smears less often than other Canadian women, even if they were at high risk. They examined their breasts less frequently, but got their blood pressure checked with comparable frequency. Lesbians had a high incidence of mental health problems and often had nontraditional support systems. Lesbians were less prone to gynecologic complaints, especially infectious diseases, but had about the same incidence of common chronic illnesses. CONCLUSIONS: Although lesbians are not afflicted uniquely by any illness, they do have special health care needs. Canadian family physicians should be aware that lesbians are part of family practice and that, like other identifiable group, they have common health concerns that differ from those of the general population.

Adult↗
PubMed1994

Interactions among calcium compartments in C6 rat glioma cells: involvement of potassium channels.

1. Variations in intracellular free Ca2+ concentration ([Ca2+]i) induced by alteration of the extracellular concentrations of Ca2+ ([Ca2+]o) and K+ ([K+]o) were imaged in single fluo-3-loaded C6 glioma cells. In addition, the effect of membrane potential on [Ca2+]i was investigated in fura-2-loaded, voltage-clamped cells. 2. Step alterations of [Ca2+]o from 0 to 10 nM were followed by proportional variations in [Ca2+]i, with a maximum 7-fold increase and an apparent half-maximum at [Ca2+]o of 1.5 mM. 3. The time to half-maximum change (t1/2) of [Ca2+]o-associated [Ca2+]i variations ranged between 10 and 50 s, and was inversely related to the amplitude of [Ca2+]o steps. 4. Transient, serotonin-induced [Ca2+]i elevations, used as a measure of Ca2+ availability in inositol 1,4,5-trisphosphate-sensitive stores, were diminished within 10 min in 0 mM [Ca2+]o, but were unaffected by [Ca2+]o changes in the 1-5 mM range. 5. Restoration of normal [Ca2+]i following its elevation by serotonin was delayed by removal of external Na+ or Cl- and was enhanced by warming the medium to 37 degrees C. These conditions did not affect [Ca2+]o-associated [Ca2+]i variations. 6. [Ca2+]o-associated [Ca2+]i variations were depressed by La3+ and Ba2+, while blockers of voltage-activated Ca2+ channels were ineffective. 7. Elevated [K+]o depressed the basal level of [Ca2+]i, and in high concentrations (70-140 mM) also diminished the response to serotonin. 8. Depolarizing the membrane potential of voltage-clamped cells reversibly reduced [Ca2+]i. These membrane-potential associated [Ca2+]i variations were blocked by La3+, Ba2+ and TEA, all of which also depolarized membrane resting potential. 9. Apamin (at 1-10 microM), a blocker of [Ca2+]i-activated K+ channel, totally and reversibly prevented [Ca2+]o-associated [Ca2+]i variations. 10. These studies indicate that C6 cells are responsive to variations in [Ca2+]o, and that a K+ channel is a possible path through which Ca2+ penetrates into the cell.

Animals↗
PubMed1994

Modulation of small conductance calcium-activated potassium channels in C6 glioma cells.

Using the patch clamp technique, we have characterized a small conductance, calcium-activated potassium (SK) channel in the C6 glioma cell line. Elevation of cytosolic Ca2+ concentration ([Ca2+]i) by applications of serotonin or ionomycin induced bursts of channel opening recorded in the cell-attached configuration. These channels underlie the serotonin-induced, [Ca2+]i-activated whole-cell K+ conductance described previously. [Ca2+]i directly activated SK channels in inside-out patches with a biphasic concentration dependence. Submicromolar [Ca2+]i induced bursts of channel openings with a unitary conductance of about 25 pS, similar to that of the serotonin-induced channels. Supramicromolar [Ca2+]i caused prolonged openings with a unitary conductance of about 35 pS, resulting in a pronounced increase of the average current in patches exposed to [Ca2+]i above 100 microM. The two modes of opening reflect the activity of the same SK channel. The channel conductance depended on external K+ concentration with KD of 5 mM. The channel was slightly permeable to cations other than K+, with a permeability ratio for K+:Ca2+:Na+ of 1:0.040:0.030, respectively. ATP was required to maintain channel activity in outside-out patches but was not essential in inside-out patches. The modulations of SK channels in C6 cells by components in their microenvironment may be related to the role of glial cells in controlling the extracellular milieu in the CNS.

Adenosine Triphosphate↗
PubMed1994

External pH effects on the depolarization-activated K channels in guard cell protoplasts of Vicia faba.

Previous studies reveal that the pH of the apoplastic solution in the guard cell walls may vary between 7.2 and 5.1 in closed and open stomata, respectively. During these aperture and pH changes, massive K+ fluxes cross the cellular plasma membrane driving the osmotic turgor and volume changes of guard cells. Therefore, we examined the effect of extracellular pH on the depolarization-activated K channels (KD channels), which constitute the K+ efflux pathway, in the plasma membrane of Vicia faba guard cell protoplasts. We used patch clamp, both in whole cells as well as in excised outside-out membrane patches. Approximately 500 KD channels, at least, could be activated by depolarization in one protoplast (density: approximately 0.6 micron-2). Acidification from ph 8.1 to 4.4 decreased markedly the whole-cell conductance, GK, of the KD channels, shifted its voltage dependence, GK-EM, to the right on the voltage axis, slowed the rate of activation and increased the rate of deactivation, whereas the single channel conductance was not affected significantly. Based on the GK-EM shifts, the estimated average negative surface charge spacing near the KD channel is 39 A. To quantify the effects of protons on the rates of transitions between the hypothesized conformational states of the channels, we fitted the experimental macroscopic steady state conductance-voltage relationship and the voltage dependence of time constants of activation and deactivation, simultaneously, with a sequential three-state model CCO. In terms of this model, protonation affects the voltage-dependent properties via a decrease in localized, rather than homogeneous, surface charge sensed by the gating moieties. In terms of either the CO or CCO model, the protonation of a site with a pKa of 4.8 decreases the voltage-independent number of channels, N, that are available for activation by depolarization.

Cell Membrane↗
PubMed1993

Point mutation in the seventh hydrophobic domain of the human thromboxane A2 receptor allows discrimination between agonist and antagonist binding sites.

Thromboxane A2, a potent platelet agonist and vasoconstrictor, exerts its actions via specific G protein-coupled receptors. cDNAs encoding the full length thromboxane receptor have been isolated from human placenta mRNA by reverse transcriptase-polymerase chain reaction. An expression construct, under control of the cytomegalovirus promoter, was introduced into human embryonic kidney 293 cells. Membranes from transfected cells bound the thromboxane antagonist SQ29,548 and the agonist [15-(1 alpha,2 beta(5z)-3 alpha(1E,3S)-4 alpha)]-7-[3-(3-hydroxy-4-(p- iodophenoxy)-1-butenyl)-7-oxabicyclo[2,2,1]hept-2-yl]-5-heptenoic acid) with high affinities, and significantly more receptors were expressed in these cells, compared with platelet preparations. The putative seventh transmembrane segment is highly related in all cloned members of the eicosanoid receptor family and forms a critical portion of the ligand binding pocket for G protein-coupled receptors. Several point mutations in this segment were generated. Binding of SQ29,548 was virtually abolished in cells transfected with all the variant receptor constructs. However, one receptor variant (TxR-W299L), in which a tryptophan at position 299 was substituted for a leucine residue, allowed a definite discrimination between agonist and antagonist binding sites in competition and saturation binding experiments. An antibody directed toward the third intracellular loop of the thromboxane receptor was able to immunoprecipitate native thromboxane receptor in solubilized membranes from human erythroleukemia cells and transfected cells.

Amino Acid Sequence↗
PubMed1992

Calcium dependence of serotonin-evoked conductance in C6 glioma cells.

Whole-cell membrane currents and imaging of intracellular calcium concentrations ([Ca2+]i) were used to investigate the role of calcium in a response to serotonin of C6 glioma cells. Activation of a high-affinity serotonin receptor induced a transient rise in calcium concentration in these cells and activated a predominantly potassium conductance, with a small chloride component. Perfusion of the cytoplasm with an internal solution containing high calcium concentration induced similar but prolonged increase of membrane conductance. The responsiveness of C6 cells to serotonin was negatively correlated with the concentration of the unbound calcium chelator BAPTA when BAPTA-buffered calcium-containing intracellular solutions were used. Responses to serotonin persisted in the absence of external calcium, decreased gradually, and then recovered partially after replenishment of extracellular calcium. These findings substantiate the direct role of intracellular calcium in mediating the serotonin response, and indicate that serotonin-induced release of calcium from intracellular stores is sufficient for the activation of conductance in the C6 glioma cell line.

Brain Neoplasms↗
PubMed1991

Characterization of NCAM expression and function in BT4C and BT4Cn glioma cells.

The neural cell adhesion molecule, NCAM, plays an important role in cell-cell adhesion. Therefore, we have studied NCAM expression in the glioma cell lines BT4C and BT4Cn. We demonstrate that the 2 cell lines differ in their metastatic ability; while BT4C cells have a very low capacity for producing experimental metastases, that of BT4Cn cells is high. In BT4C cells NCAM is synthesized as 4 polypeptides with Mr's of 190,000, 140,000, 115,000 and 97,000. The 140,000, 115,000 and 97,000 polypeptides are glycosylated and for the 140,000 and 115,000 polypeptides sulfatation is observed. Conversely, no NCAM protein synthesis is observed in BT4Cn cells, even though NCAM mRNA is expressed. Thus, development of an increased metastatic capacity is accompanied by the disappearance of NCAM protein expression in this model system. The functional importance of NCAM expression was studied by a cell-substratum binding assay in which the binding of BT4C and BT4Cn cells to NCAM immobilized to glass was assessed. We found that BT4C cells adhere specifically to NCAM, and that adhesion is inhibited by anti-NCAM Fab'-fragments, while no specific binding of BT4Cn cells to NCAM was observed. The BT4C and BT4Cn cell lines thus constitute an important new model system for the study of tumor invasion and metastasis and of the role of cell adhesion molecules in these processes.

Animals↗
PubMed1990

Sympathectomy alters acetylcholinesterase expression in adult rat heart.

STUDY OBJECTIVE: The aim of the study was to determine the significance of adrenergic nerve associated acetylcholinesterase for the pool of total acetylcholinesterase molecules. DESIGN: Acetylcholinesterase was analysed after destruction of adrenergic nerves by 6-hydroxydopamine or bilateral stellate sympathectomy. Effectiveness of treatment was verified by determining noradrenaline concentrations in right ventricle. Acetylcholinesterase activity was assayed in homogenates of atria and portions of left ventricular free wall. SUBJECTS: Adult male Sprague-Dawley rats were used, weight 225-260 g, n = 5 per experimental group. MAIN RESULTS: Sympathectomy caused a small decrease in acetylcholinesterase activity, due to a decrease in the activity of the tetrameric globular form of the enzyme. Choline acetylcholinesterase activity was not altered by sympathectomy, which is an indication that cholinergic nerves were not affected. CONCLUSIONS: The contribution of adrenergic neurones to the cardiac pool of acetylcholinesterase is measurable and consists primarily of the tetrameric globular form of the enzyme.

Acetylcholinesterase↗