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Biomedical subjects

M Stewart

Publications and source records attributed to M Stewart.

At least 361 records · Page 20Linked to original sources
PubMed1989

Two populations of rhythmically bursting neurons in rat medial septum are revealed by atropine.

1. Previous findings, such as the sensitivity of the hippocampal theta rhythm to cholinergic manipulation, support a "pacemaker" role for the cholinergic cells of the medial septal nucleus and the vertical limb of the nucleus of the diagonal band (MSN-NDB). To explore the mechanism(s) of action of systemic antimuscarinic drugs in eliminating the theta rhythm, recordings of hippocampal EEG and rhythmic MSN-NDB neurons that fired in phase with the hippocampal theta rhythm were taken during the administration of atropine in urethane-anesthetized rats. 2. Twenty-two of 33 rhythmic MSN-NDB cells continued to burst at the theta rhythm frequency after administration of a dose of atropine (25 mg/kg iv) that was sufficient to eliminate the theta rhythm (atropine-resistant cells). The remaining 11 cells lost their rhythmic firing pattern over the same time course as the loss of the theta rhythm (atropine-sensitive cells). 3. Both types of rhythmic MSN-NDB cells could be antidromically driven from the fimbria/fornix with similar latencies (range, 0.5-4.0 ms). The extracellularly recorded spike waveforms were not useful in predicting the atropine sensitivity of a given cell. Atropine-resistant cells frequently had higher firing rates than atropine-sensitive cells, but there was sufficient overlap of the two groups to make this a poor predictor of sensitivity. 4. Cooling the fimbria/fornix reversibly eliminated the hippocampal theta rhythm, but had no effect on 21/25 rhythmic MSN-NDB cells tested. This indicates that the atropine-sensitive MSN-NDB cells do not depend on the periodic output from the hippocampus for their rhythmic firing. Recordings from pairs of rhythmic MSN-NDB cells during cooling and/or atropine administration showed unchanged phase relations at the theta rhythm frequency. In rats in which the septohippocampal system was exposed by aspirating the overlying brain tissue, direct application of atropine (10 mg/ml) to the septal nuclei reversibly eliminated the hippocampal theta rhythm. 5. The rhythmic cells of the MSN-NDB are apparently composed of at least two distinct types, both of which potentially contribute to the production of the theta rhythm in the hippocampus. Elimination of hippocampal theta rhythm after local septal atropine application suggests that the loss of rhythmic activity in the group of atropine-sensitive septal cells is sufficient for the elimination of the theta rhythm. A model of the septohippocampal connections necessary for the theta rhythm is presented.

Animals↗
PubMed1989

The paradoxical stimulatory effect of morphine on LH secretion is dose-dependent and naloxone-reversible.

We previously observed that morphine stimulated luteinizing hormone (LH) secretion from ovariectomized rats when administered intravenously at a dose of 10 mg/kg body weight. The objectives of the present study were to determine: (1) if this paradoxical effect of morphine on LH secretion could be antagonized by naloxone; (2) whether beta-endorphin also stimulated LH secretion under similar conditions; (3) what influence, if any, the ovaries have on the expression of this opiate-induced LH secretion, and (4) whether this paradoxical effect of morphine extended to prolactin (PRL) secretion. An intravenous injection of morphine, 10 mg/kg body weight, to ovariectomized rats acutely increased both plasma LH and PRL concentrations. The LH and PRL responses were completely antagonized by the concurrent administration of the opiate antagonist naloxone (1 mg/kg body weight). In contrast, morphine suppressed LH concentrations and had no effect on PRL levels when injected at a dose of 1.0 mg/kg body weight. Intravenous injections of beta-endorphin, 1 mg/kg body weight, increased PRL concentrations to a level comparable to that observed following morphine, 10 mg/kg body weight, and produced a transient but insignificant inhibition of LH release. Intraventricular injections of much lower doses of beta-endorphin resulted in a dose-dependent suppression of LH release and a dose-dependent stimulation of PRL release in ovariectomized rats. Intravenous administrations of morphine (10 mg/kg), but not beta-endorphin (1 mg/kg), to normal female rats resulted in a 2-fold increase in LH concentrations similar to that observed in ovariectomized rats, whereas both treatments similarly increased PRL concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Expression in Escherichia coli of fragments of glial fibrillary acidic protein: characterization, assembly properties and paracrystal formation.

We have expressed in Escherichia coli a 1258 bp cDNA fragment corresponding to 97% of mouse glial fibrillary acidic protein (GFAP), the principal intermediate filament protein of astrocytes. High levels of expression were obtained, as a fusion protein with 32 residues of the bacteriophage lambda cII protein, using the pLcII expression vector system of K. Nagai and H.-C. Thogersen. Although removal of the cII protein fragment by proteolysis using factor X proved difficult, a protein corresponding to most of the cDNA fragment was obtained by cleaving at the endogenous thrombin site near the middle of the N-terminal non-helical domain of GFAP. A shorter 1047 bp fragment, in which the C-terminal non-helical domain of GFAP was deleted, was also produced using oligonucleotide-directed site-specific mutagenesis of the original cDNA clone. After proteolysis with thrombin, this material gave a fragment that corresponded to the alpha-helical coiled-coil rod region of the GFAP molecule, together with a portion of the non-helical N-terminal domain. The fragments produced were characterized both biochemically and ultrastructurally, and appeared to retain the conformation of native GFAP. Crosslinking showed that all fragments formed molecules containing two chains ('dimers') that associated to form four-chain molecular dimers ('tetramers') analogous to those formed by intact intermediate filament proteins. Shadowed preparations showed the presence of rod-like particles that closely resembled those observed for other intermediate filament proteins and proteolytically prepared rod domains. Remarkably, the fusion protein produced from the entire 1258 bp cDNA fragment and the cII peptide was able to form filaments that closely resembled those produced by native GFAP. However, fragments in which either the cII peptide or the C-terminal non-helical domain were removed, or in which both were removed, failed to form filaments under standard assembly conditions. Although preliminary in nature, these results suggest that both N- and C-terminal non-helical domains may have a role in intermediate filament formation. Moreover, the fragment corresponding approximately to the GFAP rod formed paracrystals similar to those observed with other coiled-coil proteins. The molecules in these paracrystals were arranged antiparallel with the two molecules in the unit cell, which may correspond to the four-chain molecular dimer (tetramer), overlapping by approximately two-thirds of their length.

Amino Acid Sequence↗
PubMed1989

An ultrastructural study of crossbridge arrangement in the fish skeletal muscle thick filament.

A procedure has been developed for isolating gold-fish skeletal muscle thick filaments that preserves the near-helical arrangement of the myosin cross-bridges under relaxing conditions. These filaments have been examined by electron microscopy and computer image analysis. Electron micrographs of the negatively stained filaments showed a clear periodicity associated with the crossbridges, with an axial repeat every 42.9 nm. Computed Fourier transforms of the negatively stained filaments showed a series of layer lines confirming this periodicity, and were similar to the X-ray diffraction patterns of fish muscle obtained by J. Hartford and J. Squire. Analysis of the computed transform data and filtered images of the isolated fish filaments demonstrated that the myosin crossbridges lie along three strands. Platinum shadowing demonstrated that the strands have a right-handed orientation, and computed transforms and filtered images of the shadowed filaments suggest that the crossbridges are perturbed both axially and azimuthally from an ideal helical arrangement.

Animals↗
PubMed1989

Action of interleukin-3, G-CSF, and GM-CSF on highly enriched human hematopoietic progenitor cells: synergistic interaction of GM-CSF plus G-CSF.

Purified preparations of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and interleukin 3 (IL-3 or multi-CSF) alone and in combination, have been compared for their stimulatory effects on human granulocyte-macrophage colony forming cells (GM-CFC). In cultures of unseparated normal human bone marrow, the combinations of G-CSF plus IL-3 and GM-CSF plus IL-3 stimulated additive numbers of GM colonies, while GM-CSF plus G-CSF stimulated greater than additive numbers of GM colonies, compared with the sum of the colony formation obtained with each factor alone. Cultures of unseparated bone marrow, harvested from patients four to six days after administration of 5-fluorouracil (5-FU), resulted in additive GM colony formation with GM-CSF plus G-CSF, GM-CSF plus IL-3, and G-CSF plus IL-3. In order to address the possibility of secondary factor involvement in the synergistic interaction of GM-CSF and G-CSF, CD33+/CD34+ colony forming cells were separated from normal and post FU marrow by two color fluorescence activated cell sorting. In cultures of CD33+/CD34+ cells the combination of GM-CSF plus G-CSF stimulated a synergistic increase in GM colonies while GM-CSF plus IL-3 stimulated additive numbers of colonies. These results suggest that GM-CSF, G-CSF, and IL-3 stimulate distinct populations of GM-CFC. Furthermore GM-CSF and G-CSF interact synergistically and this action is a direct effect on progenitor cells not stimulated by GM-CSF or G-CSF alone.

Antigens, CD↗
PubMed1988

Lesser-curve ischaemic necrosis mimicking a gastric ulcer--a complication of highly selective vagotomy. A case report.

Ischaemic necrosis of the lesser curve of the stomach is thought to be a specific but rare complication of highly selective vagotomy. While it commonly presents as a free perforation, it may also present as sloughing of the mucosa only, a gastric fistula or a sealed perforation of the lesser curve mimicking a chronic gastric ulcer. We describe a case in which ischaemic necrosis of the lesser curve presented as a chronic gastric ulcer from a sealed perforation.

Adult↗
PubMed1988

Surgical approaches to vertebral artery injuries.

Twenty patients with penetrating injuries of the vertebral artery who were treated as emergencies were subjected to the following operative approaches: five cases, Henry's approach (posterior) and modified Henry's approach (anterior); five cases, limited exposure and application of metal clips; four cases, plugging of the arterial defect with Oxycell or crushed muscle; three cases, control with ligatures and non-conventional exposure of the artery; one case, inflation of a balloon catheter within the vertebral canal; one case, repair of the lacerated first extraosseous part of the vertebral artery. One patient died from exsanguination on the operating table, before any repair was possible. The overall mortality was 20 per cent and the mean hospital stay 6.1 days. Thirty-five per cent of the patients presented with neurological complications, and 55 per cent left the hospital well. No advantage of Henry's classical approach over limited exposure and control with metal clips was shown, when mortality, hospital stay and long-term problems were compared. Because of its relative simplicity we suggest that the metal clipping of the vertebral artery, above and below the site of injury, is an effective technique that can be used to stop the bleeding. One case presented as a false aneurysm of the vertebral artery, following a stab wound. This was successfully treated with excision of the aneurysm and vertebrovertebral artery bypass, using a saphenous vein graft.

Adult↗
PubMed1988

Predictive value of clinical, laboratory, pathologic, and treatment variables in steroid/immunosuppressive resistant lupus nephritis.

Twenty-seven patients with lupus nephritis and nephrotic syndrome had persistent disease activity despite an adequate trial of corticosteroids and immunosuppressive drugs; 30% were Asians, compared with 7% of our overall SLE population. Two years later, seven had a very good outcome and seven a poor outcome. Thirty clinical, pathological, laboratory, and treatment variables were analyzed in a good versus poor responder subset comparison in an effort to determine which factors were associated with favorable outcome. Administration of pulse steroids (P = .069) and a low biopsy chronicity index (P = .048) were associated with the good responder subset. Serum creatinine, biopsy class, blood pressure, complement, and anti-DNA values at entry as well as the choice of immunosuppressive drug were not helpful in predicting outcome. All seven good responders were plasmapheresed (P = .026). Patients with refractory lupus nephritis who have a low biopsy chronicity index may benefit from the use of pulse steroids or plasmapheresis, and controlled studies are suggested.

Adult↗
PubMed1988

Introduction to the computer image processing of electron micrographs of two-dimensionally ordered biological structures.

Methods are described for the analysis of electron micrographs of regular biological objects. Fourier-based processing of one-dimensionally ordered arrays is described by way of introduction, before analysing two-dimensional crystals in projection with the aim of enhancing signal:noise ratio and thus of feint features that were initially obscured. This form of analysis is then extended to decomposing the moiré patterns formed when sheets overlap, thereby enabling the separation of interfering image patterns. Analogous forms of an analysis can also be applied to objects with rotational symmetry. Methods for treating the effect of the microscope imaging system and compensating for lattice disorder in crystalline specimens are also discussed.

Fourier Analysis↗
PubMed1988

Computer image processing of electron micrographs of biological structures with helical symmetry.

Methods are described for the analysis of electron micrographs of biological objects with helical symmetry and for the production of three-dimensional models of these structures using computer image reconstruction methods. Fourier-based processing of one- and two-dimensionally ordered planar arrays is described by way of introduction, before analysing the special properties of helices and their transforms. Conceiving helical objects as a sum of helical waves (analogous to the sum of planar waves used to describe a planar crystal) is shown to facilitate analysis and enable three-dimensional models to be produced, often from a single view of the object. The corresponding Fourier transform of such a sum of helical waves consists of a sum of Bessel function terms along layer lines. Special problems deriving from the overlapping along layer lines of terms of different Bessel order are discussed, and methods to separate these terms, based on analysing a number of different azimuthal views of the object by least squares, are described. Corrections to alleviate many technical and specimen-related problems are discussed in conjunction with a consideration of the computer methods used to actually process an image. A range of examples of helical objects, including viruses, microtubules, flagella, actin, and myosin filaments, are discussed to illustrate the range of problems that can be addressed by computer reconstruction methods.

Flagella↗
PubMed1988

Long term renal prognosis of Henoch-Schönlein purpura in an unselected childhood population.

All 270 patients presenting with Henoch-Schönlein Purpura over a 13-year period from a total childhood population of 155,000 were studied. This is an incidence of 13.5/100,000 children per year. Fifty-five (20%) were found to have initial evidence of renal involvement, and were re-examined at a mean of 8.3 years later. The 37 with isolated haematuria or haematuria with mild proteinuria (67%) recovered completely. Eighteen (33%) had nephritic or combined nephritic/nephrotic features, of these one died in the acute phase of the illness, only three others have persistent urinary abnormalities but have no biochemical evidence of renal impairment and only minor histological changes. The overall prognosis in this unselected population is therefore good with a mortality less than 1% overall and low long term morbidity of 1.1%. This study indicates a more optimistic outcome in this condition than the majority of published estimates based on more selected groups of patients.

Child↗
PubMed1988

Conductive hearing loss in autistic, learning-disabled, and normal children.

Katz (1978) has suggested that mild, fluctuating conductive hearing loss due to middle-ear anomalies may account for the language and attention problems of learning-disabled children. His position was extended here to include autism. Normal, learning-disabled, and autistic children received repeated impedance measures over 5 weeks. A repeated-measures ANOVA of central tendency and variability values led to the conclusions that (1) fluctuating, negative middle-ear pressure greater than normal characterizes both autistic and learning-disabled children, (2) the negative pressure is greater in autistic than in learning-disabled children, and (3) the condition is typically bilateral for autistic children.

Acoustic Impedance Tests↗
PubMed1988

Treatment planning using images of regret.

The lack of well-defined criteria for evaluating alternative treatment plans introduces a degree of subjectivity into the planning process. The complexity of conventional isodose charts causes further difficulty in making rapid and reliable evaluations of a plan. An objective method is described, using a prescription file to define the clinician's requirements in terms of the area of each organ which may be treated to predefined tolerance doses. The computer program OSCAR then compares the predicted dose distribution with the prescribed limits, and displays regions of noncompliance as colored "areas of regret." In addition, score functions are used to provide a quantitative measure of the acceptability of dose distributions within the target and each organ at risk. An example is described in which a plan for the treatment of ca esophagus is evaluated using both images of regret and score functions.

Esophageal Neoplasms↗
PubMed1988

Preparation of shadowed nuclear envelopes from Xenopus oocyte germinal vesicles for electron microscopy.

Methods for examining the structure of the nuclear envelope of oocytes of Xenopus laevis by electron microscopy using metal shadowing have been developed and evaluated. Minor modifications were made to existing methods for preparing specimens by freeze drying, mainly to eliminate unnecessary steps and a rapid method for examining the structure and arrangement of nuclear envelope components, based on dehydration in an ethanol series followed by amyl acetate and then air drying, was also developed. The preservation of the lamina and connections between the nuclear pore complexes using the rapid air drying method was satisfactory for observing the fibrous components of the envelope and their attachment to the pores. Furthermore, air drying required only simple laboratory apparatus and, moreover, offered several advantages compared to freeze drying when assessing the effect of various disruptive treatments on the nuclear envelope or examining the connections between its components. In specimens prepared by either the more rapid air drying method or by freeze drying, the lamina meshwork beneath the nuclear face of the envelope was clear, but the fine structure of the nuclear pore complexes was superior in freeze dried preparations. In views of the nucleoplasmic face of the envelope, the lamina meshwork was suspended above the support film in freeze dried preparations, but collapsed in most air dried specimens. This collapse was not without its advantages, however, as it facilitated observation of the connections between nuclear pore complexes and lamina fibres, which were often masked in freeze dried preparations.

Animals↗
PubMed1988

Receptor-mediated leukaemogenesis: hypothesis revisited.

The discovery of the first example of retroviral transduction of an immunological effector molecule has led us to reconsider the possible importance of cell surface receptors of the immune system in leukaemia development. Antigen receptors on lymphoid cells not only bind external ligands but are crucial in the control of cellular proliferation. The concept of autocrine stimulation in oncogenesis is already well established and we see no reason to exclude the possibility of analogous mechanism operating through antigen receptors. At present, we are investigating the oncogenic function of the retrovirus (FeLV-T17) carrying a T-cell receptor gene (v-tcr). In addressing the general concept of oncogenesis by ligand/receptor interactions in the immune system we face the problem of the diversity and, for T-cell antigen receptors, the complex nature of receptor-ligand interaction. Nevertheless, the implications of the model encourage us to continue to search for new experimental tools and approaches to the question.

Animals↗