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S J Mitchell

Publications and source records attributed to S J Mitchell.

At least 55 records · Page 3Linked to original sources
PubMed1993

Recombinant interferon-alpha in inoperable hepatocellular carcinoma: a randomized controlled trial.

To evaluate the clinical efficacy of interferon-alpha in hepatocellular carcinoma, 71 adult Chinese patients with histologically proven inoperable hepatocellular carcinoma were randomized to receive recombinant interferon-alpha 2a (50 x 10(6) IU/m2) intramuscularly three times a week (n = 35) or no antitumor therapy (n = 36). The survival of interferon-alpha-treated patients was significantly better than that of patients who received no antitumor therapy (p = 0.0471); median lengths of survival were 14.5 and 7.5 wk, respectively. Objective tumor regression greater than 50% was observed in 31.4% (11 of 35) of patients receiving interferon-alpha. Interferon-alpha induced tumor regression greater than 50% in 11 (31.4%) patients. Compared with the group receiving no antitumor therapy, the interferon-alpha therapy group had more tumor regression (p < 0.0001) and less tumor progression (p = 0.001). This high-dose interferon-alpha therapy was relatively well tolerated; only 34.3% of patients required reduction of dosage by one third or one half because of persistent fatigue. Two patients with diabetes mellitus (one also had tabes dorsalis) exhibited mental deterioration that might have been partially attributable to interferon-alpha therapy. We conclude that interferon-alpha is useful in a proportion of Chinese patients with inoperable hepatocellular carcinoma, both in prolonging survival and in inducing tumor regression.

Adult↗
PubMed1992

Reduced levels of DNA polymorphism and fixed between-population differences in the centromeric region of Drosophila ananassae.

We have estimated DNA sequence variation within and between two populations of Drosophila ananassae, using six-cutter restriction site variation at vermilion (v) and furrowed (fw). These two gene regions are located close to the centromere on the left and right X chromosome arms, respectively. In the fw region, no DNA polymorphism was detected within each population. In the v region, average heterozygosity per nucleotide was very low in both populations (pi = 0.0005 in the Burma population, and 0.0009 in the India population). These estimates are significantly lower than those from loci in more distal gene regions. The distribution of DNA polymorphisms between both populations was also striking. At fw, three fixed differences between the Burma and India populations were detected (two restriction site differences and one insertion/deletion of approximately 2 kb). At v, each DNA polymorphism in high frequency in the total sample was nearly fixed in one or the other population, although none of them reached complete fixation. The observed pattern of reduced variation within populations and fixed differences between populations appears to correlate with recombination rate. We conclude that recent hitchhiking associated with directional selection is the best explanation for this pattern. The data indicate that different selective sweeps have occurred in the two populations. The possible role of genetic hitchhiking in rapid population differentiation in gene regions of restricted recombination is discussed.

Animals↗
PubMed1991

Transient impairment of recognition memory following ibotenic-acid lesions of the basal forebrain in macaques.

To assess the contributions of the basal forebrain cholinergic nuclei to visual recognition memory in macaques, we compared the effects of lesions of (a) the nucleus basalis of Meynert, (b) the medial septal and diagonal band nuclei, and (c) all nuclei combined on performance of delayed nonmatching-to-sample with trial-unique stimuli. Whereas monkeys with the separate lesions did not differ from each other or from normal control animals, those with combined lesions showed a significant impairment. With time and extended practice, however, the performance of the animals with combined lesions recovered to normal levels. During the recovery period, these monkeys showed an initially increased sensitivity to scopolamine that later dissipated, at which time they also failed to show the improvement that follows physostigmine administration in normal animals. Postmortem assessment of cortical choline acetyltransferase activity revealed that only the group with combined lesions had significant depletion of this enzyme. The results suggest that (1) the basal forebrain cholinergic system participates in mnemonic processes in primates and that (2) extensive damage to this system is necessary before impairments in recognition memory, even transient ones, can be observed.

Acetylcholinesterase↗
PubMed1990

Changes after taking a college basic nutrition course.

A food and nutrition questionnaire was administered to students in a college basic nutrition course (basic nutrition students) and to others in unrelated general studies classes (control students) at the beginning and end of the semester to determine changes other than in academic knowledge of nutrition. Analysis with chi square (p less than .05) compared pre-semester responses (no. = 279) and post-semester responses (no. = 218) with those of 24 senior dietetics students (dietetics majors). After completing the course, all basic nutrition students responded that they had learned a lot about nutrition, and 45% indicated that they had made dietary changes because of this learning. Changes included increased confidence in the adequacy of their diets, decreased supplement use, and reduced fat content of milk usually consumed. Some misunderstandings of carbohydrates in foods were not improved. The similarity of responses by basic nutrition and control students to the pre-semester questionnaire suggests that enrollees in a basic nutrition class may be representative of the general student body in needs for nutrition education. The basic class for non-nutrition majors can effect changes in dietary practices; their nutrition education needs may be used to plan nutrition education of the general student population.

Adult↗
PubMed1988

Characterization of the sites of proteolytic activation of Newcastle disease virus membrane glycoprotein precursors.

The F1- and F2-polypeptide components of the fusion proteins and the hemagglutinin/neuraminidase proteins of the avirulent Queensland (V4) and virulent Australia-Victoria (AuV) strains of Newcastle disease virus have been isolated and subjected to extensive primary structural analysis including amino-terminal sequence analysis and fast atom bombardment-mass spectrometry mapping. Nucleotide sequence analysis was performed on the gene which encodes the V4 hemagglutinin/neuraminidase protein. Signal peptidase cleavage was found to have occurred at the Ser31-Leu32 peptide bond of the primary translation products of the fusion protein genes. Activation cleavage of the V4 fusion protein precursor generated a sequence of -Gly-Lys-Gln-Gly84 at the carboxyl terminus of the F2-polypeptide and an amino-terminal sequence of the F1-polypeptide commencing with 86Leu-Ile-Gly-. The V4 hemagglutinin/neuraminidase protein gene was found to encode a primary translation product 45 amino acids longer at the carboxyl terminus than obtainable from the corresponding gene of the AuV strain (McGinnes, L. W., and Morrison, T. G. (1986) Virus Res. 5, 343-356). However, post-translational proteolytic processing, exclusive to the primary translation product of the V4 hemagglutinin/neuraminidase protein gene, was found to have removed the last 42 residues of this carboxyl-terminal appendage.

Amino Acid Sequence↗
PubMed1987

Fluorescent labeling of cysteinyl residues. Application to extensive primary structure analysis of proteins on a microscale.

The specificity and efficiency of fluorescent labeling of proteins by reduction and subsequent alkylation with 5-N-[(iodoacetamidoethyl)amino]naphthalene-1-sulfonic acid (5-I-AEDANS) [J.J. Gorman, (1987) Anal. Biochem. 160, 376-387] has been investigated. Proteins studied include porcine insulin, chicken ovalbumin and bovine serum albumin. Amino acid analysis of the B-chain derivative of insulin revealed quantitative recovery of cysteine in its S-carboxymethyl form and no other carboxymethylated amino acid derivatives. Fast-atom-bombardment mass spectrometric (FAB-MS) analysis of this derivative also indicated specific labeling of cysteine residues and automated stepwise protein sequence analysis of the derivative was performed to completion with initial and average repetitive yields of 73% and 96%, respectively. Tryptic peptides produced from the ovalbumin and serum albumin derivatives were fractionated by HPLC and subsequently analysed by amino acid analysis, FAB-MS and automated stepwise protein sequence analysis. These analyses have revealed that the labeling procedure exhibits a high degree of efficiency and is specifically directed towards S-alkylation of cysteine residues. The high level of fluorescence intensity of the label enabled specific detection of trace quantities of cysteine-containing peptides derived from contaminating protein(s). It is apparent that in addition to facilitating isolation of small quantities of proteins the labeling procedure is compatible with standard protein chemistry techniques involved in obtaining extensive structural data on isolated proteins.

Affinity Labels↗
PubMed1987

Fiber pathways of basal forebrain cholinergic neurons in monkeys.

In rhesus monkeys, autoradiographic tracing methods, complemented by immunocytochemical and histochemical techniques, were used to delineate pathways by which cholinergic neurons of the nucleus basalis of Meynert (nbM) and nucleus of the diagonal band of Broca (ndbB) project to forebrain targets. Following injections of [3H]amino acids into these nuclei, 5 major fiber pathways were identified: axons of the nbM and ndbB project medially, principally within the cingulum bundle, to dorsomedial portions of the hemispheres; nbM and ndbB fibers exit laterally beneath the pallidum and striatum, enter the external and extreme capsules, and pass within the corona radiata to terminate in lateral and caudal regions of neocortex; axons coursing ventrally from the nbM project to portions of the temporal lobe, including the amygdala; some fibers pass through the fibrae pass orbitofrontales to the orbitofrontal cortex; and, finally axons of the nbM/ndbB project via the fimbria/rornix and a ventral pathway to the hippocampus. The presence of these 5 radiolabeled pathways arising from basal forebrain cholinergic neurons was confirmed by acetylcholinesterase histochemistry and choline acetyltransferase immunocytochemistry.

Acetylcholinesterase↗
PubMed1987

Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert.

Monkeys with bilateral ibotenic-acid lesions of the nucleus basalis of Meynert, an area rich in cholinergic neurons that innervate the cerebral cortex, were compared with unoperated control monkeys on a recognition memory task. Although animals with large lesions had substantial reductions of cortical choline acetyltransferase activity, none showed impairment in the task. Lesion effects were observed, however, when performance was assessed following administration of a muscarinic receptor blocker (scopolamine) or a cholinesterase inhibitor (physostigmine). Although scopolamine produced dose-related impairments in both groups, this effect was greater in the experimental animals. Conversely, whereas physostigmine produced modest improvement in performance in the control group, no such improvement was observed in the experimental animals. The altered sensitivity to the mnemonic effects of cholinergic agents in the experimental group suggests that the cholinergic neurons of the nucleus basalis of Meynert contribute to recognition memory.

Acetylcholinesterase↗
PubMed1987

The primate globus pallidus: neuronal activity related to direction of movement.

Neurons in the arm areas of the external and internal segments of the globus pallidus (GPe and GPi) and the ventral pallidum (VP) have been examined in a visuomotor step-tracking task. This task, which was similar to that used previously to examine neurons in the arm area of the putamen, dissociated the direction of movement from the pattern of muscle activity associated with the movement. The major finding of the present study is that, as in the putamen, the activity of almost half of the neurons in GPe and GPi was related to the direction of movement. Cells with overall patterns of activity similar to muscle were rare, although many neurons had static and/or dynamic load effects which resembled those seen in muscle. Responses of neurons to load application have also been examined in this paradigm in order to determine the nature of possible somatosensory input. Short-latency "sensory" responses to load application were found in pallidum as previously in putamen, but, by contrast, they occurred somewhat later and included bidirectional responses. Similar proportions of cells in GP and putamen were related to static loads. Some VP neurons appeared to encode information about specific features of the trials, but the majority of responses were nonspecific suggesting relations to more general features of the task.

Animals↗
PubMed1987

The primate nucleus basalis of Meynert: neuronal activity related to a visuomotor tracking task.

The activity of neurons in the nucleus basalis of Meynert (nbM), both the compact (nbMc) and interstitial (nbMi) components, has been examined in monkeys trained to perform a visuomotor step-tracking task. This study was carried out in the same animals and with the same task used to examine neuronal activity in the external and internal segments of globus pallidus (GPe and GPi) and ventral pallidum (VP). The presumed interstitial cells that are located within the laminae surrounding GPe and GPi and identified physiologically by their similarity with nbMc neurons, are referred to as border cells. A major finding of this study is that a large proportion of nbMc and border cells were active in relation to either the step-tracking movements or to load application. Moreover, a high proportion of the responses of border neurons were differential for opposite directions of load and movement. The percentages of directionally specific border and nbMc neurons were considerably less than for GP, with border neurons having more directionally specific responses than nbMc neurons. The similarity between border and GP neuronal properties in this task suggests that both may receive similar sensorimotor afferent input. In the compact portion of nbM, nonspecific neuronal responses following each behavioral event in the paradigm were common. These responses appeared to have been modified by and may have been contingent upon association with reinforcement.

Animals↗
PubMed1986

Basal forebrain neurons provide major cholinergic innervation of primate neocortex.

In 3 monkeys, lesions were made in the basal forebrain by microinjections of ibotenic acid into the nucleus basalis. Bilateral samples of multiple neocortical gyri were assayed for the activity of choline acetyltransferase. Compared to control hemispheres, enzyme activity was reduced up to 69% in the neocortex ipsilateral to the lesion; in addition, acetylcholinesterase staining was decreased at the lesioned site and in the ipsilateral cortex. These results support the concept that the principal cholinergic innervation of the primate neocortex is derived from axons and nerve terminals of neurons whose perikarya are located in the basal forebrain, particularly the nucleus basalis.

Animals↗
PubMed1984

Improved detection of rare CALLA-positive cells in peripheral blood using multiparameter flow cytometry.

A major limitation to the detection of rare cell types in the peripheral blood using monoclonal antibodies is nonspecific binding of the antibody reagent to normal cells. Detection of rare common acute lymphoblastic leukemia antigen (CALLA)-positive cells in peripheral blood is significantly improved by using multiple flow cytometric parameters to exclude a variety of mature blood cells which may nonspecifically bind the antibody reagent. Monocytes and granulocytes are excluded by gating out cells with high 90 degrees light scatter. By gating on red fluorescence, a variety of mature cell types binding to phycoerythrin (PE)-conjugated Leu 3, Leu 2, and M3 monoclonal antibodies are also excluded. CALLA-positive lymphoblasts from 6 consecutive patients were not excluded on the basis of these parameters. Gating on log 90 degrees light scatter and log red fluorescence in this fashion reduced the incidence of nonspecific binding to peripheral blood mononuclear cells of a fluorescein-conjugated irrelevant monoclonal antibody by 98% from 308 cells per million to 5 cells per million. One CALLA-positive lymphoblast per 100,000 peripheral blood mononuclear cells could be detected in mixture experiments using this method. The normal range of CALLA-positive cells in adults is less than 16 cells per million peripheral blood mononuclear cells. This low background of CALLA-positive peripheral blood cells may permit the detection of early leukemic relapse in acute lymphoblastic leukemia by analysis of the peripheral blood. This methodology can be applied to the detection of any rare cell type by using phycoerythrin-conjugated antibodies to markers that the cell type does not possess.

Adult↗
PubMed1984

Functional organization of the basal ganglia: contributions of single-cell recording studies.

Studies of single-cell discharge in the basal ganglia of behaving primates have revealed: characteristic patterns of spontaneous discharge in the striatum, external (GPe) and internal (GPi) globus pallidus, pars reticulata and pars compacta of the substantia nigra, and the subthalamic nucleus (STN); phasic changes in neural discharge in relation to movements of specific body parts (e.g. leg, arm, neck, face); short-latency (sensory) neural responses to passive joint rotation; a somatotopic organization of movement-related neurons in GPe, GPi, and STN; a clustering of functionally similar neurons in the putamen and globus pallidus; greater representation of the proximal than of the distal portion of the limb; changes in neural activity in reaction-time tasks, suggesting a greater role of the basal ganglia in the execution than in the initiation of movement in this paradigm; a clear relation of neuronal activity to direction, amplitude (?velocity) of movement, and force; a preferential relation of neural activity to the direction of movement, rather than to the pattern of muscular activity. Some of these findings suggest that the basal ganglia may play a role in the control of movement parameters rather than (or independent of) the pattern of muscular activity. Loss of basal ganglia output related to amplitude may account for the bradykinesia in Parkinson's disease. The presence of somatotopic organization in the putamen and globus pallidus, together with known topographic striopallidal connections, suggests that segregated, parallel cortico-subcortical loops subserve 'motor' and 'complex' functions.

Animals↗
PubMed1984

Role of basal ganglia in limb movements.

Recent anatomic and physiologic studies have shed new light on the functional organization of the basal ganglia and their role in movement. The basal ganglia receive topographically organized input from the entire neocortex. Influences from sensorimotor and "association" cortices appear to remain segregated in the basal ganglia. The concept of segregated parallel subcortical loops subserving "motor" and "complex" functions is discussed. Recent neurophysiologic studies in behaving primates suggest that basal ganglia output plays a role in controlling the direction and amplitude of movement but is not primarily involved in the initiation of limb movement or selection of specific muscles. These studies are generally consistent with data from patients with Parkinson's disease, which likewise indicates a deficit in the programming of movement amplitude in step-tracking tasks, with little or no change in reaction-time or pattern of muscular activity.

Animals↗
PubMed1982

Medial septal area lesions disrupt theta rhythm and cholinergic staining in medial entorhinal cortex and produce impaired radial arm maze behavior in rats.

This study was designed to determine (1) which brain area paces the theta rhythm in the medial entorhinal cortex (MEC) of rats and (2) the extent to which the behavioral effects of lesions in the medial septal area (MSA), which disrupt the cholinesterase-related pathway to the hippocampal formation, resemble the effects previously reported to result from fimbria-fornix lesions. MSA lesions abolished or decreased theta rhythm in dorsal hippocampus (DHPC) and MEC; acetylcholinesterase (AChE) staining was depleted or diminished in all of the hippocampus and entorhinal cortex. Rats with MSA lesions were impaired on acquisition of a radial arm maze task. Unilateral fimbria lesions left theta rhythm and AChE staining essentially unaltered in ipsilateral DHPC and MEC but depleted AChE in ipsilateral ventral hippocampus (VHPC) and ventral lateral entorhinal cortex (LEC). A lesion of the dorsal fornix at the level of the hippocampal flexure left ipsilateral DHPC theta rhythm and AChE stain unaltered while causing a substantial reduction in theta rhythm and depletion of AChE in ipsilateral MEC. AChE staining was complete in VHPC and LEC. These results suggest tha MSA paces MEC theta rhythm and that the presumed cholinergic projection which mediates this function travels in the dorsal fornix. The fimbria carries a presumed cholinergic projection to ventral LEC. Rats with MSA lesions can learn a radial arm maze task, unlike rats with fimbria-fornix lesions, but they learn significantly slower than normal rats.

Acetylcholinesterase↗
PubMed1981

Clinicopathological study of pancreatic and ganglioneuroblastoma tumours secreting vasoactive intestinal polypeptide (vipomas).

During a six-year period (1973-9) 52 patients with pancreatic tumours and 10 with ganglioneuroblastomas were found to have raised plasma vasoactive intestinal polypeptide (VIP) concentrations. All the patients had severe secretory diarrhoea, weight loss, dehydration, hypokalaemic acidosis, and a raised plasma urea concentration. Reduced gastric acid secretion was seen in 72% of patients. Plasma VIP concentrations were not raised in patients with diarrhoea due to other types of tumour or disease or in hormone-secreting tumours not associated with diarrhoea. Plasma VIP measurement may therefore give clinical guidance in a patient with persistent watery diarrhoea and hypokalaemic acidosis. Surgical excision was clearly the treatment of choice, but metastatic pancreatic tumours usually responded to streptozotocin.

Adult↗