Mechanisms of pain and analgesia as revealed by opiate research: summary and recommendations.
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Biomedical subjects
Publications and source records attributed to R M Brown.
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A scanning electron microscopic study of the distribution of ciliated cells in the tracheobronchial tree of 25 dogs whose ages ranged from four hours to six months was carried out. In newborn puppies, only the dorsal wall of the trachea was completely ciliated while the lateral and ventral walls showed patchy ciliation. This pattern of cilia formation persisted until five days of age when the whole tracheal wall was found to be completely ciliated. The bronchus of newborn puppies was uniformly poorly ciliated but almost complete ciliation was achieved by two days. Likewise, large and small bronchioles of newborn animals had few cilia and, although the number of ciliated cells had increased by two days, complete ciliation was never observed regardless of the age of the dog. No ciliated cells were found in the respiratory bronchioles of any of the 25 dogs.
65 patients with serious infections, including 25 with septicaemia, were treated with ceftazidime, a new extended-spectrum cephalosporin. 80% of the infection were cured by the antibiotic. 11 of 12 infected patients who had malignant disease or were otherwise immunocompromised responded satisfactorily to ceftazidime; 7 of these 12 had infections caused by Pseudomonas aeruginosa. The serum half-life of ceftazidime was 1.9 h in a patient with normal renal function. After a 1 g intravenous dose the antibiotic was present in pus, sputum, and bile in therapeutic concentrations. The antibiotics should prove a useful and non-toxic alternative to the aminoglycosides.
Five hybrids (LSB) were formed between LS174T, a human CEA-producing colonic tumor cell line, and BU25.CAPr, a HeLa derivative which does not produce CEA. All five hybrids produce CEA, but less per cell than LS174T. Approximately 10% of the chromosomes have been lost from these hybrids. In an attempt to map the gene(s) coding for the protein moiety of CEA, 7 LSPG and 28 LSR hybrids were formed between LS174T and PG19, an mouse melanoma cell line, and LS174T and RAG, a mouse kidney adenocarcinoma cell line, respectively. These hybrids retain between 4 and 21 human chromosomes, and each human chromosome is represented in at least seven hybrids. Two hybrids appeared to produce trace amounts of CEA. These results might represent repression by the mouse genome of CEA production or the production of a structurally abnormal CEA molecule.
The concentration and rates of synthesis of norepinephrine, dopamine and serotonin were determined by spectrophotofluorometric methods in various cytoarchitectonic areas of the cerebral cortex in 54 rhesus monkeys ranging in age from 1 day to 36 months. For most regions studied, norepinephrine levels exhibit steady increases from birth through 36 months while over the same period changes in dopamine concentration are more complex and variable, particularly in the frontal lobe. Among the 3 monoamines examined, endogenous serotonin content shows the least dramatic and most rapid development, reaching adult values between 2 and 5 months of age in most cortical regions. As a consequence of these developmental shifts, the relationship of monoamine levels in various cortical areas also changes with age. At maturity, however, norepinephrine concentration exceeds that of dopamine and serotonin in the cortex of the frontal and parietal lobes whereas serotonin levels are higher than norepinephrine in the occipital cortex. Changes in rates of synthesis of the catecholamines and serotonin generally parallel developmental changes in concentrations. The greatest increments in catecholamine synthesis occur in prefrontal and posterior association cortices. Smaller but significant increases in serotonin metabolism were measured in the parietal and visual cortex between birth and 36 months while in other areas of the cortex, age-related changes in serotonin synthesis were negligible. A consistent finding at all ages is that the distribution of catecholaminergic synthesis varies inversely with that of serotonergic synthesis, indicating substantial interaction in the regulation of the two cortical systems. The present findings demonstrate that in the rhesus monkey development of monoaminergic storage capacity and synthetic processes: (1) continues over a period of months and years; (2) is generally more rapid for serotonin than for catecholamines; and (3) varies greatly in different cytoarchitectonic regions of the cerebral cortex.
In vivo cellulose ribbon assembly by the Gram-negative bacterium Acetobacter xylinum can be altered by incubation in carboxymethylcellulose (CMC), a negatively charged water-soluble cellulose derivative, and also by incubation in a variety of neutral, water-soluble cellulose derivatives. In the presence of all of these substituted celluloses, normal fasciation of microfibril bundles to form the typical twisting ribbon is prevented. Alteration of ribbon assembly is most extensive in the presence of CMC, which often induces synthesis of separate, intertwining bundles of microfibrils. Freeze-etch preparations of the bacterial outer membrane suggest that particles that are thought to be associated with cellulose synthesis or extrusion may be specifically organized to mediate synthesis of microfibril bundles. These data support the previous hypothesis that the cellulose ribbon of A. xylinum is formed by a hierarchical, cell-directed, self-assembly process. The relationship of these results to the regulation of cellulose microfibril size and wall extensibility in plant cell walls is discussed.
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A combination of 500 mg each of sulbactam and ampicillin was administered intravenously into six healthy male volunteers, and subsequent serum and blister fluid levels were measured. Both dogs had similar serum half-lives of about 1 h. The concentrations of sulbactam in serum and blister fluid were about 1.5 times those of ampicillin, and appeared to be pharmacokinetically well matched when administered in equal doses.
The authors report on a five-year experience with process-oriented discussion groups at annual four-day, off-campus retreats attended by students, faculty members, and "significant others." Group sessions comprised 17 hours of each retreat, which also included community activities and recreation time. Group leaders represented a diversity of professional backgrounds. In response to questionnaires sent from one to two months after the retreats, participants rated group experiences highly, although they also considered a significant amount of time for unstructured interpersonal interaction and recreation important. Participants enjoyed meeting students and faculty members in a relatively "role-free" setting, and students derived an enhanced sense of self-awareness from group discussions. The most highly valued group leader behaviors were participation as a group member, facilitation of interpersonal communication, and attention to group members' needs. Guidance and direction by the leaders were also considered valuable, provided that they did not impose inappropriate expectations on their groups.
In order to obtain information on the possible functions of endogenous opiates in the primate cerebral cortex, we assessed the distribution of mu-like opiate receptors (which selectively bind 3H-labeled naloxone) and delta-like opiate receptors (which selectively bind 3H-labeled D-Ala2, D-Leu5-enkephalin) throughout the cerebral cortex of the rhesus monkey. Stereospecific [3H]naloxone binding sites increased in a gradient along hierarchically organized cortical systems that sequentially process modality-specific sensory information of a progressively more complex nature. Specific [3H]enkephalin binding sites, in contrast, were relatively evenly distributed throughout the cerebral cortex. These results, in combination with electrophysiological studies of monkeys and humans, suggest that mu-like opiate receptors may play a role in the affective filtering of sensory stimuli at the cortical level, that is, in emotion-induced selective attention.
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Cellulose from the Gram-negative bacterium Acetobacter xylinum has been used as a model substrate for visualizing the action of cellulase enzymes from the fungus Trichoderma reesei. High-resolution electron microscopy reveals that A. xylinum normally produces a ribbon of cellulose that is a composite of bundles of crystalline microfibrils. Visual patterns of the process of cellulose degradation have been established. Enzymes are initially observed bound to the cellulose ribbon. Within 10 min, the ribbon is split along its long axis into bundles of microfibrils which are subsequently thinned until they are completely dissolved within 30 min. Incubations with purified components of the cellulase enzyme system produced less dramatic changes in ribbon structure. Purified 1,4-beta-D-glucan cellobiohydrolase I (D) (EC 3.2.1.91) produced no visible change in cellulose structure. Purified endo-1,4-beta-D-glucanase IV (EC 3.2.1.4) produced some splaying of ribbons into microfibril bundles. In both cases, whole ribbons were present even after 60 min of incubation, visually confirming the synergistic mode of action of these enzymes.
Eight healthy male volunteers received 1 g of either ceftazidime or cefamandole as an intravenous infection. Serial blood samples were taken over the next 8 h. Urine samples were collected over 24 h. Levels of these antibiotics were measured in the fluid of blisters resulting from application of cantharides. The concentration of ceftazidime in serum at 0.25 h after intravenous injection was 83.3 micrograms/ml. The serum half-lives for the respective drugs were 1.8 and 0.8 h. The mean apparent volume of distribution of ceftazidime (13.6 liters) was greater than that of cefamandole (9.8 liters). Plasma clearance was 111 ml/min for ceftazidime and 216 ml/min for cefamandole. The maximum blister fluid concentration of ceftazidime was 45.9 micrograms/ml, and that of cefamandole was 22.1 micrograms/ml. The relative availability of each drug in blister fluid compared with serum was similar.
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3 experiments examined the notion that children's primacy and recency in the probe-type pictorial memory task are related to the spatial distinctiveness of the leftmost and rightmost items presented. The correspondence between spatial location and temporal position of pictorial items was varied systematically in each experiment. 3-year old children were observed in experiment 1; 8-year olds in experiment 2; and 2 age groups (5 years and 8 years) in experiment 3. Taken together, results of the 3 studies indicated strong primacy and recency for all age groups when temporal order was completely confounded with left-to-right spatial arrangement of the items. When spatial and temporal components were separated, so that each could be assessed independently of the other, the data showed: (a) consistent temporal recency, (b) weak or absent temporal primacy in all but 1 experiment (experiment 3), (c) little evidence of primacy and recency related solely to spatial location, and (d) no significant interactions of age with serial position (spatial location or temporal position). These data do not support the inference that spatial distinctiveness or anchoring alone is responsible for children's primacy and recency in the widely used probe-type pictorial memory task. Rather, they suggest that preschoolers and older children alike are able to code temporal order along with the corresponding pictorial and location information in this kind of task.
The fluorescent brightener, Calcofluor White ST, prevents the in vivo assembly of crystalline cellulose microfibrils and ribbons by Acetobacter xylinum. In the presence of more than 0.01 percent Calcofluor, Acetobacter continues to synthesize high-molecular-weight beta-1,4 glucans. X-ray crystallography shows that the altered product exhibits no detectable crystallinity in the wet state, but upon drying it changes into crystalline cellulose I. Calcofluor alters cellulose crystallization by hydrogen bonding with glucan chains. Synthesis of this altered product is reversible and can be monitored with fluorescence and electron microscopy. Use of Calcofluor has made it possible to separate the processes of polymerization and crystallization leading to the biogenesis of cellulose microfibrils, and has suggested that crystallization occurs by a cell-directed. self-assembly process in Acetobacter xylinum.