Functional assessment of viability of epithelial cells. Comparison of viability and mediator release in healthy subjects and asthmatics.
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Asthma↗
Biomedical subjects
A Campbell
Publications and source records attributed to A Campbell.
Binding characteristics of Escherichia coli biotin repressor-operator complex.
The genes of the operon bioA.BFCD are transcribed divergently from a single regulatory region between the bioA and, bioB genes. Transcription in both directions is co-repressed by biotinyl-5'-adenylate and the biotin repressor. The multimeric state of the biotin repressor bound to DNA and how it affects transcription have not been fully characterized. Therefore, we isolated the BirA protein from a recombinant strain which overproduced the biotin repressor and studied the repressor-operator binding characteristics through restriction enzyme site protection experiments and the mobility shift assay. We also measured the stoichiometry of the biotin repressor-operator complex directly. The results of restriction enzyme site protection studies are consistent with the postulation that the biotin operator is approx. 40 bp long. Only one retarded DNA band appeared in the mobility shift experiments, suggesting that the repressor-operator binding could be a single step reaction. The repressor-operator binding stoichiometry determination revealed that two repressor monomers may occupy the wild type or half palindromic biotin operator sequences.
Base Sequence↗
Inhibition of dopamine synthesis in rat striatal minces: evidence of dopamine autoreceptor supersensitivity to S(+)- but not R(-)-N-n-propylnorapomorphine after pretreatment with fluphenazine.
This study provides in vitro evidence that rats pretreated with fluphenazine for 10 days, but not acutely, developed moderate but significant striatal autoreceptor supersensitivity as measured by the ability of S(+)-NPA, a selective DA autoreceptor agonist and very weak postsynaptic agonist, to inhibit tyrosine hydroxylase activity. In contrast, autoreceptor supersensitivity was not found with the nonselective auto- and postsynaptic receptor agonist R(-)-NPA. Presumably, this effect represents some modification of a presynaptic regulatory mechanism controlling DA synthesis which can occur despite a reportedly high striatal DA autoreceptor reserve in rat striatum [2, 7]. Such a mechanism, by tending to reduce synaptic availability of DA, may contribute to tolerance to the transient, early DA-synthesis stimulating actions of acutely administered neuroleptics [4], and help to counterbalance increases in postsynaptic DA receptor abundance and sensitivity associated with long-term neuroleptic treatment.
Animals↗
Hemonectin mediates adhesion of engrafted murine progenitors to a clonal bone marrow stromal cell line from Sl/Sld mice.
Mutant Sl/Sld mice exhibit decreased marrow hematopoiesis. The defect is known to reside in the marrow microenvironment of these animals, which is reproduced in vitro by primary marrow explants as well as by cloned marrow stromal cell lines. Bone marrow progenitor cells are incapable of adhering to primary Sl/Sld stromal cells or cloned stromal cell lines derived from them to form cobblestone-islands and proliferate. The role of hemonectin, a marrow-specific adhesion protein in the defective hematopoiesis of the Sl/Sld mice, was studied. Indirect immunoperoxidase staining of marrow in situ from Sl/Sld mice showed little specific staining while specific staining was seen in a pericellular distribution in marrow from +/+ mice. Hemonectin expression in several cloned stromal cell lines from Sl/Sld mice was compared by immunoblotting with that in cloned stromal cell lines from normal +/+ littermates. Cell line Sld3, which has the least hematopoiesis supportive capacity in vitro, showed no detectable hemonectin by immunoblotting, while Sld1 and Sld2 showed detectable but greatly reduced amounts compared with normal +/+ 2.4, GBI/6, and D2XRII. Confluent cultures incubated with purified hemonectin and engrafted with enriched progenitors showed a significant increase in the cumulative number of cobbleston-islands and day 14 spleen colony-forming units (CFU-s) forming progenitors (39.15 +/- 3.6/dish; 16.3 +/- 3.1/dish, respectively), compared with untreated Sld3 cultures (cobblestone-islands 8.1 +/- 3.6/dish; CFU-s forming progenitors 8.8 +/- 0.05/dish). Hemonectin-mediated progenitor cell binding to the Sld3 stromal cells was specifically inhibited by antihemonectin but not by preimmune serum. These data support the role of hemonectin in early progenitor-stromal cell interactions.
Animals↗
Selective antidopaminergic effects of S(+)N-n-propylnoraporphines in limbic versus extrapyramidal sites in rat brain: comparisons with typical and atypical antipsychotic agents.
Dopamine (DA), injected unilaterally into rat forebrain after pretreatment with a monoamine oxidase inhibitor, equipotently induced locomotor arousal when placed in the nucleus accumbens septi (a limbic site) and contralateral deviation of the head when placed in the corpus striatum (an extrapyramidal target); testing was done with an ED50 dose of DA (16 micrograms). Systemic injections (IP) of the representative typical neuroleptic haloperidol showed high potency and minor striatal selectivity against the behavioral effects of intracerebral DA [accumbens ID50 = 0.090, striatum = 0.027 mg/kg (0.24 and 0.072 mumol/kg); ID50 ratio = 3.3, favoring striatum]. The atypical antipsychotic agent clozapine was less potent against DA in both brain regions but, paradoxically, showed ever greater striatal selectivity [ID50 = 12 and 1.4 mg/kg (37 and 4.2 mumol/kg); ratio = 8.8, favoring striatum], while its analog, the piperazinyl-dibenzothiazepine ICI-204,636 showed intermediate potency and the lowest striatal selectivity of these three neuroleptic agents [ID50 = 1.8 and 0.88 mg/kg (4.1 and 2.0 mumol/kg); ratio = 2.1]. In striking contrast, the S(+) isomers of N-n-propylnorapomorphine, its orally active 10,11-methylenedioxy prodrug derivative, and its 11-monohydroxy analog all induced potent antagonism of limbic DA but had little effect on extrapyramidal injections of DA except at high systemic doses [ID50, accumbens = 0.18-0.52, striatal = 10-15 mg/kg (0.50-1.6 and 29-42 mumol/kg); regional ID50 ratios = 18-69, favoring accumbens]. The S(+)aporphines showed limbic potency similar to that of haloperidol and 25-73 times greater than that of clozapine.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Creating a sense of mission.
Mission is still a relatively neglected area of management, and there is no clear agreement on what it encompasses. The Ashridge Strategic Management Centre conducted a 2-year research project designed to fill this gap. The research found that if mission is more clearly defined it can be managed better, and developed a model of mission that includes four elements--purpose, strategy, behaviour standards and values. The project identified companies where, in addition to strong links between these elements, employees also showed an emotional commitment to their company which Campbell has called a 'sense of mission'. This commitment was deepest when there was a match between the employee's values and the company's values.
Data Collection↗
Brief case: mission, vision and strategic intent.
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Decision Making, Organizational↗
R(-)2-fluoro-N-n-propylnorapomorphine: a very potent and D2-selective dopamine agonist.
A series of 2-substituted N-n-propylnorapomorphine (NPA) derivatives were synthesized and compared with other DA agonists for affinity to D1 and D2 dopamine (DA) receptors in rat brain corpus striatum tissue. The 2-substituents tested reduced D1 affinity similarly, but enhanced D2 affinity in the rank order: F greater than OH greater than Br greater than OCH3 greater than H greater than or equal to NH2. The extraordinarily high D2 affinity (Ki = 12 pM) and D2 vs. D1 selectivity (57,500) of 2-F-NPA far-exceeded that of all other DA agonists tested, and it was about 10-times more potent than NPA in vivo.
Animals↗
Innovation vs. quality control: an 'unpublishable' clinical trial of supplemental ascorbate in incurable cancer.
A computerized data bank was created recording the details of all cancer patients attending three district general hospitals in West Central Scotland over a 4.5 year period 1978-1982. At the conclusion of the trial, the records of 2804 individual patients were available for study, of whom 1826 had reached an incurable stage. 294 of these incurable cancer patients had received supplemental ascorbate at some stage in their illness, whereas 1532 had not, and served as controls. Analysis showed that the ascorbate-supplemented patients had a median overall survival time (343 days) almost double that of the controls (180 days). Our difficulties in having this simple, but important, observation published are briefly recounted in the introduction.
Ascorbic Acid↗
Obstructive congenital epulis in a newborn.
A neonate, with a rare, large, congenital epulis of the anterior maxilla, which resulted in oral feeding obstruction, is presented. Due to its easy accessibility, narrow pedicle to the alveolus, and benign clinical behavior, permanent eradication of the tumor by simple excision under local anesthesia was performed.
Female↗
OR-PACU reports. What they should tell you about your postoperative patient.
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Communication↗
High-grade T-cell lymphoma following treatment with cyclosporin A.
A 47-year-old man with persistent severe oropharyngeal ulceration developed a high-grade T-cell lymphoma soon after commencing treatment with cyclosporin A. Using Southern blotting to identify T-cell beta-chain gene rearrangements, evidence of clonal restriction was found both in blood and lymph node DNA samples. Two BamH1 rearranged bands were demonstrated in both samples. In the blood a 16 Kb band predominated, with a weaker 28 kb band. In the lymph node sample this pattern was reversed. The findings suggest that a bi-clonal population of T-lymphocytes or clonal evolution of an existing T-cell monoclone had developed, and that cyclosporin contributed to the emergence of a high-grade T-cell lymphoma.
Antigens, CD↗
Granulomatous prostatitis: a clinicopathological study.
In a clinicopathological study of granulomatous prostatitis, we have found two distinct histological patterns. Approximately one third of cases consisted of localized, often elongated or stellate lesions, resembling rheumatoid nodules. Where clinical details were available, most of these cases had a history of previous transurethral resection. The remaining cases showed more diffuse involvement of the prostate, with lesions centred on ducts and glands, and were not associated with previous prostatic surgery or systemic illness. Immunohistochemical studies of the associated inflammatory infiltrate showed an apparently random distribution of T- and B-lymphocytes in the former group, while in the latter group there was a concentration of T-cells in and around damaged ducts and glands, suggesting a possible immune-mediated destruction of these structures.
Adult↗
Reticulum cell sarcoma: two complete 'spontaneous' regressions, in response to high-dose ascorbic acid therapy. A report on subsequent progress.
In 1975, we reported the remarkable case of a 42-year-old man with histologically proven widely disseminated reticulum cell sarcoma who, in a remarkably short time, appeared to enjoy not one, but two, complete spontaneous regressions of his fatal illness. Both these regressions coincided exactly in time with intravenous high-dose ascorbate administration, and it seemed reasonable to conclude that this unconventional therapy must have been responsible for his excellent responses. For those interested in spontaneous regressions of cancer and the possible mechanisms, we now report his subsequent progress some 17 years later.
Adenocarcinoma↗
Sustained supraventricular tachyarrhythmias following coronary artery bypass surgery comparing mammary versus saphenous vein grafts.
This retrospective study was designed to determine the incidence of sustained supraventricular tachyarrhythmias (SVTs) in patients undergoing coronary artery bypass grafting (CABG) with internal mammary artery (IMA) grafts, Group A, compared with those with saphenous vein grafts (SVG), Group B. Among 569 consecutive patients who underwent CABG surgery in the same institution, a total of 80 cases from Group A and 80 cases from Group B were selected for this study after application of exclusion criteria. Excluded from this study were the following: patients with preexisting or prior history of SVTs, significant left ventricular dysfunction (ejection fraction less than 40%), postoperative myocardial infarction, drug toxicity or electrolyte imbalance, and advanced chronic obstructive lung disease. Group A consisted of 63 men and 17 women and Group B consisted of 52 men and 28 women. All patients were monitored either in ICU or by telemetry for a period of three to six days after surgery and all had a predischarge 12-lead electrocardiogram. Both groups were fairly comparable in most of their clinical profile and number of grafts. The incidence of SVTs in Group A was 31% (25 of 80 patients) and in Group B was 24% (19 of 80 patients). Furthermore, the incidence of postoperative pericarditis was noted in 35% (28 of 80 patients) of Group A and in 19% (15 of 80 patients) in Group B. The authors conclude that male tobacco smokers of Group A tended to have a significantly higher incidence of postoperative pericarditis with a higher trend for postoperative SVTs than patients from Group B.
Aged↗
Effects of the isomers of N-n-propylnorapomorphine and haloperidol on regional concentrations of neurotensin in rat brain.
Rats were treated for 10 days with haloperidol (0.2 or 3 mg/kg/day intraperitoneally [IP]), with either S(+) or R(-) N-n-propylnorapomorphine (NPA; 3 mg/kg IP three times daily) or saline as a placebo control. Brain was microdissected into 11 regions for radioimmunoassay of neurotensin (NT)-like activity under coded ("blind") conditions. Concentrations of NT in rat brain regions ranked central amygdaloid nucleus greater than ventral bed nucleus greater than ventral tegmentum greater than dorsal bed nucleus greater than arcuate nucleus greater than substantia nigra greater than nucleus accumbens septi (accumbens) greater than piriform cortex greater than nucleus caudatus (caudate) greater than mesoprefrontal cortex greater than cingulate cortex, similar to previous observations. Since untreated and placebo-injected control results were indistinguishable, a stress artifact is unlikely to account for the findings. Haloperidol at the lower dose produced no significant changes but, at the higher dose, yielded relatively large (42%-143%) increases of NT concentrations in accumbens, caudate, and substantia nigra. S(+)NPA, which has some properties as a limbic-selective dopamine antagonist, yielded smaller (55%-66%) but significant average increases of NT in accumbens and piriform cortex, and lesser trends toward increases (40%-51%) in caudate, nigra, and mesoprefrontal cortex--all persisting for 5 days after treatment, whereas the R(-) enantiomer, a potent dopaminergic agonist, increased NT only in nigra (by 112%). These observations confirm previous results with haloperidol and add to the impression that S(+)-NPA shares some properties of atypical antipsychotic agents.
Animals↗
Recombination and modular exchange in the genesis of new lambdoid phages.
Comparison of the nucleotide sequence of the integrase genes of lambdoid phages 21 and 434 with the published sequences of phages HK022 and lambda shows that lambda and 434 are very closely related (98% base sequence identity), whereas HK022 and 21 respectively show 73% and 48% identity to lambda. It is likely that several homologous recombination events occurred in the int gene and flanking DNA among the progenitors of these phages. Sequence divergence to different alternative sequences at a common site (tL4) suggests that tL4 has been repeatedly used as a recombination site, despite the very limited homology it provides. A minor constitutive transcript that terminates at tL4 of lambda has been identified. We propose that the principal selective force acting to conserve tL4 is for terminator function, but that the use of tL4 as a recombination site has allowed the formation of selectively favored recombinants. By extension, we suggest that conservation of microhomologies at functional sites serves to keep lambdoid phages within a common gene pool despite extensive drift and divergence.
Bacteriophage lambda↗
Strategies for improving dialysis decision making.
It is important that every professional involved with guiding ESRD patients through the maze of dialysis decision making critically analyze his or her own behaviors, possible biases and thought processes influencing discussions with patients. Health care professionals need to continue to strive to improve their skills for assuring optimal assistance to their patients in making decisions about the best types of treatments for them. In this era of evermore challenging patients and technologies, the skills for informing patients and assisting them with effective decision making about issues such as medical management, dialysis, transplantation or treatment termination are vital for assuring quality care.
Counseling↗