Watching aspiration after radiation therapy.
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Deglutition↗
Biomedical subjects
L Davis
Publications and source records attributed to L Davis.
Students' attitudes toward the confidentiality of computerized patient records.
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Attitude of Health Personnel↗
Effect of Withania somnifera on cytokine production in normal and cyclophosphamide treated mice.
Administration of an extract from the powdered root of the plant Withania somnifera (Family: Solanaceae) enhanced the levels of Interferon gamma (IFN-gamma) (75.87 pg/ml), Interleukin-2 (IL-2) (14.16 pg/ml) and Granulocyte macrophage colony stimulating factor (GM-CSF) (49.22 pg/ml) in normal Balb/c mice. The lowered levels of IFN gamma--(30 pg/ml), IL-2 (4.5 pg/ml) and GM-CSF (19.12 pg/ml) after treatment with cyclophosphamide (CTX) was reversed by the administration of Withania somnifera extract (IFN gamma--74 pg/ml; IL-2 7.5 pg/ml; GM-CSF 35.47 pg/ml). Withania extract lowered the levels of Tumour necrosis factor alpha (TNF alpha) production. Administration of bonemarrow cells from donor mice treated with Withania extract increased the spleen nodular colonies in irradiated mice (8.33) compared to those treated with normal bonemarrow cells (3.03). The number of nodular colonies increased significantly when these animals were continued with Withania extract treatment. These results indicate the immunopotentiating and myeloprotective effect of Withania somnifera as seen from the enhancement of cytokine production and stem cell proliferation and its differentiation.
Animals↗
Endothelin B receptor modulates inflammatory pain and cutaneous inflammation.
The role of endothelin B (ET(B)) receptors in inflammation and nociception was examined using ET(B) receptor knockout mice. Genotyping studies were used with tissues from ET(B)((+/+)), ET(B)((+/-)), and ET(B)((-/-)) mice to confirm the loss of ET(B) receptors. Algesia induced by phenylbenzoquinone was evident in the (+/+) mice, reduced by approximately 80% in the (+/-) mice, and absent in the (-/-) mice. Phenylbenzoquinone-induced algesia in (+/+) mice was inhibited 74% by the ET(B) receptor-selective antagonist A192621 (25 mg/kg p.o.), but unaffected by the ET(A) receptor-selective antagonist SB 234551 (25 mg/kg p.o.). Noninflammatory pain, induced by hotplate, was equivalent between (+/+) and (-/-) mice. The cutaneous inflammatory response to topical arachidonic acid (AA) also was evaluated. Whereas (+/+) mice had a marked inflammatory response to AA, the (+/-), and (-/-) mice had significantly reduced fluid phase responses (37 and 65% inhibition, respectively). Neutrophil infiltration also was reduced in the (+/-) and (-/-) mice (51 and 65% reduction, respectively). Topical administration of A192621 (500 microg/ear) in (+/+) mice inhibited AA-induced swelling (39%), whereas SB 234551 (500 microg/ear) was without effect. Collectively, these results implicate the ET(B) receptor in mediation of inflammatory pain and cutaneous inflammatory responses in mice.
Animals↗
Prostaglandin E2 inhibits renal collecting duct Na+ absorption by activating the EP1 receptor.
PGE2 exerts potent diuretic and natriuretic effects on the kidney. This action is mediated in part by direct inhibition of collecting duct Na+ absorption via a Ca++-coupled mechanism. These studies examine the role the Ca++-coupled PGE-E EP1 receptor plays in mediating these effects of PGE2 on Na+ transport. Rabbit EP1 receptor cDNA was amplified from rabbit kidney RNA. Nuclease protection assays demonstrated highest expression of EP1 mRNA in kidney, followed by stomach, adrenal, and ileum. In situ hybridization, demonstrated renal expression of EP1 mRNA was exclusively over the collecting duct. In fura-2-loaded microperfused rabbit cortical collecting duct, EP1 active PGE analogs were 10-1, 000-fold more potent in raising intracellular Ca++ than EP2, EP3, or EP4-selective compounds. Two different EP1 antagonists, AH6809 and SC19220, completely blocked the PGE2-stimulated intracellular calcium increase. AH6809 also completely blocked the inhibitory effect of PGE2 on Na+ absorption in microperfused rabbit cortical collecting ducts. These studies suggest that EP1 receptor activation mediates PGE2-dependent inhibition of Na+ absorption in the collecting duct, thereby contributing to its natriuretic effects.
Absorption↗
Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia-inducible factor 1.
OBJECTIVE: Our purpose was to determine whether the increase in fetal cardiac mass and cardiac output in chronic anemia is accompanied by changes in capillary density or size or changes in levels of vascular endothelial growth factor and hypoxia-inducible factor 1, a basic helix-loop-helix transcription factor that has previously been shown to activate vascular endothelial growth factor gene transcription when cultured cells are subjected to hypoxia. STUDY DESIGN: Anemia was induced in near-term ovine fetuses by daily isovolemic hemorrhage. In five fetuses the heart was arrested in diastole, isolated, and fixed at physiologic pressures with adenosine-paraformaldehyde, and morphometric measurements of capillaries were made. In six fetuses cardiac expression of vascular endothelial growth factor and hypoxia-inducible factor 1 protein was detected by Western analysis and vascular endothelial growth factor messenger ribonucleic acid by Northern blot analysis. Eleven age-matched fetuses served as controls. RESULTS: The anemic fetuses compared with controls had a lower hematocrit (14.8% +/- 0.7% vs 35.3% +/- 1.5%) and a greater heart-to-body weight ratio (10.5 +/- 1.1 vs 7.7 +/- 0.5 gm/kg). The minimal capillary diameter was increased and the intercapillary distance was decreased in both right and left ventricles of anemic fetuses compared with controls. Vascular endothelial growth factor protein was increased 4.5-fold, vascular endothelial growth factor messenger ribonucleic acid 3.2-fold, and hypoxia-inducible factor 1alpha protein 3.8-fold in ventricular tissue from anemic fetuses. CONCLUSIONS: In chronic fetal anemia cardiac hypertrophy is accompanied by anatomic changes in myocardial capillary morphometry along with induction of hypoxia-inducible factor 1 and vascular endothelial growth factor. These results provide evidence for a pathway by which anemia-hypoxia may stimulate myocardial vascularization.
Anemia↗
Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice.
Administration of Withania somnifera extract (Solanaceae) was found to significantly reduce leucopenia induced by cyclophosphamide (CTX) treatment. The total WBC count on the 12th day of the CTX-treated group was 3720 cells/mm3 and that of CTX along with Withania was 6120 cells/mm3. Treatment of Withania along with CTX was found to significantly (P < 0.001) increase the bone marrow cellularity (13.1 x 10(6) cells/femur) compared to CTX alone treated group (8 x 10(6) cells/femur). Administration of Withania extract increased the number of alpha-esterase positive cells (1130/4000 cells) in the bone marrow of CTX treated animals, compared to the CTX-alone treated group (687/4000 cells). The major activity of Withania somnifera may be the stimulation of stem cell proliferation. These studies indicate that Withania somnifera could reduce the cyclophosphamide induced toxicity and its usefulness in cancer therapy.
Animals↗
Yeast meiotic mutants proficient for the induction of ectopic recombination.
A screen was designed to identify Saccharomyces cerevisiae mutants that were defective in meiosis yet proficient for meiotic ectopic recombination in the return-to-growth protocol. Seven mutants alleles were isolated; two are important for chromosome synapsis (RED1, MEK1) and five function independently of recombination (SPO14, GSG1, SPOT8/MUM2, 3, 4). Similar to the spoT8-1 mutant, mum2 deletion strains do not undergo premeiotic DNA synthesis, arrest prior to the first meiotic division and fail to sporulate. Surprisingly, although DNA replication does not occur, mum2 mutants are induced for high levels of ectopic recombination. gsg1 diploids are reduced in their ability to complete premeiotic DNA synthesis and the meiotic divisions, and a small percentage of cells produce spores. mum3 mutants sporulate poorly and the spores produced are inviable. Finally, mum4-1 mutants produce inviable spores. The meiotic/sporulation defects of gsg1, mum2, and mum3 are not relieved by spo11 or spo13 mutations, indicating that the mutant defects are not dependent on the initiation of recombination or completion of both meiotic divisions. In contrast, the spore inviability of the mum4-1 mutant is rescued by the spo13 mutation. The mum4-1 spo13 mutant undergoes a single, predominantly equational division, suggesting that MUM4 functions at or prior to the first meiotic division. Although recombination is variably affected in the gsg1 and mum mutants, we hypothesize that these mutants define genes important for aspects of meiosis not directly related to recombination.
Alleles↗
Yeast dom34 mutants are defective in multiple developmental pathways and exhibit decreased levels of polyribosomes.
The DOM34 gene of Saccharomyces cerevisiae is similar to genes found in diverse eukaryotes and archaebacteria. Analysis of dom34 strains shows that progression through the G1 phase of the cell cycle is delayed, mutant cells enter meiosis aberrantly, and their ability to form pseudohyphae is significantly diminisehd. RPS30A, which encodes ribosomal protein S30, was identified in a screen for high-copy suppressors of the dom34delta growth defect. dom34delta mutants display an altered polyribosome profile that is rescued by expression of RPS30A. Taken together, these data indicate that Dom34p functions in protein translation to promote G1 progression and differentiation. A Drosophila homolog of Dom34p, pelota, is required for the proper coordination of meiosis and spermatogenesis. Heterologous expression of pelota in dom34delata mutants restores wild-type growth and differentiation, suggesting conservation of function between the eukaryotic members of the gene family.
Amino Acid Sequence↗
Nicotine patch and self-help video for cigarette smoking cessation.
A total of 424 smokers were randomized in a 2 x 2 factorial experiment. A pharmacologic factor contained 2 levels: transdermal nicotine path (TNP; 21 mg) and placebo. A self-help behavioral treatment factor contained 2 levels: video-enhanced self-help treatment manual and self-help treatment manual only. At 2 months, TNP produced a higher level of abstinence (36%) than placebo (20%), p < .001. No other comparison was significant. In secondary analyses, (at 2 months) and compliance with patch treatment regimen (at 2, 6, and 12 months) were associated with less relapse. Although nicotine replacement therapy has improved our ability to produce smoking cessation, the production of sustained, longer term abstinence remains an elusive goal.
Administration, Cutaneous↗
Blood transfusion during heparin-free hemodialysis.
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Adult↗
Vertebral osteomyelitis due to Pseudallescheria boydii.
A case of primary vertebral osteomyelitis due to an opportunistic fungus, Pseudallescheria boydii, in a child with acute myeloid leukemia, is reported. To our knowledge this is the first such case in a child, and only the second reported case in the international literature of primary spinal osteomyelitis due to this organism. We discuss the problems presented by this case both in terms of diagnosis and management. We also discuss the role of surgery and systemic antifungal chemotherapy in the treatment of deep infections due to Pseudallescheria boydii.
Child, Preschool↗
Micronuclei containing whole chromosomes harbouring the selectable gene do not lead to mutagenesis.
Loss of heterozygosity is one genetic change observed in many tumours. We do not know whether the loss of chromosomal material through micronucleus formation is a viable mechanism associated with, and possibly leading to, genetic disease. Previously, we treated L5178Y mouse lymphoma cells with four aneugens. Although these aneugens induced micronuclei containing predominantly whole chromosomes, they did not induce mutations at Tk1, the selectable gene, under the same non-toxic conditions in which they induced micronuclei. This suggested that the induction of micronuclei containing whole chromosomes was not an early event leading to phenotypically expressed mutations in these cells under the conditions used. However, it is possible that chromosome 11, on which Tk1 resides, may be under-represented in the micronucleus population. To find out the frequency of induction of micronuclei containing chromosome 11, we applied fluorescence in situ hybridization using a chromosome 11 paint to micronuclei induced by colcemid and vinblastine. We found that the numbers of micronuclei containing chromosome 11 are more than sufficient to be detectable as mutations if these micronuclei lead to viable mutants. We conclude that the formation of micronuclei containing whole chromosomes does not lead to viable, dividing mutants in this system.
Animals↗
Changing structure to improve function: one academic health center's experience.
Academic health centers (AHCs) have been under siege for the past few years, with decreased federal and state funding for educational and research programs and increasing competition in the health care marketplace. In addition, many AHCs are burdened with the bureaucratic red tape of large educational institutions, which makes agility in responding to a demanding health care market difficult. The authors describe the response to these threats by Oregon Health Sciences University (OHSU), an approach that has been different from those of most similar institutions. OHSU chose to change its structure from being part of the state system of higher education to being an independent public corporation. The authors outline the political process of building widespread support for the legislation passed in 1995, the key features of the restructuring, the challenges faced before and after the transition to a public corporation, and lessons learned in this metamorphosis to a new form.
Academic Medical Centers↗
Cholinesterase. Its significance in anaesthetic practice.
Plasma cholinesterase is an enzyme which has importance to the anaesthetist primarily for its role in the metabolism of suxamethonium, although other anaesthetic related drugs that this enzyme metabolises are also increasingly important. In this article we review current thoughts on the function, profile and chemistry of plasma cholinesterase. Causes of variations in the activity of the enzyme are described and the basis of genetic variations is explained.
Anesthesia↗
Cloning, expression, and regulation of rabbit cyclooxygenase-2 in renal medullary interstitial cells.
Prostaglandin synthesis requires cyclooxygenase-1 (COX1) or -2 (COX2), which mediate the conversion of arachidonate to prostaglandin H2. COX1 is the predominant constitutive isoform, whereas COX2 expression is typically low. In the present studies we cloned rabbit COX2 and determined its distribution in unstimulated tissues. Screening rabbit eye and uterine libraries yielded two cDNAs containing identical inserts with a 1,812-nucleotide open-reading frame. This encoded a 604-amino acid polypeptide, 90% identical to human, rat, and mouse COX2. Expression of the rabbit COX2 in HEK-293 cells enhanced prostanoid synthesis. Constitutive COX2 mRNA expression was highest in kidney and urinary bladder. COX2 expression was primarily in renal outer medullary interstitial cells with cortical expression in macula densa. In cultured medullary interstitial cells, COX2 mRNA predominated, with little COX1 expression. Interstitial cell COX2 mRNA but not COX1 was induced by phorbol ester and epidermal growth factor but suppressed by dexamethasone. Phorbol ester also upregulated immunoreactive COX2. Constitutive COX2 in these tissues has important implications for side effects of COX2-selective inhibitors.
Amino Acid Sequence↗
Expression of peroxisome proliferator-activated receptors in urinary tract of rabbits and humans.
Peroxisome proliferator-activated receptors (PPARs, alpha, beta/delta, and gamma) are members of the nuclear receptor superfamily of ligand-activated transcription factors. PPARs regulate the expression of genes involved in lipid metabolism. 8(S)-hydroxyeicosatetraenoic acid (8-S-HETE), leukotriene B4 (LTB4), and hypolipidemic fibrates activate PPAR alpha, whereas PPAR gamma is activated by prostaglandin metabolites. The present studies examined the intrarenal and tissue distribution of rabbit and human PPAR alpha, -beta/delta, and -gamma mRNAs. Nuclease protection showed PPAR alpha predominated in liver, heart, and kidney, whereas PPAR gamma, a putative adipose-specific transcription factor, was in white adipose tissue, bladder, and ileum, followed by kidney and spleen. Lower expression levels of PPAR beta/delta were observed in several tissues. In situ hybridization of kidney showed PPAR alpha mRNA predominated in proximal tubules and medullary thick ascending limbs of both rabbit and human. PPAR gamma was exclusively expressed in medullary collecting duct and papillary urothelium. Immunoblot confirmed the expression of PPAR gamma protein in freshly isolated inner medullary collecting ducts. mRNAs for all the PPARs were expressed in the ureter and bladder in both rabbit and human, but PPAR gamma expression was greatest. This distinct distribution of PPAR isoforms has important implications for lipid-activated gene transcription in urinary epithelia.
Animals↗
Protein extract as a surrogate mother.
Brief dynamic psychotherapy, carried out by an resident in training, can bring significant improvement to a patient who does not necessarily meet ideal selection criteria. S. had experienced early childhood deprivation resulting in adult psychosomatic manifestations of feeling hypoglycemic under pressure of responsibility or during fear of abandonment. He soothed himself with the aid of a bottle of "protein extract," which he carried at all times on his belt. The 21-week therapy resulted in his increased ability to differentiate the sources of his anxiety and allowed him to find new and more mature ways of coping with stress. Although still confronting internal conflicts and anxiety, he relinquished the protein-extract bottle and began to take a more active role in work and relationships. With the help of brief dynamic psychotherapy, this patient was able to start moving forward in his personal growth. Finally, although requiring ongoing supervision and training, resident therapists should be encouraged to treat difficult patients with brief dynamic psychotherapy despite their limited experience with such a promising therapeutic technique.
Adaptation, Psychological↗