Pharmacy services on obstetrics and gynecology and neonatology units.
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Female↗
Biomedical subjects
M D Lee
Publications and source records attributed to M D Lee.
The growth factor-like effects of tumor necrosis factor-alpha. Stimulation of glucose transport activity and induction of glucose transporter and immediate early gene expression in 3T3-L1 preadipocytes.
In the present study, the ability of tumor necrosis factor-alpha (TNF) to stimulate hexose transport in quiescent 3T3-L1 fibroblasts has been examined. Activation of transport occurred in a dose- and time-dependent manner, with maximal stimulation (6-8-fold) observed 16 h after exposure to 2.5 nM TNF. Early activation of hexose transport by TNF (2-fold within 30 min) was associated with increased plasma membrane immunoreactive glucose transporters. Prolonged exposure to TNF (16 h) resulted in a 2-fold increase in glucose transporter content of both plasma and inner membrane compartments. The magnitude of increased glucose transport (6-8-fold) was greater than the increased content of plasma membrane glucose transporters (2-fold), suggesting that the TNF-treatment altered the intrinsic activity of the glucose transporters. Increased transcription of the glucose transporter (GLUT-1) gene, as well as several immediate-early genes (c-fos, c-jun, jun-B, and beta-actin) was observed within 15 min of exposure to TNF. Transcriptional activation of immediate-early genes was tightly coupled to subsequent accumulation of their respective mRNAs. However, increased GLUT-1 mRNA (8 h after TNF treatment) was due to an apparent 3-fold increase in the stability of this message and not to increased transcription. The time course of TNF-induced hexose transport occurred concomitant with a 6-fold increase in total RNA synthesis which preceded a 3-fold increase in protein synthesis. Moreover, TNF induced cell-cycle progression through S-phase, as measured by aphidicolin-sensitive thymidine uptake. Phorbol myristate acetate also stimulated hexose transport as well as expression of the GLUT-1 gene and several immediate-early genes in quiescent 3T3-L1 cells. TNF-induced immediate-early gene expression was intact in PMA-pretreated cells (with the exception of GLUT-1 and beta-actin genes where the response was muted), suggesting the involvement of multiple pathways in TNF signal transduction. Our results indicate that TNF initiates mitogenic events in quiescent 3T3-L1 fibroblasts reminiscent of serum-derived growth factors.
Adenosine Triphosphate↗
A quantitative, automated method for determining microbial resistance to complement.
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Analysis of Variance↗
Monokine regulation of glucose transporter mRNA in L6 myotubes.
Endotoxin-induced macrophage secretory proteins (monokines) have been shown to stimulate hexose uptake in L6 myotubes (1). In those studies a doubling of the Vmax for hexose uptake was observed which correlated with elevated numbers of glucose transporters (GT) in both plasma and microsomal membranes. To determine if these changes in transporter populations were due to increased GT mRNA, we performed Northern blot analysis using L6 cell RNA and a cDNA to the HepG2 glucose transporter. The L6 myotubes contained a single 2.8 kb species of GT mRNA that increased 2.5-fold after an 8h exposure to the monokine preparation. beta-Actin mRNA levels were unaltered by the treatment, indicating specificity of monokine action. Glucose transporter mRNA content appeared to reach a maximum 8 h after exposure to the monokine. Over the next 16 h the levels of this mRNA gradually decreased, approaching control levels. Data obtained from nuclear transcription run-on assays suggest that increased levels of CT mRNA are due to an increased rate of gene transcription. A second transporter, the insulin-sensitive glucose transporter, was also observed to be expressed in the L6 cells. Monokine treatment resulted in a 60% suppression of the mRNA coding for this protein.
Actins↗
In vivo transmural potential difference: an early monitor of rejection in small bowel transplantation.
To determine if serial measurements of transmural potential difference (TMPD) can serve as an early monitor of rejection in small bowel transplantation, three groups of rats were studied. The groups are defined as follows: (1) group 1, isolated loop (N = 5): 20 cm of distal jejunum was defunctionalized (Thiry-Vella loop); (2) group 2, isotransplant (N = 5): 20 cm of distal jejunum was isotransplanted between inbred Lewis rats, as a Thiry-Vella loop; the native bowel remained in continuity; (3) group 3, allotransplant (N = 8): allotransplantation as in group 2 but between outbred Sprague-Dawley rats. Using luminal and peritoneal electrodes, TMPD was measured serially every third day. Biopsies of the stoma were taken on the same days for histologic examination of rejection. Group 1 animals (isolated loop) did not show a significant decrease in TMPD from day 1 to day 20. Group 2 (isotransplant animals) had a significant decrease in TMPD as compared with group 1 on day 5 (P less than .01), but by day 8, TMPD returned to baseline. Biopsies in groups 1 and 2 showed no signs of rejection. Group 3 (allotransplant animals) showed a significant decrease in TMPD as compared with group 1 on day 5 (P less than .01). The severity of the histologic signs of rejection parallelled the TMPD decrease throughout the remainder of the study. Monitoring TMPD is a sensitive method of detecting early rejection in small intestine transplantation.
Animals↗
Calicheamicins, a novel family of antitumor antibiotics. 3. Isolation, purification and characterization of calicheamicins beta 1Br, gamma 1Br, alpha 2I, alpha 3I, beta 1I, gamma 1I and delta 1I.
Novel antitumor antibiotics, calicheamicins beta 1Br, gamma 1Br, alpha 2I, alpha 3I, beta 1I, gamma 1I and delta 1I were recovered from the fermentation broth of Micromonospora echinospora ssp. calichensis by solvent extraction, selective precipitation, normal phase, reversed phase and partition chromatography. The individual components were characterized by their UV, IR, 1H and 13C NMR spectral data.
Aminoglycosides↗
Effect of endotoxin-induced monokines on glucose metabolism in the muscle cell line L6.
Exposure of fully differentiated L6 myotubes to a crude monokine preparation from endotoxin-stimulated RAW 264.7 cells resulted in a rapid and substantial (70%) increase in fructose 2,6-bisphosphate concentration coincident with a depletion of cellular glycogen and an increased lactate production. During the time required for glycogen depletion (3 hr), stimulation of 3-O-methyl-D-glucose and 2-deoxy-D-glucose uptake was initiated and observed to reach a maximum enhancement of 200% 12-15 hr later. The monokine had no effect on the Km value for 2-deoxy-D-glucose uptake (1.1 mM), while Vmax was increased from 912 to 2400 pmol/min per mg of protein. The increase was cytochalasin B inhibitable and was dependent on protein synthesis. Photoaffinity labeling and equilibrium binding studies with [3H]cytochalasin B support the hypothesis that this increase in hexose transport was due to an increase in hexose transporters present in the plasma membrane. Purified recombinant interleukin-1 alpha had no effect on hexose transport, whereas purified recombinant cachetin/tumor necrosis factor did stimulate hexose uptake, with half-maximal stimulation occurring at 36 nM. Although cachetin accounts for most of the biological activity associated with the crude monokine preparations, it is not the only monokine capable of inducing glucose transport in L6 cells. Specific immunoabsorption of cachectin/tumor necrosis factor from the crude monokine preparation revealed a monokine that had a similar bioactivity at extremely low concentrations on L6 cells.
3-O-Methylglucose↗
New antitumor antibiotic, LL-D05139 beta. Fermentation, isolation, structure determination and biological activities.
The LL-D05139 complex, containing LL-D05139 beta and azaserine, was recovered from the fermentation filtrate of Glycomyces harbinensis (NRRL 15337). A chemically defined medium was developed which favored the production of LL-D05139 beta. Antibiotic LL-D05139 beta was isolated from the fermentation filtrate by adsorption on granular carbon and further purified by chromatography on microcrystalline cellulose. Acid hydrolysis of LL-D05139 beta gave one molar equivalent each of alanine and serine. Both amino acids were found to have the L-configuration by GC analysis on a chiral column and alanine was assigned to be the N-terminal amino acid by Edman degradation. This information coupled with IR, UV, 1H NMR, 13C NMR and MS spectral data allowed us to assign the structure of LL-D05139 beta as alanylazaserine. LL-D05139 beta demonstrated greater antibacterial and biochemical induction assay activities than azaserine. The two drugs showed similar antitumor activities.
Antibiotics, Antineoplastic↗
Cost savings with a new combination clindamycin-gentamicin admixture policy.
Clindamycin and gentamicin are frequently prescribed by obstetricians and gynecologists (OB-GYN) for various pelvic infections in women. These two antibiotics maintain chemical stability when admixed in a small-volume parenteral. The institution of an admixture policy that recommends combining these agents when both drugs are prescribed in OB-GYN patients would decrease the frequency of administration, improve patient convenience, reduce risk of administration errors and intravenous line contamination, and reduce costs of antibiotic therapy. The authors analyzed antibiotic use in OB-GYN patients over a 3-month period and found that the anticipated cost savings appeared sufficient to warrant an admixture policy change. Six months after initiating the new policy, the authors found an increase in the use of clindamycin and gentamicin, but a decrease in the overall cost for providing antibiotic therapy to OB-GYN patients. Savings for the second quarter were due to the pharmacy providing less expensive clindamycin-gentamicin therapy.
Clindamycin↗
Transplantation of the small bowel across MHC and non-MHC disparities in the rat.
Using congenic strains of rats, the effect on the rejection of small bowel transplants across isolated major histocompatibility complex (MHC) and nonMHC antigenic disparities was examined. The medial survival time of small bowel grafts across MHC differences in the LEW anti-LEW.1N and LEW.1N anti-LEW strain combinations was 14 and 12 days, respectively. The median survival time across the nonMHC antigenic difference in the BN anti-DA.1N strain combination was 20 days, which was significantly longer than the rejection time across the MHC differences (P less than 0.005). Both hemagglutinating and cytotoxic antibodies were produced in all three strain combinations, but the magnitude of the response varied considerably and did not correlate with the time of rejection. In the case of MHC differences, the antibody was directed against both class I and class II antigens, and with the nonMHC difference, the greatest response was directed against the major blood group antigen RT2.
Animals↗
Co-carcinogenic effects of several Korean foods on gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.
In study I, 48 ACI and Fisher inbred rats were given MNNG 100 micrograms/ml, with or without 1 per cent or 3 per cent red pepper diet; in study II, 164 Sprague-Dawley rats given MNNG 100 micrograms/ml, with or without 5 per cent or 10 per cent NaCl; in study III, 181 Wistar rats given MNNG 83 micrograms/ml with or without maejoo 10 gm per cent/diet; in study IV, 78 Wistar rats given MNNG 83 micrograms/ml with or without ginseng extract 150 micrograms/ml; in study V, 120 Wistar rats given MNNG 83 micrograms/ml with or without retinyl palmitate 150,000 IU/kg. Except for study II (28 weeks), all rats were fed the diets for 37 weeks and were examined at 38 weeks or 40 weeks. In study I, tumor incidence in rats fed a red pepper diet and MNNG solution were 57 per cent (ACI rats, 1 per cent red pepper) and 63 per cent (Fisher rats, 1 per cent or 3 per cent red pepper) which were higher than control group (44 per cent, 43 per cent); in study II, gastric cancer, 61.9 per cent (10 per cent NaCl-MNNG), 27.3 per cent (control); in study III, gastric cancer, 14.8 per cent (maejoo-MNNG), 24 per cent (control); in study IV, malignant tumor of gastroduodenum, 3.4 per cent (ginseng-MNNG), 32.1 per cent (control); in study V, forestomach papilloma, 10.7 per cent (retinoid-MNNG), 29.4 per cent (control), and cancer in duodenum and small intestine, 50.0 per cent (retinoid-MNNG), 17.6 per cent (control). Thus, gastric carcinogenesis was enhanced by red pepper and a high salt diet, was inhibited by a maejoo and ginseng diet and was not effected by vitamin A.
Animals↗
Early use of oral theophylline in hospitalized chronic obstructive pulmonary disease patients: cost-containment through medical education.
This study measured the impact of an education program conducted by a clinical pharmacist on early conversion from intravenous to oral theophylline in hospitalized chronic obstructive pulmonary disease patients. Two separate two-month audit periods were conducted on the pulmonary medicine service (PMS) of a teaching hospital. During the first audit period (pre-ed), no education was provided. Prior to each month of the second two-month audit period (post-ed), an education program and handout outlining the rationale for early conversion from intravenous to oral theophylline was presented to medicine residents rotating onto the PMS. The results of this preliminary study suggest that the education program was responsible for a statistically significant decrease in intravenous aminophylline therapy from three days (pre-ed) to one day (post-ed). As a result of the reduction in length of intravenous therapy, both drug costs and patient charges were reduced by a statistically significant amount.
Administration, Oral↗
New antitumor antibiotic, LL-C10037 alpha. Fermentation, isolation and structure determination.
A new antitumor antibiotic, LL-C10037 alpha was isolated from the fermentation filtrate of a Streptomyces by adsorption, partition and reverse phase column chromatography. Its chemical structure was determined by 1H NMR, 13C NMR, UV, IR and mass spectral data. LL-C10037 alpha is a gamma-aminoepoxysemiquinone and is related to the epoxyguinone class of antibiotics.
Antibiotics, Antineoplastic↗
Pulmonary aspergillosis complicating bronchogenic carcinoma--a report of 2 cases.
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Aged↗
Respiratory obstruction in glandular fever.
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Adolescent↗
The caloric test in the supine and prone positions.
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Adult↗
Microbial fermentation-derived inhibitors of efflux-pump-mediated drug resistance.
A library of 85000 microbial fermentation extracts was screened for inhibitors of multidrug resistance efflux pumps in Pseudomonas aeruginosa and Candida albicans. New compounds EA-371alpha and EA-371delta were isolated and demonstrated to be potent and specific inhibitors of the MexAB-OprM pump in P. aeruginosa. Two series of fungal metabolites, enniatins and beauvericins, were found to be ubiquitous and potent inhibitors of ABC transporters. Milbemycins were rediscovered as potent inhibitors of the CDRI pump in C. albicans, and demonstrated to potentiate effectively the antifungal activity of fluconazole and SCH-56592 against a wide variety of Candida clinical isolates.
ATP-Binding Cassette Transporters↗
Risk factors for antihypertensive medication refill failure by patients under Medicaid managed care.
Antihypertensive medication noncompliance is common and leads to substantial morbidity for patients and increased health care costs for managed-care organizations. A retrospective cohort study using pharmacy prescription profiles to estimate noncompliance was conducted to determine important risk factors for patient noncompliance with antihypertensive therapy for Medicaid enrollees participating in a managed-care plan. The pharmacy and claims data for 1395 patients with uncomplicated hypertension who were enrollees of Tennessee's Medicaid managed-care program were analyzed to determine the frequency of the enrollees' failure to obtain timely antihypertensive medication refills (hereafter referred to as refill failure) and to identify the predictors of refill failure. Overall, refill failure occurred in 33% of 7413 refill opportunities studied, whereas refill failure occurred in 32% of the cases in which medication was dosed once daily and in 35% of the cases in which medication was dosed more than once daily. For patients taking alpha-blockers, there was a significantly lower rate of refill failure (11.0%) than for patients taking angiotensin-converting enzyme inhibitors, direct vasodilators, and thiazide diuretics. Patients taking calcium channel blockers, had a significantly lower rate of refill failure (38.5%) than for patients taking thiazide diuretics (45.5%). Younger age, medication class, multiple-daily dosing regimen, and fewer provider visits were all found to be significant independent predictors of refill failure, whereas gender and regimen complexity were not significant predictors in this population. Health care systems planning pharmacy-based interventions to improve patient compliance with antihypertensive medication for patients in a Medicaid managed-care program can expect to encounter high levels of refill failure and may want to target enrollee subgroups by age, medication class, or dosing regimen for intensive intervention efforts.
Adult↗