A drug interaction between fusidic acid and a combination of ritonavir and saquinavir.
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Adult↗
Biomedical subjects
B Foster
Publications and source records attributed to B Foster.
Fermentations of pectin-rich biomass with recombinant bacteria to produce fuel ethanol.
Pectin-rich residues from sugar beet processing contain significant carbohydrates and insignificant amounts of lignin. Beet pulp was evaluated for conversion to ethanol using recombinant bacteria as biocatalysts. Hydrolysis of pectin-rich residues followed by ethanolic fermentations by yeasts has not been productive because galacturonic acid and arabinose are not fermentable to ethanol by these organisms. The three recombinant bacteria evaluated in this study, Escherichia coli strain KO11, Klebsiella oxytoca strain P2, and Erwinia chrysanthemi EC 16 pLOI 555, ferment carbohydrates in beet pulp with varying efficiencies. E. coli KO11 is able to convert pure galacturonic acid to ethanol with minimal acetate production. Using an enzyme loading of 10.5 filter paper units of cellulase, 120.4 polygalacturonase units of pectinase, and 6.4 g of cellobiase (per gram of dry wt sugar beet pulp), with substrate addition after 24 h of fermentation, 40 g of ethanol/L was produced. Other recombinants exhibited lower ethanol yields with increases in acetate and succinate production.
Alcohol Dehydrogenase↗
Healthy people 2010: diabetes.
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Diabetes Mellitus↗
Status report. Canadian coalition on cancer surveillance.
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Canada↗
Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13).
Human mast cells are known to arise from a CD34(+)/c-kit(+) progenitor cell population that also gives rise to neutrophils, eosinophils, basophils, and monocytes. To further characterize cells within the CD34(+)/c-kit(+) population that yield mast cells, this progenitor was additionally sorted for CD13, a myeloid marker known to appear early on rodent mast cells and cultured human mast cells, but not expressed or expressed at low levels on human tissue mast cells; and cultured in recombinant human (rh) stem cell factor (rhSCF), rh interleukin-3 (rhIL-3; first week only), and rhIL-6. Initial sorts revealed that although the majority of cells in culture arose from the CD34(+)/c-kit(+)/CD13(-) cell population, mast cells arose from a CD34(+)/c-kit(+)/CD13(+) progenitor cell that also gave rise to a population of monocytes. Sequential sorting confirmed that CD34(+)/c-kit(+)/CD13(+) cells in CD34(+)/c-kit(+)/CD13(-) sorts gave rise to the few mast cells observed in CD13(-) sorted cells. CD34(+)/c-kit(+)/CD13(+) cells plated as single cells in the presence of various cytokine combinations gave rise to pure mast cell, monocyte, or mixed mast cell/monocyte progeny. Addition of either rh granulocyte-macrophage colony-stimulating factor (rhGM-CSF) or rhIL-5 to the CD34(+)/c-kit(+)/CD13(+) progenitor cell population cultured in rhSCF, rhIL-3, and rhIL-6 did increase the number of total cells cultured and in the case of rhIL-5, did increase total mast cell numbers. Neither rhGM-CSF or rhIL-5 led to additional cell populations, ie, even with the addition of rhGM-CSF or rhIL-5, only mast cells and monocytes grew from CD34(+)/c-kit(+)/CD13(+) cells. Thus, human mast cells and a population of monocytes arise from precursor cells that express CD34, c-kit, and CD13; and within which, are mast cell, monocyte, and mast/monocyte (bipotential) precursors.
Antigens, CD↗
Myasthenia gravis activities of daily living profile.
The authors have developed an MG activities of daily living (ADL) profile (MG-ADL)-a simple eight-question survey of MG symptoms. In 254 consecutive encounters with established MG patients, the authors compared scores from the MG-ADL to the quantitative MG score (QMG)-a standardized, reliable scale used in clinical trials. The mean MG-ADL score was 4.89+/-3.63. The mean QMG score was 10.80+/-5.70. Pearson's correlation coefficient was 0.583 (p < 0.001). The MG-ADL is an easy-to-administer survey of MG that correlates well with the QMG and can serve as a secondary efficacy measurement in clinical trials.
Activities of Daily Living↗
Urethral dilation in women: a questionnaire-based analysis of practice patterns.
OBJECTIVES: To assess current practice patterns among urologists and to determine the perceived efficacy of urethral dilation. Urethral dilation has been advocated as a treatment for a variety of urologic disorders in women for several decades. Recent changes in Medicare reimbursement have again focused attention on this issue. METHODS: A 15-item questionnaire was mailed to all urologists actively practicing in the state of Texas (n = 642). The questionnaire consisted of 12 items about indications for, technique of, and outcome of urethral dilation, and three demographic questions regarding location and type of practice and number of years since completing residency. RESULTS: A total of 194 physicians completed and returned the questionnaire (30%). Overall, 48.2% of practitioners used dilation six or fewer times during the past year; 23.7% reported having used it more than 30 times. Most urologists used dilation for urethral syndrome only (61.1%), although urethral stricture was also a frequently reported condition requiring dilation (29%). Most urologists trained within the past decade (60.9%) reported never offering dilation for urethral syndrome; only 34.2% of the remainder never offered it (P = 0.002). Urologists normally performed this procedure with local or no anesthesia (85%) and most commonly dilated to 32F (45%). Overall, 21% of urologists trained more than 10 years ago considered dilation very or extremely successful in treating urethral syndrome; 0 of 42 trained more recently considered it to be this successful (P = 0.014). CONCLUSIONS: The use of urethral dilation in women remains controversial. Recently trained urologists use it less frequently and find it less efficacious than those who have been practicing for longer periods. Since such obvious biases exist, it is imperative that the clinical merit of urethral dilation be carefully scrutinized.
Catheterization↗
Frequency and characterization of antigen-specific IL-4- and IL-13- producing basophils and T cells in peripheral blood of healthy and asthmatic subjects.
BACKGROUND: Both basophils and T cells are known to secrete IL-4 and IL-13 after activation with either nonspecific stimuli or specific antigen, but the relative contribution of these 2 cell types to overall cytokine production is unclear. OBJECTIVES: To further characterize basophil cytokine production and compare it with that of T cells, we examined the frequency of IL-4- and IL-13-producing basophils and T cells in human PBMCs by means of flow cytometry after activation in allergic asthmatic and normal subjects. METHODS: PBMCs obtained from whole blood after Percoll gradient were activated with specific antigen or ionomycin and fixed. PBMCs were made permeable; stained with antibodies to IgE, CD3, and either IL-4 or IL-13; and analyzed by means of flow cytometry. RESULTS: Preformed cytokines were not detected in unactivated basophils. After ionomycin activation, 60% to 90% of basophils from both control and allergic asthmatic subjects expressed IL-4 and IL-13. Specific antigen induced cytokine expression by 10% to 20% of basophils from the asthmatic group only. After specific antigen activation, basophils accounted for 4 times more IL-4-producing cells than did T cells. IL-4 and IL-13 production at 2 hours was exclusively from basophils. After allergen activation, CD40 ligand was upregulated on a subset of peripheral blood basophils. CONCLUSIONS: These data demonstrate that basophils are the predominant peripheral blood cells that express IL-4 and IL-13 in the first 6 hours after antigen activation and strengthen the putative role of basophils both in IgE production and in the generation of allergic inflammation.
Adult↗
Ethical practice and legal responsibility for duly authorized officers: achieving a balance.
In New Zealand the Mental Health (Compulsory Assessment and Treatment) Act (1992) has influenced the practice of psychiatric nurse acting as duly authorized officers by challenging traditional perceptions of the nurse-patient relationship. This paper describes the legal role and responsibilities of the duly authorized officer, and reflects on ethical principles that affect decision making using an example from practice. Performing legislative responsibilities within a bicultural context in a health climate driven by economic rationalism is problematic, and concern is raised to ensure a body of psychiatric nursing experience for the future.
Ethics, Nursing↗
TCR V alpha 24 and V beta 11 coexpression defines a human NK1 T cell analog containing a unique Th0 subpopulation.
Murine NK1 natural T (NT) cells are a population of alphabeta T cells that express NK cell receptors and an invariant TCR rearrangement. These cells rapidly produce large amounts of IL-4 upon activation and have been suggested to promote Th2 differentiation. We sought to determine whether a human NK1 T cell analogue could be detected in PBMC, and if so, characterize the TCR usage, cytokine expression, and surface phenotype of this subset. Using flow cytometry, we have demonstrated a distinct population of V alpha24+, V beta11+, CD56+ T cells consistent with NT cells. Upon sequencing, these cells expressed an invariant V alpha24-J alphaQ TCR rearrangement, verifying their identity as a human NK1 T cell analogue. NT cells demonstrated increased frequencies of both IFN-gamma and IL-4 production. Strikingly, 30 to 45% of CD4+ NT cells expressed IL-4, a sixfold greater frequency than that seen in mainstream CD4+ alphabeta T cells. Contrary to the pattern seen with mainstream T cells, virtually all IL-4-producing NT cells coexpressed IFN-gamma, indicating that this subset of NT cells has a unique Th0 phenotype. These data establish that V alpha24+ NT cells are a potent source of IL-4 and as such, may play a role in Th2 priming in human immune responses. This work demonstrates that human NT cells can be phenotypically identified and functionally studied in the blood of healthy or diseased subjects.
Animals↗
Human mast cells produce the CD4+ T lymphocyte chemoattractant factor, IL-16.
CD4+ T cell infiltration is known to occur in tissues at sites of mast cell activation. The molecules produced and released by mast cells that account for this lymphocyte accumulation are poorly characterized. Here we report that a CD4+ T cell chemoattractant cytokine, IL-16, is stored preformed in bone marrow-cultured human mast cells and a human mast cell line, HMC-1, as demonstrated by intracytoplasmic cytokine staining and flow cytometry, and in human lung mast cells, as detected by immunohistochemistry. In response to the anaphylatoxin, C5a, or to PMA treatment, IL-16 mRNA transcripts detected by Northern blot analysis in HMC-1 cells increased 6- to 10-fold. HMC-1 cell lysates and activated supernatants contained IL-16 protein, as demonstrated by both ELISA and in vitro lymphocyte chemotaxis assays, the latter of which was blocked 59 to 88% by the addition of neutralizing Ab to recombinant human IL-16. IL-16 bioactivity was detected in the supernatants 2 to 4 h after PMA or C5a activation, and this activity remained elevated through 24 h. The capacity of human mast cells to synthesize and release biologically active IL-16 provides a possible link between mast cell activation and the accumulation of T cells in mast cell-dependent inflammation, thus amplifying the immune response and perpetuating the pathologic process.
CD4-Positive T-Lymphocytes↗
Postsynaptic action potentials do not alter short-term potentiation in the dentate gyrus.
The dendrites of neocortical neurons have been shown to support active action potentials which back-propagate from the soma after an output spike has been initiated. This observation has led to speculation that dendritic action potentials may participate in various forms of synaptic plasticity. The contribution of dendritic spikes to paired-pulse facilitation (PPF), a form of short-term plasticity, was investigated in the dentate gyrus of hippocampal slices. Paired orthodromic stimulation of the perforant path produced an average facilitation of the test population spike (PS) amplitude of 167% (n = 16, conditioning response = 100%). There was also a small but significant increase in slope of the field EPSP (fEPSP) of 108%. To determine whether increased presynaptic drive could account for this facilitation, the relationship between fEPSP slope and spike amplitude (I-O) was determined for a range of stimulus intensities. An increase in fEPSP slope of 171% was associated with an increase in PS amplitude equal to the facilitation produced by paired-pulse stimulation (167%), suggesting a postsynaptic component in PPF. Electric field effects were then used as a tool to alter the excitability of granule cells during the conditioning response without changing synaptic drive. Any change in the test response associated with manipulation of the conditioning population spike amplitude would suggest that dendritic spikes may contribute to the postsynaptic component of PPF. Surprisingly, altering the number of neurons responding to the conditioning stimulus with an action potential had no effect on the test response, suggesting that dendritic action potentials do not participate in this form of short-term synaptic plasticity.
Action Potentials↗
UGT1*1 genotyping in a Canadian Inuit population.
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Asian People↗
Preclinical antitumor activity of CI-994.
CI-994 [aka: acetyldinaline; PD 123654; 4-acetylamino-N-(2'aminophenyl)-benzamide] (Figure 1) is a novel antitumor agent with a unique mechanism of action. It is the acetylated metabolite of dinaline, a compound previously identified as having cytotoxic and cytostatic activity against several murine and human xenograft tumor models. CI-994 had activity against 8/8 solid tumors tested (log cell kills at the highest non-toxic dose): pancreatic ductal adenocarcinoma #02 (4.7); pancreatic adenocarcinoma #03 (3.0; 1/6 cures); colon adenocarcinoma #38 (1.6); colon adenocarcinoma #51/A (1.1); mammary adenocarcinoma #25 (1.7); mammary adenocarcinoma #17/ADR (0.5); Dunning osteogenic sarcoma (4.0); and the human prostate carcinoma LNCaP (1.2). CI-994 had the same spectrum of activity in vivo as dinaline. It also behaved similarly in schedule comparison/toxicity trials. Prolonged administration with lower drug doses was more effective than short-term therapy at higher individual doses. If doses were kept between 40 and 60 mg/kg/injection, prolonged administration (> 50 days) was tolerated with no gross toxicity. Doses > or = 90 mg/kg/injection caused lethality after 4-5 days of administration. The maximum tolerated total dose was also increased with smaller individual doses administered for prolonged intervals. Clinical Phase I trials are ongoing with this agent.
Animals↗
Identification and antitumor activity of a reduction product in the murine metabolism of pyrazoloacridine (NSC-366140).
PURPOSE: Pyrazoloacridine (PZA) is a newly developed anticancer agent currently undergoing clinical trials. Its mode of action has not been elucidated but the presence in its chemical structure of a 5-nitro functional group and its activity against oxygen-deficient cancerous cells argue in favor of enzymatic nitro reduction as a possible pathway for its antitumor activity. In order to assess the involvement of the nitro functionality in PZA activity, as well as to determine other metabolic products, a pharmacological and chemical study of PZA was designed. METHODS: Urine and stool samples were collected from mice before and after treatment with PZA. Samples were fractionated using chromatographic methods and then evaluated using mass spectrometry (MS). One of the characterized metabolites was synthesized and tested in vitro and in vivo for anticancer activity. RESULTS: One major fraction from mouse stool was initially characterized by MS as the 5-aminopyrazoloacridine (5-APZ). This compound was chemically synthesized by catalytic hydrogenation of PZA was stabilized as the hydrochloride salt. 5-APZ was marginally cytotoxic in vitro and was inactive in vivo against a tumor cured by PZA (Panc 03). CONCLUSIONS: Bioreduction of the nitro group to an amine compound from PZA represents a pathway in the metabolic sequence of PZA. The inactivity of the chemically generated amine product does not provide conclusive evidence that this pathway is not involved in the cytotoxicity of PZA because other intermediates in the nitro reduction pathway may have a role in the activity of PZA. In particular, the hydroxylamine derivative of PZA could give answers to the involvement of this pathway in PZA cytotoxicity.
Acridines↗
Type X collagen is colocalized with a proteoglycan epitope to form distinct morphological structures in bovine growth cartilage.
Using antibodies raised against type X collagen, isolated from deer antler, we have immunolocalized type X collagen in growth plate and epiphyseal cartilage from fetal and ambulatory calves. In ambulatory calf growth plate, type X collagen was demonstrated to be present in longitudinal septa that extend from the resting zone into the underlying trabecular bone. The much more restricted distribution of type X collagen seen in fetal growth plate, both here and previously, suggested that prominent localization of type X collagen to the longitudinal septa was stimulated by weight bearing. The location of type X collagen has been compared with that of an epitope (7D4), composed of specific sulfation patterns in chondroitin sulfate of some aggrecan molecules. Colocalization of type X collagen with the 7D4 epitope in longitudinal septa of growth plates from ambulatory calves suggested these molecules contribute to the formation and function of longitudinal septa. Immunolocalization of type X collagen and 7D4 in calf epiphyseal cartilage demonstrated colocalization at an interface that appears to represent the junction of articular cartilage and cartilage associated with formation of the secondary ossification center. Immunolocalization of type X collagen and the 7D4 proteoglycan epitope in these structures suggested that type X collagen and the 7D4 epitope form structures with important mechanical roles and capacity to influence the morphology of associated bony structures.
Animals↗
Preclinical anticancer activity of cryptophycin-8.
Cryptophycin-8 was prepared by the conversion of the epoxide group on cryptophycin-1 to a chlorohydrin. In the studies reported here, cryptophycin-8 was evaluated for preclinical activity against subcutaneous tumors of both mouse and human origin. At the highest non-toxic single course treatment, the following results were obtained (Table A). Cryptophycin-8 was less potent than cryptophycin-1 by approximately 4-fold; however, it was both more water soluble and had greater therapeutic efficacy, as demonstrated by % T/C, tumor cell log kill values, range of dose effectiveness and host cures.
Animals↗
Growth factors as mediators of androgen action during the development of the male urogenital tract.
Studies on the developing prostate and SV suggest that androgens act via mesenchymal AR to elicit synthesis and secretion of various autocrine and paracrine factors that regulate epithelial and stromal growth and differentiation. Clearly, the global regulation of epithelial growth and ductal branching morphogenesis is a complex multifactorial process involving the interplay of many diffusible factors (both positive and negative regulators), extracellular matrix molecules, cell-surface receptors for growth factors, receptors for extracellular matrix molecules, and matrix-degrading enzymes. Future progress will certainly be dependent upon the utilization of appropriate, biologically relevant models to examine the respective roles of various growth factors in the growth and development of androgen target organs.
Androgens↗