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Biomedical subjects

L S Taylor

Publications and source records attributed to L S Taylor.

At least 37 records · Page 2Linked to original sources
PubMed1997

The antineoplastic agent bryostatin-1 induces proinflammatory cytokine production in human monocytes: synergy with interleukin-2 and modulation of interleukin-2Rgamma chain expression.

The antineoplastic agent bryostatin-1 (bryo-1) possesses powerful immunomodulatory properties and can function as a biological response modifier in vivo. However, there is currently little information regarding the effects of bryo-1 on cells of the monocytic lineage. In this study, we demonstrate that bryo-1 can potently induce the production of pro-inflammatory cytokines from human peripheral blood monocytes. Stimulation of monocytes with subnanomolar concentrations of bryo-1 significantly upregulated the constitutive levels of interleukin-8 (IL-8) mRNA and induced the expression of IL-1beta, tumor necrosis factor-alpha (TNF-alpha), and IL-6 mRNA in a time and dose-dependent manner. Accordingly, secretion of all four proinflammatory cytokines was induced after monocyte exposure to bryo-1. Furthermore, we showed that bryo-1 selectively synergized with IL-2 in triggering monocyte activation, and this effect seemed to be dependent, at least in part, on the ability of bryo-1 to upregulate IL-2Rgamma chain expression. Finally, we demonstrated that the responses of monocytes to bryo-1 could be blocked by the protein kinase C (PKC) inhibitors staurosporine and UCN-01, indicating a role for PKC in monocyte activation by bryo-1. These results show for the first time that bryo-1 is a powerful activator of human monocytes and suggest that stimulation of monokine secretion by bryo-1 may represent at least one of the mechanisms responsible for the in vivo antitumor activity of this drug.

Antineoplastic Agents↗
PubMed1997

Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions.

PURPOSE: To study the molecular structure of indomethacin-PVP amorphous solid dispersions and identify any specific interactions between the components using vibrational spectroscopy. METHODS: Solid dispersions of PVP and indomethacin were prepared using a solvent evaporation technique and IR and FT-Raman spectra were obtained. RESULTS: A comparison of the carbonyl stretching region of gamma indomethacin, known to form carboxylic acid dimers, with that of amorphous indomethacin indicated that the amorphous phase exists predominantly as dimers. The hydrogen bonding of alpha indomethacin is not as dimers. Addition of PVP to amorphous indomethacin increased the intensity of the infrared band assigned to non-hydrogen bonded carbonyl. Concomitantly, the PVP carbonyl stretch appeared at a lower wavenumber indicating hydrogen bonding. Model solvent systems aided spectral interpretation. The magnitude of the spectral changes were comparable for an indomethacin-PVP solid dispersion and a solution of indomethacin in methylpyrrolidone at the same weight percent. CONCLUSIONS: Indomethacin interacts with PVP in solid dispersions through hydrogen bonds formed between the drug hydroxyl and polymer carbonyl resulting in disruption of indomethacin dimers. PVP may influence the crystallisation kinetics by preventing the self association of indomethacin molecules. The similarity of results for solid dispersions and solutions emphasises the "solution" nature of this binary amorphous state.

Crystallization↗
PubMed1997

Characterization of frozen glucose solutions.

Reducing sugars may be used as additives in freeze-dried formulations. The purpose of this study is to examine the effect of freezing on nonequilibrated glucose solutions using FT-Raman spectroscopy. The methods used solutions freshly prepared from either alpha- or beta-crystalline glucose, frozen at different time intervals after dissolution. Solutions frozen immediately after dissolution showed peaks in the anomeric region of the spectrum characteristic of those observed for the parent crystalline form. No change occurred in these spectra after 24 hr in the frozen state. Solutions prepared from either alpha- or beta-crystalline glucose and left for 24 hr at room temperature before freezing showed the presence of both anomers. The glass transition temperature of maximally freeze-concentrated solutions of beta-glucose, frozen immediately after dissolution, was found to be approximately 3 degrees C lower than for solutions prepared from alpha-glucose. Freezing appears to halt the interconversion of glucose anomers, enabling the formation of predominantly alpha- or beta-frozen solutions which exhibit different properties. Freezing of nonequilibrated solutions of reducing sugars may lead to variation in the properties of freeze-dried formulations.

Calorimetry, Differential Scanning↗
PubMed1996

Molecular cloning and characterization of a novel mouse macrophage gene that encodes a nuclear protein comprising polyglutamine repeats and interspersing histidines.

Simple tandem repeats of the trinucleotide sequence CAG encode homopolymeric stretches of glutamine. Although polyglutamine has been identified in diverse proteins, it is present predominantly in transcription factors. We observed that oncogene-immortalized mouse macrophages express several genes that contain a CAG repeat motif. Therefore, we attempted to clone a novel gene that contains a CAG repeat and is associated with cytokine activation of macrophages. Screening of a mouse macrophage cDNA library with a probe comprising 12 consecutive CAG triplets identified at least one unique clone. The cDNA encodes a protein (named GRP-1 or glutamine repeat protein-1) with 171 amino acids, a calculated molecular mass of 21.6 kDa, and a predicted pI of 10.67. Greater than two-thirds of GRP-1 are only two amino acids, namely glutamine (50%) and histidine (18%). There are four polyglutamine motifs interspersed with histidine-rich regions. There is also a putative nuclear localization signal flanked by sites for possible serine phosphorylation. GRP-1 mRNA was expressed constitutively in some macrophage cell lines and B and T cell lines. Interferon-gamma or lipopolysaccharide augmented GRP-1 mRNA expression in the mouse macrophage cell line ANA-1. Western blot analyses using an antipeptide serum revealed that GRP-1 was localized in the nucleus of ANA-1 macrophages and transfected 3T3 fibroblasts. Overexpression of GRP-1 decreased Sp1-driven chloramphenicol acetyltransferase gene expression in transient cotransfection experiments. Because polyglutamine motifs can cause protein oligomerization and can function as transcriptional activation domains, we suggest that GRP-1 may be a transcription factor associated with interferon-gamma- or lipopolysaccharide-induced activation of macrophages.

Amino Acid Sequence↗
PubMed1996

Regulation of inducible nitric oxide synthase expression in IFN-gamma-treated murine macrophages cultured under hypoxic conditions.

We recently reported that a hypoxia-responsive element mediates a novel pathway of transcriptional activation of the inducible nitric oxide synthase (iNOS) promoter in murine macrophages treated with IFN-gamma plus hypoxia (1% O2). In this study, we investigated the expression of NOS activity and the regulation of NOS induction in IFN-gamma treated ANA-1 murine macrophages or thioglycollate-elicited peritoneal macrophages cultured under hypoxic conditions. We found that murine macrophages stimulated with IFN-gamma plus hypoxia, despite a significant accumulation of iNOS mRNA, did not release nitrite into culture supernatant. However, cytosol from macrophages treated with IFN-gamma plus hypoxia contained significant levels of iNOS protein and enzymatic activity. Experiments in which cells were treated with IFN-gamma plus hypoxia and then cultured in normoxic conditions (20% O2) demonstrated that reoxygenation was required to achieve detectable accumulation of nitrite in the culture supernatant. Furthermore, we demonstrated that IL-4 inhibited IFN-gamma plus hypoxia-dependent induction of iNOS mRNA expression, iNOS protein, and enzymatic activity. Experiments in which ANA-1 macrophages were transfected transiently with the full-length iNOS promoter linked to a chloramphenicol acetyltransferase reporter gene demonstrated that IL-4 also down-regulated the IFN-gamma plus hypoxia-induced activation of the iNOS promoter. These data establish that hypoxia is a costimulus with IFN-gamma for the induction of iNOS activity in ANA-1 macrophages as well as in murine peritoneal macrophages, and they provide the first evidence that IL-4 inhibits hypoxia-inducible gene expression. In addition, our results suggest that hypoxia, which occurs in many pathologic conditions, may play an important role in the activation of murine macrophages.

Animals↗
PubMed1996

The imperative of outcomes analysis: an integration of traditional and nontraditional outcomes measures.

The health care industry is compelled to reduce costs while providing high-quality patient care. Outcomes analysis enables monitoring and maintenance of quality of care in our rapidly changing practice environment. Comprehensive outcomes research cannot occur, however, without a database incorporating practice-related data, interventions and components of care, and outcomes of care. The article reports the design and proposed implementation of an outcomes assessment infrastructure in a multifacility health maintenance organization in Northern California. The infrastructure integrates traditionally measured outcomes and cost data with nontraditional, nurse-influenced, health-related outcomes.

California↗
PubMed1995

A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter.

Picolinic acid, a catabolite of L-tryptophan, activates the transcription of the inducible nitric oxide synthase gene (iNOS) in IFN-gamma-treated murine macrophages. We performed functional studies on the 5' flanking region of the iNOS gene linked to a CAT reporter gene to identify the cis-acting element(s) responsible for the activation of iNOS transcription by picolinic acid. Transient transfection assays showed that the full-length iNOS promoter in the murine macrophage cell line ANA-1 was activated by the synergistic interaction between IFN-gamma and picolinic acid. Deletion or mutation of the iNOS promoter region from -227 to -209, containing a sequence homology to a hypoxia-responsive enhancer (iNOS-HRE), decreased picolinic acid- but not LPS-induced CAT activity by more than 70%. Functional studies using a tk promoter-CAT reporter gene plasmid demonstrated that the iNOS-HRE was sufficient to confer inducibility by picolinic acid but not by IFN-gamma or LPS. Electrophoretic mobility shift assays confirmed that picolinic acid alone induced a specific binding activity to the iNOS-HRE. Furthermore, we found that the iNOS-HRE activity was inducible by hypoxia and that hypoxia in combination with IFN-gamma activated the iNOS promoter in transient transfection assays and induced iNOS transcription and mRNA expression. These data establish that the iNOS-HRE is a novel regulatory element of the iNOS promoter activity in murine macrophages and provide the first evidence that iNOS is a hypoxia-inducible gene.

Animals↗
PubMed1995

Sucrose reduces the efficiency of protein denaturation by a chaotropic agent.

Sugars and polyols are used to stabilize proteins. The degree of stabilization conferred on a model protein by sucrose was calculated in terms of the free energy of folding. Phosphoglycerate kinase (PGK) was denatured by guanidine hydrochloride (GuHCl) in different sucrose concentrations. The linear extrapolation method [1,2] was used to calculate the free energy of folding in the absence of denaturant. Although sucrose increased the concentration of GuHCl required to unfold the protein, the free energy of folding in water was unchanged. In order to probe the nature of the stabilizing effect of sucrose, an FT-Raman spectroscopic study of denaturant-polyol systems was undertaken. Investigations of interactions between GuHCl, urea or formamide and polyhydric compounds, revealed no evidence for hydrogen bonding or dipole-dipole associations. Polyhydric compounds caused minor changes in denaturant spectra although the converse was not observed. The structure of deuterated water changed on addition of denaturants. For non-ionic denaturants, addition of polyhydric solutes countered this change in water structure. Thus polyhydric compounds oppose the effect of denaturants on water structure. The observed increase in GuHCl concentration required to unfold PGK in the presence of sucrose may be attributed to this property of sucrose.

Formamides↗
PubMed1992

Flanged coaxial microwave probes for measuring thin moisture layers.

We obtain an analytical, closed-form expression for the input admittance of a flanged, open-ended coaxial line radiating into a layered lossy material. The effect of higher modes as well as the dominant mode have been taken into consideration. The results obtained in the experimental measurement of the microwave reflection coefficient of the probe radiating into very thin water layers are described and compared with the results obtained from numerical calculations based on a theoretical model. The measurements were made in the 5.0-7.0 GHz range. The results demonstrate, for example, the usefulness of this type of device in measuring thin moisture layers in the outer layer of the human skin.

Body Water↗
PubMed1990

School district compliance with regulations for resource and special class programs.

This article reports the results of a survey of special education teachers in New York State regarding state regulations for resource and special class programs. Three hundred and fifty-seven special education teachers in 31 randomly selected school districts responded to a questionnaire. Results indicated that the majority of districts were in compliance with the regulations the survey addressed; however, 13% to 31% of the teachers' responses indicated noncompliance with specific regulations in some school districts. Other problems in special education programs were also identified in the survey.

Child↗
PubMed1989

Screening for cancer and coronary risk factors through a nurse practitioner-staffed preventive health clinic.

The Preventive Health Examination (PHE) program was designed to screen for cancer of the lung, colon, skin, and prostate (or breast) and to detect the risk factors for coronary artery disease, i.e., arterial hypertension, hypercholesterolemia, cigarette smoking, and obesity. To investigate the cost-effectiveness of PHE performed by nurse practitioners, the first 176 subjects enrolled in the PHE program at a northeastern, suburban VA Medical Center were evaluated prospectively. The subjects were recruited through random mailing. The direct cost of PHEs was $80 per patient. PHEs were performed on 171 men and 5 women, mean age 57.2 years, divided into groups according to the date of evaluation. Nine percent of patients had findings highly suspicious of cancer (lung nodules in 7, skin lesions in 9). As a consequence, one patient underwent lobectomy for squamous carcinoma of the lung and another underwent prostatectomy for adenocarcinoma of the prostate. Fifty-five percent of patients had high cholesterol levels, 53% were obese, 30% were heavy cigarette smokers, and 19% were hypertensive. Nineteen percent of the patients had three or more coronary artery disease risk factors. We conclude that low cost PHEs performed by nurse practitioners have a high yield in detecting risk factors for coronary artery disease, and for detecting potentially treatable malignancies.

Adult↗
PubMed1988

Will radiation control be by reason or regulation?

Following a very brief review of the development of our present radiation-protection philosophy, attention is directed to what the author sees as current problems. The only prognostication will be that at least certain of the problems outstanding or developing today will be among those that will have to be addressed in the coming four decades. For the past six decades, the major effort has been the development of the science and philosophy of radiation biology and its application to protection against radiation hazards, whether real or imagined. For three decades there has been public concern about radiation generally, the core of the problem being inadequate education of the public and the media on the subject. For a little over one decade, there has been rapidly developing growth of tort litigation generally, involving ionizing radiation in particular. These are the three major lines of attention in the radiation-protection area today; between two of them there are already some of the aspects of "the arena." Behind all three lies an overwhelming lack of understanding by, and education of, the public, which shows mostly in the public fetish for absolute safety which, of course, cannot be. These must be the major concerns of the radiation-protection community in the coming four decades.

History, 20th Century↗