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Biomedical subjects

L Phillips

Publications and source records attributed to L Phillips.

At least 37 records · Page 2Linked to original sources

Impact of peritoneal absorption of glucose on appetite, protein catabolism and survival in CAPD patients.

Dietary protein and calorie intake, protein catabolism and peritoneal kinetics were measured in 97 CAPD patients to establish the effect of peritoneal glucose absorption on appetite and survival. There was a large variability in the number of calories obtained from the dialysate, mean 5.89 cal/kg (median 5.43 cal/kg), with a skewed distribution, due to the increased requirement for hypertonic solutions by patients with more rapid glucose absorption and poor ultrafiltration. On average calories derived from peritoneal absorption accounted for 19% of the total energy intake which in itself was well below that recommended. Patients with > 6 cal/kg, obtained from the dialysate (top 20th percentile, n = 19) were compared with those with < 6 cal/kg, but no significant differences in oral protein or calorie intake, protein catabolism or total calorie intake were found. Age, body mass index (BMI) and KT/V were also similar in both groups. Patients were followed-up prospectively for a minimum of 24 months and a comparison made of actuarial survival. Patients with high peritoneal calorie intake tended to survive longer but this was not significantly different (p = 0.25). This study suggests that calories derived from the peritoneum in CAPD patients do not suppress appetite, provide a useful and significant proportion of the total energy intake, that does not cause excessive obesity or have a negative effect on patient survival.

Absorption

The predictive value of KT/V and peritoneal solute transport in CAPD patients is dependent on the type of comorbidity present.

Comorbidity, age, dialysis dose (KT/V(urea)), plasma albumin, and peritoneal function (D/P(creat) were measured cross-sectionally in 228 continuous ambulatory peritoneal dialysis (CAPD) patients, who were then followed up for a mean of two years. Comorbidity, utilizing a semi-quantitative score described previously, was the most powerful predictor of mortality in both univariate and multivariate analysis. Using univariate analysis, all the variables predicted outcome with statistical significance, mortality being associated with lower KT/V and plasma albumin and a higher D/P(creat). On multivariate analysis only comorbidity, age, and KT/V remained independent predictors. Data was further analyzed on the basis of type of comorbid condition. In those patients without comorbid disease (n = 127) neither KT/V, albumin nor D/P(creat) predicted outcome. In patients with clinical evidence of ischemic heart disease the KT/V was a significant predictor of favorable outcome. In those with clinical evidence of left ventricular function, mortality was significantly and independently associated with low plasma albumin, high D/P(creat), and KT/V. It is suggested that the concept of treatment adequacy in CAPD patients must include both measures of dialysis dose and peritoneal function, particularly in the context of the patient's comorbidity.

Adolescent

Lipoteichoic acid-induced neutrophil adhesion via E-selectin to human umbilical vein endothelial cells (HUVECs).

We investigated whether lipoteichoic acid (LTA) induces the expression of E-selectin and neutrophil adhesion to human umbilical vein endothelial cells (HUVECs). LTA (0.01-30 micrograms/ml) induced the expression of E-selectin in a concentration-dependent manner with maximal response at 10 micrograms/ml. The expression level of E-selectin increased from 2 h after stimulation by LTA with the maximal level at 4-8 h. Neutrophil adhesion to LTA-treated HUVECs correlated with the levels of E-selectin expression. In addition, the adhesion was clearly inhibited by anti-human E-selectin monoclonal antibody CY-1787 as well as a sialyl Lewis X (SLeX) oligosaccharide. LTA-induced expression of E-selectin was inhibited by protein kinase C inhibitors, H-7 and staurosporine. These results indicate that LTA induced the expression of E-selectin and neutrophils adhered to HUVECs via E-selectin.

Cell Adhesion

A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group.

BACKGROUND: We evaluated the effectiveness of three treatment strategies for the prevention of a first episode of Pneumocystis carinii pneumonia in patients infected with the human immunodeficiency virus (HIV). METHODS: In an open-label trial, 843 patients with HIV infection and fewer than 200 CD4+ cells per cubic millimeter received zidovudine plus one of three randomly assigned prophylactic agents, beginning with trimethoprim-sulfamethoxazole, dapsone, or aerosolized pentamidine and followed by a defined sequence of other drugs to be used in cases of intolerance. RESULTS: The estimated 36-month cumulative risks of P. carinii pneumonia were 18 percent, 17 percent, and 21 percent in the trimethoprim-sulfamethoxazole, dapsone, and aerosolized-pentamidine groups, respectively (P = 0.22). The difference in risk among treatment strategies was negligible in patients entering the study with 100 or more CD4+ lymphocytes per cubic millimeter. In those entering with fewer than 100 CD4+ cells per cubic millimeter, the risk was 33 percent with aerosolized pentamidine, as compared with 19 percent with trimethoprim-sulfamethoxazole and 22 percent with dapsone (P = 0.04). The lowest failure rates occurred in patients receiving trimethoprim-sulfamethoxazole, and failures were more common with 50 mg of dapsone than with 100 mg. Toxoplasmosis developed in less than 3 percent of patients. Of the patients assigned to the two systemic therapies, only 23 percent were receiving their assigned drug and dose when they completed the study. The median survival was approximately 39 months in all three groups, and the mortality attributable to P. carinii pneumonia was only 1 percent. CONCLUSIONS: In patients with advanced HIV infection, the three treatment strategies we examined have similar effectiveness in preventing P. carinii pneumonia. Strategies that start with trimethoprim-sulfamethoxazole or with high-dose dapsone, rather than aerosolized pentamidine, are superior in patients with fewer than 100 CD4+ lymphocytes per cubic millimeter.

AIDS-Related Opportunistic Infections

Both MHC and background gene heterozygosity alter T cell receptor repertoire selection in an antigen-specific response.

Many autoimmune diseases are associated with specific class II MHC alleles; however, this association is not complete. One explanation for the variable expression of disease in susceptible individuals is that variability in the TCR repertoire may alter the potential to generate pathogenic autoreactive T cells. The current study was undertaken to examine the possibility that MHC and background heterozygosity, which is the norm in the outbred human population, alters the expressed TCR repertoire and, if so, whether this has an impact on peptide recognition and antigenic specificity. We, therefore, systematically analysed the beef insulin-specific TCR repertoire in inbred BALB/c mice before and after introduction of MHC heterozygosity (BALB/c x BALB.K)F1 mice, or MHC and background gene heterozygosity (BALB/c x A/J)F1 mice. We show that T cells from all three repertoires are predominantly Ad-restricted and recognize the same immunodominant peptide. Despite this, the beef insulin-specific TCR repertoires in F1 mice differ from those seen in BALB/c mice with the most dramatic changes seen in (BALB/c x A/J)F1 mice. These changes are accompanied by subtle differences in the antigenic specificity of the T cells. The results demonstrate that both MHC and background gene heterozygosity affect TCR repertoire selection, suggesting that the variable expression of autoimmune disease in individuals with a susceptible MHC allele may result, in part, from variability in the TCR repertoire introduced by this heterozygosity.

Amino Acid Sequence

Comorbidity, urea kinetics, and appetite in continuous ambulatory peritoneal dialysis patients: their interrelationship and prediction of survival.

Comorbidity, urea kinetics (Kt/V and normalized protein catabolic rate), dietary protein, total calorie intake, and plasma albumin were measured in 97 continuous ambulatory peritoneal dialysis patients followed prospectively for 30 months. Comorbid disease was graded severe in 12 patients, intermediate in 29, and absent in 56. At entry to the study comorbidity was associated with increased age (P = 0.001), lower dietary protein (P = 0.015) and calorie intake (P = 0.02), and a lower plasma creatinine (P = 0.026). Trends toward lower Kt/V and albumin were not significant, and normalized protein catabolic rate was unaffected. Ability of these measures to predict mortality was assessed by univariate and multivariate analysis using Cox's proportional hazard model. On univariate analysis, comorbidity (P < 0.0001), age (P = 0.0001), Kt/V (P = 0.009), plasma albumin (P = 0.009), calorie intake (P = 0.035), and dietary protein intake (P = 0.03) predicted outcome, whereas normalized protein catabolic rate did not (P = 0.46). Multivariate analysis indicated that comorbidity (P = 0.0003) and age (P = 0.0085) were the only independent predictors of outcome. The addition of plasma albumin and Kt/V increased the significance of the Cox model. Further analysis of comorbidity demonstrated the relative importance of vascular disease and left ventricular dysfunction. This study illustrates the profound influence of comorbid disease on mortality in continuous ambulatory peritoneal dialysis patients and suggests that it causes suppression of appetite independent of the dialysis dose.

Adolescent

Chattanooga Creek: case study of the public health nursing role in environmental health.

Public health nurses have two primary roles in protecting their communities from hazardous substances: community assessment and health education. Developing assessment skills in environmental health enables public health nurses to collaborate with other federal, state, and county agencies in identifying public health hazards and making health-based recommendations at hazardous waste sites needing remedial or removal interventions. Community health education empowers communities to minimize their exposure to hazardous wastes in their environment. Methods for community environmental health assessment and interventions are demonstrated in this article by activities conducted at the Chattanooga Creek site in Chattanooga, Tennessee. A thorough assessment and collaborative approach between government agencies, local health professionals, and community members resulted in a successful community health education program and this site's placement on the National Priorities List.

Environmental Health

Isolation of a highly cytopathic lentivirus from a nondomestic cat.

A feline immunodeficiency virus-like virus (FIV-Oma) isolated from a Pallas' cat (Otocolobus manul) is highly cytopathic in CrFK cells, in contrast to the chronic, noncytolytic infection established by an FIV isolate from a domestic cat (FIV-Fca). The virions have typical lentivirus morphology, density, and magnesium-dependent reverse transcriptase activity. The major core protein is antigenically cross-reactive with that of FIV-Fca; however, FIV-Oma transcripts do not cross-hybridize with FIV-Fca. A conserved region of the FIV-Oma pol gene has 76 to 80% nucleic acid identify with the corresponding pol regions of other feline lentiviruses and 64 to 69% identity with those of human, ovine, and equine lentiviruses.

Animals

5-Aminoimidazole-4-carboxamide ribotide transformylase-IMP cyclohydrolase from human CCRF-CEM leukemia cells: purification, pH dependence, and inhibitors.

The bifunctional enzyme 5-aminoimidazole-4-carboxamide ribotide (AICAR) transformylase-IMP cyclohydrolase has been purified 780-fold to apparent homogeneity from human CCRF-CEM leukemia cells, completed with chromatography on Affi-Gel Blue followed by AICAR-Sepharose 4B. Using a sensitive radioassay, IMP cyclohydrolase has a Ks value for 5-formamidoimidazole-4-carboxamide ribotide (FAICAR) at pH 7.4 of 0.87 +/- 0.11 microM. The following purine nucleotide derivatives were potent competitive inhibitors of IMP cyclohydrolase: 2-mercaptoinosine 5'-monophosphate (Ki = 0.094 +/- 0.024 microM), xanthosine 5'-monophosphate (Ki = 0.12 +/- 0.01 microM), 2-fluoroadenine arabinoside 5'-monophosphate (Ki = 0.16 +/- 0.02 microM), 6-mercaptopurine riboside 5'-monophosphate (Ki = 0.20 +/- 0.02 microM), adenosine N1-oxide 5'-monophosphate (Ki = 0.28 +/- 0.03 microM), and N6-(carboxymethyl)adenosine 5'-monophosphate (Ki = 1.7 +/- 0.42 microM). The pH dependencies of Vmax and Vmax/Ks values for IMP cyclohydrolase are consistent with a single ionizable amino acid residue (pKa = 7.57 +/- 0.09) of the enzyme which must be unprotonated for catalysis to occur and a residue (pKa = 7.57 +/- 0.14) which must be unprotonated for FAICAR to bind. The pKa values of 5.81 +/- 0.03 and 9.41 +/- 0.04 determined for FAICAR indicate that ionization of the substrate does not contribute significantly to the pH effects observed. Chemical modification of IMP cyclohydrolase provides evidence for arginine and cysteine residues at the active site, and roles for these residues in the mechanism of catalysis are proposed.

Acyltransferases

Development and validation of an air-to-beef food chain model for dioxin-like compounds.

A model for predicting concentrations of dioxin-like compounds in beef is developed and tested. The key premise of the model is that concentrations of these compounds in air are the source term, or starting point, for estimating beef concentrations. Vapor-phase concentrations transfer to vegetations that cattle consume, and particle-bound concentrations deposit onto soils and these vegetations as well. Congener-specific bioconcentration parameters, coupled with assumptions on cattle diet, transform soil and vegetative concentrations into beef fat concentrations. The premise of the validation exercise is that a profile of typical air concentrations of dioxin-like compounds in a United States rural environment is an appropriate observed independent data set, and that a representative profile of United States beef concentrations of dioxin-like compounds is an appropriate observed dependent result. These data were developed for the validation exercise. An observed concentration of dioxin toxic equivalents in whole beef of 0.48 ng/kg is compared with a predicted 0.36 ng/kg. Principal uncertainties in the approach are identified and discussed. A major finding of this exercise was that vapor phase transfers of dioxin-like compounds to vegetations that cattle consume dominate the estimation of final beef concentrations: over 80% of the modeled beef concentration was attributed to such transfers.

Air Pollutants

Interleukin-1 beta induces differential adhesiveness on human endothelial cell surfaces.

The adhesive strength between HL-60 and endothelial cells activated with IL-1 beta was investigated according to the region (area) on the endothelial cell surface where the HL-60 cell was attached (nuclear, junctional, or cytoplasmic). Using a micropipette single-cell manipulation system, we demonstrated that the increase of adhesive force was due to the activation of the endothelial cell with IL-1 beta and a function of the region of the endothelial cell. The increase in adhesion strength due to the increased expression of E-Selectin on the endothelial cell was studied by the addition of monoclonal antibodies against E-Selectin, ICAM-1, VCAM, and PECAM-1. Our findings suggest that the greatest adhesive strength was seen in the junctional region where the antibodies could not block the adhesion. However, the contribution of E-Selectin was significant in the nuclear region.

Antibodies, Monoclonal

Cytotoxic effects of inhibitors of de novo pyrimidine biosynthesis upon Plasmodium falciparum.

The malarial parasite Plasmodium falciparum can only synthesize pyrimidine nucleotides via the de novo pathway which is therefore a suitable target for development of antimalarial drugs. New assay procedures have been developed using high-pressure liquid chromatography (HPLC) which enable concurrent measurement of pyrimidine intermediates in malaria. Synchronized parasites growing in erythrocytes were pulse-labeled with [14C]bicarbonate at 6-h intervals around the 48-h asexual life cycle. Analysis of malarial extracts by HPLC showed tht incorporation of [14C]bicarbonate into pyrimidine nucleotides was maximal during the transition from trophozoites to schizonts. The reaction, N-carbamyl-L-aspartate-->L-dihydroorotate (CA-asp-->DHO) catalyzed by malarial dihydroorotase is inhibited by L-6-thiodihydroorotate (TDHO) in vitro (Ki = 6.5 microM), and TDHO, as the free acid or methyl ester, induces a major accumulation of CA-asp in malaria. Atovaquone, a naphthoquinone, is a moderate inhibitor of dihydroorotate dehydrogenase in vitro (Ki = 27 microM) but induces major accumulations of CA-asp and DHO. Pyrazofurin induces accumulation of orotate and orotidine in malaria, consistent with inhibition of orotidine 5'-monophosphate (OMP) decarboxylase with subsequent dephosphorylation of the OMP accumulated. Although TDHO, atovaquone, and pyrazofurin arrest the growth of P. falciparum, only moderate decreases in UTP, CTP, and dTTP were observed. 5-Fluoroorotate also arrests the growth of P. falciparum with major accumulations of 5-fluorouridine mono-, di-, and triphosphates and the most significant inhibition of de novo biosynthesis of pyrimidine nucleotides.

Amides

Ethical reasoning concerning the feeding of severely demented patients: an international perspective.

Structured interviews were held with 149 registered nurses in seven countries in America, Asia, Australia and Europe concerning the feeding of severely demented patients who do not accept food. The most common reasons for nurses being willing to change their decision to feed or not to feed were an order from the medical head, a request from the patient's husband and/or the staff meeting. There was a connection between the willingness to feed and the ranking of ethical principles. Nurses who were most prone to feed the patient most often gave a high rank to the ethical principle of sanctity of life, while those who primarily chose not to feed the patient gave a high rank to the ethical principle of autonomy. All nurses stressed the ethical principle of beneficence.

Adult

Expression and post-translational processing of a broad-spectrum organophosphorus-neurotoxin-degrading enzyme in insect tissue culture.

A recombinant baculovirus, Autographa californica nuclear polyhedrosis virus (AcNPV), has been utilized to express the opd (organophosphate-degrading) gene from Pseudomonas diminuta in insect tissue-culture cells (Sf9) of the fall armyworm (Spodoptera frugiperda). The broad-spectrum organophosphate hydrolase (EC 3.1.8.1) encoded by this gene is a member of a general class of enzymes [organophosphate (OP) anhydrolases] that include parathion hydrolases, di-isopropyl-fluorophosphatases (DFPases), somanases, and OP phosphotriesterases. This particular enzyme possesses the ability to hydrolyse paraoxon (P-O bond), DFP, sarin (P-F bond), VX (P-S bond) and tabun (P-CN bond), as well as a number of other extensively used organophosphorus pesticides. The enzyme produced in infected Sf9 cells is post-translationally processed and resembles the mature form of the enzyme expressed in various bacterial cells as identified by immunoprecipitation on Western blots. N-terminal sequence analysis of enzyme expressed in insect cells revealed Gly-29 as the terminal residue, whereas expression in Escherichia coli removes this residue, exposing Ser-30 at the N-terminus. Conditions for optimal expression of the enzyme in this system are described. Furthermore, hydrolytic efficiency of some OPs with purified enzyme from this system is discussed in relation to the in situ activity of Pseudomonas diminuta MG cells.

Animals

Prevalence of shigellosis and other enteric pathogens in a zoologic collection of primates.

An epidemiologic study of shigellosis was the preliminary step in the formulation of a plan for the control of devastating infectious diseases in nonhuman primates at the National Zoological Park. Data were collected from primate groups with enzootic shigellosis and included the following species: white-cheeked and siamong gibbons (Hylobates concolor and H syndactylies); lion-tailed, celebes, and Barbary macaques (Macaca silenus, M nigera, and M sylvanus); black and white colobus monkeys (Colobus guerzea); grey-cheeked mangabeys (Cerecocebus albigena); spider monkeys (Ateles susciceps robusuts); ruffed lemurs (Lemur varrigatus); lowland gorillas (Gorilla gorilla); and orangutans (pongo pygmaeus). Data included results of physical examination, proctoscopy with biopsy, fecal parasitologic and cytologic examinations, and bacteriologic culturing of swabbed specimens of rectum and gingiva. Repetitive fecal examinations were subsequently performed and included bacteriologic culturing of fecal specimens for enteropathogenic bacteria and parasites and cytologic examination of feces. Data were collected for a 1-year period from 82 primates, and 14 gibbons were studied intensively. White-cheeked and siamang gibbons shed Shigella flexneri sporadically, but persistently. All gibbons were affected with a mean point prevalence of 30.7% (range 0 to 71%). Shigella flexneri also was isolated from feces of lion-tailed macaques. Shigella sonnei was isolated from feces of grey-cheeked mangabeys, celebes macaques, and spider monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Focus on psychometrics. Development and administration of a survey instrument for cross-cultural research.

The purpose of this article is to provide a brief review of guidelines for development of culturally appropriate measures of phenomena. The principles are illustrated by citing an example of their use in developing a survey instrument to be used with a rural Mexican American and Euro American population. Discussion focuses on practical issues of implementing the approaches suggested in the literature and adds to the literature about issues in formatting and administration of survey instruments used in cross-cultural research.

Cross-Cultural Comparison