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Biomedical subjects

C C Williams

Publications and source records attributed to C C Williams.

At least 37 records · Page 2Linked to original sources

Macrophages kill T9 glioma tumor cells bearing the membrane isoform of macrophage colony stimulating factor through a phagocytosis-dependent pathway.

Rat T9 glioma cells transfected with the gene for the membrane isoform of macrophage-CSF (mM-CSF) but not for the secreted isoform of M-CSF were directly killed by bone marrow-derived macrophages. Macrophage-mediated cytolysis of the mM-CSF-transfected clone was blocked by using chemical inhibitors of phagocytosis such as iodoacetate, 2-deoxyglucose, gadolinium chloride, and cytochalasin B. In contrast, macrophage-mediated killing of mM-CSF-expressing tumor cells was augmented by the microtubule inhibitor, colchicine. Use of nitric oxide and reactive oxygen intermediate inhibitors failed to alter the macrophage-mediated killing of the mM-CSF-transfected tumor cells. Photomicroscopy, using immunohistochemical staining with the anti-Hck Ab to distinguish macrophages from tumor cells, revealed that phagocytosis began within 2 h after addition of the mM-CSF-bearing tumor cells. Photocinematography confirmed that macrophages first phagocytosized and then lysed the internalized mM-CSF transfectant cells. Using annexin V and acridine orange staining techniques, macrophages phagocytosized living mM-CSF-transfected tumor cells.

Animals↗

Induction of Arabidopsis tryptophan pathway enzymes and camalexin by amino acid starvation, oxidative stress, and an abiotic elicitor.

The tryptophan (Trp) biosynthetic pathway leads to the production of many secondary metabolites with diverse functions, and its regulation is predicted to respond to the needs for both protein synthesis and secondary metabolism. We have tested the response of the Trp pathway enzymes and three other amino acid biosynthetic enzymes to starvation for aromatic amino acids, branched-chain amino acids, or methionine. The Trp pathway enzymes and cytosolic glutamine synthetase were induced under all of the amino acid starvation test conditions, whereas methionine synthase and acetolactate synthase were not. The mRNAs for two stress-inducible enzymes unrelated to amino acid biosynthesis and accumulation of the indolic phytoalexin camalexin were also induced by amino acid starvation. These results suggest that regulation of the Trp pathway enzymes under amino acid deprivation conditions is largely a stress response to allow for increased biosynthesis of secondary metabolites. Consistent with this hypothesis, treatments with the oxidative stress-inducing herbicide acifluorfen and the abiotic elicitor alpha-amino butyric acid induced responses similar to those induced by the amino acid starvation treatments. The role of salicylic acid in herbicide-mediated Trp and camalexin induction was investigated.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Preliminary investigation of the use of dried-blood spots for the assessment of in utero exposure to environmental pollutants.

We determined the concentration of dichlorodiphenyldichloroethylene (p,p'-DDE) in dried-blood spot specimens from 2-day-old infants from rural Texas who had never been breast fed. Anonymous, residual whole blood spots on filter paper, previously used for routine newborn screening procedures, were soaked in a phosphate buffer, extracted with an organic solvent, and eluted through silica gel. The concentrated eluates were analyzed by capillary gas chromatography with electron capture detection (ECD). The blood collected from 10 newborns was analyzed and found to contain DDE concentrations ranging from 0.13 to 1.87 pg/microliter with a mean of 0.72 pg/microliter. One of the 10 newborns had a whole blood DDE concentration of 1.87 pg/microliter, which was greater than the concentration of 1.34 pg/microliter in a freshly drawn sample from an adult donor whose blood serum was shown to contain DDE. With improvement in detection limits, this approach has the potential to displace the analyses of mothers' blood (as a surrogate indicator of infants' exposures) and cord blood as standard procedures for determining the newborns' body burden of environmental pollutants.

Adult↗

Nitrogen metabolism and hormonal responses of steers fed wheat silage and infused with amino acids or casein.

Four Holstein steers (159 kg) surgically fitted with abomasal-infusion cannulas were used in a 4 x 4 Latin square study to test amino acid (AA) and casein (CAS) infusions on nitrogen balance and hormonal status of steers consuming vegetative wheat (Triticum aestivum L.) silage (12.3% CP). Treatments were 5-d infusions of 1) water (CONT), 2) arginine (ARG; 13.69 g/d), 3) limiting amino acids (LAA, 13.69 g/d arginine + 10.92 g/d histidine + 28.97 g/d lysine + 10.88 g/d methionine + 16.96 g/d threonine, and 4) Na-CAS (300 g/d). Whole blood was collected for plasma AA, growth hormone (GH), insulin, and IGF-I concentrations. Data were analyzed by ANOVA, and the following orthogonal contrasts were used to separate treatment means: CONT vs ARG; ARG vs LAA; and LAA vs CAS. Urinary N increased (P < .02) for CAS vs LAA. Arginine increased N retention, as did CAS, compared to LAA. Total plasma essential AA were decreased by arginine. Mean plasma insulin concentrations were increased by CAS (P < .034). Arginine increased mean plasma GH levels, but not IGF-I. The CAS treatment increased (P < .015) IGF-I levels, but not GH. These data suggest that performance of steers fed wheat silage was limited by duodenal AA flow and that arginine was the first-limiting AA. Casein infusion increased plasma insulin and IGF-I, which would explain the improved growth noted in calves and lambs fed forages supplemented with ruminally undegraded protein.

Amino Acids↗

Individualized care for frail elders: theory and practice.

Individualized care for frail elders is defined as an interdisciplinary approach which acknowledges elders as unique persons and is practiced through consistent caring relationships. The four critical attributes of individualized care for frail elders are: 1) knowing the person, 2) relationship, 3) choice, and 4) participation in and direction of care. Cognitively impaired elders can direct their care through the staff's knowledge of individual past patterns and careful observation of behavior for what is pleasing and comfortable to each resident.

Aged↗

Pesticide residues in urine of adults living in the United States: reference range concentrations.

We measured 12 analytes in urine of 1000 adults living in the United States to establish reference range concentrations for pesticide residues. We frequently found six of these analytes: 2,5-dichlorophenol (in 98% of adults); 2,4-dichlorophenol (in 64%); 1-naphthol (in 86%); 2-naphthol (in 81%); 3,5,6- trichloro-2-pyridinol (in 82%); and pentachlorophenol (in 64%). The 95th percentile concentration (95th PC) for 2,5-dichlorophenol (indicative of p-dichlorobenzene exposure) was 790 micrograms/liter; concentrations ranged up to 8700 micrograms/liter. 2,4-Dichlorophenol concentrations ranged up to 450 micrograms/ liter, and the 95thPC was 64 micrograms/liter. 1-Naphthol and 2-naphthol (indicative of naphthalene exposure) had 95thPCs of 43 and 30 micrograms/liter, respectively; concentrations of 1-naphthol ranged up to 2500 micrograms/liter. Chlorpyrifos exposure was indicated by 3,5,6-tricholoro-2-pyridinol concentrations of 13 (95thPC) and 77 micrograms/liter (maximum observed). Pentachlorophenol had a 95thPC of 8.2 micrograms/liter. Other analytes measured included 4-nitrophenol (in 41%); 2,4,5-trichlorophenol (in 20%); 2,4,6-trichlorophenol (in 9.5%); 2,4-dichlorophenoxyacetic acid (in 12%); 2-isopropoxyphenol (in 6.8%); and 7-carbofuranphenol (in 1.5%). The 95thPCs of these analytes were < 6 micrograms/liter. p-Dichlorobenzene exposure is ubiquitous; naphthalene and chlorpyrifos are also major sources of pesticide exposure. Exposure to chlorpyrifos appears to be increasing. Although pentachlorophenol exposure is frequent, exposure appears to be decreasing. These reference range concentrations provide information about pesticide exposure and serve as a basis against which to compare concentrations in subjects who may have been exposed to pesticides.

2,4-Dichlorophenoxyacetic Acid↗

Determination of pesticide metabolites in human urine using an isotope dilution technique and tandem mass spectrometry.

A method that measures 12 analytes in urine and reflects possible exposure to pesticides was developed. The sample preparation involves enzyme hydrolysis and solvent extraction through the use of laboratory robotics, followed by phase-transfer catalysis derivatization and silica cleanup. Samples are analyzed by capillary gas chromatography and tandem mass spectrometry using an isotope dilution technique with 13C-labeled internal standards. The limit of detection is 1 microgram/L (1 part per billion) for most analytes, and most analytes have a linear response up to 100 micrograms/L. The precision of the method is reflected in the variation observed in quality control materials over 33 months; the variation averaged 17% for these analytes. On the basis of the detectable analyte levels of unspiked urine samples collected from unexposed volunteers, this method can be used to measure the low levels necessary for establishing reference range values of the selected pesticides or metabolites.

Calibration↗

Syncope in athletes.

Syncope is a brief sudden loss of consciousness and muscle tone secondary to cerebral ischaemia, inadequate oxygen or glucose delivery to the brain. The causes of syncope may be benign and require very little in the way of evaluation or treatment. However, syncope may be the harbinger of sudden death, and extensive evaluation, monitoring and detailed recommendations regarding advisability of participating in sports should be reviewed with the patient. The history is the most important clue when attempting to identify which patient with syncope is at risk for sudden death. A careful cardiac and neurological examination should be performed in any patient presenting with syncope. Selective use of laboratory testing and cardiac monitoring may assist the practitioner in making the diagnosis. Most often patients with syncope will have a benign cause such as vaso-vagal events, hyperventilation or orthostatic hypotension. Patients with a cardiac condition causing their syncope are at increased risk for sudden death. The ominous, cardiac-related causes of syncope in the younger population include hypertrophic cardiomyopathy, aberrant coronary arteries and aortic dissection secondary to Marfan's syndrome. In the older athletic population, coronary atherosclerosis may present with syncope. Dysrhythmias may be the cause of syncope in both populations.

Adolescent↗

Effects of inoculation and wilting on the preservation and utilization of wheat forage.

Wheat forage was harvested at an early head stage of maturity and ensiled in 12 900-kg experimental silos at three percentages of DM (20.8% for direct-cut forage and 27.9 or 39.3% for wilted forage) either with or without application of a lactic acid bacterial inoculant. The objective was to test the efficacy of the inoculant to alter silage fermentation, preservation, and nutritive value of wheat forage ensiled at different moisture percentages because of wilting. Wilting enhanced DM preservation and decreased fermentation end products. Inoculation made the fermentation more homolactic but did not enhance DM preservation. Silage rations (80% DM as silage) were fed at 1.8% of BW/d to six ruminally and abomasally fistulated steers (350 kg) in an experiment with a Latin-square design and a 3 x 2 factorial arrangement of treatments. Digestive responses to silage diets were not influenced by inoculation. Intake was depressed with direct-cut silage rations. Wilting improved fiber digestibility and was associated with changes in ruminal contents and fermentation end products. Wilting appears to be more effective than inoculation as a postharvest management tool to improve small grain silage.

Animal Feed↗

Macrophage-colony-stimulating factor expression by anti-CD45 stimulated human monocytes is transcriptionally up-regulated by IL-1 beta and inhibited by IL-4 and IL-10.

Macrophage (M)-CSF is a survival and differentiation factor for mononuclear phagocytes. Stimulation of human monocytes with immobilized mAb directed to CD45 induces M-CSF message and small amounts of protein, which is strongly augmented by costimulation with IL-1 beta. This study was undertaken to study the mechanisms leading to the IL-1 beta-induced up-regulation of M-CSF production and to determine how the antiinflammatory cytokines, IL-4 and IL-10, affect M-CSF production in this system. We demonstrate that IL-1 beta enhanced M-CSF mRNA levels, in part, by increasing M-CSF gene transcription but had no effect on M-CSF message half-life. The enhancement of M-CSF message levels in the presence of IL-1 beta was blocked by cycloheximide, suggesting that de novo protein synthesis was required. Moreover, soluble IL-1 receptors inhibited the effect of IL-1 beta on M-CSF production thus confirming that these effects were IL-1 receptor mediated. Both IL-4 and IL-10 strongly inhibited M-CSF secretion by anti-CD45/IL-1 beta-induced monocytes that was accompanied by decreased M-CSF message levels. IL-4 and IL-10 repressed M-CSF gene transcription but did not affect M-CSF message half-life. These findings demonstrate that IL-1 beta, at least in part, transcriptionally up-regulates M-CSF production in anti-CD45-stimulated human monocytes, a process that can be negatively regulated by both IL-4 and IL-10. These results suggest that IL-1 beta, IL-4, and IL-10 control the survival and differentiation of human monocytes through a regulation of autocrine M-CSF production.

Cycloheximide↗

Effects of supplemental protein source on ruminal fermentation, protein degradation, and amino acid absorption in steers and on growth and feed efficiency in steers and heifers.

In Exp. 1, four Holstein steers with cannulas in the rumen, abomasum and terminal ileum were used to determine the effects of 1) soybean meal (SBM), 2) heated SBM (HSBM), 3) corn gluten meal (CGM), or 4) a combination of HSBM and CGM (COMBO) as protein supplements on ruminal and total tract nutrient digestibilities and intestinal amino acid flows and absorption. In Exp. 2, 24 Holstein steers and 16 Holstein heifers were used in a 56-d growth trial to study the effects of these protein supplements on growth, feed efficiency, and apparent digestibility of DM, OM, CP, and fiber components. Increasing undegradable intake protein (UIP) in diets with HSBM, CGM, and COMBO decreased ruminal fluid ammonia N concentrations (P < .05) and ruminal DM and OM digestion (P < .05) and increased flow to the abomasum and absorption from the small intestine of CP (P < .05), total amino acids (P < .05), and total essential amino acids (P < .01). Increasing UIP increased bacterial and nonbacterial CP and amino acids flowing to the abomasum (P < .05). However, UIP supplementation did not affect DMI, ADG, or feed efficiency in steers or heifers (P < .05).

Amino Acids↗

Response of early lactation cows to fat supplementation in diets with different nonstructural carbohydrate concentrations.

Twenty-four high producing (36.7 kg/d, initially) Holstein cows in early lactation were used in a 63-d lactation trial to study the effects of low (28%), medium (31%), and high (37%) nonstructural carbohydrate concentrations in diets with added fat. Diets with isonitrogenous (17% CP) and fed as TMR with 41% sorghum silage. Nonstructural carbohydrate concentrations were altered by substitution of corn gluten feed and soybean hulls (50:50) for wheat and corn in the concentrate portion of the diet. Fat was added at 3% of DM in the form of yellow grease. Production of milk (38.5, 38.9, and 40.4 kg/d) and 3.5% FCM (38.2, 37.0, and 37.6 kg/d) was not significantly different for the cows fed low, medium, and high nonstructural carbohydrate diets, respectively. Milk fat percentages (3.47, 3.22, and 3.10%) decreased, and milk output per unit of DMI (1.5, 1.6, and 1.7) increased, as nonstructural carbohydrate concentration increased. Increasing nonstructural carbohydrate concentrations of the diet increased digestibilities of DM (58.4, 60.6, and 61.5%) and nonstructural carbohydrates (76.5, 79.6, and 80.4%) and decreased digestibilities of NDF (44.3, 43.7, and 40.6%) and ADF (46.3, 45.2, and 38.8%). Altering nonstructural carbohydrate content of the diet had no effect on AA supply to or uptake by the mammary gland or efficiency of utilization of AA for milk protein synthesis.

Animal Feed↗

The bacterial endotoxin test in the PET facility.

A method by which the gel-clot Limulus amebocyte lysate test may be performed in 20 rather than 60 min with sufficient sensitivity to satisfy the needs of the nuclear medicine or positron emission tomography laboratories has been developed and validated for use as a substitute for the Bacterial Endotoxin Test described in the United States Pharmacopeia, 22nd revision. Using this method, results may be obtained from the test prior to the human administration of radiopharmaceuticals without extensive loss of activity and with increased safety when compared to tests performed after administration. Additionally, studies on the shelf-lives of the reagents used in the test were conducted. When refrigerated between use, control standard endotoxin dilutions of 5 EU/ml or greater may be used for at least 1 mo after preparation and reconstituted lysate retains its labeled sensitivity for at least 10 days, considerably longer than the manufacturer's stated shelf-lives.

Ammonia↗

Safety and efficacy of repeated sequential administrations of Re-186(Sn)HEDP as palliative therapy for painful skeletal metastases. Initial case reports of two patients.

Single intravenous injections of 30 to 35 mCi (1,110 to 1,295 MBq) of Re-186(Sn)HEDP previously have been shown to result in palliation of painful skeletal metastases from prostate cancer. There are no reports of patients receiving repetitive Re-186(Sn)HEDP therapy. We have followed two such patients who received multiple (five to seven) injections of Re-186(Sn)HEDP at 2-month intervals. Each experienced a sustained decrease in both pain and analgesic intake. The only evident clinical or biochemical toxicity was a mild progressive decline in their total platelet counts.

Adenocarcinoma↗