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Biomedical subjects

S B Williams

Publications and source records attributed to S B Williams.

At least 19 recordsLinked to original sources
PubMed2005

Effects of supplemental dietary phytase and pharmacological concentrations of zinc on growth performance and tissue zinc concentrations of weanling pigs.

Three experiments were conducted to determine the effects of phytase, excess Zn, or their combination in diets for nursery pigs. In all experiments, treatments were replicated with five to seven pens of six to seven pigs per pen, dietary Ca and available P (aP) levels were decreased by 0.1% when phytase was added to the diets, excess Zn was added as ZnO, a basal level of 127 mg/kg of Zn (Zn sulfate) was present in all diets, and the experimental periods were 19 to 21 d. In Exp. 1, pigs (5.7 kg and 18 d of age) were fed two levels of phytase (0 or 500 phytase units/kg) and three levels of excess Zn (0, 1,000, or 2,000 ppm) in a 2 x 3 factorial arrangement. Added Zn linearly increased ADG and ADFI during Phase 1 (P = 0.01 to 0.06), Phase 2 (P = 0.02 to 0.09), and overall (P = 0.01 to 0.02). Gain:feed was linearly increased by Zn during Phase 1 (P = 0.01) but not at other times. Dietary phytase decreased ADG in pigs fed 1,000 or 2,000 ppm Zn during Phase 2 (Zn linear x phytase interaction; P = 0.10), did not affect (P = 0.27 to 0.62) ADFI during any period, and decreased G:F during Phase 2 (P = 0.01) and for the overall (P = 0.07) period. Plasma Zn was increased by supplemental Zn (Zn quadratic, P = 0.01) but not affected (P = 0.70) by phytase addition. In Exp. 2, pigs (5.2 kg and 18 d of age) were fed two levels of phytase (0 or 500 phytase units/kg) and two levels of Zn (0 or 2,000 ppm) in a 2 x 2 factorial arrangement. Supplemental Zn increased ADG and G:F during Phase 2 (P = 0.02 to 0.09) and overall (P = 0.07 to 0.08), but it had no effect (P = 0.11 to 0.89) on ADG during Phase 1 or ADFI during any period. Phytase supplementation increased ADG (P = 0.06) and G:F (P = 0.01) during Phase 2. Gain:feed was greatest for pigs fed 2,000 ppm Zn and phytase (Zn x phytase interaction; P = 0.01). Bone (d 20) and plasma Zn (d 7 and 20) were increased (P = 0.01) by added Zn but not affected (P = 0.51 to 0.90) by phytase. In Exp. 3, pigs (5.7 kg and 19 d of age) were fed a basal diet or the basal diet with Ca and aP levels decreased by 0.10% and these two diets with or without 500 phytase units/kg. Supplemental phytase had no effect (P = 0.21 to 0.81) on growth performance. Reduction of dietary Ca and aP decreased (P = 0.02 to 0.08) ADG, ADFI, and G:F for the overall data. These results indicate that excess dietary supplemental Zn increases ADG and plasma and bone Zn concentrations. Dietary phytase did not affect plasma or bone Zn concentrations.

6-Phytase↗
PubMed2004

Effect of phytase addition and dietary calcium and phosphorus levels on plasma metabolites and ileal and total-tract nutrient digestibility in pigs.

Two experiments were conducted to determine the effect of phytase on plasma metabolites and AA and energy digestibility in swine. In Exp. 1, eight barrows (surgery BW = 52 kg) were fitted with steered ileocecal cannulas. The experiment was a Latin rectangle and the treatments were 1) corn-soybean meal diet adequate in Ca and P (0.5% Ca, 0.19% available P [aP]), 2) corn-soybean meal diet with reduced Ca and P (0.4% Ca, 0.09% aP), 3) Diet 1 with 500 phytase units/kg, or 4) Diet 2 with 500 phytase units/kg. Pigs were fed twice daily to a total daily energy intake of 2.6 x maintenance (106 kcal of ME/kg of BW(0.75)). For each ileal digesta sample, digesta samples were collected for two 24-h periods and combined for each pig. The combination of supplementing with phytase and decreasing the concentration of dietary Ca and P increased average ileal AA (P < 0.02), starch (P < 0.02), GE (P < 0.04), and DM (P < 0.03) digestibilities. In Exp. 2, a feeding challenge was conducted with barrows (eight per treatment; average BW of 53 kg). The treatments consisted of a corn-soybean meal diet or corn-soybean meal diet + 500 phytase units per kilogram of diet. In the diet with no phytase, Ca and aP were at 0.50% and 0.19%, respectively, and, in the diet with phytase, Ca and aP were each decreased by 0.12%. A catheter was surgically inserted into the anterior vena cava of each pig 6 d before the start of the feeding challenge. The barrows were penned individually, and the diets were fed for 3 d before the challenge. The pigs were held without feed for 16 h, and blood samples were obtained at -60, -30, and 0 min before the pigs were fed (2% of BW). Blood samples were then collected at 10, 20, 30, 40, 50, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min after feeding. Glucose area under the response curve and plasma glucose, insulin, urea N, and total alpha-amino N concentrations were increased (P < 0.05) in pigs fed the diet with reduced Ca and P and the phytase addition. Area under the response curve for insulin, urea N, and total alpha-amino N; insulin:glucose; and plasma NEFA concentration, clearance, and half-life were not affected by diet. In conclusion, the combination of Ca and P reduction and phytase addition increased nutrient and energy digestibility in diets for pigs and increased plasma concentrations of glucose, insulin, urea N, and alpha-amino N.

6-Phytase↗
PubMed2003

A cyanobacterial circadian timing mechanism.

Cyanobacteria such as Synechococcus elongatus PCC 7942 exhibit 24-h rhythms of gene expression that are controlled by an endogenous circadian clock that is mechanistically distinct from those described for diverse eukaryotes. Genetic and biochemical experiments over the past decade have identified key components of the circadian oscillator, input pathways that synchronize the clock with the daily environment, and output pathways that relay temporal information to downstream genes. The mechanism of the cyanobacterial circadian clock that is emerging is based principally on the assembly and disassembly of a large complex at whose heart are the proteins KaiA, KaiB, and KaiC. Signal transduction pathways that feed into and out of the clock employ protein domains that are similar to those in two-component regulatory systems of bacteria.

Circadian Rhythm↗
PubMed2001

Conformational regulation of the fibronectin binding and alpha 3beta 1 integrin-mediated adhesive activities of thrombospondin-1.

The recognition of extracellular matrix components can be regulated by conformational changes that alter the activity of cell surface integrins. We now demonstrate that conformational regulation of the matrix glycoprotein thrombospondin-1 (TSP1) can also modulate its binding to an integrin receptor. F18 1G8 is a conformation-sensitive TSP1 antibody that binds weakly to soluble TSP1 in the presence of divalent cations. However, binding of the antibody to melanoma cells was strongly stimulated by adding exogenous TSP1 in the presence of calcium, suggesting that TSP1 undergoes a conformational change following its binding to the cell surface. This conformation was not induced by known cell surface TSP1 receptors, whereas binding of F18 was stimulated when TSP1 bound to fibronectin but not to heparin or fibrinogen. Conversely, binding of F18 to TSP1 enhanced TSP1 binding to fibronectin. Exogenous fibronectin also stimulated TSP1-dependent binding of F18 to melanoma cells. Binding of the fibronectin-TSP1 complex to melanoma cells was mediated by alpha4beta1 and alpha5beta1 integrins. Furthermore, binding to F18 or fibronectin strongly enhanced the adhesive activity of immobilized TSP1 for some cell types. This enhancement of adhesion was mediated by alpha3beta1 integrin and required that the alpha3beta1 integrin be in an active state. Fibronectin also enhanced TSP1 binding to purified alpha3beta1 integrin. Therefore, both fibronectin and the F18 antibody induce conformational changes in TSP1 that enhance the ability of TSP1 to be recognized by alpha3beta1 integrin. The conformational and functional regulation of TSP1 activity by fibronectin represents a novel mechanism for extracellular signal transduction.

Animals↗
PubMed2001

Attenuation and activation characteristics of steel and tungsten and the suitability of these materials for use in a fast neutron multileaf collimator.

A computer controlled multileaf collimator (MLC) is being designed to replace the multirod collimator (MRC) at present used to shape the d(48.5) + Be neutron beam from the Harper Hospital superconducting cyclotron. The computer controlled MLC will improve efficiency and allow for the future development of intensity modulated radiation therapy with neutrons. The existing MRC uses tungsten rods, while the new MLC will use steel as the leaf material. In the current study the attenuation and activation characteristics of steel are compared with those of tungsten to ensure that (a) the attenuation achieved in the MLC is at least equivalent to that of the existing MRC, and (b) that the activation of the steel will not result in a significant change in the activation levels within the treatment room. The latter point is important since personnel exposure (particularly to the radiation therapy technologists) from induced radioactivity must be minimized. Measurement of the neutron beam attenuation in a broad beam geometry showed that a 30 cm thick steel leaf yielded 2.5% transmission. This compared favorably with the 4% transmission obtained with the existing MRC. Irradiation of steel and tungsten samples at different depths in a 30 cm steel block indicated that the activation of steel should be no worse than that of tungsten.

Biophysical Phenomena↗
PubMed2000

CikA, a bacteriophytochrome that resets the cyanobacterial circadian clock.

The circadian oscillator of the cyanobacterium Synechococcus elongatus, like those in eukaryotes, is entrained by environmental cues. Inactivation of the gene cikA (circadian input kinase) shortens the circadian period of gene expression rhythms in S. elongatus by approximately 2 hours, changes the phasing of a subset of rhythms, and nearly abolishes resetting of phase by a pulse of darkness. The CikA protein sequence reveals that it is a divergent bacteriophytochrome with characteristic histidine protein kinase motifs and a cryptic response regulator motif. CikA is likely a key component of a pathway that provides environmental input to the circadian oscillator in S. elongatus.

Alleles↗
PubMed2000

A kaiC-interacting sensory histidine kinase, SasA, necessary to sustain robust circadian oscillation in cyanobacteria.

Both regulated expression of the clock genes kaiA, kaiB, and kaiC and interactions among the Kai proteins are proposed to be important for circadian function in the cyanobacterium Synechococcus sp. strain PCC 7942. We have identified the histidine kinase SasA as a KaiC-interacting protein. SasA contains a KaiB-like sensory domain, which appears sufficient for interaction with KaiC. Disruption of the sasA gene lowered kaiBC expression and dramatically reduced amplitude of the kai expression rhythms while shortening the period. Accordingly, sasA disruption attenuated circadian expression patterns of all tested genes, some of which became arrhythmic. Continuous sasA overexpression eliminated circadian rhythms, whereas temporal overexpression changed the phase of kaiBC expression rhythm. Thus, SasA is a close associate of the cyanobacterial clock that is necessary to sustain robust circadian rhythms.

Adaptation, Physiological↗
PubMed2000

Use of advance information in patients with schizophrenia.

To document possible motor disturbance in schizophrenia, we examined the ability to use advance information (or cues) to plan movements in a sequential button pressing task in 12 Clozapine medicated patients. Programming of movements under various cues revealed that patients with schizophrenia, relative to controls, initiated movements slower to the right than left, providing possible evidence for right hemineglect (left hemisphere dysfunction). Additionally, patients with schizophrenia had difficulty in the initiation of movements in the absence of a cue, suggesting internal cue generation difficulty for movement related to some form of fronto-striatal disturbance. Motor abnormalities were predominantly observed at the level of movement initiation, but not execution, contrary to basal ganglia disorders such as Parkinson's and Huntington's disease.

Adult↗
PubMed1999

Functional similarities among two-component sensors and methyl-accepting chemotaxis proteins suggest a role for linker region amphipathic helices in transmembrane signal transduction.

Signal-responsive components of transmembrane signal-transducing regulatory systems include methyl-accepting chemotaxis proteins and membrane-bound, two-component histidine kinases. Prokaryotes use these regulatory networks to channel environmental cues into adaptive responses. A typical network is highly discriminating, using a specific phosphoryl relay that connects particular signals to appropriate responses. Current understanding of transmembrane signal transduction includes periplasmic signal binding with the subsequent conformational changes being transduced, via transmembrane helix movements, into the sensory protein's cytoplasmic domain. These induced conformational changes bias the protein's regulatory function. Although the mutational analyses reviewed here identify a role for the linker region in transmembrane signal transduction, no specific mechanism of linker function has yet been described. We propose a speculative, mechanistic model for linker function based on interactions between two putative amphipathic helices. The model attempts to explain both mutant phenotypes and hybrid sensor data, while accounting for recognized features of amphipathic helices.

Amino Acid Sequence↗
PubMed1998

Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo.

BACKGROUND: Endothelial function is impaired in patients with diabetes mellitus. However, the factors contributing to this defect are currently unknown. Hyperglycemia attenuates endothelium-dependent relaxation in normal rabbit arteries in vitro and rat arterioles in vivo. Accordingly, this study examined the effect of acute hyperglycemia on endothelium-dependent vasodilation in nondiabetic humans in vivo. METHODS AND RESULTS: Endothelium-dependent vasodilation was assessed through brachial artery infusion of methacholine chloride both before and during 6 hours of local hyperglycemia (300 mg/dL) achieved by intra-arterial infusion of 50% dextrose. Forearm blood flow was determined by plethysmography. In a group of 10 subjects, there was a trend toward attenuated methacholine-mediated vasodilation during hyperglycemia compared with euglycemia (P=.07 by ANOVA; maximal response, 13.3+/-2.8 versus 14.7+/-1.5 mL x min(-1) x 100 mL(-1), respectively). In these subjects, the systemic serum insulin levels increased significantly during the dextrose infusion (P<.001). To eliminate the confounding vasoactive effects of insulin, the protocol was repeated during systemic infusion of octreotide (30 ng x kg(-1) x min(-1)) to inhibit pancreatic secretion of insulin. In these subjects (n=10), hyperglycemia significantly attenuated the forearm blood flow response to methacholine (P<.01 by ANOVA; maximal response, 16.9+/-2.5 before versus 12.7+/-1.8 mL x min(-1) x 100 mL(-1) during hyperglycemia). Methacholine-mediated vasodilation was not attenuated by an equimolar infusion of mannitol (P>.40), nor did hyperglycemia reduce endothelium-independent vasodilation to verapamil (P>.50). CONCLUSIONS: Acute hyperglycemia impairs endothelium-dependent vasodilation in healthy humans in vivo. This finding suggests that elevated glucose may contribute to the endothelial dysfunction observed in patients with diabetes mellitus.

Acute Disease↗
PubMed1998

Managed health care and resident education.

OBJECTIVE: We wished to determine the impact of managed health care on resident education in obstetrics and gynecology. STUDY DESIGN: A multiquestion survey was mailed to program directors of the 267 obstetrics-gynecology resident training programs in the United States. The questions ascertained departmental philosophy regarding the role of obstetrician-gynecologists as primary care versus specialist physicians, the extent of involvement with managed health care companies, educational curriculum content, the effect of managed care on patient volume, faculty time available for resident teaching, and the effect of managed care on resident education. RESULTS: Completed surveys were received from 210 (79%) program directors. One hundred twenty-six (63%) program directors responded that obstetrician-gynecologists should be primary care physicians for women, and 120 (60%) believed that the role of subspecialists will be reduced in the near future. In 1996, 177 (94%) programs had managed care contracts; many (57%) had >20 contracts. All programs participate with other specialties to teach primary care to their residents. One hundred twelve (59%) programs have had a decrease in patient volume, prompting 90 (45%) programs to increase their number of teaching sites. Of concern, 54 (26%) program directors noted that managed care companies discourage but do not restrict resident participation in the care and treatment of managed care patients, and 41 (20%) programs had some restrictions placed on such resident involvement. Budgetary constraints have decreased resources to 97 (47%) programs and threaten the time available for faculty teaching. CONCLUSIONS: Managed health care is having an effect on many resident teaching programs. Program directors are integrating managed care concepts into the educational curriculum and are negotiating with managed care organizations to involve residents in the care and treatment of managed care patients.

Curriculum↗
PubMed1998

Glycocalicin levels in the plasma of HIV+ patients: an indicator of platelet turnover.

Glycocalicin (GC) is the carbohydrate-rich portion of platelet membrane glycoprotein Ib(alpha) that can be cleaved from circulating platelets by proteases. The plasma GC level is an indicator of platelet turnover. Using an ELISA for GC, we assayed the plasma of 20 normal children (age 6 to 13 years), 50 HIV+ children (ages 4 to 18 years), 32 normal adults (ages 21 to 53 years), and 50 HIV+ adults (ages 24 to 66 years). The results were adjusted for individual platelet counts to give GC indexes (GCI). The normal children and the normal adults had significantly different GCI distributions (P = .002). In both normal and HIV+ individuals the GCI decreased with increasing platelet count (-.73 < r < -.34). Twenty-eight percent of the HIV+ children and 28% of the HIV+ adults had elevated GCI values. The majority of these elevated values occurred in patients with platelet counts >100,000/microL. Neither the GCI nor the platelet count was correlated with viral load. The platelet count, however, was weakly correlated with the CD4 count in both children (r = .31) and adults (r = .30) infected with HIV. Also, the CD4 count was weakly and inversely correlated with GCI in HIV+ adults (r = -.34) and in children (r = -.24). We conclude that increased GCI and, by implication, increased platelet turnover is a relatively common feature of advanced HIV disease. Furthermore, GCI may be elevated in HIV+ patients even with a platelet count >100,000/microL, suggesting increased platelet turnover before thrombocytopenia develops.

Adolescent↗
PubMed1997

Discrimination between structurally related ligands nitrate and nitrite controls autokinase activity of the NarX transmembrane signal transducer of Escherichia coli K-12.

Anaerobic respiratory gene expression in Escherichia coli is differentially controlled by nitrate and nitrite through dual interacting two-component regulatory systems. The NarX sensor is one of two membrane-spanning sensor kinases that control the phosphorylation state of two DNA-binding response regulators. We have studied NarX autophosphorylation in crude membrane preparations from cells that overexpress NarX protein. The low basal autophosphorylation rate was stimulated about sixfold and threefold by nitrate and nitrite respectively. This demonstrates that nitrate and nitrite differentially activate NarX autokinase activity. We also isolated single-residue substitutions in NarX that affect its ability to respond to or discriminate between nitrate and nitrite. Most of these substitutions affect residues within the conserved P-box sequence in the periplasmic domain. We characterized several of the mutants in vivo, by monitoring ligand-regulated gene expression, and in vitro, by monitoring ligand-responsive autophosphorylation. At least one change, K491 (Lys at position 49 changed to Ile), resulted in a protein with greatly impaired ability to discriminate between nitrate and nitrite. Other changes (H45E and R59K) resulted in proteins that responded normally to nitrate but were unable to respond to nitrite. These results implicate the P-box region in discrimination between subtly different small molecules.

Bacterial Proteins↗