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Biomedical subjects

J C Williams

Publications and source records attributed to J C Williams.

At least 127 records · Page 7Linked to original sources
PubMed1995

Effect of treatment with an ivermectin sustained-release bolus on productivity of stocker beef calves.

Three groups of 30 crossbred beef steers, 8-10 months of age and ranging in weight from 158 to 320 kg, were used to compare effects of treatment with an ivermectin sustained-release bolus or two ivermectin injectable treatments on parasite control and productivity in relation to untreated controls during a 168 day winter-spring grazing period. Each group of 30 consisted of five cattle on each of six separate 1.6 ha pastures. Treatments on Day 0 (12 December) were: Group 1: untreated controls; Group 2: ivermectin injectable at 200 micrograms kg-1 bodyweight, s.c., on Day 0 and Day 56; Group 3: ivermectin sustained-release bolus to deliver ivermectin at 12 mg day-1 over approximately 135 days. All cattle were weighed at 28 day intervals and fecal samples were collected for egg per gram counts (EPG). Geometric mean EPG for Group 3 remained consistently less than 1.0 after Day 0 and were highest (2.4) on Day 168. All group EPG were significantly different (P < 0.01) by Day 56, and EPG of Group 2 had increased to 10.5 following initial treatment and to 42.8 on Day 112. With the exception of a low mean EPG of 6.8 for Group 1 on Day 112, EPG of the group were consistently highest (range 24.9-36.0) to the end of the experiment. Ostertagia ostertagi was predominant, along with smaller proportions of Haemonchus placei and Cooperia spp. Throughout the experiment Group 3 had highest liveweights and gains that were most often different from those of Group 1 at P < 0.01 or greater.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Efficacy of a spring strategic fenbendazole treatment program to reduce numbers of Ostertagia ostertagi inhibited larvae in beef stocker cattle.

Efficacy of a spring strategic treatment program with fenbendazole (FBZ) to reduce the accumulation of Ostertagia ostertagi inhibited early fourth-stage larvae (EL4) was investigated in two groups of crossbred beef heifers which were 7-9 months of age and ranged in weight from 155 to 223 kg. The cattle were allocated to groups and treated on 27 April (Day 0). Group 1 calves served as nontreated controls. Group 2 calves were treated with FBZ 10% drench suspension at 5 mg kg-1 on Day 0 and with 6-day courses of FBZ free-choice mineral (to provide 5 mg kg-1 per animal) on Days 28 and 56. Each group grazed on a separate 4.9 ha pasture for 105 days to 10 August. On 10 August the cattle were taken off pasture and each original group was re-allocated to subgroups of three cattle which were treated orally with FBZ (5 mg kg-1), oxfenbendazole (OXF, 4.5 mg kg-1) or left nontreated (CONT). The cattle were necropsied on Days 120 and 121. Mean actual and cumulative fecal egg counts indicated near total suppression of egg output in the strategically treated group (high of 5.2 eggs g-1 feces (EPG) on Day 28). Egg counts of the nontreated group remained above 100 or 200 EPG to Day 63 and then decreased to less than 100. Ostertagia was the predominant genus, followed by Cooperia on most sampling dates. The largest O. ostertagi worm burdens were recovered from the CONT-CONT subgroup; numbers of EL4 ranged from 18,922 to 51,137. Reduction in numbers of EL4 in original controls, treated with FBZ or OXF in August, were low, being 60.2% and 74.3%, respectively. The numbers of O. ostertagi recovered from subgroups originally treated strategically with FBZ were generally lower than in original controls. The largest reduction in O. ostertagi numbers was in the FBZ-CONT subgroup, which was not treated in August. Percent reduction values for O. ostertagi adults, developing L4 (DL4) and EL4 were 84.6%, 96.7%, and 99.0%, respectively. Percent reduction values for adults, DL4 and EL4 in the FBZ-FBZ and FBZ-OXF subgroups were 90.7%, 61.3%, 85.6% and 92.4%, 45.5%, and 73.0%, respectively. Variability in numbers of EL4 acquired during grazing by original controls and strategically treated cattle and variability in efficacy of August treatments was evident as observed in high outlier numbers of worms in all subgroups except the FBZ-CONT subgroup. Liveweights and gains were nearly identical in the two groups on 10 August.

Animals↗
PubMed1995

Paraphimosis in elderly men.

Paraphimosis occurs when the foreskin of the penis is retracted over the glans and cannot be replaced in its normal position. The tight ring of preputial skin constricts the distal penis causing vascular occlusion, much like a tourniquet. The condition is painful and, if not dealt with quickly, can lead to necrosis of the glans. Simple reduction of the prepuce can be achieved by compressing the edematous fluid out of the glans and repositioning the foreskin. Irreducible paraphimosis is treated by dorsal slit procedure and subsequent circumcision. We present two cases illustrating the treatment techniques and possible complications of paraphimosis in men.

Age Factors↗
PubMed1995

Fatal genitourinary mucormycosis in a patient with undiagnosed diabetes.

We present what we believe is the first report in the world literature of penile necrosis due to mucormycosis, a rare and often fatal fungal infection. This case of rhizopus mucormycosis began with a penile lesion in a 27-year-old patient with undiagnosed diabetes; it led to necrosis of the phallus, lower urinary tract, rectum, and pelvic musculature and finally to death. Despite repeated aggressive surgical debridement in conjunction with medical therapy, we were unable to halt the progression of the fungal and synergistic bacterial infections.

Adult↗
PubMed1995

Acquired renal cystic disease and renal cell carcinoma in an allograft kidney.

Acquired renal cystic disease has been reported in the kidneys of patients with end stage renal disease who have been untreated, treated with dialysis or undergone renal transplantation. The incidence of renal tumor development in patients with acquired renal cystic disease is greater than 5% in those undergoing chronic hemodialysis. Recently, cases of renal cell carcinoma occurring with acquired renal cystic disease of the native kidneys of transplant recipients have been reported. Transplant patients have an increased incidence of malignancy when compared to the general population. Including our case, 19 cases of de novo renal neoplasms developing in renal allografts have been reported. To the best of our knowledge we report the longest interval to presentation of a de novo renal tumor in an allograft kidney (228 months) and the first case of renal cell carcinoma associated with acquired renal cystic disease in an allograft kidney.

Carcinoma, Renal Cell↗
PubMed1995

Cell-mediated and humoral immune responses after vaccination of human volunteers with the live vaccine strain of Francisella tularensis.

The specific humoral and cell-mediated immune responses of human volunteers vaccinated with the Francisella tularensis live vaccine strain (LVS) were evaluated. In the search for an optimal antigen to measure the immunogenicity of the vaccine in an enzyme-linked immunosorbent assay, we tested irradiation-killed LVS, an aqueous ether extract of the LVS (EEx), lipopolysaccharide (LPS) from LVS, and a virulent strain (SCHU4). Volunteers were immunized with LVS by scarification. Immunoglobulin G (IgG) responses to LVS and LPS gave the highest background titers when tested with sera from unimmunized volunteers, whereas IgA, IgG, and IgM background titers to EEx and SCHU4 were low. Vaccination caused a significant rise (P < 0.01) in IgA, IgG, and IgM titers to all antigens tested, except for the IgG response to LPS. Eighty percent of vaccinated volunteers developed a positive IgG response to EEx 14 days postvaccination, while 50% were positive to LVS. By day 14 after vaccination, 70% of immunized volunteers exhibited a positive response to EEx in an in vitro peripheral blood lymphocyte proliferation assay. EEx, a specific and sensitive antigen for evaluating immune responses of vaccinated volunteers, may be a superior antigen for the diagnosis of tularemia.

Adolescent↗
PubMed1995

Persistent anthelmintic activity of ivermectin against gastrointestinal nematodes of cattle.

Two experiments were conducted to determine persistence of ivermectin (IVM) anthelmintic activity. In the first experiment, the injectable (INJ) formulation at a dosage of 200 micrograms/kg of body weight and pour-on (PO) formulation at a dosage of 500 micrograms/kg were compared in 5 groups of calves (n = 6/group). Calves were treated at 14 and 7 days prior to experimentally induced infection. Experimental groups were: 1--untreated, infected controls; 2--IVM PO, day -14; 3--IVM PO, day -7; 4--IVM INJ, day -14; and 5--IVM INJ, day -7. Calves were necropsied on days 28 and 29 after infection. Results of this experiment indicated a high degree of efficacy of IVM PO product (93.8%) for all nematodes up to 14 days, in contrast to poor activity for IVM INJ (26.3%) for all nematodes. Seven-day persistence was excellent for both IVM formulations against Ostertagia ostertagi and Cooperia spp, but a lower degree of efficacy (77.0% for PO and 88.5% for INJ) was observed against Haemonchus placei. In the second experiment, persistent efficacy of IVM PO in preventing establishment of O ostertagi inhibited larvae was observed. In 3 trials, groups of 4 treated and 4 untreated control calves were exposed to natural pasture infection at 0 to 7, 10 to 17, and 20 to 27 days after treatment. Calves were necropsied 15 to 16 days after removal from pasture. After the day 0 to day 7 infection exposure, IVM PO efficacy was 100% for all stages of O ostertagi, 3 adult male Cooperia spp, and Oesophagostomum radiatum; 94.9% for H placei; and 98.2% for Cooperia spp adult females.(ABSTRACT TRUNCATED AT 250 WORDS)

Abomasum↗
PubMed1995

Nutritional therapy for pregnant women with a metabolic disorder.

Nutritional therapy is essential for a normal reproductive outcome in phenylketonuric women. In homocystinuria, fetal outcome is good in women whose disorder is responsive to vitamin B6 therapy and is poor in women whose disorder is unresponsive to therapy. Pregnancy in galactosemia is rare because of the almost universal ovarian dysfunction present in female patients with this disorder. Transplantation of the fertilized ovum is a promising possibility for these women. In women with MSUD, there has been only one case of pregnancy reported to date.

Adolescent↗
PubMed1995

Coxiella burnetii antibody prevalences among human populations in north-east Africa determined by enzyme immunoassay.

Retrospective serosurveys were conducted to determine the prevalence of antibody to phase-I Coxiella burnetii among humans in various locations of north-east Africa. Sera were tested by the enzyme immunoassay (EIA). Initially the EIA was compared with the standard indirect fluorescent antibody (IFA) method for the detection of antibody to C. burnetii. Results indicated that the EIA was slightly less sensitive (88%), but highly specific (94%) and less subjective than the IFA technique. EIA was subsequently adopted for estimating prevalences in the studied human populations. Data obtained by EIA indicated that the prevalence of C. burnetii antibody among adult Egyptian blood donors was 20% (n = 358) in the Suez Canal area, 16% (n = 501) in the Nile Valley and 10% (n = 427) in the Nile Delta. Among adult patients with acute, undifferentiated fever in Egypt, the prevalence was 28% (n = 50) of acute sera, with seroconversion in 12% of convalescent sera. Antibody to C. burnetii was detected by EIA in the sera of 25% (n = 71) of cattle workers in Egypt, 10% (n = 100) of housewives in Sudan, and 37% (n = 104) of adults in north-west Somalia. Following a fever outbreak affecting all ages in northern Sudan, IgG antibody to C. burnetii was present in 54% of the febrile persons (n = 185) and in 53% of afebrile persons (n = 186). IgM antibody to C. burnetii was demonstrated in 29% of the febrile persons and 15% of the afebrile persons. These results implicate C. burnetii as a possibly important and under-reported cause of human disease and undiagnosed fevers in north-east Africa.

Adult↗
PubMed1994

Relationship between rate and free energy difference for electron transfer from cytochrome c2 to the reaction center in Rhodobacter sphaeroides.

The rate of electron transfer from cytochrome c2 to the bacteriochlorophyll dimer of the reaction center from the photosynthetic bacterium Rhodobacter sphaeroides has been investigated using time-resolved optical spectroscopy. Measurements were performed on a series of mutant reaction centers in which the midpoint potentials of the bacteriochlorophyll dimer vary over a range of 350 mV. Dramatic changes in the characteristic time of electron transfer were observed, with the measured values ranging from 7730 to 80 ns compared to 960 ns for wild type. The binding constants (0.15 to 0.25 microM-1) and the second-order rate constants for the slow component (5.5 x 10(8) to 9.4 x 10(8) M-1 s-1) for the mutants are similar to the corresponding values for wild type (0.35 microM-1 and 11 x 10(8) M-1 s-1), indicating that the binding of the cytochrome to the reaction center is not changed in the mutants. In the mutants with the fastest rates, an additional minor component was resolved that is probably due to formation of a reaction center-cytochrome complex in an unfavorable configuration with a binding constant an order of magnitude weaker than the major component. The altered midpoint potentials in the mutants result in values for the free energy difference for this electron transfer reaction ranging from -65 to -420 meV compared to -160 meV for wild type. The relationship between the rate and free energy difference was well fit by a Marcus equation using a reorganization energy of 500 meV.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteriochlorophylls↗
PubMed1994

Specific alteration of the oxidation potential of the electron donor in reaction centers from Rhodobacter sphaeroides.

The effects of multiple changes in hydrogen bond interactions between the electron donor, a bacteriochlorophyll dimer, and histidine residues in the reaction center from Rhodobacter sphaeroides have been investigated. Site-directed mutations were designed to add or remove hydrogen bonds between the 2-acetyl groups of the dimer and histidine residues at the symmetry-related sites His-L168 and Phe-M197, and between the 9-keto groups and Leu-L131 and Leu-M160. The addition of a hydrogen bond was correlated with an increase in the dimer midpoint potential. Measurements on double and triple mutants showed that changes in the midpoint potential due to alterations at the individual sites were additive. Midpoint potentials ranging from 410 to 765 mV, compared with 505 mV for wild type, were achieved by various combinations of mutations. The optical absorption spectra of the reaction centers showed relatively minor changes in the position of the donor absorption band, indicating that the addition of hydrogen bonds to histidines primarily destabilized the oxidized state of the donor and had little effect on the excited state relative to the ground state. Despite the change in energy of the charge-separated states by up to 260 meV, the mutant reaction centers were still capable of electron transfer to the primary quinone. The increase in midpoint potential was correlated with an increase in the rate of charge recombination from the primary quinone, and a fit of these data using the Marcus equation indicated that the reorganization energy for this reaction is approximately 400 meV higher than the change in free energy in wild type. The mutants were still capable of photosynthetic growth, although at reduced rates relative to the wild type. These results suggest a role for protein-cofactor interactions--in particular, histidine-donor interactions--in establishing the redox potentials needed for electron transfer in biological systems.

Amino Acid Sequence↗
PubMed1994

Nonpeptidic inhibitors of human leukocyte elastase. 2. Design, synthesis, and in vitro activity of a series of 3-amino-6-arylopyridin-2-one trifluoromethyl ketones.

A series of potent nonpeptidic inhibitors of the enzyme human leukocyte elastase (HLE) is reported. These inhibitors contain a 3-amino-2-pyridone ring as a central template in which the pyridone carbonyl and 3-position NH group are thought to form important hydrogen bonding interactions with the Val-216 residue of HLE. Substitution of the 6-position of the pyridone ring by various alkyl and aryl groups was found to afford increases in the in vitro potency of these inhibitors. A 6-position phenyl group, compound 10f, was found to result in a large increase in binding affinity, which was not obtained when the phenyl group was placed in either the 4- or 5-position of the molecule. Compound 10f was found to have good selectivity for HLE over other proteolytic enzymes, with the exception of bovine pancreatic chymotrypsin (BPC). Substitution of the 6-phenyl group in these molecules was found to decrease binding affinity for BPC without adversely affecting affinity for HLE.

Acetamides↗
PubMed1994

Thermodynamics of hydrogen cyanide and hydrogen fluoride binding to cytochrome c peroxidase and its Asn-82-->Asp mutant.

The thermodynamics of binding of fluoride and cyanide to cytochrome c peroxidase (CCP) and its Asn-82-->Asp mutant (D82CCP) in phosphate and acetate buffer at an ionic strength of 0.15 mol.kg-1 from pH 5.0 to 7.1 were investigated by titration calorimetry at 289 and 297 K. The binding reactions are enthalpically driven. The fluoride-binding constants determined from the titration calorimetry results were in agreement with those determined from difference-spectroscopy measurements. For cyanide binding to CCP at 297.9 K, the binding constant decreased from 8.95 (+/- 0.83) x 10(5) M-1 at pH 7.0 to 4.04(+/- 0.23) x 10(5) M-1 at pH 5.0, and the binding enthalpy increased from -57.2 +/- 1.4 kJ.mol-1 at pH 7.0 to -48.6 +/- 1.8 kJ.mol-1 at pH 5.0. For fluoride binding to CCP, the binding constant increased from 8.41(+/- 0.54) x 10(3) M-1 at pH 7.0 to 3.11(+/- 0.09) x 10(5) M-1 at pH 5.0 and the binding enthalpy increased from -71.9 +/- 1.1 kJ.mol-1 at pH 7.0 to -67.0 +/- 1.9 kJ.mol-1 at pH 5.0. The binding enthalpies for D82CCP were about the same as those for CCP. However, the binding constants for cyanide and fluoride to D82CCP were respectively a factor of two less and at least an order of magnitude less than the corresponding binding constants of CCP. Decreased ligand-binding strength in the D82CCP mutant is thus entirely due to entropic effects.

Asparagine↗
PubMed1994

Interaction between cytochrome c2 and reaction centers from purple bacteria.

The kinetics of electron transfer of cytochrome c2 from Rhodobacter sphaeroides, Rhodobacter capsulatus, and Rhodospirillum centenum to reaction centers from Rb. sphaeroides and Rb. capsulatus have been measured. Observed in the kinetics of decay of the oxidized donor are a rapid first-order rate and one or more slower rates that are due to diffusion-limited complex formation. For reaction centers from Rb. sphaeroides, the fast component had time constants of 1.0 and 0.5 microsecond for cytochrome c2 from Rb. sphaeroides and Rb. capsulatus, respectively, but only a slow component was observed for cytochrome c2 from Rs. centenum. For reaction centers from Rb. capsulatus, the kinetics from all three cytochromes had a fast component with time constants of 1.0, 0.7, and 1.9 microseconds for cytochrome c2 from Rb. sphaeroides, Rb. capsulatus, and Rs. centenum, respectively, although the dissociation constant for cytochrome c2 from Rs. centenum was approximately 20 times larger than that of the other cytochromes. The observation of the fast component for cytochrome c2 from Rs. centenum in reaction centers from Rb. capsulatus but not Rb. sphaeroides demonstrates that the binding interactions for the two reaction centers differ, and the involvement of amino acid residues in the binding is discussed. The kinetics of electron transfer from cytochrome c2 to reaction centers of Rb. sphaeroides from wild type and three mutant strains that have altered carboxyl-terminal regions of the M subunit of the reaction center have also been measured. For cytochrome c2 from Rb. sphaeroides, the kinetics are very similar between the mutants and wild type.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytochrome c Group↗
PubMed1994

Time-dependent thermodynamics during early electron transfer in reaction centers from Rhodobacter sphaeroides.

The temperature dependence of fluorescence on the picosecond to nanosecond time scale from the reaction centers of Rhodobacter sphaeroides strain R-26 and two mutants with elevated P/P+ midpoint potentials has been measured with picosecond time resolution. In all three samples, the kinetics of the fluorescence decay is complex and can only be well described with four or more exponential decay terms spanning the picosecond to nanosecond time range. Multiexponential fits are needed at all temperatures between 295 and 20 K. The complex decay kinetics are explained in terms of a dynamic solvation model in which the charge-separated state is stabilized after formation by protein conformational changes. Many of these motions have not had time to occur on the time scale of initial electron transfer and/or are frozen out at low temperature. This results in a time- and temperature-dependent enthalpy change between the excited singlet state and the charge-separated state that is the dominant term in the free energy difference between these states. Long-lived fluorescence is still observed even at 20 K, particularly for the high-potential mutants. This implies that the driving force for electron transfer on the nanosecond time scale at low temperature is less than 200 cm-1 (25 meV) in R-26 reaction centers and even smaller on the picosecond time scale or in the high-potential mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

Cold Temperature↗
PubMed1994

Relationship between thermodynamics and mechanism during photoinduced charge separation in reaction centers from Rhodobacter sphaeroides.

Detailed fast transient absorption measurements have been performed at low temperature on reaction centers from Rhodobacter sphaeroides strain R-26 and on a double mutant, [LH(L131) + LH-(M160)], in which the P/P+ oxidation potential is roughly 140 mV (1100 cm-1) above that of wild-type reaction centers. In both samples, the decay of the excited singlet state of the initial electron donor is not well described by a single-exponential decay term. This is particularly true for reaction centers from the double mutant where at least three exponential kinetic components are required to describe the decay, with time constants ranging from a few picoseconds to hundreds of picoseconds. However, singular value decomposition analysis of the time-dependent absorption change spectra indicates the presence of only two spectrally distinct states in reaction centers from both R-26 and the double mutant. Thus, the complex decay of P* at low temperature does not appear to be due to formation of either the state P+BA- as a distinct intermediate in electron transfer or P+BB- as an equilibrated side product of electron transfer. Instead, the decay kinetics are modeled by assuming dynamic solvation of the charge-separated state, as was done for the long-lived fluorescence decay in the accompanying paper [Peloquin, J. M., Williams, J. C., Lin, X., Alden, R. G., Taguchi, A. K. W., Allen, J.P., & Woodbury, N. W. (1994) Biochemistry 33, 8089-8100]. The results of assuming a static distribution of electron-transfer rates at early times followed by dynamic solvation of the charge-separated states on longer time scales are also presented. Regardless of which model is used to describe the early time kinetics of excited-state decay, the time-dependent excited-state population on the 100-ps or longer time scale is best described in terms of thermal repopulation of P* from the charge-separated state, even at 20 K. This results in a time- and temperature-dependent driving force estimated for initial electron transfer of less than 200 cm-1 on all time scales from picoseconds to nanoseconds. Assuming a nonzero internal reorganization energy associated with charge separation, the small driving force does not appear to be consistent with the lack of temperature dependence of electron transfer and the fact that a mutant with a P/P+ oxidation potential 140 mV (1100 cm-1) higher than wild type is still able to undergo electron transfer, even at low temperature.(ABSTRACT TRUNCATED AT 400 WORDS)

Electron Transport↗
PubMed1994

Studies of oligonucleotide interactions by hybridisation to arrays: the influence of dangling ends on duplex yield.

Effects of dangling ends on duplex yield have been assessed by hybridisation of oligonucleotides to an array of oligonucleotides synthesised on the surface of a solid support. The array consists of decanucleotides and shorter sequences. One of the decanucleotides in the array was fully complementary to the decanucleotide used as solution target. Others were complementary over seven to nine bases, with overhangs of one to three bases. Duplexes involving different decanucleotides had different overhangs at the 3' and 5' ends. Some duplexes involving shorter oligonucleotides had the same regions of complementarity as these decanucleotides, but with fewer overhanging bases. This analysis allows simultaneous assessment of the effects of differing bases at both 5' and 3' ends of the oligonucleotide in duplexes formed under identical reaction conditions. The results indicate that a 5' overhang is more stabilising than a 3' overhang, which is consistent with previous results obtained with DNA overhangs. However, it is not clear whether this is due to the orientation of the overhang or to the effect of specific bases.

Base Sequence↗