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Biomedical subjects

J C Williams

Publications and source records attributed to J C Williams.

At least 91 records · Page 5Linked to original sources
PubMed1997

Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) triggered by valproate therapy.

UNLABELLED: We report in this study a patient who developed repeated convulsions as a result of valproate therapy. MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) was subsequently diagnosed and a nucleotide 3243 A-->G mutation was detected in the mitochondrial DNA. This mutation predisposes the patient to the detrimental effects of valproate on oxidative phosphorylation. CONCLUSION: We support the suggestion of Ponchaut et al. [14] that valproate should not be given to patients suspected of having mitochondrial diseases. In addition, for patients whose seizures worsen with valproate therapy, an inborn error of mitochondrial metabolism should be suspected. The underlying mitochondrial DNA defects should be sought for family screening and genetic counselling.

Anticonvulsants↗
PubMed1997

Quantitation of shock wave cavitation damage in vitro.

Acoustic cavitation damage was quantitated using aluminum foil targets placed within 2-mL polypropylene cryovials. The vials contained various media tested for their potential to support cavitation and were exposed to shock waves using an unmodified Dornier HM3 lithotripter. Foil damage, expressed in terms of a "damage index," was measured from digitized light microscopy images by quantitating the spread of gray-scale histograms. Target sensitivity was demonstrated by reproducible dose-response curves over the range (1-200 shock waves) commonly used for in vitro cell injury studies. Increased shock wave repetition rate reduced the damage index. Untreated foils showed a very low damage index (0.001% +/- 0.001%), while treated foils submerged in Ringer buffer yielded significant damage (2.2% +/- 0.3%, p < 0.001). Degassing the buffer reduced damage to 0.3% +/- 0.1% (p < 0.001). Foils submerged in castor oil showed virtually no damage. These results implicate acoustic cavitation in target damage. Targets immersed in biological fluids (blood and urine) had significantly less damage than in Ringer. The effect of degassing was also evaluated in a red blood cell lysis assay. Hemoglobin release in degassed preparations was significantly reduced compared to nondegassed controls (p < 0.001) and correlated with reduced foil damage index in cell-free vials. These findings characterize a sensitive method to quantitate acoustic cavitation and implicate a role for cavitation in shock wave lithotripsy-induced cell lysis.

Body Fluids↗
PubMed1997

Duration of anthelmintic efficacy of doramectin and ivermectin injectable solutions against naturally acquired nematode infections of cattle.

A comparison of persistent efficacy of doramectin injectable (D) and ivermectin injectable (I) was investigated under field conditions with treated permanent principal (PP) and interval-grazed principal (IGP) calves. The experiment was initiated on October 13, 1992 (day 0). Cattle used were crossbred beef heifers of 185 kg average weight and 8 to 10 months old. By random allotment, 66 calves were divided into two groups of 15 PP-D and PP-I calves for each treatment and two groups of 15 IGP-D and IGP-I calves for each treatment. Three extra or replacement calves were allotted for each group. Permanent principal calves in three replicates of five cattle per treatment grazed continuously on nematode-contaminated replicate pastures from day 0 to day 70. At 2-week intervals, i.e., days 0 to 14, 14 to 28, 28 to 42, 42 to 56 and 56 to 70, one IGP-D and one IGP-I calf was grazed with each of the respective PP-D and PP-I calf replicates and necropsied 21 days after removal from pasture. All respective PP calves and IGP calves were treated with doramectin at 200 micrograms kg-1 or ivermectin at 200 micrograms kg-1 by s.c. injection on day 0. After the day 0-14 interval, all IGP-D calves had zero egg counts. From the day 14-28 interval through the next three grazing intervals, the arithmetic mean egg counts of IGP-D calves were 18, 90, 281 and 31; those of IGP-I calves were 30, 226, 74 and 185. This suggested a persistence effect of approximately 2 to 4 weeks. In PP-D calves, egg counts reached a mean maximum at day 56 of only five eggs per gram, while counts of PP-I calves reached a peak of 40 on day 42. From the day 14-28 interval and through all subsequent intervals, arithmetic mean total worm counts from IGP-I calves were 58 to 73% greater than those in IGP-D tracers. A maximal total worm count of 4159 was observed in IGP-D calves of the day 42-56 interval; total worm counts in IGP-I calves from the day 14-28 interval through the day 42-56 interval were: 5420, 6739 and 9979, respectively. Haemonchus and Cooperia were higher in prevalence than Ostertagia in both treatments. Results of PP-D egg counts and total worm burdens in IGP-I calves indicated a high level of doramectin persistent activity for approximately 4 to 5 weeks and an advantage over persistence activity of ivermectin.

Animal Feed↗
PubMed1997

A comparison of the efficacy of two treatments of doramectin injectable, ivermectin injectable and ivermectin pour-on against naturally acquired gastrointestinal nematode infections of cattle during a winter-spring grazing season.

Four groups of 18 crossbred beef steer calves (three replicates of six per group) were used to compare persistent efficacy of doramectin injectable, ivermectin injectable and ivermectin pour-on against naturally acquired infections of gastrointestinal nematodes during winter-spring grazing in Louisiana. The experiment was initiated on January 11. Treatments administered on Day 0 and again on April 5 (Day 84, 12-week interval) were: Group 1, untreated controls (CONT); Group 2, doramectin (DOR) at 200 micrograms/kg, s.c. injection; Group 3, ivermectin (IVM-INJ) at 200 micrograms/kg, s.c. injection; Group 4, ivermectin pour-on (IVM-PO) at 500 micrograms/kg, back midline. The cattle were weighed and fecal samples (for egg counts and for culture-larval identification) were collected at regular intervals throughout the 161 day experiment. In the interval between Day 0 and 84, arithmetic mean egg counts of the CONT group averaged about 890 eggs per gram, but then decreased markedly between Days 119 and 126, and remained at a lower plane for the remainder of the experiment. From Day 28 to 56, egg counts of the DOR group were consistently lower (P < 0.05) than those of controls and both IVM-treated groups. Egg counts of the DOR group were always lowest after the second treatment, but differed (P < 0.05) only from IVM-PO counts between Days 119 and 140 (35 and 56 days after the second treatment). Ostertagia was the predominant genus, followed by Cooperia in all four groups. Oesophagostomum, Trichostrongylus, Haemonchus, and Bunostomum were other genera identified. Bodyweights of the DOR group remained significantly greater (P < 0.05) than those of all other groups from Day 112 through the end of the experiment. Total gains for the CONT, DOR, IVM-INJ, and IVM-PO groups were 96, 159, 147, and 150 kg, respectively; treated groups were significantly (P < 0.05) greater than CONT, but differences among treated groups was not significant (P > 0.05).

Administration, Oral↗
PubMed1997

Anthelmintic treatment strategies: current status and future.

Despite the array of anthelmintics and endectocides and delivery systems available for use in the prevention and control of nematode parasites of ruminants, the number of highly effective control programs that have been developed and even the number of such programs that have been successfully implemented in commercial animal production, there have been no recent innovations or discoveries in regard to strategies, new anthelmintics, or systems for controlling nematode parasites through anthelmintic use. In the traditional sense of chemotherapy-chemoprophylaxis, we have probably achieved the maximum effect of what is possible from excellent anthelmintics developed by the pharmaceutical industry over the last 35 years, i.e. from thiabendazole through levamisole and morantel tartrate, to more advanced benzimidazoles and to the avermectins and milbemycins. At the core of all anthelmintic treatment-related problems is the lingering conception among a large body of animal producers that anthelmintic treatment is the only effort needed to control parasitism and its effects on host animals. This concept has given rise to the long-standing difficulty of drug resistance in sheep nematodes and the not remote possibility of its development in nematodes of cattle. Along with this are serious concerns over environmental toxicity, tissue residues and enormous financial investment to develop new and novel anthelmintic compounds. Progress is being made in current and intensive searches for development and testing of control approaches alternative to anthelmintics, e.g. helminth vaccines, biological control agents such as fungi, selection of resistant sires, alternative chemicals and nematode growth regulators. A timetable for when alternative controls can be developed fully and put into practical use cannot be predicted. It is universally acknowledged among parasitologists that existing anthelmintics must be preserved and utilized judiciously to ensure continued effectiveness. A major example is to be found in strategic or integrated control programs in Australia developed over the last 10 years to combat widespread drug resistance in sheep. Major imperatives for future programs and systems of controlling nematode parasites of ruminants are improved means of getting producers to adopt proven and sustainable methods.

Animal Husbandry↗
PubMed1997

Dietary vitamin E supplementation inhibits thrombin-induced platelet aggregation, but not monocyte adhesiveness, in patients with hypercholesterolaemia.

Several recent studies have indicated the possible beneficial effects of antioxidants, specifically vitamin E, in primary and secondary coronary prevention. These studies suggest that a diet enriched in vitamin E is insufficient to have a significant protective effect, whereas supplements, in excess of 200 international units (IU) per day, are efficacious in preventing coronary disease in both men and women. The mechanisms by which vitamin E may exert its protection are uncertain, but, vitamin E is lipophilic and has been shown to inhibit the oxidative modification of low density lipoprotein (LDL), a process thought to be of crucial importance in atherogenesis. We have also previously shown that alpha-tocopherol (the biologically most potent isomer of vitamin E) has important direct effects on vascular endothelial and smooth muscle cells. In the present study we have investigated the effects of oral supplements of vitamin E (400 IU per day) on platelet and mononuclear cell function in patients with hypercholesterolaemia. We found that although vitamin E supplementation had no significant effect on mononuclear cell adhesion ex vivo, it had a significant effect on the thrombin-induced platelet aggregation (P < 0.01; ANOVA): 6 weeks after starting the vitamin E supplements, the mean EC50 for thrombin-induced aggregation increased 132% (P < 0.05; paired t-test) compared to treatment with placebo. The effects of vitamin E on platelet function may, in part, explain its anti-atherogenic properties.

Adult↗
PubMed1997

Prenatal ultrasound characterization of the suprarenal mass: distinction between neuroblastoma and subdiaphragmatic extralobar pulmonary sequestration.

With the increased routine use of prenatal ultrasonography, subdiaphragmatic masses in the fetus are identified more frequently. Suprarenal masses often are presumed to be neuroblastoma and are removed surgically postnatally. We sought to better understand the natural history of subdiaphragmatic extralobar pulmonary sequestration, and to determine if subdiaphragmatic extralobar pulmonary sequestration can be distinguished preoperatively from neuroblastoma. The literature was reviewed for cases of prenatally diagnosed suprarenal masses that proved ultimately to be either subdiaphragmatic extralobar pulmonary sequestration or neuroblastoma. The distinguishing features of the two lesions were identified and an algorithm was created on the basis of these distinctions. Prenatally diagnosed subdiaphragmatic extralobar pulmonary sequestration is no longer rare, with one case being reported for every 2.5 cases of neuroblastoma. On prenatal ultrasonography subdiaphragmatic extralobar pulmonary sequestration usually is echogenic, is left-sided, and can be identified in the second trimester. Neuroblastoma is most often cystic, right-sided, and identified in the third trimester. In summary, subdiaphragmatic extralobar pulmonary sequestration must be considered in the differential diagnosis of the suprarenal mass identified on prenatal ultrasonography. Using the algorithm which we propose, the correct diagnosis can be determined prenatally in 95% of patients.

Adolescent↗
PubMed1997

Efficacy of a pour-on formulation of eprinomectin (MK-397) against nematode parasites of cattle, with emphasis on inhibited early fourth-stage larvae of Ostertagia spp.

OBJECTIVE: To evaluate efficacy of topically applied eprinomectin against inhibited early fourth-stage larvae (IL4) of Ostertagia spp in calves. ANIMALS: 4 groups (n = 6 [replicates]) for dose titration; 2 groups (n = 8 calves [replicates]) for dose confirmation. PROCEDURE: 2 dose titration studies-0, 125, 250, and 500 micrograms of eprinomectin/kg of body weight-Louisiana and Georgia- and 2 dose confirmation studies of selected therapeutic dosage (500 micrograms/kg) in Scotland and France. Monitor calves were used to determine inhibition percentage of Ostertagia IL4. Test calves were ranked by weight in replicates of 4 (titration trials) or 2 (confirmation trials) animals each, and within replicates, were randomly allocated to treatment groups. Drug treatments were done on day 0, and animals were euthanatized by replicate, with holding time between treatment and euthanasia varying among trials from 14 to 27 days. RESULTS: Observations indicated high efficacy (> 99%) of 500 micrograms of eprinomectin/kg in removal of Ostertagia IL4. Ostertagia and Cooperia were only genera common across sites, with efficacy of aforementioned dosage against adult and larval stages of both genera consistently high (> 99%). Results of 1 or both titration studies (500 micrograms/kg) indicated > 99 to 100% efficacy against adult Haemonchus placei, Trichostrongylus axei, T colubriformis, Bunostomum phlebotomum, Dictyocaulus viviparus, and Oesophagostomum radiatum. Lower efficacy values were observed at minimal (125 micrograms/kg) dosage. In France, 500 micrograms/kg was 85% effective against Trichostrongylus spp adults; however, numbers of control calves infected with Trichostrongylus spp and degree of infection were low. Adverse reactions were not evident. CONCLUSION: Eprinomectin given topically (500 micrograms) was highly effective against Ostertagia IL4 and other common nematodes of cattle.

Administration, Topical↗
PubMed1996

Ultrafast exciton relaxation in the B850 antenna complex of Rhodobacter sphaeroides.

Spectral changes were measured with femtosecond resolution following low-intensity, broad-band excitation of the peripheral antenna complex of the purple photosynthetic bacterium Rhodobacter sphaeroides. Absorption anisotropy decays also were measured. We identified a 35-fs relaxation of the absorption and emission spectra of the excited state, as well as a 20-fs anisotropy decay. We interpret these results as interlevel relaxation and dephasing, respectively, of extensively delocalized exciton states of the circular bacteriochlorophyll aggregate.

Bacterial Chromatophores↗
PubMed1996

Efficacy of moxidectin pour-on against gastrointestinal nematodes and Dictyocaulus viviparus in cattle.

Twenty crossbred beef heifer calves were used for an efficacy evaluation of 0.5% moxidectin pour-on against gastrointestinal nematodes and Dictyocaulus viviparus. The latter parasite and Bunostomum phlebotomum were the target species. The calves were exposed to natural infection on pasture from late September to December 22. Additionally, all calves were experimentally infected with B. phlebotomum at 71 and 29 days before treatment and with D. viviparus at 29 days before treatment. The 20 calves were randomly allocated into two groups of ten, based on presence of patent lungworm and hookworm infections on days -6 and -1. Treatments were as follows: Group A, moxidectin 0.5% pour-on (PO) at 500 micrograms kg-1 BW; Group B, moxidectin vehicle (controls) by PO application. General strongyle and hookworm egg counts and lungworm larval counts were reduced to zero at 13 days after moxidectin treatment; treatment effect was significant (P < 0.05) only for the strongyle and hookworm counts. Percentage reduction for adult hookworms and mature-immature adult lungworms was 100.0 and also for adults and L4 Haemonchus placei and Ostertagia ostertagi and Trichostrongylus axei adults, adult males of Cooperia pectinata and C. spatulata, and Oesophagostomum radiatum adults. Efficacy values for C. punctata adult males, Cooperia spp. adult females, and Cooperia spp. L4 were > 99.9%, > 99.9%, and 92.4%, respectively. All efficacy values were significant (alpha = 0.05, 1-sided) except for Cooperia spp. L4.

Administration, Topical↗
PubMed1996

Pore-forming activity of Coxiella burnetii outer membrane protein oligomer comprised of 29.5- and 31-kDa polypeptides. Inhibition of porin activity by monoclonal antibodies 4E8 and 4D6.

Envelopes of large-cell variant Coxiella burnetii, the agent of Q fever, were the starting material for purification of an outer membrane protein (OMP) oligomer with aggregate molecular mass of approximately 2 x 10(4) kDa. The oligomer was resistant to trypsin and dissociation by SDS at 100 degrees C. Reducing agents dissociated the oligomer into monomers of 29.5 and 31 kDa, which migrated as a doublet during SDS-polyacrylamide gel electrophoresis. Both monomers were reactive in an immunoblot assay with monoclonal antibodies (mAbs) 4E8 and 4D6, which were previously selected for their reactivity with purified and SDS-denatured 29.5 kDa protein. Proteoliposomes were functional in an equilibrium assay at pH 7 and a swelling assay at pH 7 and 4.5. The pores in proteoliposomes allowed the passage of arabinose, glucose, and sucrose, but restricted stachyose. Polyclonal antibodies to C. burnetii cells and the mAbs were able to bind C. burnetii at pH 7 and 4.5. The uptake of 14C-glucose at pH 4.5 was inhibited by polyclonal antibodies and mAbs after binding to cells at pH 7. The mAbs did not inhibit 14C-glucose uptake at pH 4.5 after binding to cells at pH 4.5. Although the mAbs bind C. burnetii porin epitopes before and after acid activation, the mAbs bound under acidic conditions were unable to inhibit porin function. The inhibition of porin channel function by mAbs confirms the role of porin as a permeability barrier for the subsequent active transport of glucose by C. burnetii. In another study, we showed that the 29.5 kDa OMP antigen induced active immunity against virulent challenge. This information, combined with the recent confirmation that porins are important antigens in the induction of specific protective immune responses against infection by gram-negative bacteria, suggests that humoral immunity directed against C. burnetii porins might play an important role in immunity against Q fever (human infection) and coxiellosis (animal infection), global enzootic diseases.

Animals↗
PubMed1996

Effects of hydrogen bonding to a bacteriochlorophyll-bacteriopheophytin dimer in reaction centers from Rhodobacter sphaeroides.

The properties of the primary electron donor in reaction centers from Rhodobacter sphaeroides have been investigated in mutants containing a bacteriochlorophyll (BChl)--bacteriopheophytin (BPhe) dimer with and without hydrogen bonds to the conjugated carbonyl groups. The heterodimer mutation His M202 to Leu was combined with each of the following mutations: His L168 to Phe, which should remove an existing hydrogen bond to the BChl molecule; Leu L131 to His, which should add a hydrogen bond to the BChl molecule; and Leu M160 to His and Phe M197 to His, each of which should add a hydrogen bond to the BPhe molecule [Rautter, J., Lendzian, F., Schulz, C., Fetsch, A., Kuhn M., Lin, X., Williams, J. C., Allen J. P., & Lubitz, W. (1995) Biochemistry 34, 8130-8143]. Pigment extractions and Fourier transform Raman spectra confirm that all of the mutants contain a heterodimer. The bands in the resonance Raman spectra arising from the BPhe molecule, which is selectively enhanced, exhibit the shifts expected for the addition of a hydrogen bond to the 9-keto and 2-acetyl carbonyl groups. The oxidation--reduction midpoint potential of the donor is increased by approximately 85 mV by the addition of a hydrogen bond to the BChl molecule but is only increased by approximately 15 mV by the addition of a hydrogen bond to the BPhe molecule. An increase in the rate of charge recombination from the primary quinone is correlated with an increase in the midpoint potential. The yield of electron transfer to the primary quinone is 5-fold reduced for the mutants with a hydrogen bond to the BPhe molecule. Room- and low-temperature optical absorption spectra show small differences from the features that are typical for the heterodimer, except that a large increase in absorption is observed around 860-900 nm for the donor Qy band in the mutant that adds a hydrogen bond to the BChl molecule. The changes in the optical spectra and the yield of electron transfer are consistent with a model in which the addition of a hydrogen bond to the BChl molecule increases the energy of an internal charge transfer state while the addition to the BPhe molecule stabilizes this state. The results show that the properties of the heterodimer are different depending on which side is hydrogen-bonded and suggest that the hydrogen bonds alter the energy of the internal charge transfer state in a well-defined manner.

Amino Acid Sequence↗
PubMed1996

Temperature dependence of the reorganization energy for charge recombination in the reaction center from Rhodobacter sphaeroides.

The rate of charge recombination from the primary quinone to the bacteriochlorophyll dimer of the reaction center from the photosynthetic purple bacterium Rhodobacter sphaeroides has been investigated using time-resolved optical spectroscopy. Measurements were performed at temperatures from 293 to 10 K on reaction centers that have specific mutations that result in a range of 425-780 meV for the free energy difference of charge recombination compared to 520 meV for wild type [Lin, X., Murchison, H. A., Nagarajan, V., Parson, W. W., Allen, J. P., & Williams, J.C. (1994) Proc.Natl.Acad.Sci.U.S.A. 91, 10265-10269]. In all cases, the rate increased as the temperature decreased, although the details of the dependence were different for each mutant. The observed dependence of the rate upon temperature is modeled as arising principally from a several hundred meV change in reorganization energy. The relationships among the rate, temperature, and free energy differences can be well fit by a Marcus surface using two modes centered near 150 and 1600 cm(-1)with a total reorganization energy that decreases from 930 to 650 meV as the temperature decreases from 293 to 10 K. In the inverted region, where the driving force is greater than the reorganization energy, the rate is found to be approximately independent of the free energy difference. This is modeled as due to the additional coupling of high frequency modes to the reaction. An alternative model is also considered in which a 140 meV increase in the reorganization energy is matched by a 140 meV increase in the free energy difference as the temperature decreases. The possible role of solvent dipoles in determining this temperature dependence of the reorganization energy and the implications for other electron transfer reactions are discussed.

Bacteriochlorophylls↗
PubMed1996

Immunogenicity of a new lot of Francisella tularensis live vaccine strain in human volunteers.

A new lot of Francisella tularensis live vaccine strain (LVS) was tested for immunogenicity in 19 human volunteers. Scarification vaccination induced specific cell-mediated and humoral immune responses. We noted a significant rise in antibodies against irradiation-killed LVS, formalin-killed virulent strain SCHU4, and an ether extracted antigen preparation (EEx) beginning 14 days after vaccination. A main target of the humoral immune response was lipopolysaccharide. Eighty percent of vaccinated volunteers developed a positive IgG response to EEx by day 14 and 100% of vaccinees responded positively by day 21. Background IgA titers were lower than corresponding IgG or IgM titers. No early IgM rise was noted with any antigen. By day 14 after vaccination, in vitro lymphocyte responses to LVS, the rough variant of LVS, and EEx were significantly increased compared to controls. Seventy percent of volunteers had a positive in vitro lymphocyte response to EEx within 14 days of vaccination. We predict that EEx will be a useful antigen for diagnosing tularemia and for evaluating the immunogenicity of vaccines against tularemia. We are testing this antigen using sera from human cases of tularemia and control sera.

Antibodies, Bacterial↗