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Biomedical subjects

J C Williams

Publications and source records attributed to J C Williams.

At least 163 records · Page 9Linked to original sources
PubMed1993

Immunotherapy of tularemia: characterization of a monoclonal antibody reactive with Francisella tularensis.

An IgM monoclonal antibody (mAb) recognized surface antigens specific to Francisella tularensis wild-type (Schu4) and live vaccine strain (LVS), and reacted with both in ELISA and slide agglutination tests. This mAb also reacted with LVS microorganisms in tissues of infected mice as assessed by an indirect fluorescence technique. Western blot analysis showed the mAb to react with antigens associated with F. tularensis LPS.

Animals↗
PubMed1993

Epidemiology of Ostertagia ostertagi in weaner-yearling cattle.

Epidemiologic events in the life cycle of Ostertagia ostertagi are best known in the weaner-yearling phase of cattle development throughout the concentrated cattle-rising areas of the world. Animal and pasture management demands placed on this age class are greater than for suckling calves and adult stock in either beef or dairy breeds. This fact alone would likely account for a higher prevalence of clinical and subclinical disease in weaner-yearlings. Additionally, the developing immune response provides relatively early protection against intestinal genera such as Cooperia and Oesophagostomum, but is delayed against Ostertagia ostertagi and Trichostrongylus axei. Both Type I and Type II disease may occur within the weaner-yearling stage. Factors affecting population changes of Ostertagia ostertagi have been described as extrinsic, i.e. weather-climate and grazing management, and intrinsic or host factors, i.e. age, sex, immune status, heredity and reproductive state. Immune status, particularly in weaner-yearlings, may be of primary importance, as affected by host and extrinsic factors. With slow development of protective immunity against Ostertagia ostertagi in calves, the possible role of immunity in both induction of inhibition and larval maturation, the potential immunopathologic involvement in pathogenesis of Type II disease, hypersensitivity to larval intake in resistant adult cows, and the reported delay of a protective response following anthelmintic prophylaxis in younger cattle, the immune response may have profound influence on epidemiologic variation through age classes. Although continual epidemiological observations from birth to early adulthood in the same cattle have not been undertaken, some notable studies in the UK, the Netherlands, and Denmark have closely examined epidemiological events through first and second grazing seasons.

Animals↗
PubMed1993

Prevalence of medium-chain acyl-coenzyme A dehydrogenase deficiency in the sudden infant death syndrome.

Disorders of fatty acid beta-oxidation have been suggested as playing a significant role in the sudden infant death syndrome (SIDS). To elucidate the role of medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency in SIDS, we identified all cases of SIDS occurring in Los Angeles County between January 1986 through December 1991. A total of 1304 SIDS deaths were identified; tissue samples were collected in 1236 cases (94.8%). Extraction of DNA was successful in 1224 tissue samples (93.9%), which were examined for the presence of the G985 mutation, identified as occurring in more than 88% of affected cases of MCAD deficiency. Three heterozygotes and no homozygotes were identified; this incidence does not differ from that reported in the general population. Review of the pathologic specimens from the identified heterozygotes and from 18 ethnic-, age-, and sex-matched control subjects revealed significant fatty infiltration of all organs examined in one of the three heterozygotes and in none of the control subjects. We conclude that MCAD deficiency does not play a significant role in the causation of SIDS.

Acyl-CoA Dehydrogenase↗
PubMed1993

A circulating protein that depolarizes cells increases after hemorrhage in dogs.

Recent evidence suggests that a circulating factor or factors may mediate cell membrane depolarization after hemorrhage in rats. To test for the presence of a similar factor in dogs, conscious adult splenectomized dogs with chronic arterial cannulae were either (1) bled 30% of measured blood volume over 3 minutes (HEM, n = 8); (2) bled 30% of measured blood volume over 3 minutes and reinfused with the shed blood 10 minutes later (HEM + REINF, n = 6); or (3) observed without hemorrhage (CONTROL, n = 5). Treatments were applied in random order, 72 hours apart. Arterial blood was sampled at rest and for 1 hour. Depolarizing activity of the plasma was measured in an in vitro bioassay using resting dog RBCs and a membrane potential-sensitive oxonol dye (DIBAC). Fluorescence was measured by spectrofluorometry and the percentage of change from resting values was calculated. Fluorescence intensity increased after hemorrhage in the HEM and the HEM + REINF groups. Fluorescence intensity decreased to CONTROL values in the HEM + REINF group by 10 minutes after reinfusion of shed blood, but remained greater than CONTROL values in the HEM group. The magnitude of early cell membrane depolarization was approximately 20 mV. Similar depolarization was observed in cultured canine skeletal myocytes and pre-adipocytes. Changes in fluorescence intensity correlated with changes in mean arterial pressure at all times after hemorrhage except at 15 minutes (5 minutes after reinfusion in the HEM + REINF group). The depolarizing activity in dog plasma after hemorrhage shares several physical chemical properties with a similar substance identified in rats after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Safety and immunogenicity in human volunteers of a chloroform-methanol residue vaccine for Q fever.

Current Q fever vaccines, consisting of Formalin-inactivated phase I whole Coxiella burnetii, are highly efficacious in preventing disease in high-risk settings but are associated with a risk of unacceptable local reactions in previously immune individuals and require cumbersome preliminary immunologic evaluation of potential vaccinees. A vaccine prepared from the residue of chloroform-methanol extraction of phase I Henzerling strain C. burnetii (CMR) has been shown to be less reactogenic but still immunogenic and protective in small animals and sheep. In a placebo-controlled trial, we immunized 35 healthy adults unscreened for markers of prior C. burnetii immunity with a single subcutaneous CMR dose of 30, 60, 120, or 240 micrograms. None of those receiving the 30- or 60-micrograms CMR dose and none of the placebo recipients experienced any adverse effects. Five of 15 120-micrograms dose CMR recipients complained of transient discomfort in the inoculated arm; erythema or induration of > or = 100 mm2 was noted in three and four, respectively, and two had malaise and low-grade fever (< 101 degrees F, orally). No 240-micrograms dose vaccinee reported limb discomfort, but 7 of 10 had erythema and/or induration of > or = 100 mm2 (P < 0.001 versus placebo). Two reported malaise, and one had low-grade fever. All adverse effects were self-limited. Serum immunoglobulin M responses were optimally detected with CMR antigen and occurred in 50, 60, 73, and 90% of recipients of the 30-, 60-, 120-, and 240-micrograms doses, respectively; results with phase I whole-cell antigen were similar. Serum immunoglobulin G responses were best detected with phase II antigen and were seen in 20, 20, and 40% of those receiving the 60-, 120-, and 240-micrograms doses, respectively. Peripheral blood T-cell proliferative responses to C. burnetii recall antigens were transient and of low magnitude but were seen with CMR antigen in 33% of 120-micrograms dose recipients and 40% of 240-micrograms dose recipients. Data from this study and those from comparative-efficacy trials in primates should provide the basis for field trials of the CMR vaccine.

Antibodies, Bacterial↗
PubMed1993

Oncotic effects across isolated perfused renal tubular basement membrane.

Peritubular protein concentration affects the rate of volume absorption by the proximal tubule, and this effect may be mediated across the tubular basement membrane. To examine the permeability properties of this membrane, segments of mouse proximal straight tubule were isolated and perfused, and cells were removed using deoxycholate. Volume loss from the isolated perfused basement membrane was measured using blue dextran as a volume marker. Each segment was exposed alternately to solutions containing either no colloid or 6% bovine serum albumin. With rates of perfusion averaging 15.9 +/- 1.3 nl/min, rates of volume loss averaged 0.7 +/- 1.7 with no protein in the bath but were significantly higher with albumin, 16.5 +/- 2.1 nl.min-1.mm-1 (n = 14; mean length = 0.4 +/- 0.04 mm). Significant volume flux was also seen when the bath was changed to contain dextran [weight-averaged mol wt (Mw) approximately 70,000 or approximately 500,000]. In separate experiments, the net flux of albumin with albumin in the bath averaged 4.2 +/- 1.2 pmol.min-1.mm-1 (n = 5). The results show that this basement membrane has a high water permeability and significantly restricts the movement of albumin. Permeabilities for osmotic water flow and albumin were estimated from modeling fluxes in individual segments and found to average 70.6 +/- 9.8 cm/s (sigma = 0.1; 11.4 +/- 1.6 for sigma = 1) and 1.6 +/- 0.3 micron/s (assuming sigma = 0.1; 0.8 +/- 0.2 for sigma = 1), respectively. Using these permeabilities, it is demonstrated that interstitial protein may significantly reduce hydrostatic pressure in the intercellular space by oncotic action across the basement membrane.

Animals↗
PubMed1993

Acrolein increases airway sensitivity to substance P and decreases NEP activity in guinea pigs.

The effects of acrolein exposure on airway responses to intravenous substance P were determined in guinea pigs exposed to vehicle or 1.6 ppm acrolein for 7.5 h on 2 consecutive days and examined 1, 4, 8, 15, and 28 days after exposure by use of pulmonary mechanics and bronchoalveolar lavage (BAL). Lung, trachea, liver, and BAL fluid were also assayed for neutral endopeptidase (NEP) activity 1, 7, and 28 days after exposure. Pulmonary inflammation and epithelial damage were prominent 1 day after acrolein exposure. NEP activity was decreased in the lungs, trachea, and liver 1 and 7 days after acrolein. Twenty-eight days after exposure, NEP activity in the lungs and liver was not significantly different in vehicle- and acrolein-exposed guinea pigs but was still reduced in tracheal tissue. The BAL NEP activity in acrolein-exposed guinea pigs was approximately twice that of vehicle control guinea pigs at all three time points. Acrolein caused a prolonged increase in airway sensitivity to substance P. Experiments performed in the presence of thiorphan suggested that the acrolein-induced reduction in NEP may contribute to increased airway sensitivity to aerosolized substance P, but the increase in airway sensitivity to intravenous substance P may occur by additional mechanisms.

Acrolein↗
PubMed1993

Protective role for neuropeptides in acute pulmonary response to acrolein in guinea pigs.

To determine the potential role of neuropeptides in acrolein-induced airway responses, capsaicin-treated guinea pigs were exposed to acrolein aerosol in a regimen causing increased airway sensitivity to substance P. Acrolein exposure resulted in 100% mortality after capsaicin pretreatment compared with only 14% mortality in guinea pigs not pretreated with capsaicin. Acrolein exposure by itself caused marked pulmonary inflammation and large airway epithelial necrosis and denudation. Pretreatment with capsaicin exacerbated these responses throughout the lung. Intravenous acrolein caused an acute dose-related bronchoconstriction in naive guinea pigs that was diminished by capsaicin treatment and potentiated by thiorphan pretreatment, which suggests that arolein exposure causes an acute release of capsaicin-sensitive C-fiber neuropeptides. To determine whether acrolein-induced C-fiber release altered neuronal viability, either rhodamine or Fast Blue dye was instilled intratracheally into vehicle- or acrolein-exposed guinea pigs. Acrolein exposure did not reduce the neuronal uptake or retrograde transport of these dyes, as indicated by the number of fluorescent cell bodies in the nodose ganglia. To determine the functional state of airway neurons, the dose response to intravenous capsaicin was measured in vehicle-exposed and acrolein-exposed guinea pigs; no differences were observed. Thus, acrolein appears to activate airway C-fibers, which release neuropeptides that are protective against this insult, with no suggestion of an accompanying reduction in C-fiber function.

Acrolein↗
PubMed1993

Immunization of dogs with Q fever vaccines: comparison of phase I, II and phase I CMR Coxiella burnetii vaccines.

Q fever vaccines were tested in mixed breed dogs by vaccinating them with formalin-killed Coxiella burnetii whole cells (WC) in either phase I (WCI) or phase II (WCII), or the chloroform: methanol residue (CMR) subunit of phase I cells. Phase I vaccines mixed (1:1) with Freund's incomplete adjuvant (FIA) induced humoral immune responses to phases I and II antigens as measured by microagglutination assay. The CMR vaccine mixed (1:1) with FIA induced greater antigen-specific antibody levels to both phases I and II antigens than the corresponding WCI vaccine. The WCII vaccine induced antibody responses to only phase II antigens. The time course of erythema and induration after skin testing with C. burnetii antigens were suggestive of cell-mediated immunity (CMI). Although granulomas were observed with only WCI and WCII, none of the skin test antigens induced abscesses at the injection site. In contrast, axillary nodes draining the vaccine injection site developed sterile draining abscesses in all dogs by days 19 to 24 for the WCI and CMR, and day 104 for the WCII vaccines. The abscesses had resolved within 30 days after first appearance. Responses to Con A and PHA and recall antigens of lymphocytes from the blood, axillary and mesenteric nodes, and spleen at 222 days after vaccination were variable among dogs. Lymphocytes from various organs responded to one or more of the recall antigens and to both mitogens in the absence or presence of indomethacin. Although these Q fever vaccines induced humoral and CMI, either the antigens or FIA caused sterile draining abscesses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Effects of mutations near the bacteriochlorophylls in reaction centers from Rhodobacter sphaeroides.

Mutations were made in four residues near the bacteriochlorophyll cofactors of the photosynthetic reaction center from Rhodobacter sphaeroides. These mutations, L131 Leu to His and M160 Leu to His, near the dimer bacteriochlorophylls, and M203 Gly to Asp and L177 Ile to Asp, near the monomer bacteriochlorophylls, were designed to result in the placement of a hydrogen bond donor group near the ring V keto carbonyl of each bacteriochlorophyll. Perturbations of the electronic structures of the bacteriochlorophylls in the mutants are indicated by additional resolved transitions in the bacteriochlorophyll absorption bands in steady-state low-temperature and time-resolved room temperature spectra in three of the resulting mutant reaction centers. The major effect of the two mutations near the dimer was an increase up to 80 mV in the donor oxidation-reduction midpoint potential. Correspondingly, the calculated free energy difference between the excited state of the primary donor and the initial charge separated state decreased by up to 55 mV, the initial forward electron-transfer rate was up to 4 times slower, and the rate of charge recombination between the primary quinone and the donor was approximately 30% faster in these two mutants compared to the wild type. The two mutations near the monomer bacteriochlorophylls had minor changes of 25 mV or less in the donor oxidation-reduction potential, but the mutation close to the monomer bacteriochlorophyll on the active branch resulted in a roughly 3-fold decrease in the rate of the initial electron transfer.

Bacteriochlorophylls↗
PubMed1992

Axial evolution of the negative glow in a hollow cathode discharge.

The purpose of these studies was to examine the axial evolution of the negative glow in a hollow cathode discharge. The time-average negative glow profiles along the central axis of a hollow cathode were recorded for 81 pulse widths over the range of 5-25 microseconds in increments of 0.25 microseconds at a constant interpulse delay of 206.4 microseconds. Subsequent numerical processing yielded the instantaneous negative glow profile. The negative glow was viewed through a mesh-covered slot along the length of the hollow cathode. The negative flow profiles were imaged using a vidicon video camera. A PC-based frame grabber digitized the video images and stored them for subsequent processing.

Chemistry Techniques, Analytical↗
PubMed1992

Efficacy of moxidectin against gastrointestinal nematodes of cattle.

Three groups of 11 naturally infected crossbred beef calves were injected subcutaneously with moxidectin 1 per cent injectable at 0.2 or 0.3 mg moxidectin/kg bodyweight or with the unmedicated vehicle. Nematode infections had been acquired during grazing from December to April. Based on the faecal egg counts and total worm counts of the control calves at necropsy (11 to 13 days after treatment) most of the calves had heavy parasitic burdens. Ostertagia ostertagi was predominant and the mean numbers of adults, developing fourth stage larvae (L4) and inhibited early L4 were 45,906, 10,061 and 68,918, respectively. Haemonchus placei and Trichostrongylus axei were also present in the abomasa. Three species of Cooperia, Oesophagostomum radiatum L4 and T colubriformis adults were found in the intestinal tract. Both dosages of moxidectin were equally effective (P < 0.05) against all the abomasal nematodes (99.9 to 100 per cent) and the intestinal tract nematodes (99.4 to 100 per cent). No adverse reactions to the moxidectin treatment were observed. Abomasal pathology characteristic of heavy O ostertagi infection was observed in the control calves, but not in the treated calves.

Animals↗
PubMed1992

Thermodynamic analysis of heparin binding to human antithrombin.

The binding of heparin to human antithrombin III (ATIII) was investigated by titration calorimetry (TC) and differential scanning calorimetry (DSC). TC measurements of homogeneous high-affinity pentasaccharide and octasaccharide fragments of heparin in 0.02 M phosphate buffer and 0.15 M sodium chloride (pH 7.3) yielded binding constants of (7.1 +/- 1.3) x 10(5) M-1 and (6.7 +/- 1.2) x 10(6) M-1, respectively, and corresponding binding enthalpies of -48.3 +/- 0.7 and -54.4 +/- 5.4 kJ mol-1. The binding enthalpy of heparin in phosphate buffer (0.02 M, 0.15 M NaCl, pH 7.3) was estimated from TC measurements to be -55 +/- 10 kJ mol-1, while the enthalpy in Tris buffer (0.02 M, 0.15 M NaCl, pH 7.3) was -18 +/- 2 kJ mol-1. The heparin-binding affinity was shown by fluorescence measurements not to change under these conditions. The 3-fold lower binding enthalpy in Tris can be attributed to the transfer of a proton from the buffer to the heparin-ATIII complex. DSC measurements of the ATIII unfolding transition exhibited a sharp denaturation peak at 329 +/- 1 K with a van 't Hoff enthalpy of 951 +/- 89 kJ mol-1, based on a two-state transition model and a much broader transition from 333 to 366 K. The transition peak at 329 K accounted for 9-18% of the total ATIII. At sub-saturate heparin concentrations, the lower temperature peak became bimodal with the appearance of a second transition peak at 336 K. At saturate heparin concentration only the 336 K peak was observed. This supports a two domain model of ATIII folding in which the lower stability domain (329 K) binds and is stabilized by heparin.

Animals↗
PubMed1992

Effect of aging the hollow cathode by sputtering on the analytical precision of the hollow cathode discharge emission source.

Sputtering changes the analytical performance of the hollow cathode as an emission source. Proper conditioning (aging) of the hollow with sputtering greatly improves precision. Conditioning decreases the blank emission signal and changes the shape of the hollow. Micrographs which show the evolution of the bottom of the hollow into a stable bulb shape are presented. The blank emission signal decreases with aging of the hollow and approaches a constant value when the hollow is properly conditioned. A short-term stability (n = 5) of approximately 1.8% RSD has been observed frequently. An average long-term stability over several days (n = 45) of 4.5% for Li and 3.5% for Na in the emission signal from microsamples (less than 50 nL) deposited in the hollow cathode discharge source is reported here. Instrumentation, operation, and sample preparation procedures are described.

Electrodes↗
PubMed1992

Vaccines against coxiellosis and Q fever. Development of a chloroform:methanol residue subunit of phase I Coxiella burnetti for the immunization of animals.

We have demonstrated the safety, immunogenicity, and efficacy of the WC and CMR vaccines in guinea pigs. Vaccination of guinea pigs with either WC or CMR protects animals against challenge with virulent C. burnetii. A total of 2 micrograms of either WC or CMR vaccine was a significant priming dose. A total of 20 micrograms gave complete protection against lethal challenge. Detection of antibodies to phase II cells by microaglutination, after vaccination with either WC or CMR and before lethal challenge, correlated with the ability of guinea pigs to mount a protective immune response. The PD50 values for WC and CMR vaccines, administered as a single dose, were 0.3 and 1.4 micrograms per animal, respectively. In contrast, the PD50 values for the WC and CMR vaccines, administered as two doses, were 0.83 and 0.72 micrograms per animal, respectively. Although the PD50 values for the two vaccines are similar, the CMR vaccine is preferred over the WC vaccine because it induces significantly fewer adverse reactions, and repeat injections can be given. Unvaccinated guinea pigs do not clear infectious microorganisms after challenge infection. Vaccination before challenge infection reduces the infectious load of C. burnetti in the blood and in various organs of the animals. When vaccinated animals were challenge infected and treated with rifampicin, the microorganisms were not eliminated from various organs. However, the combination of vaccination, challenge, and rifampicin treatment is effective in reducing the number of infectious microorganisms in some of these sites. We have demonstrated the safety and immunogenicity of the CMR vaccine in sheep and goats. Animals that were seropositive for one or more antigens developed significant levels of antibodies to alternate antigens, but no adverse reactions were observed at the site of s.c. injection of the CMR vaccine. This demonstrates that seropositive animals can be successfully immunized with this vaccine. These results also indicate that a long-term vaccination program using the CMR vaccine has the potential for producing animals with significant antibody titers to C. burnetii and perhaps lifelong immunity. The goal of a Q fever vaccination program is to produce immunized animals that are able to clear completely the infectious microorganisms. The appropriate vaccination schedule to render adult animals and their offspring "Q fever-free" should now be thoroughly investigated.

Animals↗
PubMed1992

Aspartylglycosaminuria in a non-Finnish patient caused by a donor splice mutation in the glycoasparaginase gene.

Aspartylglycosaminuria is a lysosomal storage disease caused by deficient activity of glycoasparaginase (EC 3.5.1.26), and it occurs with a high frequency among Finns. We have recently shown that the molecular defect in all Finnish aspartylglycosaminuria patients examined to date consists of two single base changes in the heavy chain of glycoasparaginase (Mononen, I., Heisterkamp, N., Kaartinen, V., Williams, J. C., Yates, J. R., III, Griffin, P. R., Hood, L. E., and Groffen, J. (1991) Proc. Natl. Acad. Sci U.S.A. 88, 2941-2945). This is the first report on the identification of the molecular defect causing aspartylglycosaminuria in a patient of non-Finnish origin. Total RNA from fibroblasts of a black American aspartylglycosaminuria patient was isolated, first-strand cDNA was synthesized, and the cDNA encoding glycoasparaginase was amplified by the polymerase chain reaction. The patient's mRNA nucleotide sequence was different from the normal sequence by a deletion of 134 nucleotides at positions 807-940. Nucleotide sequence analysis of the normal glycoasparaginase gene demonstrated that the deletion corresponded precisely to a 134-base pair exon. Moreover, analysis of the splice sites demonstrated a single base change, G to T, that altered the donor splice site of the exon deleted in the patient's mRNA. This change led to an exon-skipping event resulting in a frame shift and generation of a stop codon.

Amino Acid Sequence↗