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J C Williams

Publications and source records attributed to J C Williams.

At least 199 records · Page 11Linked to original sources
PubMed1991

Efficacy of levamisole against Ostertagia ostertagi in Louisiana cattle during maturation of inhibited larvae (September) and during minimal inhibition (December/January).

Levamisole (LEV) was tested in four experiments to compare efficacy values against Ostertagia ostertagi when larval maturation was occurring (September), following inhibition and also when populations were expected to be largely adult (winter). A primary objective was to determine the importance of developing fourth-stage larvae (DL4) and inhibited, early fourth-stage larvae (EL4) in replacing adult worms lost through treatment and the effect of this on reduced efficacy against adult worms. Young crossbred beef calves ranging in weight from 150 to 230 kg were used in the first (September 1981), second (September 1983) and third experiments (January 1987). Jersey calves of 110 kg average weight were used in the fourth experiment (December 1988). Calves were randomized to groups according to weight and group sizes ranged from three to five calves. All parasite infections were naturally acquired, but a mixture of nematode third-stage larvae (L3) (22,500 per calf), including 20% Ostertagia ostertagi, was inoculated into Jersey calves of Experiment 4 following a 2 week exposure to natural infection. All LEV treatments were by subcutaneous injection at dosages of 6 and 8 mg kg-1. Treatment with ivermectin was used only in Experiment 3 as an efficacy reference. All calves were killed at 8-10 days after treatment. The efficacy of LEV against all developmental stages of Ostertagia ostertagi was consistently low in all experiments and a dose-dependent response was not evident. Large numbers of all Ostertagia ostertagi developmental stages were present in non-treated calves in both September experiments. Percent reduction of adults, DL4 and EL4 at the 6 mg kg-1 and 8 mg kg-1 dosages, respectively, were adults, 51.7 and 23.6 (1981), 8.7 and 51.3 (1983); DL4 40.3 and 13.2 (1981), 37.9 and 33.1 (1983); EL4, 19.6 and 0 (1981), 59.6 and 42.9 (1983). Smaller numbers of Ostertagia ostertagi were present in winter experiments and adult worms greatly outnumbered larval stages. Percent reductions of adults, DL4 and EL4, respectively, were (1987) LEV 6 mg kg-1, 40.2, 0 and 0; ivermectin 200 micrograms kg-1, 98.7, 97.7 and 100.0; (1988) LEV 6 mg kg-1, 62.4, 100.0 and 100.0; LEV 8 mg kg-1, 49.1 65.0 and 74.1. Too few larval stages were present in the latter experiment for valid efficacy values.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1991

Structural changes induced by osmotic water flow in rabbit proximal tubule.

When a transepithelial osmotic difference was imposed in perfused proximal straight tubules (270 mOsm/kg H2O in the lumen and 290 in the bath) in the absence of bath colloid, a severe vacuolation (appearance of lucent spaces) developed within the epithelium such that view of the lumen border was obscured within 5 +/- 1 min (N = 13 tubules at 23 degrees C). This vacuolation was less severe if the bath was hypotonic to the lumen or if the magnitude of the osmotic difference was reduced. If colloid (6% wt/vol of either bovine serum albumin or 70,000 molecular wt dextran) was included in the bathing medium, vacuolation was either not observed or was minimal, but became severe upon removal of the colloid and obscured the lumen within 6 +/- 1 min (N = 8 for albumin and N = 4 for dextran at 23 degrees C). At 38 degrees C, vacuolation obscured the lumen within 4 +/- 1 min following the removal of albumin (N = 5). ANOVA suggests that none of the times for vacuolation to occur differed. The rate of passive volume flow due to the osmotic difference was unaffected by vacuolation (0.9 +/- 0.1 nl.min-1.mm-1 with albumin to 0.8 +/- 0.1 without albumin and vacuolated, N = 8 at 23 degrees C, P greater than 0.2 using a paired t-test). Electron microscopic examination of tubules fixed after vacuolation showed lucent spaces within the cytoplasm. These results suggest that the presence of serosal colloid protected the epithelial cells from injury during rapid transepithelial water flow. The mechanism for this protective effect is not apparent, but may be related to effects of colloid in maintaining normal volume absorption in the proximal nephron.

Animals↗
PubMed1991

Biochemistry and pharmacology of ICI 200,880, a synthetic peptide inhibitor of human neutrophil elastase.

ICI 200,880 is representative of a new chemical class of inhibitors of human neutrophil elastase (HNE). The compound demonstrated competitive kinetics vs HNE with a Ki value of 5.0 x 10(-10) M. The selectivity of ICI 200,880 for HNE versus a variety of enzymes ranged from 150- (relative to porcine pancreatic elastase [PPE]) to greater than 360,000-fold in favor of HNE. In pharmacokinetic studies ICI 200,880 displayed a long retention time when administered directly to the lung and was rapidly eliminated when administered intravenously. Aerosol pretreatment of hamsters with ICI 200,880 before intratracheal administration of HNE produced a long-lasting inhibition of enzyme-induced increases in lung weight, total lavageable red cells, and total lavageable white cells. Subcutaneous administration of either 50 or 100 mumol/kg (twice/day) of ICI 200,880 for 14 or 28 days prevented the time-dependent increase in alveolar diameter produced by a single intratracheal dose of PPE when compound dosing was initiated 24 hours following the enzyme. Treatment of hamsters with ICI 200,880 using the same protocol and doses for 8 weeks prevented the destructive lesion induced by a single intratracheal dose of HNE. It is concluded that ICI 200,880 has biochemical, pharmacokinetic, and pharmacologic profiles that make it a useful therapeutic agent for understanding the role of HNE in various diseases. ICI 200,880 is presently being evaluated in man.

Animals↗
PubMed1991

Antigenic differences between Coxiella burnetii cells revealed by postembedding immunoelectron microscopy and immunoblotting.

The aim of this study was to investigate the antigenic structures of the morphologically distinct cells of the Coxiella burnetii developmental cycle. Postembedding immunoelectron microscopy with polyclonal antibodies produced in rabbits to (i) phase I cells, (ii) a chloroform-methanol residue fraction of cells, (iii) the cell walls (CW) of large and small cells and small dense cells (SDC), and (iv) the peptidoglycan-protein complexes of small cells and SDC labelled the continuum of morphologically distinct cells. But these antibodies did not distinguish between the antigenic structures of the various cells. Monoclonal antibodies to the phase I lipopolysaccharide labelled the CW of a majority of the smaller cells, but there was diminished reactivity to the larger cells. Although monoclonal antibodies to a 29.5-kDa outer membrane protein labelled the CW of the large mother cells, the large cells, and the small cells, a minority of the SDC with compact CW were not labelled. The endogenous spore within the mother cell was not labelled by the polyclonal or monoclonal antibodies to cellular components. A selected population of SDC was prepared by osmotic lysis of large cells, differential centrifugation, Renografin step-gradient fractionation, and breakage of the small cells in a French press at 20,000 lb/in2. The pressure-resistant SDC collected as fraction CL did not contain the 29.5-kDa protein, as evidenced by the lack of (i) Coomassie brilliant blue staining of protein in the 29.5-kDa region of sodium dodecyl sulfate-polyacrylamide gels and (ii) reactivity of the 29.5-kDa protein antigenic epitopes in immunoblotting with monoclonal antibodies to the protein. In contrast, CW of the pressure-sensitive small cells contained the 29.5-kDa protein. Therefore, the observed ultrastructural differences between large and small cells and SDC reflect differences in sensitivity to breakage by pressure treatment and in cell-associated antigens. Although the process of differentiation in C. burnetii remains an enigma, we have taken steps toward identifying cellular antigens as markers of differentiation. The pressure-resistant SDC in fraction CL that are devoid of the 29.5-kDa protein may be useful for answering questions about the physiological events required for triggering outgrowth and sequential regulation of the Coxiella developmental cycle.

Animals↗
PubMed1991

Acute blood pressure effects of selected serine proteases in normotensive rats and dogs.

The effects of bolus intravenous injections of various serine proteases (thrombin, trypsin, plasmin, neutrophil elastase and chymotrypsin) on arterial blood pressure were evaluated in anesthetized, normotensive rats. The activity to intravenous trypsin was also studied in anesthetized, normotensive dogs. In the rat, both thrombin (0.33-10 nmol/kg) and trypsin (4.2-420 nmol/kg) produced pronounced vasodepressor responses. The activity on blood pressure was observed immediately following injection of either protease, and both the magnitude and duration of the responses were dose dependent. Plasmin (37-350 nmol/kg) and neutrophil elastase (91-910 nmol/kg) also induced dose-dependent hypotension but at much higher dose levels. In addition, the magnitude of the blood pressure responses after plasmin and neutrophil elastase was less than those produced by thrombin and trypsin. Chymotrypsin, on the other hand, had a more diverse blood pressure profile. The protease induced a modest decrease in pressure at doses of 40 and 120 nmol/kg, a pressor response after 400 and 1,200 nmol/kg and at the highest dose tested (4,000 nmol/kg) profound hypotension. In the dog, trypsin produced a dose-dependent vasodepressor response similar to that observed in the rat. The doses of proteases producing alterations of blood pressure in the rat correlated inversely with the ability of rat serum or plasma to completely inhibit those proteases. The pharmacology of the trypsin or thrombin blood pressure response suggests the requirement of specific active enzymes to mediate the vasodepression induced by both proteases.

Animals↗
PubMed1991

Biologic characterization of ICI 200,880 and ICI 200,355, novel inhibitors of human neutrophil elastase.

ICI 200,880 and its close structural analog, ICI 200,355, are representatives of a new chemical class of inhibitors of human neutrophil elastase (HNE). Both compounds are substituted tripeptide ketones, which demonstrated competitive kinetics versus HNE, with identical Ki values of 5.0 x 10(-10) M. The selectivity of ICI 200,880 for HNE versus a variety of enzymes ranged from 150-fold [relative to porcine pancreatic elastase (PPE)] to greater than 360,000-fold in favor of HNE. The compound effectively inhibited HNE-hydrolysis of bovine ligamentum nuchae elastin. In pharmacokinetic studies, ICI 200,880 and ICI 200,355 displayed long retention times when administered directly to the lung and were rapidly eliminated after intravenous administration. Pretreatment of hamsters with either inhibitor before intratracheal administration of HNE produced dose- and time-dependent inhibition of enzyme-induced increases in lung weight, total lavageable red cells, and total lavageable white cells. Aerosol administration of ICI 200,880 produced similar results. Subcutaneous administration of either 50 or 100 mumol/kg (twice/day) of ICI 200,880 for 14 or 28 days prevented the time-dependent increase in alveolar diameter produced by a single intratracheal dose of PPE when compound dosing was initiated 24 h after the enzyme. Treatment of hamsters with the same protocol and doses of ICI 200,880 for 8 wk prevented the destructive lesion induced by a single intratracheal dose of HNE. It is concluded that ICI 200,880 and ICI 200,355 have biochemical, pharmacokinetic, and pharmacologic profiles that make them useful therapeutic agents for understanding the role of HNE in various diseases. ICI 200,880 is presently being evaluated in humans.

Animals↗
PubMed1991

Epidemiology of Q fever in Sweden.

Q fever is known to be a worldwide disease, with Sweden supposed to be one of a few exceptions. The purpose of this pilot study was to elucidate whether or not a potential risk group for obtaining Q fever in Sweden was seropositive to the causative agent Coxiella burnetii. Blood samples were collected from sheep farmers on the island of Gotland, and from members of their families. Serum samples were examined by ELISA for the presence of antibodies against C. burnetii, phases I and II. Positive reactions were confirmed with Western blot analysis. It was found that 30% of the study group were seropositive to C. burnetii, thus indicating that Q fever is endemic in this area of Sweden.

Adolescent↗
PubMed1991

Electron microscopy of Coxiella burnetii in tissue culture. Induction of cell types as products of developmental cycle.

An in vitro ultrastructural study was carried out on tissue cultures (J774, murine macrophage-like tumour cell line, and BHK-21, baby hamster kidney cell line) persistently infected with C. burnetii to investigate whether the events of cellular differentiation could be visualized. At a given stage of the developmental cycle, a proportion of the cells within the affected phagolysosomes clearly underwent cellular differentiation. The cells initially showed asymmetrical septation, the primary stage of cellular differentiation, and ended with the formation of the differentiated product, a precursor to the small cell. The results verified our initial observation that the events occurring during growth in a phagolysosome represent stages of a complex developmental cycle consisting not only of i) vegetative growth by typical transverse binary fission, but also ii) cellular differentiation.

Animals↗
PubMed1991

Developmental changes in the regulation of plasma growth hormone concentrations in Holstein calves.

A study was initiated to determine whether development of a functional ruminant digestive system was associated with alterations in plasma growth hormone (GH) concentration. Holstein bull calves were fed milk or milk with grain until studied at the age of 1 month (n = 12). Calves placed on pasture with some grain supplementation were studied at the age of 3 months (n = 6) to determine plasma GH concentration in an animal with fully developed ruminant metabolism. Blood samples were taken at 10-minute intervals for 5 hours, followed by administration of bovine GH-releasing factor (0.075 micrograms/kg of body weight) and subsequent blood sample collection for 1 hour. On the following day, a blood sample was collected via jugular cannula, clonidine (10 micrograms/kg) was administered, and blood samples were subsequently obtained. Data indicated that milk-fed calves had higher mean plasma GH concentration than did either milk/grain-fed or older calves. The difference in mean plasma GH concentration was related to higher secretory pulse amplitude. Pituitary responses to bovine GH-releasing factor did not differ among the 3 groups, but response to clonidine were greater in milk-fed calves than in calves of the other groups. These data indicate that the change from a nonruminant to a ruminant-type gastrointestinal tract, perhaps attributable to subsequent changes in metabolism, may induce changes in hypothalmic function to decrease GH concentration.

Aging↗
PubMed1990

Effect of solute permeability in determination of elastic modulus using the vesicular swelling method.

The modulus of elasticity of artificial and biological membranes can be determined in membrane vesicles by monitoring the limitation of vesicular swelling during a slow decrease in medium tonicity. The higher the elastic modulus of the membrane, the more effectively the vesicles will resist swelling. This method assumes that the solutes in the system are impermeant, so that the final volume of the vesicles is determined solely by a balance of osmotic and hydrostatic forces. In this paper, we present the results of computer simulation of vesicular swelling in which the solute permeability of the membrane was varied. We find that even a small permeability will lead to a loss of solute from the vesicle that will retard the increase in vesicular volume during dilution of the medium, and thereby cause the apparent modulus of elasticity to be much greater than the true value. For example, if one takes the mannitol permeability in brush border membrane vesicles from small intestine to be 0.004 micron/s (a reasonable estimate), one finds that a vesicular swelling study using mannitol as the principal solute will show the apparent elastic modulus of the vesicles to be greater than 10 times larger than the true value. With higher permeabilities, the effect is even more dramatic. We conclude that determination of impermeance of solutes is a critical prerequisite for making valid determinations of membrane elastic modulus using the vesicular swelling method.

Elasticity↗
PubMed1990

Isolated Coxiella burnetii synthesizes DNA during acid activation in the absence of host cells.

Two populations of Coxiella burnetii were isolated from fibroblast tissue cultures and examined for their ability to synthesize DNA when incubated in a defined medium. Both the populations released by mechanical lysis of heavily infected host cells, as well as those recovered from the tissue culture medium, incorporated H3 32PO4 into DNA. Incorporation occurred at pH 4.5 but not at pH 7.0, and proceeded for 12-15 h. When incorporation of [3H]thymidine was studied, only the organisms obtained by mechanical lysis of host cells were active. Those which had been released by natural means into the tissue culture medium, and then recovered for study, did not incorporate precursor thymidine but were extremely active in protein biosynthesis. In mechanically released organisms, thymidine incorporation was inhibited immediately by rifamycin (40 microM) and hydroxyurea (10 mM), but it was not affected by chloramphenicol (310 microM) until 4 h after addition of the drug. Incorporation of H3 32PO4 by both populations of organisms was also inhibited by rifamycin, chloramphenicol and hydroxyurea, but the time sequence of inhibition differed. Southern hybridization utilizing 32P-labelled DNA suggested that both populations synthesized authentic chromosomal DNA sequences, as well as QpH1 plasmid DNA, during acid activation of metabolism.

Blotting, Southern↗
PubMed1990

Localization of DNA in Coxiella burnetii by post-embedding immunoelectron microscopy.

The deoxyribonucleic acid of Coxiella burnetii was detected with monoclonal antibodies against single-stranded and double-stranded DNA by post-embedding immunoelectron microscopy. The antibody labeled the nucleoid of the spore, the small cell variant (SCV), and the large cell variant (LCV). The DNA was segregated completely in both the spore and the mother cell. At the terminal stage of development of the spore, the loss of nuclear morphology in the mother cell was related to the reduction in the labeling of the nucleoid. The mother cell was therefore killed for the development and release of the spore.

Coxiella↗
PubMed1990

The immune response to phase I and phase II Coxiella burnetii antigens as measured by western immunoblotting.

To determine the utility of Western immunoblotting in distinguishing chronic Q fever from acute Q fever, we first examined serum samples from individuals who had no antibodies to Coxiella burnetii by either the indirect immunofluorescence antibody test or by the enzyme-linked immunosorbent assay. In these subjects, the IgG fraction in low dilutions of serum (1:8, 1:16) reacted with as many as 10 proteins in phase I and phase II antigens. This number of reacting bands seen in Western blots was reduced by using serum in a dilution of 1:1024. In contrast, IgA antibodies were uncommon even at low dilutions. Likewise, IgA antibodies were infrequently observed in patients with acute Q fever. However, in chronic Q fever there were many IgA antibodies to phase I and phase II proteins. Antibodies to phase I proteins were more common than those to phase II proteins. Several antigenic protein bands were recognized only by serum from chronic Q fever patients. Three of these antigens had molecular masses of, respectively, 50 kDa, 80 kDa, and 160 kDa. Serial serum samples from patients with chronic Q fever revealed that the number of antigens recognized by the IgA fraction decreased after the initiation of antibiotic therapy. The decline was faster for antibodies to phase II proteins. We conclude that immunoblotting is useful in the diagnosis of chronic Q fever.

Acute Disease↗
PubMed1990

Injection of inactivated phase I Coxiella burnetii increases non-specific resistance to infection and stimulates lymphokine production in mice.

The encounter of phase I C. burnetii with the host results in seemingly disparate consequences. On the one hand, in vitro lymphocyte responses to mitogens and homologous recall antigen are suppressed. On the other, host resistance to a variety of infectious agents and to a tumor is increased. An explanation for this augmented immune response surely involves the ability of C. burnetii to stimulate cytokines, such as interferon and TNF, which enhance host immune function.

Animals↗