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Biomedical subjects

J C Williams

Publications and source records attributed to J C Williams.

At least 325 records · Page 18Linked to original sources
PubMed1984

Sensitivity of Coxiella burnetii peptidoglycan to lysozyme hydrolysis and correlation of sacculus rigidity with peptidoglycan-associated proteins.

The protease-resistant proteins associated with the peptidoglycan (PG) of the phase I small-cell variant Coxiella burnetii were either partially released from the PG by boiling the PG-protein complex (PG-PC) in sodium dodecyl sulfate containing 2-mercaptoethanol and EDTA or totally released by 1 N NaOH hydrolysis at 23 degrees C. An 18,300-dalton protein was released from the PG-PC under reducing conditions, whereas 1 N NaOH treatment extracted PG-associated proteins without apparent dissolution of the PG. Purified PG was composed of muramic acid, glucosamine, glutamic acid, alanine, and meso-diaminopimelic acid in a molar ratio of 0.9:0.9:1.0:1.4:1.0. Lysozyme hydrolysis of cell walls, PG-PC, and purified PG caused an increase in reducing groups which correlated with roughly 60 to 100% digestion of disaccharides. There was no significant decrease in turbidity during lysozyme hydrolysis of cell walls and PG-PC; however, hydrolysis of purified PG caused about 90% decrease in turbidity. Approximately 60% of the meso-diaminopimelic acid groups of PG were not susceptible to dinitrophenylation, thus, demonstrating an apparent contribution of PG-associated proteins, rather than cross-linkage between peptides, to sacculus rigidity of cell wall and PG-PC. This association of PG and protease-resistant covalently bound proteins may be important structural and functional determiners of resistance to both environmental conditions and intracellular digestion of C. burnetii by eucaryotic cells.

Amino Acids↗
PubMed1984

Chemical and immunological characterization of lipopolysaccharides from phase I and phase II Coxiella burnetii.

Lipopolysaccharides (LPSs) isolated from phase I and phase II Coxiella burnetii (LPS I and LPS II, respectively) were analyzed for chemical compositions, molecular heterogeneity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunological properties. The yields of crude phenol-water extracts from phase I cells were roughly three to six times higher than those from phase II cells. Purification of LPSs by ultracentrifugation gave similar yields for both LPS I and LPS II. Purified LPS I and LPS II contained roughly 0.8 and 0.6% protein, respectively. The fatty acid constituents of the LPSs were different in composition and content, with branched-chain fatty acids representing about 15% of the total. beta-Hydroxymyristic acid was not detected in either LPS I or LPS II. A thiobarbituric acid-periodate-positive compound was evident in the LPSs; however, this component was not identified as 3-deoxy-D-mannooctulosonic acid by gas and paper chromatographies. LPS II contained D-mannose, D-glucose, D-glyceromannoheptose, glucosamine, ethanolamine, 3-deoxy-D-mannooctulosonic acid-like material, phosphate, and fatty acids. LPS I contained the unique disaccharide galactosaminuronyl glucosamine and nine unidentified components in addition to the components of LPS II. The hydrophobic, putative lipid A fraction of LPS I and LPS II contained the above constituents, but the hydrophilic fraction was devoid of ethanolamine. The LPS I disaccharide galactosaminuronyl glucosamine was found in both fractions of the acetic acid hydrolysates. Analysis of LPSs by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver staining indicated that LPS II was composed of only one band, whereas LPS I consisted of six or more bands with irregular spacing. Ouchterlony immunodiffusion tests demonstrated that LPS I reacted with phase I but not with phase II whole-cell hyperimmune antibody, and LPS II reacted neither with phase I nor phase II hyperimmune antibody. From these results, it was concluded that the chemical structures of LPSs from C. burnetii were different from those of the LPSs of gram-negative bacteria; however, the LPS structural variation in C. burnetii may be similar to the smooth-to-rough mutational variation of saccharide chain length in gram-negative bacteria.

Acetylation↗
PubMed1984

Seroepidemiology of Q fever in Nova Scotia and Prince Edward Island.

The prevalence of Coxiella burnetti infection (Q fever) was determined among Nova Scotia (N.S.) and Prince Edward Island (P.E.I.) blood donors by using the complement fixation and microimmunofluorescence (IF) test. The complement fixation and IF antibody tests measured antibody prevalence for the phase II or phase I and II antigens, respectively. Complement-fixing antibodies to phase II antigen were detected in 4.1% of 997 N.S. and 5.0% of 219 P.E.I. blood donors. Anti-phase II antibodies were detected by microimmunofluorescence in 11.8 and 14.6% of the blood donors in the two provinces, respectively. Anti-phase I antibodies were detected among 2.8% of the N.S. blood donors and 6.3% of the P.E.I. blood donors. Comparison of rates of anti-phase II IF by counties in N.S. revealed that there was at least one county where infection by C. burnetti is hyperendemic. Rates of antibody prevalence were similar in all three areas of P.E.I. examined. We conclude that "Q fever" is endemic in N.S. and P.E.I. and that the microimmunofluorescence test is more suitable than the complement fixation test for seroepidemiologic studies.

Adolescent↗
PubMed1984

Efficacy of fenbendazole against inhibited larvae of Ostertagia ostertagi in yearling cattle.

Efficacy of fenbendazole, at doses of 7.5 and 10.0 mg/kg of body weight, against inhibited early 4th-stage larvae of Ostertagia ostertagi and other nematodes of the abomasum and intestinal tract, was investigated in naturally infected yearling heifers in late May 1982. In Louisiana, this is near the end of the period (March to May) in which maximal numbers of inhibition-prone larvae are acquired. The mean numbers of O ostertagi in 10 untreated control cattle were: adults, 4,880; developing 4th-stage larvae, 12,546; and inhibited early 4th-stage larvae, 167,931. At the 7.5 mg/kg dose level (10% liquid suspension) in 10 cattle, percentage reduction of O ostertagi in comparison with controls was: adults, 95.7%; developing 4th stages, 91.1%; and inhibited 4th stage, 55.0%. Percentage reductions of other genera were as follows: abomasum--Trichostrongylus axei, 99.6%; Haemonchus sp, 95.1%; intestinal tract--Cooperia spp, 97.8%; Trichostrongylus colubriformis, 100.0%; and Oesophagostomum radiatum 4th stage and adults, 100.0%. At the 10.0 mg/kg dose (10% liquid suspension) in 11 cattle, the percentage reduction of O ostertagi in comparison with controls was: adults, 98.6%; developing 4th stages, 92.9%; and inhibited 4th stage, 80.0%. Percentage reductions of other genera were: abomasum--T axei, 99.9%; Haemonchus sp, 98.8%; intestinal tract--Cooperia spp, 99.3%; T colubriformis, 100.0%; and Oes radiatum 4th stage and adults, 100.0%. Variability of efficacy against inhibited larvae was observed, particularly at the 7.5 mg/kg dose; at this dose, 7 of the 10 heifers in the group yielded in excess of 54,000 surviving larvae.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Physiological consequences of beta-adrenoceptor desensitization in guinea pigs.

The effects of repetitive doses of beta-adrenoceptor stimulants on the resting tone and responsiveness of bronchopulmonary smooth muscle were studied in guinea pigs. Collapse time was used to assess bronchospasm in conscious animals while resistance and compliance measurements were used in the anesthetized guinea pigs. Repetitive administration of either isoproterenol or salbutamol, at effective bronchodilator doses, caused an exacerbation of the histamine-induced bronchospasm in the presence or absence of anesthesia. Repetitive administration of either prostaglandin E1, 20 micrograms/kg i.m., or aminophylline, 400 micrograms/kg i.m. did not enhance histamine-induced bronchospasm. Furthermore, in guinea pigs preselected for lack of histamine sensitivity, treatment with salbutamol caused a decrease in both dynamic compliance values and peak expiratory flow rate as well as an increase in resistance values. Trachea removed from guinea pigs treated with isoproterenol or salbutamol retained normal responsiveness to histamine and dibutyryl cAMP while the responsiveness to isoproterenol was reduced. These studies indicate that repetitive administration of beta-adrenoceptor stimulants can produce a specific desensitization of beta-adrenoceptors in pulmonary tissue and an alteration of resting baseline values of pulmonary mechanics measurements.

Albuterol↗
PubMed1983

Cost effectiveness of operator features in equipment design.

In design negotiation, the attribution of credible values to the incorporation or deletion of operator features allows engineers the freedom to judge the overall effect of human factors recommendations in relation to the achievement of a design specification. Likewise in the development phase, product planners frequently need more precise statements about productivity, training needs and general operational performance than, "it will be greater/less, worse/better than...". The method described utilises measured and synthetic data, learning theory and Markov processes to calculate the likelihood of operator task failure. These failure rates are then treated via filter factors derived from the application of the Nominal Groups Technique to give a global statement of the likelihood of operator failure resulting in unscheduled calls for service. Using the relationship between the cost of service calls and the overall life cost of developing, manufacturing, marketing and supporting a leased product, it is then possible to place credible values on the design features in question. Thus during the design process it becomes feasible to calculate the likely effects of human factors recommendations and modifications in relation to manufacturing costs, and thereby facilitate rational assessment of their implementation on a sound economic basis. This technique has been used to considerable effect, and represents a useful additional tool for the human factors practitioner in the design negotiation process. Further developments and refinements are planned, and it is anticipated that a similar technique will shortly be available to enable assessment of the effectiveness of product training programmes and job aids.

Journal Article↗
PubMed1983

Experimental and natural infection of calves with Bunostomum phlebotomum.

An experiment was conducted to determine the efficiency of a method of experimental infection of weaner beef calves with Bunostomum phlebotomum and to compare such infection with that established by natural infection. Six calves, maintained on a concrete-floored pen, were inoculated with B. phlebotomum L3 by placing the larval inocuulum, in small volume, in the outer chamber of the ear while the animal was restrained for 18 min. Inoculation doses of 20, 30, 40, 50, 60, and 80 thousand L3 were used. Six other calves were grazed on pasture known to be heavily contaminated with hookworm. All animals were killed 72 days after experimental infection and 93 days after initial exposure to pasture infection. The experimental and naturally-infected calves became patent at 55 and 66 days, respectively, after exposure to L3. Red blood cell counts and hemoglobin values were markedly depressed in both groups and lowest values coincided with onset of patency. There was difference in liveweight changes, but both groups lost weight during the prepatent period of infection and gained weight with the onset of patency. The largest number of hookworms was established at the 30000 L3 inoculation level; little or no establishment was observed at the 2 highest levels. Sizeable adult hookworm burdens were established in 4 out of 6 pastured calves. Intestinal pathology was generally more severe in experimentally-infected calves, consisting of a thickened mucosa and masses of punctate, hemorrhagic foci. Pastured calves also acquired large burdens of Ostertagia ostertagi, particularly inhibited early fourth-stage larvae. Moderate to severe abomasal pathology and elevated plasma pepsinogen were associated with ostertagiasis in the pastured calves. The experimental infection method is efficient in establishing high levels of B. phlebotomum infection in calves currently or previously infected with other gastrointestinal nematodes.

Abomasum↗
PubMed1983

Primary structure of the M subunit of the reaction center from Rhodopseudomonas sphaeroides.

The reaction center is a membrane-bound bacteriochlorophyll-protein complex that mediates the primary photochemical events in the photosynthetic bacterium Rhodopseudomonas sphaeroides. The previously determined amino-terminal sequences of the three subunits of the reaction center protein were used to design synthetic mixed oligonucleotide probes for the structural genes encoding the subunits. One of these probes was used to isolate and clone a fragment of DNA from R. sphaeroides that contained the gene encoding the M subunit. The nucleotide sequence of this gene was determined by the dideoxy method. In addition, a number of tryptic and chymotryptic peptides from the M protein were isolated and subjected to sequence analysis, and the sequence of the carboxyl terminus was determined. Together with the amino-terminal sequence, the data establish the primary structure of the M protein. The distribution of hydrophobic residues in the amino acid sequence suggests the presence of five membrane-spanning segments. A significant homology was found between the amino acid sequence of the M subunit and a thylakoid membrane protein (M(r) 32,000) from spinach that has been implicated in herbicide and quinone binding.

Journal Article↗
PubMed1983

Partial characterization of peptidoglycan-associated proteins of Legionella pneumophila.

The proteins associated with the peptidoglycan (PG) of Legionella pneumophila are resistant to proteolysis by trypsin, protease VI and proteinase K. These protease-resistant proteins are associated with the PG noncovalently and covalently. Analysis of cell walls and PG-protein complex by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions revealed one major protein (38.5K) and several minor Coomassie and silver staining components. The 38.5K protein seemed to be a major component which was co-purified with the PG. The cleavage of the PG-protein complex by 1 N NaOH treatment yielded PG free of proteins which was subjected to alkali hydrolysis. This association of PG and protease-resistant covalently-bound proteins may be an important structural and functional determinant of resistance to both environmental conditions and intracellular digestion of L. pneumophila by eukaryotic cells.

Bacterial Proteins↗
PubMed1983

Serological evaluation of O fever in humans: enhanced phase I titers of immunoglobulins G and A are diagnostic for Q fever endocarditis.

Serological parameters were compared in 15 cases of Coxiella burnetii infection comprising 5 cases each of primary Q fever, chronic granulomatous hepatitis, and endocarditis. The diagnosis was made on the basis of clinical history and serology and on the isolation of C. burnetii phase I from biopsy specimens of liver and bone marrow from two patients with granulomatous hepatitis and from the aortic valve vegetations of five patients with endocarditis. The temporal sequences of immunoglobulin levels, rheumatoid factor, and specific antibody responses to phase II and phase I antigens of C. burnetii were evaluated as predictive correlates of the three Q fever entities. Serum levels of immunoglobulin classes G, M, and A were variable in all the entities of Q fever. Increased mean levels (in milligrams per deciliter) of immunoglobulin G (IgG) and IgA were noted with chronic disease in the sera of some patients, whereas IgM levels were not significantly different from normal values. Rheumatoid factor was significantly elevated in chronic disease but not in primary Q fever. The temporal sequence of C. burnetii phase II and phase I antibodies were compared by microagglutination, complement fixation, and indirect microimmunofluorescence tests. All of these serological tests were useful in distinguishing primary from chronic disease. Thus, the ratio of anti-phase II to anti-phase I antibodies was greater than 1, greater than or equal to 1, and less than or equal to 1 for primary Q fever, granulomatous hepatitis, and Q fever endocarditis, respectively. Moreover, the high phase-specific IgA antibody titers in the indirect microimmunofluorescence test were diagnostic for endocarditis.

Antibodies, Bacterial↗
PubMed1983

Dermal granulomatous hypersensitivity in Q fever: comparative studies of the granulomatous potential of whole cells of Coxiella burnetii phase I and subfractions.

Dermal granulomatous reactivity to Q fever antigens in guinea pigs has been described as a model for vaccine reactions seen in previously sensitized humans. This model has now been applied to study the ability of subfractions of Coxiella burnetii to produce granulomas. Q fever organisms in phase I, trichloroacetic acid-soluble and -insoluble fractions, and the extract and residue of chloroform-methanol extraction were tested for their relative ability to elicit and immunize for dermal granulomatous reactions and specific lymphocyte proliferative responses in guinea pigs. The results suggest that a determinant(s) causing granulomas can be removed by chloroform-methanol extraction of phase I whole cells. The chloroform-methanol residue elicited strong delayed-type hypersensitivity without subsequent granuloma formation. The chloroform-methanol residue appears to possess a determinant(s) for lymphocyte stimulation equivalent to that of whole phase I organisms.

Animals↗
PubMed1983

Peptidoglycan of Legionella pneumophila: apparent resistance to lysozyme hydrolysis correlates with a high degree of peptide cross-linking.

Peptidoglycan (PG) from Legionella pneumophila was composed of muramic acid, glucosamine, glutamic acid, alanine, and meso-diaminopimelic acid in a molar ratio of 0.8:0.8:1.1:1.7:1. Partially purified PG contained trypsin-insensitive proteins which were extracted by 1 N NaOH hydrolysis without apparent dissolution of the PG. Lysozyme hydrolysis of purified PG or cell walls caused an increase in reducing groups which correlated with roughly 70 to 100% digestion of disaccharides. However, there was no significant decrease in turbidity during lysozyme hydrolysis of purified PG or cell wall. Additionally, 80 to 90% of the meso-diaminopimelic acid epsilon-amino groups were not susceptible to dinitrophenylation. Collectively, the PG of L. pneumophila was sensitive to lysozyme hydrolysis and insensitive to alkali dissolution, and 80 to 90% of the NH2 groups of meso-diaminopimelic acid were apparently involved in cross-linkages between peptides.

Alanine↗
PubMed1983

pH dependence of the Coxiella burnetii glutamate transport system.

The transport of glutamate, apparently a primary energy source for Coxiella burnetii, has been examined. C. burnetii is shown to possess a pH-dependent active transport system for L-glutamate with an apparent Kt of 61.1 microM and Vmax of 8.33 pmol/s per mg at pH 3.5. Both L-glutamine and L-asparagine competitively inhibited transport of glutamate, but D-glutamate, L-aspartate, L-glutamate-gamma-methyl ester, methionine sulfoximine, or alpha-ketoglutarate did not compete. This transport system is both temperature and energy dependent. Uptake of glutamate is highly sensitive to uncouplers of oxidative phosphorylation such as 2,4-dinitrophenol and carbonyl cyanide-m-chlorophenyl hydrazone that decrease the proton motive force across the cytoplasmic membrane. ATPase inhibitors such as dicyclohexylcarbodiimide or metabolic poisons such as KCN, NaF, or arsenite were much less effective as inhibitors of glutamate transport. Uptake of glutamate did not appear to be coupled to Na+ symport as in Escherichia coli since no monovalent cation requirement could be demonstrated. Instead, the Vmax of glutamate transport showed good correlation with the transmembrane pH gradient (delta pH). From these results, we propose that L-glutamate transport by C. burnetii is energized via a proton motive force.

Adenosine Triphosphate↗
PubMed1983

Acid alpha-glucosidase from human heart.

An alpha-glucosidase maximally active at acid pH has been purified from human heart some 2,600-fold and its properties compared to a purified alpha-glucosidase from human liver. Molecular weight was evaluated using three different analytical procedures. The effect of various cations was determined. Thermal lability was evaluated using three different substrates. Affinity and hydrolysis velocity constants for maltose, glycogen and 4-methylumbelliferyl-alpha-D-glucose were determined for both preparations at optimal hydrogen ion concentration. Inhibition studies were carried out using the disaccharide turanose. From this study, we conclude there are no significant differences in molecular weight or kinetic properties between the cardiac and hepatic alpha-glucosidase enzymes.

Cations↗
PubMed1983

Foetal safety of nitrofurantoin macrocrystals therapy during pregnancy: a retrospective analysis.

Urinary tract infection during pregnancy poses increased risk to mother and foetus and warrants prompt detection and treatment. Currently, there are no antibacterials approved for use in pregnant women. A retrospective analysis was undertaken to evaluate the safety to the human foetus of nitrofurantoin macrocrystals (Macrodantin) when administered during pregnancy. The records of ninety-one pregnancies in eighty-one obstetric patients who were treated with nitrofurantoin macrocrystals for urinary tract infection were reviewed. Safety was assessed according to incidence of foetal death, neonatal death, malformation, prematurity, low birth weight, low Apgar score and jaundice. The incidence of abnormal events in the pregnancies evaluated was not significantly different from that in the United States population. No abnormal event was considered to be drug-related. This study yielded no evidence that would implicate nitrofurantoin macrocrystals as toxic to the foetus or unsafe for treatment of maternal urinary tract infection during pregnancy.

Abnormalities, Drug-Induced↗