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Biomedical subjects

R L Ward

Publications and source records attributed to R L Ward.

At least 181 records · Page 10Linked to original sources
PubMed1977

Discovery of an agent in wastewater sludge that reduces the heat required to inactivate reovirus.

An agent that causes heat inactivation of reovirus to occur at reduced temperatures has been found in both raw and anaerobically digested sludge. This agent is originally associated with sludge solids but can be washed from these solids by blending with water. The activity of the agent was considerably greater in alkaline than in acid solutions, probably because it is insoluble at low pH. The agent was shown to be nonvolatile and heat stable up to 300 degrees C but was inactivated within 30 min at 400 degrees C. The rate of heat inactivation of reovirus by the agent was found to occur in a bimodal fashion and to be relatively rapid, even at 35 degrees C. Finally, it was found that this agent did not accelerate heat inactivation of poliovirus, but instead may be the component of sludge previously found to protect poliovirus against inactivation by heat.

Ammonia↗
PubMed1976

Effect of edetate disodium and reduced glutathione on absorption of acetazolamide from GI tract of rats.

The absorption of acetazolamide suspensions from in situ rat gastric and intestinal loop segments was studied. In 1 hr, 66.2 and 64.3% remained unabsorbed from the rat stomach and intestine, respectively. Although 1% (w/v) reduced glutathione and 1% (w/v) (24 mM) edetate disodium had no effect on gastric absorption, drug absorption from the rat intestine (1 hr) was increased 1.5 and 2 times, respectively. It was hypothesized that the relatively poor intestinal absorption was due primarily to the formation of a pH-dependent (pH 4.5-10), nonabsorbable complex between acetazolamide and carbonic anhydrase present in the gut and that reduced glutathione acted as an inhibitor to promote intestinal absorption. Equilibrium dialysis studies showed that reduced glutathion could reduce the fraction of drug bound to human carbonic anhydrase B by one-half when present in a molar ratio 10 times that of acetazolamide; edetate disodium had no effect on the in vitro binding. It was, therefore, assumed that edetate disodium promoted an increase in intestinal absorption by altering the permeability of intestinal epithelium. Based upon present experimentation, however, the alteration of intestinal epithelium by reduced glutathione cannot be ruled out.

Acetazolamide↗
PubMed1976

Inactivation of poliovirus in digested sludge.

The effect of anaerobically digested sludge on poliovirus during incubation at temperatures between 28 and 4 C was studied. Although virus was fully recoverable from sludge, its infectivity decreased in proportion to the time and temperature of incubation. The rate ranged from greater than 1 log per day at 28 C to about 1 log every 5 days at 4 C. The mechanism of inactivation was studied at the lower temperature where the sedimentation coefficients of most inactivated particles were not detectably modified. The ribonucleic acid (RNA) of these particles appeared to have been nicked and had an average sedimentation value about 70% that of RNA from infectious virus. Since the specific infectivity of RNA from particles recovered from sludge was directly proportional to that of the particles from which it was extracted, loss of infectivity was probably due to inactivation of RNA. Some breakdown was also found in the two largest viral proteins of inactivated particles. Thus, the mechanism of inactivation may be cleavage of viral proteins followed by nicking of encapsulated RNA. Because no virucidal activity was found in raw sludge, this component of digested sludge appears to be a product of the digestion process.

Anaerobiosis↗
PubMed1976

Heat inactivation of poliovirus in wastewater sludge.

The effect of raw and anaerobically digested sludge on heat inactivation of poliovirus was investigated. Raw sludge was found to be very protective of poliovirus plaque-forming ability at all temperatures studied, but digested sludge had variable effects that were highly dependent upon the experimental conditions. In low concentrations and at relatively low inactivation temperatures, digested sludge is nearly as protective of poliovirus as raw sludge. However, at higher tempeatures and concentrations, digested sludge caused a significant acceleration of poliovirus inactivation. The difference between the protective capability of raw and digested sludge is not due to loss of protective material, because this component is present in the solids of digested sludge as well as in those of raw sludge. Instead, the difference is due to a virucidal agent acquired during digestion. Addition of this agent to the solids of either raw or digested sludge reverses the protective potential of these solids during heat treatment of poliovirus.

Anaerobiosis↗
PubMed1975

Monoanion inhibition and 35Cl nuclear magnetic resonance studies of renal dipeptidase.

Kinetic analyses of monoanion inhibition and 15Cl nuclear magnetic resonance at 5.88 MHz were employed to study monoanion interactions with the zinc metalloenzyme, renal dipeptidase. The enzyme-catalyzed hydrolysis of glycyldehydrophenylalanine exhibited competitive inhibition when the reaction rate was determined in the presence of the monovalent anions fluoride, chloride, bromide, iodide, azide, nitrate, or thiocyanate or upon the addition of the divalent anion, sulfate. Competitive inhibition was produced by these anions. One anion was bound per enzyme molecule, and except in the case of fluoride all of the anions appeared to bind at the same site. Cyanide ion produced a much more effective inhibition of renal dipeptidase than the other monoanions, and it was shown that two cyanide ions were bound per enzyme molecule. An investigation of the effect of pH upon monoanion inhibition suggested that the anion inhibitors bind to the group with a pK of approximately 7.8. Complete dissociation of this group (approximately pH 8.4) eliminates the inhibitory effect of anions. The 35Cl line broadening produced by renal dipeptidase in 0.5 M NaCl solutions was 100 times more effective than that produced by equivalent concentrations of aquozinc(II). The line broadening was dependent upon the concentration of the metalloenzyme and independent of the frequency of the exciting radiation. When zinc ion was removed from the metalloenzyme by dialysis or when chloride was titrated from the metalloenzyme by cyanide, line broadening was decreased. Treatment of renal dipeptidase with saturating concentrations of the competitive inhibitor, guanosine triphosphate, in the presence of 0.5 M NaCl also produced a significant decrease in the 35Cl line width. The 35Cl line broadening produced by renal dipeptidase was shown to decrease with increasing pH through the range pH 5.8-10.8. This line-width variation with pH appeared to result from the titration of a site on the metalloprotein with an approximate pK of 7.4. Temperature studies of 35Cl line broadening by the metalloenzyme in the presence of chloride and cyanide inhibitors suggest that the fast exchange process pertains and that the dominant relaxation mechanism is quadrupolar in nature.

Animals↗
PubMed1975

Effect of cytosine arabinoside on viral-specific protein synthesis in cells infected with herpes simplex virus.

The relationship between viral DNA and protein synthesis during herpes simplex virus type 1 (HSV-1) replication in HeLa cells was examined. Treatment of infected cells with cytosine arabinoside (ara-C), which inhibited the synthesis of HSV-1 DNA beyond the level of detection, markedly affected the types and amounts of viral proteins made in the infected cell. Although early HSV-1 proteins were synthesized normally, there was a rapid decline in total viral protein synthesis beginning 3 to 4 h after infection. This is the time that viral DNA synthesis would normally have been initiated. ara-C also prevented the normal shift from early to late viral protein synthesis. Finally, it was shown that the effect of ara-C on late protein synthesis was dependent upon the time after infection that the drug was added. These results suggest that inhibition of progeny viral DNA synthesis by ara-C prevents the "turning on" of late HSV-1 protein synthesis but allows early translation to be "switched off."

Arginine↗
PubMed1975

Lifetimes of mRNA molecules directing the synthesis of viral proteins in herpes simplex virus-infected cells.

Possible variations in the functional lifetimes of herpes simplex virus type 1 mRNA molecules in infected HeLa cells were studied. As shown by the rate of decrease of radioactive amino acid incorporation into viral proteins after the addition of actinomycin, the average lifetime of early viral mRNA's are shorter than those for the late messenger species. In addition, when the viral proteins made after the addition of actinomycin were further analyzed by gel electrophoresis, it was found that messengers for individual viral proteins translated within the early or late time period also had some differences in their functional lifetimes. These results indicate that the synthesis of herpes simplex virus type 1 proteins during the replicative cycle is regulated in part by mechanisms controlling the functional lifetimes of viral mRNA's.

Cycloheximide↗
PubMed1974

Nature of the scrapie agent: evidence against a viroid.

The postulated viroid nature of scrapie agent was tested. Since the agent could not be recovered after a carefully controlled phenol extraction of infected mouse brains, it is suggested that this agent is not a viroid.

Animals↗
PubMed1973

Acute intermittent porphyria: response of tachycardia and hypertension to propranolol.

In four young adult patients with acute attacks of acute intermittent porphyria tachycardia and hypertension were prominent features of the illness. Urinary catecholamine excretion was increased in both patients in whom it was measured. The effect of the beta-adrenergic blocking drug propranolol was assessed in each case. The dose varied from 40 to 240 mg daily. A response in the form of a reduction in heart rate and blood pressure was noted in each case, and in one case a marked alleviation of abdominal pain followed administration of the drug.Propranolol, when given in high dosage to rats, did not induce an increase in hepatic delta-aminolaevulic acid synthetase, an enzyme which is raised in human and drug-induced animal porphyria. The use of propranolol is therefore unlikely to aggravate or precipitate an attack of acute intermittent porphyria.

5-Aminolevulinate Synthetase↗