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Biomedical subjects

W L Williams

Publications and source records attributed to W L Williams.

At least 55 records · Page 3Linked to original sources
PubMed1987

Effects of palindrome size and sequence on genetic stability in the bacteriophage phi X174 genome.

By inserting palindromes of varying length and sequence into a non-essential region of the bacteriophage phi X174 genome we have investigated the effect of palindrome size and sequence on their genetic stability. Multimers of increasing size of the EcoRI linker CCGAATTCGG (E), the BamHI linker CCGGATCCGG (B) or mixtures of both (E, B) were inserted into the PvuII site of a previously constructed bacteriophage strain phi X174 J-F ins6. The largest inserts that could be maintained in the genome without significant loss of genetic stability were 2B, 4E, and 4(E, B), respectively. Polymers exceeding this size could be inserted but resulted in rapid and precise deletion from the phage genome, whereby nB was more unstable than nE, and nE was more unstable than n(E, B). Analysis of the resulting deletion mutants provided evidence for two different types of deletions. The more frequent deletion arose from either type palindrome and removed nucleotides in blocks of ten base-pairs (one linker unit), but only from the palindromic sequence, and always left at least an 18 base-pair long palindrome (one linker plus 8 neighboring base-pairs) behind. The less frequently occurring deletions arose only from nB type palindromes, removing the complete palindromic sequence plus adjacent nucleotides. At least the first type of deletion occurred in the absence of recA activity. Our results show a correlation between the sequence, as well as size, and the genetic stability of palindromes, i.e. sequences that could decrease the stability of a cruciform increased their genetic stability. This supports the theory that palindrome deletion occurs via extrusion of the palindrome into a cruciform or cruciform-like structure.

Bacteriophage phi X 174↗
PubMed1987

Do symptoms reflect a change in left ventricular function after aortocoronary bypass grafting in patients with depressed left ventricular function?

Seventy-nine patients with moderate to severe left ventricular dysfunction who underwent aortocoronary bypass grafting between 1971 and 1977 had follow-up heart catheterization at a mean interval of 3 years. Thirty-three patients (42%) had angiographic improvement in left ventricular function at follow-up and 18 (25%) had a decrease in left ventricular end-diastolic pressure. Fifty-eight patients (73%) had improvement in angina of at least one New York Heart Association class at follow-up. There was no correlation between late improvement in left ventricular function and improvement in angina. Improvement in left ventricular function did not correlate with preoperative indices of severity of coronary disease or with indices of completeness of surgical repair.

Adult↗
PubMed1987

The effects of cyclophosphamide and irradiation singly and in combination upon SaI growth in A/J mice.

The effects of various doses of cyclophosphamide and low-dose (15 rads) radiation upon the size of tumors caused by 10(4) Sarcoma I (SaI) cells was determined. In intact A/Jax (A/J) recipients, the effect of the two agents singly and in combination was found to be dependent especially upon the dosage of cyclophosphamide and the time of its administration in relation to tumor inoculation. In cell transfer experiments to adult thymectomized, lethally irradiated, bone-marrow-restored (ATxXBM) mice, the effects of cyclophosphamide and irradiation appeared to be either overlapping (low dosages of cyclophosphamide) or additive (dosages of cyclophosphamide greater than or equal to 50 mg/kg), suggesting that the two agents exert their influence in dissimilar fashion, perhaps by injuring different cell types with the same basic function. The most pronounced conjoint effects are seen when low dosages of cyclophosphamide are given 3 days after the adoptive transfer of spleen cells from mice pretreated with low-dose irradiation. The implications of this observation with respect to immunotherapy are discussed.

Animals↗
PubMed1986

The cumulative risk of tuberculin skin test conversion for five years of hospital employment.

We studied tuberculin skin test conversions in a cohort of 550 new employees followed for five years after assignment to adult inpatient services at Charity Hospital at New Orleans, Louisiana. There were 17 known conversions, an overall five-year cumulative probability of converting of 5.2 per cent. Proportional hazards regression analysis found that race and type of job (nursing vs other) were independent explanatory variables. To examine further the job effect, we compared the conversion curves for Blacks in nursing and Blacks in other jobs and found those in nursing to have higher rates.

Adult↗
PubMed1985

Antitumor agents 68: effects of a series of helenalin derivatives on P-388 lymphocytic leukemia nucleic acid and protein synthesis.

A series of analogues related to helenalin demonstrated moderate capability for inhibiting the growth of murine P-388 lymphocytic leukemia cells in vivo and in vitro. The growth inhibition correlated with suppression of both DNA and protein synthesis in P-388 cells. The inhibition of protein synthesis occurred at a relatively low concentration and appeared to occur at the level of initiation. The suppression of DNA synthesis in P-388 cells correlated positively with inhibition of inosine 5'-monophosphate dehydrogenase activity. Although nuclear and alpha DNA polymerase activities were suppressed by certain analogues, the inhibition of the polymerases did not correlate positively with DNA synthesis inhibition and, furthermore, the magnitude of suppression of DNA polymerase activity did not appear to be sufficient to account for the observed suppression of DNA synthesis in P-388 cells.

Animals↗
PubMed1985

Persistence and change in the berdache tradition among contemporary Lakota Indians.

This article explores the gender non-conformity role of berdache, which ethnographers have often assumed has died out among contemporary American Indians. Ethnohistorical sources indicate intense suppression of berdaches by missionaries and government officials. The authors fieldwork in 1982 on Lakota reservations in South Dakota reveals that individuals recognized as berdaches continue to hold a social and ceremonial role. A gender-mixing status seldom talked about with outsiders (including heterosexual ethnographers) was observed. This role involves more emphasis on sexual contact with men that has been noted in recent anthropological writings.

Adult↗
PubMed1984

Indirect inactivation of rabbit reticulocyte initiation factor eIF-2 by helenalin and bis(helenalinyl) malonate.

Helenalin and bis(helenalinyl) malonate, sesquiterpene lactones that react primarily with exposed sulfhydryl groups, were shown to be equally effective inhibitors of endogenous protein synthesis in rabbit reticulocyte lysates. By use of partially fractionated systems, it was possible to show that helenalin preferentially inhibited the conversion of the ternary initiation complex to the 48S preinitiation complex. Previous experiments have shown that this preferential inhibition is due to selective inactivation of eIF-3 [Williams, W. L., Chaney, S. G., Willingham, W., Considine, R. T., Hall, I. H., & Lee, K.-H. (1983) Biochim. Biophys. Acta 740, 152-162]. Bis(helenalinyl) malonate was much less active as an inhibitor of 48S complex formation than helenalin and clearly did not possess sufficient activity in that assay to explain its effectiveness as a protein synthesis inhibitor in whole lysates. Kinetic studies also showed a clear difference between the mechanism of action of these two drugs. Bis(helenalinyl) malonate inactivated protein synthesis in reticulocyte lysates only after a lag of 10 min, and the inhibition of protein synthesis could be completely reversed by the addition of 5 mM cAMP. Helenalin showed more complex kinetics. While full inhibition only occurred after a lag of 10-15 min, a partial inhibition was observed from very early times. cAMP at 5 mM was only partially able to reverse inhibition by helenalin. Phosphorylation studies showed that both helenalin and bis(helenalinyl) malonate were equally effective at activating eIF-2 alpha kinase and indirectly causing phosphorylation of eIF-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Hypolipidemic activity of tetrakis-mu-(trimethylamine-boranecarboxylato)-bis(trimethylamin e- carboxyborane)-dicopper(II) in rodents and its effect on lipid metabolism.

A binuclear copper(II) complex was shown to have potent hypolipidemic activity in rats and mice at low doses, i.e., 2.5-10 mg/kg/d. The agent moderately lowered liver ATP-dependent citrate lyase, acetyl CoA synthetase, and phosphatidate phosphohydrolase activities in vivo. The appetite of the animal was reduced by drug treatment, and orally administered cholesterol absorption from the intestine was markedly lowered. Higher lipid levels were found in the chyme and the feces, indicating accelerated excretion of lipids by the drug, probably via the biliary route. Organs, e.g., liver and small intestine, as well as serum lipoprotein levels, demonstrated lower lipid content after drug administration. Thus, this chemical class of agents may have potential as a hypolipidemic agent in humans.

Animals↗
PubMed1984

Biological activity of the hypolipidemic agent, N2-n-butylindazolone.

Previously, a series of N-substituted indazolone derivatives proved to be effective hypolipidemic agents in rodents. The most effective agent, N2-n-butylindazolone, at 20 mg/kg/d was shown to suppress the levels of cytoplasm acetyl coenzyme A required for cholesterol and fatty acid synthesis as well as sn-glycerol-3-phosphate acyl transferase and phosphatidate phosphohydrolase activities. Lipid content of the liver, small intestine, and serum lipoprotein fractions was lowered, whereas lipid content was increased in fecal excretions by drug treatment for 14 d. The absorption of orally administered cholesterol from the intestine was severely reduced after drug administration. The mode of action of N2-n-butylindazolone appears to be similar to cyclic imides possessing hypolipidemic activity.

Animals↗
PubMed1984

Hypolipidemic activity of 4-pyrimidinecarboxylic acids in CF1 mice.

A series of 4-pyrimidinecarboxylic acids were evaluated for hypolipidemic activity in mice at 20-30 mg/kg/d ip. A number of these derivatives were observed to be active at this dose. Substitution of the hydroxyl group in position 2 and 6 of the 4-pyrimidinecarboxylic acid with a sulfhydryl and an amino group, respectively, led to a compound which produced a greater than 40% reduction of serum cholesterol and triglyceride levels in mice. Similarly, a compound which was substituted with an amino group in position 2 and an isobutyl group in position 5 led to equally potent activity as a hypolipidemic agent.

Animals↗
PubMed1984

Comparison of clinical and treadmill variables for the prediction of outcome after myocardial infarction.

To assess the relative prognostic merits of 15 clinical and 10 predischarge exercise test variables, 226 patients who had sustained an acute myocardial infarction were studied. A submaximal treadmill test was performed on 205 patients to a mean work load of 5.7 +/- 2.9 METS. Testing was performed an average of 11.7 (range 6 to 33) days after myocardial infarction. During the first year of observation, major cardiac events were noted in 33 patients (16%), unstable angina in 7 (3.4%), recurrent myocardial infarction in 14 (6.8%) and death in 12 patients (5.9%). Cardiac mortality correlated with mean peak serum creatine kinase (CK) (p less than 0.05), history of previous myocardial infarction (p less than 0.01) and ST segment depression at rest (p less than 0.01). The only exercise variable that correlated with cardiac mortality was poor exercise endurance (p less than 0.05). Multivariate risk stratification of clinical and treadmill variables from these 205 patients using linear discriminant analysis produced a function that correctly classified 95% of those who were event-free and 80% of those who died. The first four discriminant variables that contributed independent information for the prediction of cardiac mortality were: 1) ST segment depression at rest; 2) CK greater than 1,280 IU/liter; 3) exercise duration less than 3 minutes; and 4) a history of previous myocardial infarction. ST segment depression on the predischarge treadmill test did not predict any event, nor did it improve the predictive accuracy of the clinical variables. It is concluded that a history of previous myocardial infarction and ST segment depression on the rest electrocardiogram indicate a poor prognosis after acute myocardial infarction. Poor endurance is the only exercise variable that suggests a future cardiac event. Prognosis after acute myocardial infarction is more accurately predicted by these clinical data than by variables derived from the predischarge treadmill test.

Adult↗
PubMed1983

Selective inactivation of rabbit reticulocyte initiation factor eIF-3 by helenalin.

Helenalin, a sesquiterpene lactone which reacts primarily with exposed sulfhydryl groups, was shown to be an effective inhibitor of protein synthesis in rabbit reticulocyte lysates. Optimal inhibition required a 30 min preincubation in the absence of any added thiol compound. Beta-Mercaptoethanol was more effective than reduced glutathione in protecting enzyme sulfhydryl groups from inactivation by helenalin. Using partially fractionated systems, it was possible to show that helenalin had no effect on the elongation reactions or on the formation of the ternary initiation complex. However, the conversion of the ternary complex to the 48 S initiation complex was strongly inhibited. In this assay, only the initiation factor(s) were sensitive to helenalin. Using an assay system which requires all the initiation factors for optimal activity it was possible to show that the 0-40% ammonium sulfate cut of initiation factors (containing eIF-3 and eIF-4B) was sensitive to helenalin, while the 40-50% ammonium sulfate cut (containing eIF-2 and eIF-5) was not. Both ammonium sulfate cuts were equally sensitive to inhibition by the sulfhydryl reagent N-ethylmaleimide. Three purified rabbit reticulocyte initiation factors were then tested in the same assay system. Only eIF-3 showed appreciable sensitivity to helenalin, while eIF-2, eIF-3 and eIF-4B were all sensitive to inactivation by N-ethylmaleimide. These data suggest that helenalin may possess a relatively high degree of specificity as a sulfhydryl reagent.

Animals↗
PubMed1983

Investigation of sesquiterpene lactones as protein synthesis inhibitors of P-388 lymphocytic leukemia cells.

The mode of action of helenalin and bis(helenalinyl) malonate as protein synthesis inhibitors of P-388 lymphocytic leukemia cells was investigated. The initial characterizations were carried out in crude lysates of the P-388 cells. In the lysate, there was a 4 min lag after the addition of drug before inhibition of protein synthesis occurred. Both drugs allowed run-off of preformed polysomes, but did significantly inhibit the formation of the 80 S initiation complex suggesting a preferential inhibition of one or more initiation reactions. The effect of these drugs on inhibition of both elongation and initiation reactions was further investigated using more fractionated systems prepared from P-388 cells. Poly(U)-directed polyphenylalanine synthesis was marginally inhibited by both drugs, but the degree of inhibition was not sufficient to explain the inhibition observed in either the lysate or in whole cell preparations of P-388. The formation of the ternary initiation complex was not significantly inhibited by either drug, but the conversion of this complex to the 48 and 80 S initiation complexes was inhibited. The inhibition of 48 S initiation complex formation by both drugs was sufficient to explain their inhibition of protein synthesis in whole cells.

Animals↗
PubMed1982

Apparent ketoconazole failure in candidal cholecystitis.

Fungal acalculous cholecystitis is a rarely recognized complication of disseminated candidal infections. We report such a case of systemic candidiasis that developed in a man who was diabetic while he was receiving broad-spectrum antibiotic therapy for an infected foot ulcer. Ketoconazole, a new imidazole antifungal agent, was used successfully to treat the systemic candidal infection but it failed to eradicate the fungus in the biliary tract.

Antifungal Agents↗