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Biomedical subjects

K J Williams

Publications and source records attributed to K J Williams.

At least 109 records · Page 6Linked to original sources
PubMed1986

Recognition of vesicular lipoproteins by the apolipoprotein B,E receptor of cultured fibroblasts.

Vesicular lipoproteins (e.g., lipoprotein-X) are found in plasma in cholestasis or following infusion of Intralipid or phospholipid. To investigate the metabolism of vesicular lipoproteins, we isolated them from the plasma of subjects with cholestasis or following chronic or single Intralipid infusion. Cholestasis and chronic Intralipid therapy were found to be associated with elevated plasma concentrations of apoE, as determined by radioimmunoassay. Vesicular lipoproteins purified from each of the three types of plasma contained apoE, as well as other proteins. In cholestasis, in which levels of apoE were up to five times normal, a major portion of the plasma apoE was on vesicular lipoproteins. Normalized for apoE content, all preparations of vesicular lipoproteins displaced 125I-labeled LDL from apoB,E receptors of cultured fibroblasts identically. This displacement was inhibited by monoclonal antibodies that block receptor binding of apoE. Vesicular lipoproteins containing 125I-labeled apoE were internalized and degraded by fibroblasts. Different preparations caused small losses or gains of cellular cholesterol, with appropriate stimulation or suppression of apoB,E receptors. Thus, vesicular lipoproteins contain apoE, and apoE mediates their interaction with the apoB,E receptor. Our results suggest that the catabolism of cholesterol-rich vesicular lipoproteins, formed during cholestasis or following infusions of Intralipid or phospholipid, may be receptor-mediated.

Antibodies, Monoclonal↗
PubMed1984

The failure of serum albumin to affect capillary permeability in the isolated rabbit heart.

The method of local tissue clearance was used to measure capillary permeability-surface area products (PS) for [3H]inulin and [14C]sucrose in the left ventricular wall of the isolated rabbit heart. As soon as a heart was excised, its coronary arteries were perfused with Ringer solution at 37 degrees for at least 30 min before clearance trials were begun. In paired trials, Ringer perfusion fluid containing 1% bovine serum albumin (Sigma) was compared with protein-free Ringer solution in terms of sucrose PS (PSs), inulin PS (PSi), and the PS ratio (Pi/Ps). With or without protein, the mean Pi/Ps was significantly less than the ratio of the free diffusion coefficients. With the untreated albumin, flow resistance rose markedly, and the PSs of both solutes fell but not Pi/Ps. To remove the unidentified vasoactive contaminant (which apparently resisted dialysis), the albumin was "defatted" by the procedure of R. F. Chen (1967, J. Biol. Chem. 242, 173-181). Defatted albumin (1% in the perfusion fluid) did not affect the volume of distribution (lambda) of sucrose or inulin in the myocardium, the heart rate, coronary flow, flow resistance, PSs, PSi, or Pi/Ps. Apparently bovine serum albumin does not influence capillary permeability in the rabbit heart. A protein effect on permeability, however, could have been missed if it has a long latent period (more than 15 min) or a long persistence (more than 30 min).

Animals↗
PubMed1984

Structure-activity relationships of retinoids in developmental toxicology. I. Studies on the nature of the polar terminus of the vitamin A molecule.

The teratogenic activities of all-trans-retinoyl fluoride, all-trans-3-retinylidene-2,4-pentanedione, all-trans-2-retinylidene-1,3-cyclopentanedione, all-trans-2-retinylidene-5,5-dimethyl-1,3-cyclohexanedione, all-trans-2-retinylidene-5-p-methoxyphenyl-1,3-cyclohexanedione, all-trans-2-retinylidene-1,3-cyclooctanedione, all-trans-5-[2,6-dimethyl-8-(2,6,6-trimethylcyclohexen-1-yl)-1,3, 5,7-octatetrae n-1-yl]tetrazole, ethyl all-trans-9-(exo-2-bicyclo[2.2.1.]heptyl)-3,7-dimethyl-2,4,6,8- nonatetraenoate, ethyl all-trans-4-[2-methyl-4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-1,3- butadien-1-yl]benzoate, 13-cis-N-(4-hydroxyphenyl)retinamide, and 13-cis-N-(2-hydroxyethyl)retinamide were determined in the hamster and compared with that of all-trans-retinoic acid. Administration of a single oral dose of the retinoids failed to induce signs of the hypervitaminosis A intoxication syndrome in any of the dams, and the maternal weight gain was not significantly different from the vehicle control value, except following intubation of the retinamides where maternal weight gain was significantly depressed. All of the retinylidene 1,3-diketones studied here were devoid of significant teratogenic activity. The retinamides failed to induce either an elevated mean litter frequency of malformed fetuses or a syndrome of anomalies similar to that induced by administration of an equimolar dose of all-trans-retinoic acid. All of the other retinoids induced a syndrome of malformations similar to that induced by administration of all-trans-retinoic acid and were associated with a significant increase in the number of litters containing one or more malformed fetuses and an elevated mean litter frequency of malformed fetuses. The teratogenic activity in the hamster of this series of retinoids was independent of structural modifications in either the beta-cyclogeranylidene ring or the polyene chain of the molecule. The results of the present study suggest that the changes in teratogenic activity associated with structural modification of vitamin A at C15 were primarily dependent upon the presence of or biotransformation to a free carboxyl or a moiety with an equivalent pKa at C15, not upon the molecular size of the substituent or the stereochemical position about C13. Since major structural modifications of vitamin A were made without the substantial loss of teratogenic activity, the structural requirements of retinoids for induction of terata were not extraordinarily exacting.

Animals↗
PubMed1984

A direct bone marrow chromosome technique for acute lymphoblastic leukemia.

We describe a direct bone marrow chromosome technique that was developed especially for use in studies of acute lymphoblastic leukemia (ALL). The features responsible for technical improvements include: the use of RPMI 1640 medium, supplemented with 30% fetal calf serum, to support cellular activity during both specimen transport and Colcemid treatment; the processing of only 0.1 ml of sedimented cells or less per centrifuge tube; the exposure of cells to Colcemid for a maximum of 25 min; control of the total time of exposure to hypotonic solution; the use of a steel wire as a stirring rod (fashioned to fit the centrifuge tube) for mixing cells; slide preparation by a specific edging-flaming technique; the natural aging of the slides to achieve optimal drying; and the use of a modified G-banding procedure that employs Wright's stain. This technique has been used in more than 350 cases of ALL and has consistently provided analyzable banded chromosomes, even in hyperdiploid cases with up to 91 chromosomes. It makes the previously recognized morphological difference between metaphases of residual normal cells and those from the leukemic clone less apparent. The edging-flaming technique of slide preparation is the most important component and is especially appropriate for spreading large numbers of chromosomes in ALL.

Bone Marrow↗
PubMed1984

Teratogenic dose-response relationships of etretinate in the golden hamster.

Etretinate (Ro 10-9359; Tigason; 4-methoxy-2,3,6-trimethylphenyl analog of retinoic acid, ethyl ester) was evaluated for teratogenic activity in the Syrian golden hamster. Groups of pregnant hamsters were given a single oral dose of 2.8-88 mg/kg etretinate during the early primitive streak stage of gestation. No signs of maternal intoxication were observed in any of the hamsters given the retinoid and maternal body weight changes throughout gestation were not significantly different from those of the vehicle-treated group. Etretinate administration was associated with a dose-dependent increase in the incidence and severity of malformations. The average fetal body weight was significantly less in litters recovered from dams given 44 or 88 mg/kg of etretinate when compared to the average body weight of fetuses recovered from dams given an equivalent volume of the vehicle. The average crown-rump lengths also were significantly shorter in fetuses taken from the dams given 44 or 88 mg/kg etretinate as compared to the control group. The malformations induced by etretinate administration were similar to those noted following an oral dose of all-trans-retinoic acid (Willhite and Shealy, 1984). A comparison of the dose-response curves for induction of terata following treatment with etretinate or all-trans-retinoic acid revealed that etretinate was twice as potent as a teratogen in the hamster as all-trans-retinoic acid. Teratogenic activity of etretinate in the hamster was achieved at doses (mg/kg body wt) used in patients at current clinical therapeutic levels.

Abnormalities, Drug-Induced↗
PubMed1984

Pharmacokinetics of ceftazidime in normal and impaired renal function.

The concentration of ceftazidime in serum and urine was measured after 2 g i.v. in 10 healthy volunteers and 19 patients with various degrees of renal insufficiency. Elimination observed in normal volunteers can best be described by a two-compartment model. In renal insufficiency elimination of ceftazidime is markedly diminished, resulting in a larger area under the serum level curve (area under the curve; AUC). AUC and glomerular filtration rate (as well as AUC and plasma creatinine) can be brought into a mathematical relation. From these relations a dose reduction factor (DRF) can be derived. By means of this factor a dose can be calculated for each degree of renal impairment which causes the same AUC that would be anticipated in a subject with normal renal function. Dose recommendations in tabular form are presented. The urinary recovery decreases with impaired renal function; nevertheless therapeutical urine levels are observed down to dialysed patients.

Ceftazidime↗
PubMed1983

Cytogenetic features of acute nonlymphoblastic leukemia in 73 children and adolescents.

We examined the leukemia cells of 81 consecutively admitted children and adolescents with acute nonlymphoblastic leukemia (ANLL) to determine the frequency and specificity of chromosomal abnormalities. Karyotypes were obtained for 73 (90%) of the 81 children, and 36 (49%) were abnormal. The modal karyotypes for the cases were tightly clustered in the diploid range; only 5 (7%) were hypodiploid, with 45 chromosomes each, and only 2 (3%) had greater than 50 chromosomes. Specific chromosomal abnormalities in the abnormal karyotypes were compared to morphologic subgroups of ANLL. An 8;21 translocation was found in 6 of 9 cases with M2 morphology but was also found in 1 case with M1 morphology. One of 4 with M3 (progranulocytic) morphology had a 15;17 translocation, and another had a 17q deletion. A structural abnormality in 11q was found in 3 of 7 patients with M5 (monoblastic) morphology, 2 of whom had a 9;11 translocation. The only case of M6 had a 22q-or Philadelphia chromosome in addition to other abnormalities. Statistical analysis of 27 abnormal karyotypes showed preferential structural rearrangement of 8q and 21q. We conclude that, in children as well as adults, specific structural abnormalities are correlated with certain morphologic subgroups of ANLL. However, other chromosomal changes associated with prior mutagenic exposure of adult ANLL were uncommon in children, which may suggest a difference in pathogenesis.

Acute Disease↗
PubMed1983

The pharmacokinetics of ceftazidime in normal and impaired renal function.

The concentration of ceftazidime in serum and urine was measured in ten healthy volunteers and 19 patients with renal impairment following a 2 g iv dose of ceftazidime. In impaired renal function the elimination rate of ceftazidime is decreased considerably, whereupon the area under the curve (AUC) rises sharply. Dose reduction factors (DRF) for several degrees of renal function are presented. The urinary recovery decreases with renal function; but therapeutic urine levels can still be detected in patients on dialysis. Patients with renal insufficiency should be given reduced dosage according to a dose reduction factor and according to the table.

Ceftazidime↗
PubMed1983

Penetration of ceftazidime into human tissue in patients undergoing cardiac surgery.

The penetration of ceftazidime into human heart muscle, skeletal muscle, skin, fat and bone was measured in 39 patients undergoing cardiac surgery. Mean serum levels of 70 mg/l were measured 1.5 h after dosing with mean levels of 27 mg/l after 4 h and 5.5 mg/l after 12 h. Tissue levels of ceftazidime were measured up to 280 min after dosing. These levels were high with mean corrected levels after 120 min of 20.0 mg/l in bone, 7.1 mg/l in skin (after 100 min), 9.2 mg/l in fat, 12.7 mg/l in heart muscle and 9.4 mg/l in skeletal muscle. Serum and tissue levels were sufficient to prevent infection by all likely pathogens, including Staphylococcus aureus, 98% of which have a ceftazidime minimum inhibitory concentration of 8 mg/l or less. There were no post-surgical infections.

Adipose Tissue↗
PubMed1983

A comparative study of the efficacy of ceftazidime versus cefazolin and tobramycin in patients with acute exacerbations of chronic bronchitis.

Fifty-nine adult patients have entered this study. The initial pathogens were eradicated from the infection sites and all except two of the patients who were assessed clinically in the ceftazidime group and 4 cases in the comparative group were cured or improved. No adverse reactions were connected to ceftazidime or to tobramycin and cefazolin.

Adolescent↗
PubMed1983

Ceftazidime in the treatment of complicated respiratory and urinary tract infections.

The efficacy of ceftazidime was examined in 46 patients, 33 with respiratory and 13 with urinary tract infections. Ceftazidime was given following the failure of conventional therapy or when bacteria had been isolated within a week of treatment. It was also used in infections arising as a complication of an indwelling catheter or in emergency situations when alternative antibiotics were inappropriate. Ceftazidime was found to be very successful in the treatment of these infections and only two patients failed to respond clinically, one of these being a patient with an indwelling catheter and one treated as an emergency who had severe underlying pathology. One patient was considered unevaluable because he died of his underlying condition during treatment. Serum levels of ceftazidime are described following im and iv administration of 0.5 and 1 g doses.

Bacterial Infections↗
PubMed1983

Randomized study of ceftazidime versus gentamicin plus cefotaxime for infections in severe granulocytopenic patients.

A randomized study of gentamicin plus cefotaxime versus ceftazidime alone was performed in 87 patients, with a neutrophil count of less than 1000/mm3 at the start of the treatment. The overall cure rate for the ceftazidime group was 71% and for the gentamicin plus cefotaxime 47%. This difference was shown to be statistically significant at a level of P less than 0.05. The cure rates for the microbiologically proven infections were 90 and 63% respectively. Serious adverse effects, causing preliminary withdrawal of therapy, have not been observed.

Adolescent↗
PubMed1982

How to make committees work for you.

The forum for many hospital managerial concerns is the medical staff committee meeting. This article focuses on the misuses and abuses of committees and offers suggestions for improving their effectiveness. The issues of composition, size, tenure, and formats are discussed, and guidelines for chairman are recommended.

Efficiency↗