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Biomedical subjects

S Wong

Publications and source records attributed to S Wong.

At least 217 records · Page 12Linked to original sources
PubMed1990

Nonuniform radiolabeling of VLDL apolipoprotein B: implications for the analysis of studies of the kinetics of the metabolism of lipoproteins containing apolipoprotein B.

Radiolabeling of whole lipoproteins or individual apolipoproteins has been an essential tool for the determination of the kinetics of apolipoprotein metabolism in vivo. Mathematical analysis of specific radioactivity (SA) or total radioactivity data has demonstrated the existence of significant complexity in the plasma decay curves of several apolipoproteins. Results obtained during development of methods to study the metabolism of apolipoprotein B (apoB) in very low density lipoprotein (VLDL) subclasses isolated according to flotation (Sf) rates from whole radiolabeled (d less than 1.006 g/ml) VLDL suggested nonuniform radiolabeling of apoB in the three Sf subclasses being studied. We therefore determined apoB SA in VLDL Sf subclasses in ten hypertriglyceridemic and five normal subjects. After radioiodination of apoB in whole VLDL, different apoB SA were found in Sf 400-100, Sf 100-60, and Sf 60-20. The pattern of labeling was quite variable among subjects. On average, apoB SA in the VLDL tracer was greatest in Sf 400-100, and least in Sf 60-20. Nonuniform labeling could also be demonstrated in five studies in which samples were obtained 3 min after intravenous injection of the tracer into subjects with a wide range of plasma triglycerides. Nonuniform labeling of apoB in whole VLDL was also demonstrated in two of the subjects by isolating subclasses of their VLDL that did not bind to an anti-apolipoprotein E immunoaffinity column. These results indicate that the usual assumption of homogeneous labeling of apoB may be erroneous. We have derived a simple mathematical formula to study the consequences of this assumption in estimating kinetic parameters. It is shown that an erroneous assumption of homogeneous tracer labeling may significantly underestimate or overestimate the true production rate, even in a simple two-pool model. Identification of labeling characteristics and incorporation of this information into the mathematical analysis of the plasma radioactivity data can improve the accuracy of the analysis as well as the sensitivity of compartmental models generated by such data.

Apolipoproteins B↗
PubMed1989

Endogenous Nocardia asteroides subretinal abscess diagnosed by transvitreal fine-needle aspiration biopsy.

The authors report a case of an endogenous Nocardia asteroides subretinal abscess in an immunosuppressed cardiac transplant recipient. On clinical grounds, the metastatic subretinal abscess was initially thought to be a fungal, atypical bacterial, or viral lesion. Transvitreal fine-needle aspiration biopsy of the lesion yielded a sufficient specimen for immediate preliminary identification of the microorganism and permitted prompt initiation of an appropriate antibiotic regimen. The definitive diagnosis was based on culture of the organism from the needle aspirate.

Abscess↗
PubMed1989

Psychosocial factors influencing outcome in patients with low-back pain.

A psychosocial analysis of 58 patients with low-back pain was conducted. Three groups of patients with different outcomes were delineated with distinctly different psychosocial profiles. Patients who recovered uneventfully had a better income, reported more satisfaction with hospitalization or medical personnel, and had prolonged pain-free periods. Patients with the worst outcomes in terms of poor work role adjustment and severe pain complaints were more likely to be immigrants from mainland China, to be engaged in heavy manual labor, to be involved in compensation claims for work-related injuries, manifested a high degree of anxiety and depressive symptoms, and were hostile toward medical personnel. An intermediate group of patients with adequate work role adjustment but severe to moderate levels of pain were characterized by being females with varying combinations of anxiety and depressive symptoms. A preliminary clinical interview guide for screening potential problematic patients was developed.

Adult↗
PubMed1989

Contribution of permeability and sensitivity to inhibition of DNA synthesis in determining susceptibilities of Escherichia coli, Pseudomonas aeruginosa, and Alcaligenes faecalis to ciprofloxacin.

To examine the correlation between bacterial cell susceptibility to ciprofloxacin and the magnitude of uptake and cell target sensitivity, the relative contribution of ciprofloxacin accumulation in intact cells and its ability to inhibit DNA synthesis were investigated among strains of Escherichia coli, Pseudomonas aeruginosa, and Alcaligenes faecalis. Uptake studies of [14C]ciprofloxacin demonstrated diffusion kinetics for P. aeruginosa and E. coli. Ciprofloxacin was more readily removed from E. coli J53 and A. faecalis ATCC 19018 by washing than from P. aeruginosa PAO503. These results indicate that the process of cell accumulation is different for P. aeruginosa in that the drug is firmly bound at an extracellular site. Whatever the washing conditions, A. faecalis accumulated less drug than either of the other two bacteria. Magnesium chloride (10 mM) caused a substantial decrease of ciprofloxacin accumulated and an increase in the MIC, depending upon the nature of the medium. The addition of carbonyl cyanide m-chlorophenylhydrazone caused a variable increase in drug accumulated, depending on the medium and the bacterial strain. The concentration of ciprofloxacin required to obtain 50% inhibition (ID50) of DNA synthesis for P. aeruginosa PAO503 and A. faecalis ATCC 19018 did not correlate with their corresponding MICs but did for E. coli J53. Treatment with EDTA decreased the ID50 of ciprofloxacin for P. aeruginosa PAO503 and its gyrA derivative by 5- and 2-fold, respectively, and decreased the ID50 for E. coli JB5R, a strain with a known decrease in OmpF, by 1.4-fold but did not decrease the ID50 for the normally susceptible E. coli J53. The ID(50) for P. aeruginosa obtained after EDTA treatment or in ether-permeabilized cells was higher than that obtained for the other two strains. The protonophore carbonyl cyanide m-chlorophenylhydrazone prevented killing by low ciprofloxacin concentrtaions, but sodium azide did not. The latter compound did not enhance killing in association with inhibition of a previously described energy-dependent efflux of ciprofloxacin susceptibility being the susceptibility to inhibition of DNA synthesis in E. coli, poor premeability associated with the small pore size of A. faecalis, and a combination of low permeability and reduced susceptibility of DNA synthesis to inhibition for P. aeruginosa.

Alcaligenes↗
PubMed1989

Quinolone antimicrobial agents: mechanism of action and resistance development.

The primary target of fluoroquinolone antimicrobial agents is the A subunit of DNA gyrase. In several cases a close relationship to ID50 (inhibitory dose-50%) and minimum inhibitory concentration (MIC) has been shown for gram-negative bacteria, although this has not been regularly observed for gram-positive bacteria to date. Cellular entry is by means of diffusion and involves, at least in part, the porin pathway in the outer membrane of gram-negative bacteria. An energy dependent efflux occurs which is more active in brain heart infusion broth than nutrient broth and which, to date, has not been shown to contribute to inhibition of growth or bacterial lethality. The extent of uptake by different gram-negative bacteria varies and may contribute in some cases to determination of the MIC. Resistance to fluoroquinolones is by means of mutations affecting the gyrase gene coding for the A subunit and mutations which affect cell permeability particularly involving porin proteins of the outer membrane. Combined target and permeability resistance has been reported but involves two or more mutational steps. Resistance during clinical treatment has been observed, but is most likely to be of low magnitude and to be detected in patients with significantly compromised host defenses.

4-Quinolones↗
PubMed1989

Properties and applications of photodynamic therapy.

Photodynamic therapy (PDT) is the treatment of malignant lesions with visible light following the systemic administration of a tumor-localizing photosensitizer. Pharmacological and photochemical properties of the photosensitizer are combined with precise delivery of laser-generated light to produce a treatment which can offer selective tumoricidal action. Hematoporphyrin derivative (HD) and a purified component called Photofrin II are currently being used in clinical PDT. Initial patient results have been encouraging, and considerable interest has developed in the synthesis and evaluation of new photosensitizers with improved photochemical and pharmacological characteristics. In addition, there has been a gradual increase in knowledge related to in vitro and in vivo mechanisms of action of PDT. This report provides an overview of the properties and applications of PDT. Information and data related to drug development, photochemistry, subcellular targets, in vivo responses, and clinical trials of PDT are presented.

Clinical Trials as Topic↗
PubMed1988

Low dose postoperative adjuvant radiation therapy for rectal cancer is ineffective.

Ninety-seven patients with rectal cancer which had either penetrated through the rectal wall or involved regional lymph nodes received postoperative adjuvant radiation therapy of 24 Gy in 12 fractions or 25 Gy in 10 fractions in 2 weeks. The crude pelvic recurrence rate was 48/97 (49%) and the actuarial local relapse-free rate at 5 years was 41%. The radiation doses used produced no late morbidity, but had no discernible effect on the risk of local recurrence, and may have compromised the subsequent use of radiation for symptomatic pelvic recurrence.

Adenocarcinoma↗
PubMed1988

Effect of tolmetin glycine amide (McN-4366), a prodrug of tolmetin sodium, on adjuvant arthritis in the rat.

The glycine amide of tolmetin sodium (TGA) functions as a prodrug and was demonstrated to be more potent than the parent compound as an inhibitor of developing and established adjuvant arthritis in the female Lewis rat. In contrast, the glycine amide of indomethacin was less potent than indomethacin. The superiority of TGA relative to tolmetin sodium in alleviating this condition was demonstrated by inhibition of paw swelling and reduction of the degenerative bone changes that are associated with the progression of this chronic animal model of rheumatoid arthritis in humans. These properties were not evident when equimolar mixtures of tolmetin sodium and glycine were administered concurrently. Pharmacokinetic analyses revealed that TGA was absorbed completely and hydrolyzed to tolmetin in the female adjuvant arthritic rat. The combined effects of absorption, distribution and hydrolysis of TGA produced lower peak plasma tolmetin levels than an equivalent dose of tolmetin sodium, but plasma concentrations were sustained for a longer period of time contributing to an apparent increase in potency. Furthermore, TGA displayed a decreased propensity to cause gastrointestinal irritation compared to tolmetin sodium. Several additional amino acid amides of tolmetin were similar to the glycine amide in exhibiting increased potency and reduced gastrointestinal toxicity in comparison to equivalent doses of tolmetin sodium.

Animals↗
PubMed1987

Eicosapentaenoic acid inhibits the secretion of triacylglycerol and of apoprotein B and the binding of LDL in Hep G2 cells.

The consumption of long chain polyunsaturated fatty acids by fish oils leads to profound lowering of plasma triacylglycerol but not of plasma cholesterol. Reasons for this were investigated with the human hepatoma cell line, the Hep G2 cell. Incubations with oleic acid (18:1 n9), linoleic acid (18:2 n6) and the characteristic marine fatty acid eicosapentaenoic acid (EPA, 20:5 n3) enriched cellular triacylglycerol mass, though least with EPA. However, secretion of very low density lipoprotein (VLDL) triacylglycerol and apoprotein B (measured by formation from [3H]glycerol and [3H]leucine) was markedly inhibited by EPA. Preincubation with linoleic acid reduced VLDL triacylglycerol but not apo B secretion in comparison with oleic acid which stimulated both. A possible effect on low density lipoprotein (LDL) removal was studied by measuring [125I]LDL binding. Preincubation with either EPA or linoleic acid inhibited the saturable binding of LDL, observed with oleic acid and control incubations. The binding of lipoproteins containing chylomicron remnants was not affected by any of the fatty acids.

Apolipoproteins B↗
PubMed1987

Why are (or are not) patients given the option to enter clinical trials?

Much attention has been paid to the use of ethical principles to guide the conduct of clinical trials. Less has been done to clarify and assess the "weights" assigned by clinicians (and others) to the values that come into conflict when patients are offered entry into trials. Quantitative techniques of value assessment were used to measure the relative importance of variables frequently identified as barriers to the entry of patients into clinical trials. Responses were obtained from 52 oncologists, 26 clinical trials and senior nurses, and 23 family physicians. The group of oncologists identified the scientific design of the trial as the most important factor. In contrast, the groups of nurses and family physicians gave higher weight to effects of the trial on the doctor-patient relationship. The results illustrate ways in which methods of value assessment may be used to clarify and rank values.

Clinical Trials as Topic↗
PubMed1987

Towards effective clinical teaching in nursing.

During the last two decades, the structure and function of clinical learning and teaching have undergone significant changes. Nursing students demand quality teaching rather than supervision in the clinical area alone. At the same time, expectations and demands of university nursing faculty also change. Nurse educators are under increasing pressure to engage in scholarly activities. Clinical instruction in baccalaureate nursing programmes becomes the primary responsibility of either the inexperienced or part-time, sessional instructors. This pattern of faculty teaching assignment is not without problems. This paper critically examines these problems and proposes strategies for dealing with them.

Clinical Competence↗
PubMed1987

Accumulation of enoxacin by Escherichia coli and Bacillus subtilis.

Several methods were used to determine enoxacin uptake in Escherichia coli strains because washing of cells removed all or most cell-associated enoxacin whereas no washing was associated with large amounts of cell-bound enoxacin. Washing after up to 40 to 45 min of exposure to enoxacin followed by suspension in drug-free medium prevented a significant effect of enoxacin on cell growth. Cell uptakes obtained with different methods showed no difference in the shape of the timed uptake curves but did show significant quantitative differences. These results are consistent with cell-associated enoxacin comprising a freely exchangeable pool of drug. Lineweaver-Burk plots of uptake were consistent with uptake of enoxacin by simple diffusion. No saturability and no competition with ciprofloxacin were observed. Low temperature (4 degrees C) was associated with decreased uptake. Arsenate, carbonyl cyanide m-chlorophenylhydrazone, sodium fluoride, sodium azide, and 2,4-dinitrophenol had no effect on uptake. We conclude that the mechanism of transport of enoxacin into cells is by simple diffusion. Mutants of E. coli with deficiency of outer membrane proteins F and C and an enoxacin-resistant mutant selected by serial passage with increasing enoxacin concentrations demonstrated that F porins play a significant role in enoxacin uptake and influence susceptibility to enoxacin. Uptake was shown to be similar in a strain of Bacillus subtilis.

Bacillus subtilis↗
PubMed1987

Metal-dependent binding of a factor in vivo to the metal-responsive elements of the metallothionein 1 gene promoter.

Using the technique of genomic footprinting, we demonstrate cadmium-inducible protection from dimethyl sulfate (DMS) modification of guanine residues in vivo in five metal-responsive elements (MREs) in the promoter of the rat metallothionein 1 (MT-1) gene. We also identify a site of extreme DMS hyperreactivity which, like the MRE protection, occurs only after metal ion induction. With this hyperreactive site as an indicator, we can measure the kinetics of induction and deinduction. Changes in the intracellular metal ion concentrations are reflected in alterations in the reactivity with DMS of guanine residues in the MT-1 gene promoter. Lastly, for both control and metal-induced cells, we observe DMS protection and enhancement of a binding site (located 5' of the distal MRE) which is a consensus sequence for the Sp1 transcription factor. Transfection experiments with deletion mutations of a fusion gene construct indicate both that a sequence region which includes this GC box regulates the basal level of expression of the MT-1 gene and that increasing the number of MREs in the promoter increases the induced level of transcription. Our genomic footprinting and transfection data together suggest that (i) a transcription factor, possibly Sp1, plays an important role in regulating the basal level of expression of the MT-1 gene and (ii) metal induction involves the metal-dependent binding to a sequence-specific binding factor which responds to changes in intracellular metal ion levels.

Animals↗