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Biomedical subjects

T G Cleary

Publications and source records attributed to T G Cleary.

80 records · Page 5Linked to original sources

Polymorphonuclear leukocytes of human colostrum. I. Oxidative metabolism and kinetics of killing of radiolabeled Staphylococcus aureus.

Polymorphonuclear leukocytes (PMNLs) were isolated from the colostrum of 57 women. Colostral cells were identified by fluorescent microscopy after supravital staining with acridine orange. Numerous intracellular fat globules within colostral PMNLs were shown by Oil Red O stain and electron microscopy. Oxidative metabolic activity during phagocytosis of opsonized zymosan particles was significantly greater in blood PMNLs compared with colostral PMNLs. The total uptake and killing of [methyl-3H]thymidine-labeled Staphylococcus aureus by blood PMNLs were significantly greater than by colostral PMNLs. Similar defects were produced in blood PMNLs incubated with the lipid fraction of colostrum, but not in those incubated with the aqueous fraction. Surface Fc receptors of colostral PMNLs and blood PMNLs incubated with colostral lipid were significantly reduced in number compared with those of control PMNLs or PMNLs preincubated with the aqueous fraction of colostrum. The metabolic and phagocytic defects of PMNLs from human colostrum appear to be related to colostral substances that alter PMNL surface structure and subsequent function.

Cell Count↗

Human colostral cytotoxicity. II. Relative defects in colostral leukocyte cytotoxicity and inhibition of peripheral blood leukocyte cytotoxicity by colostrum.

Colostral cells have been previously shown to mediate antibody-dependent cellular cytotoxicity (ADCC) to herpes to simplex virus-infected cells. A comparison of colostral cells to matched peripheral blood mononuclear cells has revealed significantly lower ADCC activity, higher antibody requirements, and slower kinetics of colostral cell ADCC against infected cells. Colostral cells failed to mediate natural killer cytotoxicity. Lymphocytes, monocyte macrophages, and polymorphonuclear leukocytes isolated from peripheral blood and incubated with colostrum from virus-immune or nonimmune women markedly inhibited ADCC. Inhibitory activity was found in lipid and aqueous fractions and was due to an effect on leukocytes, not target cells. A partial explanation was inhibition of expression of leukocyte Fc receptors, a prerequisite for ADCC, by acellular colostrum. These results raise questions concerning the potential antiviral activity of colostral cells in vitro.

Antibody-Dependent Cell Cytotoxicity↗

Amikacin pharmacokinetics in pediatric patients with malignancy.

The pharmacokinetics of amikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and normal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 min produced concentrations in serum of 29.3 +/- 5.7 micrograms/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 +/- 1.7 micrograms/ml and at 6 h of 1.2 +/- 0.3 microgram/ml. The serum half-life was 1.24 +/- 0.09 h, volume of distribution was 0.26 +/- 0.02 liter/kg, and total body clearance rate was 131 +/- 10 ml/min per 1.73 m2. No accumulation of amikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.

Adolescent↗

Serum immunoglobulins in the nephrotic syndrome. A possible cause of minimal-change nephrotic syndrome.

To assess immunologic factors in the pathogenesis of idiopathic minimal-change nephrotic syndrome (INS), serum immunoglobulin concentrations were measured in 37 children with this syndrome and compared with those found in 36 with nephrotic syndrome secondary to chronic glomerulonephritis (CGN). Serum IgG and IgA levels were significantly reduced in nephrotic patients with either INS or CGN, IgG averaging 18.5 and 25.9 per cent of normal (P less than 0.001) and IgA 59.8 and 44.1 per cent of normal (P less than 0.01) respectively. Values increased after treatment of INS with prednisone, but mean values remained low. Serum IgM concentrations in INS averaged more than twice normal before, during, and after successful treatment with steroids. Patients with CGN did not have equivalent elevations of serum IgM. Thus, the primary defect in INS may be immunologic and could consist of deficiency in the T-cell function that mediates conversion of IgM synthesis to IgG synthesis.

Animals↗

Effect of subinhibitory concentrations of antibiotics on extracellular Shiga-like toxin I.

Patients with diarrhea due to strains of enterohemorrhagic Escherichia coli (EHEC) (e. g. O157:H7) might be at a higher risk of developing hemolytic uremic syndrome when treated with antimicrobial agents. It has been suggested that this might be due to an increase of release or production of vero or shiga-like toxin from such organisms, possibly as a stress response to antimicrobial agents. The aim of this study was to detect such increases in extracellular toxin in vitro with a newly developed method that exposed EHEC to high sublethal concentrations followed by a recovery phase at progressively lower concentrations. Five strains of EHEC were exposed to continuously changing concentrations of ciprofloxacin, co-trimoxazole, cefixime and tetracycline. The amount of free shiga-like toxin I (SLT-I) released was compared to the amount released from inocula that were not exposed to antibiotics. There were significant differences between the five EHEC strains in the amount of toxin detected after exposure to antimicrobial agents (p less than 0.001). Equally important was the type of antibiotic (p less than 0.001), with ciprofloxacin inducing the largest increase ranging from 169 to 436%, followed by co-trimoxazole, cefixime and tetracycline. In addition, the increases in free toxin correlated with the concentration of the antibiotics (p less than 0.001). The association between antibiotic-induced increases in SLT-I produced by strains of EHEC and certain classes of antibiotics might influence the analysis of future epidemiological studies on risk factors for HUS.

Anti-Bacterial Agents↗