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Biomedical subjects

R Lawrence

Publications and source records attributed to R Lawrence.

At least 55 records · Page 3Linked to original sources
PubMed1997

An in vitro assessment of the antineoplastic potential of 2H-1,3-oxazine-2,6(3H)-dione (3-oxauracil), a novel pyrimidine.

The pyrimidine (uracil) analogue 3-oxauracil (OU) previously had been shown to completely inhibit the growth of E. coli B and decrease by 96% the replication of herpes simplex virus type 2 when present in the culture fluid at a concentration of 10(2) microM. Limited in vivo studies in mice demonstrated antiviral effects without significant toxicity when given i.p. daily for two weeks at a concentration of 3.23 mg/kg. However, the antineoplastic properties of OU were unknown. We assessed the ability of OU to inhibit the proliferation of various human tumor cell lines (3 pancreatic, 1 colon, 1 neuroendocrine, and 1 lung) in an in vitro radiometric (Bactec) system. In the pancreatic lines (RWP-2, MiaPaCa-2, and PANC-1), the colon line (HT-29), the neuroendocrine line (COLO 320DM), and the lung cancer cell line (SK-MES-1), OU at a concentration of 10(3) microM, produced a dramatic decrease in percent cell survival. When compared with cytotoxic drugs of choice for these tumor cells (gemcitabine, 5-fluorouracil, and adriamycin, respectively) a significantly higher concentration of OU was required usually to achieve comparable results with two exceptions. These were the HT-29 and the COLO 320DM cell lines. These results indicate OU has significant (p < 0.05) cytotoxic activity against pancreatic, colon, neuroendocrine, and nonsmall cell lung cancer lines, when compared to untreated control cultures. Additional in vivo testing of this potential antineoplastic agent is warranted.

Antimetabolites, Antineoplastic↗
PubMed1997

Activity of TER286 against human tumor colony-forming units.

Glutathione S-transferase (GST) isozymes have been shown to be elevated in many human cancer types as compared to normal tissues. TER286, one in a class of glutathione-based GST-activated cytotoxins, was tested in a soft agar cloning assay to determine its in vitro activity against primary human tumor colony-forming units. Breast and lung specimens from patients who had received prior therapy and those who were previously untreated were exposed to TER286 at concentrations of 1, 10 and 50 microM using both 1 h and continuous exposures. Overall in vitro responses (50% or less survival compared to untreated controls) were observed in 0% (0/14), 14% (2/14) and 29% (4/14), respectively, in specimens exposed to TER286 for 1 h, and in 5% (2/41), 10% (4/41) and 61% (25/41), respectively, in specimens exposed to TER286 continuously. TER286 has cytotoxic activity against both breast and lung cancer colony-forming units, and demonstrates a concentration-response effect. At 50 microM, there is a significant difference between 1 h and continuous exposures in head-to-head comparisons. These data suggest that TER286 can be activated in human tumor colony-forming units and should be pursued as a treatment candidate for patients whose tumors are resistant to drug treatment based on up-regulation of GST.

Antineoplastic Agents, Alkylating↗
PubMed1997

Acutely administered melatonin reduces oxidative damage in lung and brain induced by hyperbaric oxygen.

Hyperbaric oxygen exposure rapidly induces lipid peroxidation and cellular damage in a variety of organs. In this study, we demonstrate that the exposure of rats to 4 atmospheres of 100% oxygen for 90 min is associated with increased levels of lipid peroxidation products [malonaldehyde (MDA) and 4-hydroxyalkenals (4-HDA)] and with changes in the activities of two antioxidative enzymes [glutathione peroxidase (GPX) and glutathione reductase (GR)], as well as in the glutathione status in the lungs and in the brain. Products of lipid peroxidation increased after hyperbaric hyperoxia, both GPX and GR activities were decreased, and levels of total glutathione (reduced+oxidized) and glutathione disulfide (oxidized glutathione) increased in both lung and brain areas (cerebral cortex, hippocampus, hypothalamus, striatum, and cerebellum) but not in liver. When animals were injected with melatonin (10 mg/kg) immediately before the 90-min hyperbaric oxygen exposure, all measurements of oxidative damage were prevented and were similar to those in untreated control animals. Melatonin's actions may be related to a variety of mechanisms, some of which remain to be identified, including its ability to directly scavenge free radicals and its induction of antioxidative enzymes via specific melatonin receptors.

Aldehydes↗
PubMed1996

Biomonitoring human exposure to environmental carcinogenic chemicals.

A coordinated study was carried out on the development, evaluation and application of biomonitoring procedures for populations exposed to environmental genotoxic pollutants. The procedures used involved both direct measurement of DNA or protein damage (adducts) and assessment of second biological effects (mutation and cytogenetic damage). Adduct detection at the level of DNA or protein (haemoglobin) was carried out by 32P-postlabelling, immunochemical, HPLC or mass spectrometric methods. Urinary excretion products resulting from DNA damage were also estimated (immunochemical assay, mass spectrometry). The measurement of adducts was focused on those from genotoxicants that result from petrochemical combustion or processing, e.g. low-molecular-weight alkylating agents, PAHs and compounds that cause oxidative DNA damage. Cytogenetic analysis of lymphocytes was undertaken (micronuclei, chromosome aberrations and sister chromatid exchanges) and mutation frequency was estimated at a number of loci including the hprt gene and genes involving in cancer development. Blood and urine samples from individuals exposed to urban pollution were collected. Populations exposed through occupational or medical sources to larger amounts of some of the genotoxic compounds present in the environmental samples were used as positive controls for the environmentally exposed population. Samples from rural areas were used as negative controls. The project has led to new, more sensitive and more selective approaches for detecting carcinogen-induced damage to DNA and proteins, and subsequent biological effects. These methods were validated with the occupational exposures, which showed evidence of DNA and/or protein and/or chromosome damage in workers in a coke oven plant, garage workers exposed to diesel exhaust and workers exposed to ethylene oxide in a sterilization plant. Dose reponse and adduct repair were studied for methylated adducts in patients treated with methylating cytostatic drugs. The biomonitoring methods have also demonstrated their potential for detecting environmental exposure to genotoxic compounds in nine groups of non-smoking individuals, 32P-postlabelling of DNA adducts being shown to have the greatest sensitivity.

Antineoplastic Agents, Alkylating↗
PubMed1996

Monocyte activity in Behçet's disease.

Monocytes obtained from patients with Behçet's disease (BD) were examined for differentiation markers (expression of CD14 and antigens reacting with monoclonal antibodies 25F9 and G16/1) and for expression of selected adhesion molecules. There was significantly raised expression of the CD14 molecule, and increased staining with 25F9 and G16/1 antibodies in monocytes obtained from patients with BD. A monocyte activation marker, soluble CD14, was also found to be raised in patients' serum compared with normal serum (8.1 +/- 9.2 vs 1.4 +/- 0.7 micrograms/ml). Furthermore, BD patients' monocyte culture supernatants caused significantly increased adhesion of normal neutrophils to endothelial cell monolayers in vitro. All these findings show that BD patients' monocytes are active in vivo and produce a number of pro-inflammatory cytokines which may play a role in the chronic inflammation found in these patients.

Behcet Syndrome↗
PubMed1996

Neutrophil adhesion to endothelial cells and factors affecting adhesion in patients with Behçet's disease.

OBJECTIVES: To study the in vitro adhesion of polymorphonuclear leucocytes (PMNLs) to endothelial cells in patients with Behçet's disease (BD), and the humoral and cellular factors which may contribute to adhesion. METHODS: A total of 118 patients with BD and 60 healthy controls were studied. In vitro adhesion of chromium-51 labelled normal neutrophils to human umbilical vascular endothelial cell (HUVEC) monolayers were studied in the presence of normal serum or serum obtained from patients with BD. Adhesion of neutrophils from patients with BD to HUVEC stimulated with tumour necrosis factor (TNF), interleukin-1 (IL-1), and lipopolysaccharide (LPS) and adhesion molecule (CD11a, CD11b, CD18 and L-selectin) expression on the patient's neutrophils and lymphocytes were determined, and the serum concentration of IL-8 was measured. RESULTS: Sera from patients with BD were found to enhance the adherence of normal PMNLs to HUVEC monolayers in vitro. Patients' sera induced an increase in surface expression of CD11a and CD18 on normal neutrophils and intercellular adhesion molecule-1 (ICAM-1) expression on HUVECs. The number of CD11a positive neutrophils was greater in the blood of patients with BD than in that of healthy controls (89.4% v 71%; p < 0.001). Pretreatment of HUVECs with IL-1 alpha, TNF alpha or LPS resulted in an increased adhesion of patients' PMNLs greater than that observed for normal PMNLs. Monoclonal antibodies to CD11a, CD11b, CD18, and ICAM-1 caused varying degrees of inhibition of neutrophil adhesion. The concentration of IL-8 was also found to be significantly increased in sera of patients with BD (490 (SD 470) pg/ml) compared with normal controls (97.5 (56.3) pg/ml). CONCLUSION: Abnormalities of neutrophils, endothelial cells, or both, have been suggested to be responsible for many of the clinical manifestations of BD. Our findings may explain the underlying mechanism of neutrophil accumulation in Behçet's lesions.

Antibodies, Monoclonal↗
PubMed1996

Refractory duodenal ulcer healing and relapse: comparison of omeprazole with Helicobacter pylori eradication.

OBJECTIVE: To investigate differences between omeprazole and Helicobacter pylori eradication in patients with duodenal ulcers refractory to H2-receptor antagonists and to compare the recurrence rates after the two treatments. DESIGN AND METHODS: Forty-five patients with endoscopically proven duodenal ulcers refractory to H2-receptor antagonists and H. pylori infection were randomly assigned to 8 weeks of treatment with omeprazole 40 mg/day or 4 weeks of treatment with colloidal bismuth subcitrate 480 mg/day plus metronidazole 750 mg/day and tetracycline 1000 mg/day from day 1 to day 14. Patients were evaluated endoscopically and clinically at the end of treatment. Patients with healed ulcers were followed up for 1 year after cessation of the treatment. Endoscopy was performed at 3 and 12 months. RESULTS: Ulcer healing occurred in 100% (21/21) of patients on triple therapy and 70.5% (12/17) of those treated with omeprazole alone (P = 0.0123). The relapse rate at the 3rd month was 11.7% (2/17) in the triple therapy group and 60% (6/10) in the omeprazole group (P = 0.0248). Of the patients followed to study endpoint (relapse or endoscopy at 12 months) three of 12 (25%) receiving triple therapy, compared to six of eight (75%) receiving omeprazole, relapsed (P = 0.0648). CONCLUSION: These results show that triple therapy is more effective than omeprazole in the treatment of refractory duodenal ulcers and reduces the rate of ulcer relapse.

Adult↗
PubMed1995

The clinician's role in teaching proper infant feeding techniques.

The species-specific advantages and significant nutritional and health benefits of breast-feeding are widely acknowledged. Less recognized are the advantages of the process of breast-feeding itself. Adherence to the natural mechanics of breast-feeding will preclude many of the problems associated with improper bottle feeding. For example, the semiupright position of the infant during breast-feeding helps eliminate the entry of milk into the middle ear and reduces choking and regurgitation. The action of suckling during breast-feeding minimizes the intake of air. In addition, the direct eye contact that is natural to breast-feeding fosters bonding, and the close body contact promotes a sense of security in the child. These advantages, so natural to breast-feeding, are likely to be absent from bottle feeding unless some of the natural techniques associated with breast-feeding are adopted. This article describes various aspects of the breast-feeding process with the goal of urging practitioners to instruct patients to transfer these techniques to bottle feeding. In so doing, clinicians may help their patients avoid the hazards of improper bottle feeding.

Bottle Feeding↗
PubMed1995

Nipple confusion: toward a formal definition.

The purposes of this article are to introduce a formal definition of nipple confusion and to propose various hypotheses concerning its cause. The term nipple confusion refers to an infant's difficulty in achieving the correct oral configuration, latching technique, and suckling pattern necessary for successful breast-feeding after bottle feeding or other exposure to an artificial nipple. Many early breast-feeding failures are attributed to nipple confusion, although scientific data are lacking to document its prevalence, the mechanisms involved, or various factors that predispose an infant to this phenomenon. Two classifications of nipple confusion are recommended to distinguish the impact of artificial nipples during the newborn period from their influence after breast-feeding is well established. Maternal and infant risk factors making an infant more susceptible to nipple confusion are discussed. Future studies are planned to help elucidate the nature of nipple confusion and identify the circumstances under which infants are most vulnerable to this phenomenon. Meanwhile, it would seem prudent for clinicians to identify newborns at risk for nipple confusion and to minimize the use of bottle feedings in such babies. Medically indicated supplements in the early days of life could be provided by alternative methods, such as cup, spoon, or dropper feeding, until breast-feeding can be established.

Bottle Feeding↗
PubMed1995

The effect of 1,25 dihydroxyvitamin D3 on lymphocyte transformation in patients with chronic renal failure.

The changes in mitogen-induced lymphocyte response occurring in nine patients undergoing chronic hemodialysis and treated with 1,25 dihydroxyvitamin D3 (0.5 micrograms/day) were investigated. Prior to treatment the stimulation indices (SI) in patients with 15.4 +/- 4.2 for phytohemagglutinin (PHA) and 7.2 +/- 0.7 for conconavalin A (Con A). In the controls, stimulation indices were 44.4 +/- 13.5 and 20.2 +/- 5.3 for PHA and Con A, respectively. Following treatment, the stimulation indices increased to 36.9 +/- 6.2 for PHA (p < 0.05) and 18.6 +/- 3.9 for Con A (p > 0.05) indicating the beneficial effect of oral 1,25 dihydroxyvitamin D3 treatment on lymphocyte function in patients with chronic renal failure.

Administration, Oral↗