PubMed HealthSearch

Biomedical subjects

W Harvey

Publications and source records attributed to W Harvey.

At least 19 recordsLinked to original sources

Sensitization of oral bacteria to killing by low-power laser radiation.

Twenty-seven compounds were screened for their ability to sensitize Streptococcus sanguis to killing by light from a 7.3-mW Helium/Neon (HeNe) laser. Bacteria were mixed with various concentrations of the test compounds, spread over the surfaces of agar plates, and then exposed to light from the HeNe laser for various time periods. The plates were then incubated and examined for zones of inhibition. Those compounds found to be effective photosensitizers were then tested against Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Fusobacterium nucleatum. Toluidine blue O, azure B chloride, and methylene blue at concentrations of 0.005% (wt/vol) were effective photosensitizers of all four species, enabling killing of bacteria following exposure to laser light for only 30 s.

Aggregatibacter actinomycetemcomitans

Stimulation of bone collagen and non-collagenous protein synthesis by products of 5- and 12-lipoxygenase: determination by use of a simple quantitative assay.

The influence of 5- and 12-lipoxygenase products on the rate of collagen and non-collagenous protein (NCP) synthesis by murine calvarial explants has been investigated using a new assay based on the resistance of native collagen to degradation by pepsin. The reproducibility and simplicity of this assay allows the quantitative estimation of the rate of bone formation in large numbers of cultures. Hydroxyeicosatetraenoic acids (HETEs) stimulated both the rate of collagen and NCP synthesis with maximal stimulation occurring at 10-100 pM. All leukotrienes stimulated collagen synthesis. LTB4, C4 and D4 showed similar dose-responses with maximal activity occurring at 100 pM. LTE4 was less potent only showing activity at 1-10 nM. Only LTD4 demonstrated the capacity to stimulate NCP synthesis with significant stimulation being seen at 10 nM. The extreme sensitivity of bone collagen and NCP synthesis to lipoxygenase products suggests that these mediators may play a physiological role in bone remodelling.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid

A preliminary evaluation of the use of a redox agent in the treatment of chronic periodontitis.

A small-scale clinical trial was carried out to evaluate the effect of a redox agent, methylene blue, on microbiological and clinical indices of chronic periodontitis. Methylene blue was applied subgingivally on a daily basis for 7 d to 25 test sites in 7 patients and the sites evaluated clinically and microbiologically for up to 14 d: 25 control sites in the same patients received sterile water. The test sites showed statistically significant differences from the control sites in terms of changes in a number of clinical and microbiological indices. In the test sites the proportions of anaerobes, Gram-negative anaerobes, spirochetes and motile bacteria decreased, as did the crevicular fluid flow, while the proportions of facultative anaerobes and cocci increased. These changes are indicative of a shift towards periodontal health. No significant differences were observed between the test and control sites in terms of bleeding on probing or pocket depth. The encouraging results of this preliminary study suggest that the use of redox agents in the treatment of chronic periodontitis warrants further investigation.

Adult

Characterization of a new cell line (ESKOL) resembling hairy-cell leukemia: a model for oncogene regulation and late B-cell differentiation.

A B-lymphoblastoid cell line ESKOL, composed of differentiated cells resembling hairy-cell leukemia (HCL) has been established from the peripheral blood (PB) of a HCL patient. Morphologically, ESKOL cells share several features with HCL B cells. Flow cytometric analysis revealed that ESKOL cells express HC2, CD21, PCA-1, CD24, FMC7, and CD25. Analysis by Northern-blot hybridization indicated that cultured cells expressed the oncogenes c-myc, H-ras and c-fos. RNA from 3T3 cells transfected with ESKOL DNA hybridized with H-ras and c-fos DNA probes. The ESKOL cells cultured in the presence of increasing concentrations, of alpha interferon demonstrated a decrease in the rate of cellular growth and an increase in the expression of CD21, CD25, FMC7 and PCA-1. Scanning electron microscopy revealed that cells incubated in the presence of alpha interferon underwent membranous changes with a loss of villosity. These observations suggest that IFN tends to drive HC out of their developmental arrest towards maturation.

Aged

A single-blind comparison of intravenous ondansetron, a selective serotonin antagonist, with intravenous metoclopramide in the prevention of nausea and vomiting associated with high-dose cisplatin chemotherapy.

Ondansetron (GR 38032F), a selective antagonist of serotonin subtype 3 receptors, is effective in the prevention of emesis associated with cisplatin as well as other chemotherapeutic agents. In this randomized, single-blind, multicenter, parallel group study, we compared the efficacy and safety of intravenous (IV) ondansetron with IV metoclopramide in the prevention of nausea and vomiting associated with high-dose (greater than or equal to 100 mg/m2) cisplatin chemotherapy. Three hundred seven patients receiving their first dose of cisplatin, either alone or in combination with other antineoplastic agents, were randomized to receive ondansetron 0.15 mg/kg IV every 4 hours for three doses or metoclopramide 2 mg/kg IV every 2 hours for three doses, then every 3 hours for three additional doses. The study prohibited the concurrent administration of other antiemetics or dexamethasone. Patients receiving ondansetron had a higher rate of complete protection from emesis (40% v 30%, P = .07), a higher complete plus major response rate (65% v 51%, P = .016), a lower rate of failure (21% v 36%, P = .007), and a lower median number of emetic episodes (one v two, P = .005) than did those receiving metoclopramide. The median time to the first emetic episode was longer on ondansetron (20.5 v 4.3 hours, P less than .001). Adverse events occurred in 48% of patients receiving ondansetron and 69% of those receiving metoclopramide (P less than .001). Akathisia and acute dystonic reactions occurred only on metoclopramide; headache (controlled with acetaminophen) was significantly more frequent with ondansetron. Ondansetron is more effective, produces fewer adverse events, and is easier to administer than metoclopramide for the prevention of emesis associated with high-dose cisplatin chemotherapy.

Adult

Measurement of radiation-induced DNA double-strand breaks by pulsed-field gel electrophoresis.

We have examined the use of pulsed-field gel electrophoresis (PFGE) to measure DNA double-strand breaks induced in CHO cells by ionizing radiation. The PFGE assay provides a simple method for the measurement of DNA double-strand breaks for doses as low as 3-4 Gy ionizing radiation, and appears applicable for the measurement of damage produced by any agent producing double-strand breaks. The conditions of transverse alternating field electrophoresis determined both the sensitivity of the assay and the ability to resolve DNA fragments with different sizes. For example, with 0.8% agarose and a 1-min pulse time at 250 V for 18 h of electrophoresis, 0.39% of the DNA per gray migrated into the gel, and only molecules less than 1500 kb could be resolved. With 0.56% agarose and a 60-min pulse time at 40 V for 6 days of electrophoresis, 0.55-0.90% of the DNA per gray migrated into the gel, and molecules between 1500 and 7000 kb could be resolved.

Animals

Selection criteria for local excision with or without adjuvant radiation therapy for rectal cancer.

As an alternative to radical surgery, local excision with or without adjuvant pelvic radiation therapy has been used in selected patients with rectal cancer. To determine which clinical and pathologic features can predict the presence of positive lymph nodes (LN+), a retrospective review of 168 patients who underwent potentially curative surgery for rectosigmoid and rectal cancer was performed. By univariate analysis, tumor penetration, grade, and histology were significant predictive features. This was confirmed by logistic regression analysis. The incidence of LN+ increased with increasing tumor penetration (T1, 0%; T2, 28%; T3, 36%; T4, 53%; P = 0.04), grade of adenocarcinoma (well-differentiated, 0%; moderately differentiated, 30%; poorly differentiated, 50%; P = 0.07, [borderline significance]), and the presence of any colloid histology (pure adenocarcinoma, 30%; total colloid, 52%; P = 0.04). Using 2 X 2 contingency tables, the presence of blood vessel invasion (BVI), lymphatic vessel invasion (LVI), vascular invasion (VI), total colloid histology, and high grade further increased the incidence of LN+ with increasing tumor penetration. Regardless of tumor size, grade, histology, BVI, LVI, or VI, none of the nine patients with Stage T1 tumors or the seven with well-differentiated adenocarcinomas had LN+. For this group, local excision alone is recommended. The incidence of LN+ was greater than or equal to 19% in all other categories. For this group of patients, if there is no evidence of gross tumor in the pelvis, then a local excision plus adjuvant pelvic radiation may be an alternative to radical surgery.

Adenocarcinoma

Macrophage responsiveness to light therapy.

Macrophages are a source of many important mediators of wound repair. It was the purpose of this study to see if light could stimulate the release of these mediators. In this study an established macrophage-like cell line (U-937) was used. The cells were exposed in culture to the following wavelengths of light: 660 nm, 820 nm, 870 nm, and 880 nm. The 820-nm source was coherent and polarised, and the others were non-coherent. Twelve hours after exposure the macrophage supernatant was removed and placed on 3T3 fibroblast cultures. Fibroblast proliferation was assessed over a 5-day period. The results showed that 660-nm, 820-nm, and 870-nm wavelengths encouraged the macrophages to release factors that stimulated fibroblast proliferation above the control levels, whereas the 880-nm wavelength either inhibited the release of these factors or encouraged the release of some inhibitory factors of fibroblast proliferation. These results suggest that light at certain wavelengths may be a useful therapeutic agent by providing a means of either stimulating or inhibiting fibroblast proliferation where necessary. At certain wavelengths coherence is not essential.

Animals

Murine osteoblasts release bone-resorbing factors of high and low molecular weights: stimulation by mechanical deformation.

Murine calvarial osteoblasts in monolayer culture were found to constitutively produce bone-resorbing factors; mechanical deformation significantly increased the synthesis and/or release of these factors. In short-term cultures (2 h) the resorptive activity was largely dialysable, indicating a relative molecular mass (Mr) less than 2000. Intermittent mechanical deformation stimulated the synthesis of these low Mr factors irrespective of serum conditions. Continuous deformation, however, was without effect. When the culture period was extended to 24 h, bone resorptive activity was stimulated by both intermittent and continuous deformation in the presence of 10% serum. This activity was dialysable. Over this same period in cultures with 2% serum, intermittent deformation also produced a non-dialysable bone-resorbing factor. We also cultured osteoblasts for 72 h in serum-free conditions and deformed the cells intermittently. Fractionation of the medium by high pressure liquid chromatography (HPLC) resolved three peaks of bone resorptive activity: peak I (Mr 50-60,000); peak II (Mr 5-20,000); and peak III (Mr less than 1000). Only peaks II and III were stimulated by mechanical deformation. These bone-resorbing factors remain as yet poorly characterized, but none of the activity in the HPLC fractions was attributable to interleukin-1 or prostaglandin E2.

Animals

Interleukin 1-like activity in cystic lesions of the jaw.

Odontogenic cyst capsules were cultured in vitro and the culture media analysed for bone-resorption and interleukin 1-like activity. Five cysts synthesised a non-dialysable bone resorbing factor with significant interleukin 1-like activity. One specimen thought to be a cyst with little interleukin 1 activity proved to be antral lining. The results indicate that interleukin 1 may play an important role in cyst expansion by its direct effects on fibroblast proliferation and bone resorption and by stimulating prostaglandin synthesis in stromal fibroblasts of the cyst capsule.

Adult

Prevention of bacterial adhesion to denture acrylic.

A range of non-toxic polysaccharides were screened for their ability to prevent bacterial adhesion to denture acrylic in vitro. Sodium alginate, karaya gum and carrageenan were found to be the most effective, reducing adhesion of Streptococcus salivarius by 98.7, 97.9 and 99.2 per cent respectively. These three polysaccharides were then tested for their ability to reduce the number of bacteria adhering to dentures in vivo. Sodium alginate was the most effective, reducing the attachment of bacteria to the palate-contacting surface of the denture after 5 h of normal wear by 84 per cent compared with uncoated controls. The results of this investigation suggest that the accumulation of denture plaque may be prevented by frequent application of a renewable, sacrificial coating of a non-toxic polysaccharide.

Acrylic Resins

Tooth root resorption induced in rats by diphenylhydantoin and parathyroidectomy.

Changes in bone, cartilage and the dentition in animals and man following the administration of anticonvulsant drugs resemble those seen in hypoparathyroidism and pseudohypoparathyroidism. Groups of 21-day-old rats were treated with diphenylhydantoin, parathyroidectomized, or made hypocalcaemic with a calcium-deficient diet. Histological examination revealed extensive resorption of cementum and dentine in the molars of the drug-treated and parathyroidectomized rats, but not in the hypocalcaemic or control groups. Localization of injected tetracycline by fluorescence showed that the resorption affected the distal side of the tooth roots and had occurred after root formation. No changes in cementum formation on the mesial side of the roots had occurred in any of the experimental groups. These results suggest that diphenylhydantoin induces a condition similar to pseudohypoparathyroidism in which the resistance of tooth roots to resorption is reduced.

Animals

The use of human gingival fibroblasts in culture for studying the effects of phenytoin on testosterone metabolism.

In initial experiments, monolayer cultures of human gingival fibroblasts from healthy male and female subjects were incubated for various time intervals with [4-14C]-testosterone. This was rapidly taken up by the cells to reach 1.8 fmol/50,000 cells by 2 h. At 6, 12 and 24 h, the values were considerably lower (0.1-0.2 fmol/50,000 cells). In order to maintain a sufficient intracellular concentration of testosterone, unlabelled testosterone was incubated in the presence of [14C]-testosterone. This gave optimum yields of metabolites, which were separated by thin-layer chromatography and provisionally identified by comparison of their mobilities with those of authentic steroids. Final characterization of 5 alpha-dihydrotestosterone was achieved by combined capillary gas chromatography-mass spectrometry. The metabolites of testosterone were 5 alpha-dihydrotestosterone (5 alpha-DHT), 4-androstenedione, 5 alpha-androstanedione and 5 alpha-androstanediols, but the quantities formed varied with different cell lines. A similar pattern of metabolites was noted for minced human gingival tissue. Low concentrations of phenytoin generally increased the production of 5 alpha-DHT and 4-androstendione but there were marked variations between individual cell lines with regard to the magnitude of stimulation. Higher concentrations of phenytoin generally caused inhibition of steroid formation but the concentration required for this again varied with different cell lines. Thus human gingival fibroblasts in culture provide a suitable model for the study of testosterone metabolism and of the effects of drugs such as phenytoin. Variation in these effects may be reflected in individual susceptibility to phenytoin-induced gingival overgrowth.

Animals

Heterogeneity of bone resorbing factors produced by unstimulated murine osteoblasts in vitro and in response to stimulation by parathyroid hormone and mononuclear cell factors.

The bone resorbing activity of factors released from monolayer cultures of osteoblasts (OB) was examined by measurement of calcium released by neonatal mouse calvaria in vitro. Unstimulated conditioned media (CM) were found to contain significant bone resorbing activity, which was partially inhibited by indomethacin, dexamethasone and nordihydroguaiaretic acid. Ultrafiltration of CM (molecular weight cut-off of 5000) revealed bone resorbing activity in the filtrate and retentate. Fractionation of the CM by high-performance liquid chromatography revealed four major peaks of bone resorbing activity. Stimulation of the OB by mononuclear cell factor and parathyroid hormone significantly increased the synthesis and/or release of these factors with a relatively greater increase of lipid-soluble, low molecular-weight activity. These results suggested an important role for relatively small non-popular mediators in hormonally stimulated bone resorption.

Animals