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Biomedical subjects

W Harvey

Publications and source records attributed to W Harvey.

At least 19 recordsLinked to original sources

Granulosa cell tumour of the ovary with bilateral mature cystic teratomas. A case report.

Granulosa cell tumour with synchronous mature cystic teratoma is extremely rare and only eight cases are documented in the literature. Granulosa cell tumours are low-grade malignancies and need a close follow-up for recurrences which may be late. We report a case of granulosa cell tumour and mature cystic teratoma occurring synchronously in the same ovary in a post-menopausal woman.

Diagnosis, Differential↗

Stabilographic analysis of unconstrained standing.

Natural standing is characterized by postural changes and several hypotheses have been proposed to explain these changes. In this paper, four hypotheses were investigated by quantifying the number of postural changes in the centre of pressure data from unconstrained standing in different experimental conditions, studying the effects of mechanical loading, visual conditions, and type of support surface and sole of the shoes. The subjects stood for 30 min with no specific instructions other than not to step off a force plate. There were no significant effects on the number of centre of pressure patterns associated with the postural changes due to load, vision, surface and shoes during standing; on average, approximately two centre of pressure patterns per minute were observed in all conditions. The analysis of the centre of pressure data by the commonly used statistical parameters (standard deviation, velocity, and mean frequency of the centre of pressure displacement and area of the stabilogram) also did not reveal any effect of the different conditions.

Adult↗

Interleukin-2 and concanavalin A upregulate a cat2 isoform encoding a high affinity L-arginine transporter in feline lymphocytes.

The immunological responses of activated lymphocytes are associated with increased nitric oxide (NO) biosynthesis. Studies in the literature have primarily approached control of NO by focusing on the regulation of the nitric oxide synthase (NOS) isoforms. However, the present study approaches the control of NO synthesis by addressing the regulation of L-arginine availability to lymphocytes via regulation of membrane transport. The guanidino nitrogen of L-arginine is the sole biosynthetic precursor of NO. We investigated cytokine and mitogen regulation of membrane L-arginine transporters for the first time in feline cells. Feline peripheral blood mononuclear cells were treated with interleukin-2 and concanavalin A, then alternatively spliced isoforms of L-arginine transporters known in other species were probed by RT-PCR, using various oligonucleotide primers that hybridized to several regions in common with the isoforms. Both high affinity and low affinity isoforms are encoded by mRNAs arising from mutually exclusive alternative splicing of the primary transcript. A region of 123 bp was obtained that encoded an extracellular polypeptide loop of 41 amino acids. The sequence of this region represented the high affinity L-arginine substrate binding site of a CAT2 transporter polypeptide isoform, but not the CAT2a isoform low affinity binding site. Neither of the inducible isoforms were constitutively expressed in unstimulated feline cells. This is the first report demonstrating that domestic cats possess the cat2 gene encoding an inducible L-arginine transporter, and, furthermore, that the high affinity isoform transcript is activated by interleukin-2 and concanavalin A in feline lymphocytes.

Animals↗

The stimulation of bone formation in vitro by therapeutic ultrasound.

A controlled study was performed to evaluate the effects of different ultrasound (US) intensities on 5-day-old mouse calvaria bone in tissue culture. A special technique to apply the US was developed, and the following parameters were measured: collagen and noncollagenous protein (NCP) synthesis (bone formation), and temperature change. It was found that ultrasound at 0.1 W/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min, significantly stimulates bone formation (i.e., the synthesis of collagen and NCP) (p < 0.001 and p < 0.01). However, pulsed ultrasound at higher doses (1.0-2.0 W/cm2 (SATA), pulsed 1:4, 3 MHz, 5 min) significantly inhibited the synthesis of both collagen and NCP (p < 0.05). The temperature measurements showed a maximum rise of 1.8 degrees C [at 2.0 W/cm2 (SATA)] and no detected rise at 0.1 W/cm2 (SATA), suggesting that the effects in this study were primarily nonthermal. These results may reflect the healing effect of US on fractures and osteoradionecrosis and reinforces the use of low intensity US regimens [0.1 W/cm2 (SATA)] in clinical practice.

Animals↗

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↗