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Biomedical subjects

D Powell

Publications and source records attributed to D Powell.

At least 37 records · Page 2Linked to original sources

Antiinflammatory and antiarthritic properties of a substituted quinoline carboxylic acid: CL 306,293.

CL 306,293, a substituted quinoline carboxylic acid at a daily oral dose between 1.5 and 3.0 mg/kg suppressed the inflammation and joint destruction (radiological criteria) associated with both developing and established adjuvant arthritis. When a weekly oral dosing regimen was used, joint destruction was attenuated when this agent was administered at a dose of 50 to 200 mg/kg. Inflammation associated with a delayed type hypersensitivity reaction in dogs was suppressed at a daily dose of 0.25 mg/kg or a weekly dose of 1 mg/kg. At efficacious doses, CL 306,293 had no effects on cyclooxygenase or lipoxygenase activities nor did it have an effect on carrageenin induced paw edema. In acute tests, the compound was not ulcerogenic. The above observations indicate that the antiinflammatory effects of CL 306,293 are distinct from those observed with nonsteroidal antiinflammatory agents. Mechanistic studies conducted and to be published indicate that CL 306,293 down regulates T cell function and this mechanism may account, at least in part, for the antiinflammatory and antiarthritic properties observed in animal models of inflammation and joint destruction.

Administration, Oral

Nuclear magnetic resonance studies of sodium/calcium exchange in frog perfused, beating hearts.

This study explores the effect of extracellular Ca2+ concentration ([Ca2+]o), on the intracellular Na+ concentration ([Na+]i), in frog intact hearts using nuclear magnetic resonance spectroscopy, which allows for the measurement of [Na+]i in perfused, beating hearts. Decreases in [Ca2+]o yielded marked increases in [Na+]i. A similar effect was seen during inhibition of the Na+/K+ pump and was fully reversible. This sensitivity of [Na+]i to [Ca2+]o, previously observed using microelectrodes, supports a crucial physiological role for Na+/Ca2+ exchange in frog intact, beating hearts.

Animals

The binding of endogenous and exogenous substance-P in human plasma.

High levels of substance-P are present in the plasma of patients with carcinoid tumours and some thyrotoxic conditions. The majority of the substance-P in the blood plasma was shown, by immunoassay, to be associated with high molecular-weight material in a complex that could be dissociated by repeated gel-filtration. Smaller amounts of an intermediate molecular-weight (about 65,000 Da) complex were also detected. Chemical crosslinking with glutaraldehyde was used to show that the radioactively-labelled derivative [125I]Tyr-8-substance-P was able to bind to the high-Mr fraction of human plasma and also to human serum albumin. Binding to serum albumin was also demonstrated by equilibrium gel-filtration. Substance-P added to human plasma from a thyrotoxic subject, which contained high endogenous levels of the tachykinin (980 pg/mL), was rapidly degraded during incubation at 37 degrees, whereas the endogenous substance-P was considerably more stable. These results suggest that the binding of substance-P to blood plasma components may play an important role in protecting it against degradation. Furthermore, immunoassay techniques involving prior extraction, which fail to detect the bound substance-P, will give inaccurate measurements of the levels of this peptide in plasma.

Chromatography, Gel

Elevated lipid peroxidation products and depleted transferrin levels in the plasma of kidney transplant recipients.

Lipid peroxidation products were measured in the plasma of 24 kidney transplant patients and 12 healthy volunteers (controls) by: (1) 2-thiobarbituric acid assay and (2) the intensity of fluorescence products of malonaldehyde cross-linked proteins. Plasma levels of creatinine, ceruloplasmin, transferrin, prealbumin, albumin and total protein were also measured. Elevated lipid peroxidation products and lowered transferrin levels were observed in transplant patients compared to controls. Ceruloplasmin levels were slightly but significantly elevated in recent transplant recipients (less than 6 months, n = 12, Group A) while no difference was observed between older transplant recipients (greater than 6 months, n = 12, Group B) and controls. Serum, creatinine levels were also slightly but significantly elevated in both groups of patients compared to controls. Serum prealbumin, albumin and total protein levels in both groups of transplant recipients were not different from controls or reference range values.

Blood Proteins

Spatial organization of repetitive DNA sequences in the bovine sperm nucleus.

During spermatogenesis, DNA in the sperm head becomes more tightly condensed as histones are replaced by protamine-like molecules. In this article, the question is asked whether, during the production of this highly differentiated cell, controls are imposed on the spatial organization of DNA within the nucleus. Heads from bull spermatozoa were isolated by a technique that removed the plasma membrane and acrosomal contents, and the DNA was induced to decondense by addition of 2-mercaptoethanol and trypsin. Under these conditions, decondensation was induced in all regions of the head. To determine whether there was any spatial restraint on packaging of the genome, three DNA probes were used (pl.709-512, containing an interspersed repetitive sequence; pCSIH, containing a copy of the major bovine centromeric statellite sequence; p18 s and p28 s, containing the 18 S and 28 S ribosomal genes) that might be expected to hybridize to different regions. Results showed that the interspersed repetitive probe hybridized to all regions of the head, whereas the ribosomal and centromeric probes hybridized to sequences that were largely confined to the equatorial region of the sperm. We conclude that organization of the genome in the bovine sperm nucleus is not random.

Animals

Clinical study of relative biological effectiveness for cervical carcinoma treated by 252Cf neutrons and assessed by histological tumour eradication.

Clinical data of the University of Kentucky trial using californium (252Cf), or caesium (137Cs), are reviewed for dose-response based on the endpoint of tumour eradication estimated from hysterectomy specimens obtained 4-6 weeks after preoperative irradiation. These data are used to assess the relative biological effectiveness (RBE) for 252Cf neutrons compared with 137Cs gamma radiation. Tumours treated were of common stage but were of bulky or barrel shape suitable for "radiosurgical" therapy. Dose-response curves were constructed, and additional data from the literature used to analyse the curve shape. The photon dose-response curve is complex on a logarithmic plot, whereas the 252Cf neutron curve is exponential. This indicates that the RBE can be different depending on the number of implants, schedule and size of dose delivered per session. The RBE values were approximately 8.0 at low doses or for multiple implants but they may rise to approximately 16 at larger doses or for single 252Cf implants.

Brachytherapy

Management of children with short stature.

325 patients referred to an endocrine clinic with short stature were reviewed, 32 (9.8%) were above the third centile for height and maintained normal growth velocities, fourteen (4.3%) have not had assessment completed. Of 279 children in whom the cause of short stature was established, 140 (50%) had constitutional short stature/delayed puberty (CSS/DP). Seventy-three (26%) had idiopathic growth hormone deficiency (GHD), complete in 23, while 66 patients (34%) had short stature due to other causes. Girls presented earlier (mean age 11.9) than boys (mean age 13.3) and GHD patients earlier than CSS/DP patients with bimodal peaks at 12 and 16 years. Male CSS/DP patients reached their mid pubertal point later than normal at 16.06 +/- 1.19 years (p less than .05) while in GHD males the mid pubertal age was 16.6 years (p less than .05). In female patients with short stature no significant pubertal delay was observed. The average growth velocity of complete GHD patients pre treatment was 3.7 cms/year. Velocity rose to 6.2 cms/year on human growth hormone (HGH) extract and rose further to 8.1 cms/year on biosynthetic HGH. In partial GHD patients the average pre-treatment velocity of 4.3 cm/year rose to an average of 6.0 cm/yr on HGH extract and maintained this velocity on biosynthetic HGH.

Adolescent

Monokine regulation of human immunodeficiency virus-1 expression in a chronically infected human T cell clone.

A T cell clone (ACH-2) derived from T cells infected with HIV-1 was found to produce HIV-1 in response to stimulation with a monokine-enriched supernatant prepared by culturing human monocyte/macrophages with bacterial LPS (LPS-MO SN). Monokine induction of ACH-2 cells resulted in augmented virus production reflected by an increase in reverse transcriptase activity and in the synthesis of all major viral proteins. Examination of the cells by indirect immunofluorescence revealed that 10 to 15% of uninduced cells constitutively expressed HIV proteins, whereas 100% showed positive immunofluorescence in response to LPS-MO SN. This induction of virus by LPS-MO SN resulted in approximately a 100-fold increase of infectious virus production over uninduced ACH-2 cells. LPS alone could not induce HIV-1 expression, whereas LPS-MO SN resulted in the greatest virus expression. Cell separation studies confirmed the source of the inducing factor(s) to be cells bearing the mature monocyte/macrophage marker, Leu M3. Biochemical fractionation of the LPS-MO SN suggested that one or more factors, having apparent Mr of approximately 45 kDa, were involved in this induction. Absorption of the LPS-MO SN with immunoaffinity gels specific for human TNF-alpha was shown to completely remove the HIV inducing activity for the ACH-2 cell line.

Biological Factors

Dose-response and failure pattern for bulky or barrel-shaped stage IB cervical cancer treated by combined photon irradiation and extrafascial hysterectomy.

From 1975 to 1987, 80 patients with bulky or barrel-shaped Stage IB cervical cancer were treated with preoperative irradiation and Cs-137 intracavitary implant therapy, before a planned extrafascial abdominal hysterectomy, using a consistent treatment policy. Of the hysterectomy specimens obtained, 37% were positive histologically at 89 +/- 2.3 days after the start of radiotherapy and at 4 to 6 weeks after the completion of radiation therapy. Sixty-three percent were negative after a total external and internal cervix irradiation dose of 9642 cGy at point T. The average point A dose contributed by intracavitary therapy was 2104 cGy. The survival rate at 5 years was 84%: At 10 years the survival rate was 78%. The failure pattern was analyzed for patients who had positive and negative specimens. The patients with positive specimens failed pelvically or pelvically and distantly. Patients with negative specimens failed in extrapelvic or distant metastatic sites. Preoperative radiotherapy led to excellent local and pelvic control of tumor, and the failures became predominantly distant metastases. The combined radiosurgical therapy was tolerated well and allowed surgical staging of disease. This permitted earlier and selective consideration of adjunctive therapy (i.e., paraaortic irradiation, chemotherapy, or chemoradiotherapy). The dose-response data give insight into the effects of photon radiotherapy on bulky or barrel Stage IB cervical cancers and correlate histologic status with failure pattern, outcome, and long-term survival.

Adult

An outbreak of paratyphoid fever in the UK associated with a fish-and-chip shop.

An outbreak of Salmonella paratyphi B infection in the UK associated with a fish-and-chip shop is reported. The source of infection for the first three cases was believed to be a food handler who was infected overseas 6 years earlier. His wife whose faeces and urine were originally culture negative continued to run the shop but subsequently her faeces became positive on one occasion. She was considered to have been the source of two further cases, and secondary household spread of infection from these two cases resulted in one symptomatic and two asymptomatic infections. A second household contact of the proprietor also became a faecal excretor 2 months later. We recommend that food handlers living in households or in intimate contact with cases or carriers of S. paratyphi B should be put off work until all household contacts cease excreting the organism.

Adolescent

Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion.

Simian immunodeficiency virus (SIV) and human immunodeficiency virus share the property of tropism for CD4-bearing cells. Infection is initiated by a high-affinity interaction between CD4 and conserved domains on the viral envelope glycoprotein. In this report, we demonstrated that SIV had a restricted host range among human CD4+ cells when compared with human immunodeficiency virus type 1 or type 2. This restricted tropism was associated with the inability of the SIV envelope glycoprotein to induce membrane fusion in cells not susceptible to productive exogenous infection by SIV. We conclude that the major route of SIV entry into CD4+ cells is by envelope-mediated direct fusion with the cell and that additional envelope-cell interactions after CD4 binding are required for productive infection.

Antigens, Surface

Retrospective study of early postoperative convulsions after intracranial surgery with isoflurane or enflurane anaesthesia.

Retrospective analysis of the case records of 383 patients undergoing elective intracranial surgery showed that, in the first 24 h after surgery, 13.9% of patients receiving low concentrations (0.4-1 MAC) of isoflurane had one or more convulsions after operation, compared with 8% receiving enflurane (0.4-1 MAC). Controlled ventilation was required as part of the therapy for convulsions in 4.9% of the isoflurane group and 3.6% of the enflurane group. These differences between the groups were not statistically significant.

Anesthesia, Inhalation

Effect of insecticidal ear tags on populations of lice (Damalinia ovis) infesting sheep.

Polymer matrix ear tags containing 13.7% w/w tetrachlorvinphos or 8.5% w/w cypermethrin were applied to Merino wethers infested with lice and carrying two months wool. The cypermethrin tags reduced louse numbers by a maximum of 89% in comparison to controls at 16 weeks after treatment and by 85% at the conclusion of the experiment 38 weeks after application. Lice were not eradicated from any sheep. The number of lice counted on sheep treated with tetrachlorvinphos-impregnated tags was not significantly different from controls.

Analysis of Variance

Insulin-like growth factor binding proteins from cultured human fibroblasts. Characterization and hormonal regulation.

Specific, high affinity insulin-like growth factor (IGF) binding proteins are secreted by human fibroblasts in culture. By multiple criteria, the species of IGF binding proteins produced by human fibroblasts are distinct from the HepG2/amniotic fluid IGF binding protein, but share many characteristics with the growth hormone-dependent IGF binding protein forms predominant in normal adult human plasma. Treatment of cultured human fibroblasts with growth hormone produced an increase in IGF binding protein activity in the medium, while addition of glucocorticoids markedly diminished IGF binding activity. Insulin, epidermal growth factor, platelet-derived growth factor, and progesterone had no effect on IGF binding activity in fibroblast media. In comparison, HepG2 IGF binding activity was enhanced by progesterone, decreased by insulin, and unaffected by growth hormone or glucocorticoid treatment. Five molecular forms of IGF binding proteins were identified by Western ligand blots in human fibroblast conditioned medium, with Mr = 41,500, 37,000, 32,000, 28,000, and 23,000. In human fibroblast conditioned medium, the Mr = 41,500 and 37,000 IGF binding protein species were abundant, as in normal human plasma, with a major Mr = 23,000 form which was a minor component in plasma.

Animals

Efficacy of brachytherapy with californium-252 neutrons versus cesium-137 photons for eradication of bulky localized cervical cancer: single-institution study.

A fast-neutron-emitting radioisotope, 252Cf, is being tested in clinical trials of neutron brachytherapy for cervical cancer. The efficacy for histological eradication of bulky stage IB cervical tumors (mean diameter, approximately 6 cm) using combined radiation and surgery was studied in 65 patients treated with 137Cs or 252Cf before surgery during 1983-1986. Forty-four patients were treated with 137Cs and 21 were treated with 252Cf at equivalent doses of radiation. Fifteen of the 44 specimens (34%) were positive after 137Cs therapy. Only one of the 21 specimens was positive after 252Cf therapy (P = .025), and that patient was treated in a delayed schedule 21 days after the start of external-beam irradiation rather than early in the course. 252Cf therapy required a much lower radiation dose and shorter treatment time. The study compared tumor destruction of an identically staged human cervical tumor in situ by direct histological means, using 252Cf neutron therapy or conventional photon therapy at an identical and equivalent dose adjusted by a relative biological effectiveness of 6.0 for 252Cf.

Adult