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Biomedical subjects

C Warren

Publications and source records attributed to C Warren.

At least 19 recordsLinked to original sources
PubMed1997

Absence of mutations in the ATM gene in breast cancer patients with severe responses to radiotherapy.

The effectiveness of cancer radiotherapy is compromised by the small proportion (approximately 5%) of patients who sustain severe normal tissue damage after standard radiotherapy treatments. Predictive tests are required to identify these highly radiosensitive cases. Patients with the rare, recessively inherited, cancer-prone syndrome ataxia-telangiectasia (A-T) sustain extremely severe normal tissue necrosis after radiotherapy and their cultured cells are also highly radiosensitive. Clinically normal carriers (heterozygotes) of the A-T gene have an increased risk of breast cancer, account for approximately 4% of all breast cancer cases and show a modest increase in cellular radiosensitivity in vitro. It has been suggested that a substantial proportion of highly radiosensitive (HR) breast cancer patients may be A-T heterozygotes, and that screening for mutations in the A-T gene could be used as a predictive test. We have tested this hypothesis in a group of cancer patients who showed adverse reactions to radiotherapy. Sixteen HR breast cancer patients showing mainly acute reactions (and seven HR patients with other cancers) were tested for ATM mutations using the restriction endonuclease fingerprinting assay. No mutations typical of those found in obligate A-T heterozygotes were detected. If the estimate that 4% of breast cancer cases are A-T gene carriers is correct, then ATM mutations do not confer clinical radiosensitivity. These early results suggest that screening for ATM mutations in cancer patients may not be of value in predicting adverse reactions.

Ataxia Telangiectasia Mutated Proteins↗
PubMed1997

Results from the 1995 National College Health Risk Behavior Survey.

Results from the 1995 National College Health Risk Behavior Survey, which monitored health risk behaviors among US college and university undergraduates, suggest that many students' behaviors increase their likelihood of adverse health outcomes. During the 30 days preceding the survey, 34% of the participants had consumed five or more alcoholic drinks on at least one occasion, and 27% had drunk alcohol and driven a car. Thirty-one percent had smoked cigarettes regularly during their lifetimes, 49% had ever used marijuana, 30% had used a condom during their last sexual intercourse, 21% were overweight, and 38% had participated in vigorous physical activity on 3 or more of the 7 days preceding the survey. These data were analyzed by gender, age group, race and ethnicity, and institution type. They can be used by those responsible for the health and education of college students to reduce risks associated with the leading causes of mortality and morbidity.

Adolescent↗
PubMed1997

Beneficence toward whom? Ethical decision-making in a maternal-fetal conflict.

Ethical dilemmas and conflicts occur frequently in critical care units. When these dilemmas involve a pregnant patient, the conflicts are further complicated, because they also involve the interests of the fetus. Using an ethical decision-making process facilitates the analysis of ethical dilemmas and their resolutions. This process is used to analyze the dilemma of selecting appropriate treatment for a woman at 30 weeks' gestation, diagnosed with acute lymphocytic leukemia. The case is examined from the perspective of the mother and the fetus, using the decision-making process. The medical indications include the patient's physical state, disease process, and treatment options. Patient preferences are the ethical and legal center of the patient-physician, and patient-nurse relationship. Contextual features include religious beliefs, cultural values, family dynamics, and financial and legal aspects of the care options. Finally, the ethical principles, relevant and in conflict, are assessed. Exploring these areas clarifies the best treatment option in consideration of the issues and facts of the case.

Adult↗
PubMed1997

Effects of dietary manipulations and glucose infusion on glucagon response during exercise in rats.

The purpose of the present investigation was to test the hypothesis that blood glucose concentration is not always related to glucagon response during exercise. Three groups of rats were submitted to a prolonged (3-h) swimming exercise. Two groups of rats had their normal food intake restricted by 50% the night before the experiment. One of these two groups of rats was intravenously infused with glucose throughout exercise to maintain euglycemia. The third group of rats swam while under normal dietary conditions. Plasma glucose, sampled in arterial blood, was reduced (P < 0.05) at 75, 105, 150, and 170 min of exercise (from approximately 130 to 110 mg/dl) in the food-restricted animals without glucose infusion, whereas a significant (P < 0.05) increase was measured in the two other groups during exercise. A significant (P < 0.01) difference in the mean integrated areas under the glucose-concentration curve was found only between the fed and the two food-restricted groups. Plasma insulin concentrations decreased (P < 0.05) similarly in all groups during exercise, whereas plasma epinephrine and norepinephrine concentrations increased significantly (P < 0.01) in all groups. Despite differences between groups in plasma glucose response during exercise, and despite the absence of any decrease in exercising blood glucose levels in at least two of the three groups, plasma glucagon responses were increased (P < 0.05) similarly in all groups (from approximately 250 to 550 pg/ml) at the end of the exercise period. The increase in glucagon was significant after 90 min of exercise in the food-restricted groups, with or without glucose infusion, but only after 140 min in the fed group. These results indicate that the glucagon response during exercise is not always linked to the decrease in plasma glucose.

Animals↗
PubMed1996

The relationship between hyaluronidase activity and hyaluronic acid concentration in sera from normal controls and from patients with disseminated neoplasm.

Serum hyaluronidase activity (HAE) and hyaluronic acid (HA) concentration were measured in sera from patients with disseminated neoplasm and compared to those of normal controls. The serum HAE activity in disseminated neoplasm (mean, 12.6 mumol N-acetylglucosamine (NAG)/min/1; range, 5.2-24.7 mumol NAG/min/1) was significantly lower (t = 6.7, p < 0.001) than in normal controls (mean, 17.1 mumol NAG/min/1; range, 11.5-27.0 mumol NAG/min/1). The serum HA concentration in patients with disseminated neoplasm (mean, 8199.7 micrograms/l; range, 42.0-496,000 micrograms/l) was significantly higher (t = 2.63, 0.01 > p> 0.001) than in normal age-matched controls (mean, 55.6 micrograms/l; range, 10.0-348.0 micrograms/l). A negative correlation was found between the serum HAE activity and the HA concentration (r = -0.45, t = 5.92, p < 0.001). The possible reasons for the low serum HAE activity and the raised serum HA concentration in patients with disseminated neoplasm and the negative correlation between the results are discussed.

Adult↗
PubMed1996

Phage display vectors for in vivo recombination of immunoglobulin heavy and light chain genes to make large combinatorial libraries.

New phage display vectors for in vivo recombination of immunoglobulin (Ig) heavy (VH) and light (VL) chain variable genes, to make single-chain Fv fragments (scFv), were constructed. The VH and VL genes of monoclonal antibody (mAb) EP-5C7, which binds to both human E- and P-selectin, were cloned into a pUC19-derived plasmid vector, pCW93, and a pACYC184-derived phagemid vector, pCW99, respectively. Upon induction of Cre recombinase (phage P1 recombinase), the VH and VL genes were efficiently recombined into the same plasmid via the two loxP sites (phage P1 recombination sites), one located downstream from a VH gene in pCW93 and another upstream from a VL gene in pCW99. In the resulting phagemid, the loxP sequence also encodes a polypeptide linker connecting the VH and VL domains to form a scFv of EP-5C7. Whether expressed on the phage surface or as a soluble form, the EP-5C7 scFv showed specific binding to human E- and P-selectin. This phagemid vector system provides a way to recombine VH and VL gene libraries efficiently in vivo to make extremely large Ig combinatorial libraries.

Amino Acid Sequence↗
PubMed1996

Measurement of hyaluronidase activity in normal human serum.

A detailed evaluation of the assay for serum hyaluronidase (HAE) activity originally developed by Bonner and Cantey [W.M. Bonner, Jr. and E.Y. Cantey, Clin. Chim. Acta, 13 (1966) 746-752] is described, together with studies of its precision. The method is based on the liberation of saccharides with N-acetylglucosamine (NAG) end-groups from hyaluronic acid. The NAG is quantitated by heating with alkaline tetraborate to form an intermediate which reacts with p-dimethylaminobenzaldehyde in acidic medium to form a coloured product. The optimised assay, which requires less that 50 microliters of serum, was used to study the HAE activity of 70 normal sera. The mean HAE activity was 17.1 mumol NAG min-1 l-1 (range 11.5-27.0 mumol NAG min-1 l-1); there was no significant difference with age (t = 1.65, 0.5 > P > 0.1) or sex (t = 0.33, P > 0.5).

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Characterization of the major transcripts encoded by the regulatory MuDR transposable element of maize.

The MuDR element controls the transposition of the Mutator transposable element family in maize. Previous studies reported the presence of two major MuDR-homologous transcripts that correlate with Mutator activity. In this study, we describe the structure and processing of these two major transcripts. The transcripts are convergent, initiating from opposite ends of the element within the 220-bp terminal inverted repeats. The convergent transcripts do not overlap, and only 200 bp of internal MuDR sequences are not transcribed. Cloning and sequencing of multiple MuDR cDNAs revealed unusual intron/exon junctions, differential splicing, and multiple polyadenylation sites. RNase protection experiments indicated that some splicing failure occurs in young seedlings, and that a low level of antisense RNA exists for both transcripts. On a whole plant level, the presence of the major MuDR transcripts strictly correlates with Mutator activity in that no MuDR transcripts are observed in non-Mutator or inactive Mutator stocks. Examination of various tissues from active Mutator stocks indicates that the two transcripts are present in all organs and tissues tested, including those with no apparent transposition activity. This suggests that Mutator activity is not simply controlled by the level of the major MuDR transcripts.

Amino Acid Sequence↗
PubMed1994

Results of excimer laser photorefractive keratectomy for the correction of myopia.

PURPOSE: This report summarizes the authors' 3-year experience with excimer laser photorefractive keratectomy on 240 eyes of 161 patients. METHODS: With constant laser emission parameters, nitrogen flow across the cornea was used on 79 eyes, whereas 161 eyes had no nitrogen flow. Of the 240 eyes, 74 were operated on without suction ring fixation. Postoperative pain management included patching and oral analgesics in 77 eyes and the use of topical diclofenac or ketorolac and a therapeutic soft contact lens in 163 eyes. Follow-up ranged from 1 month (206 eyes) to 36 months (10 eyes). RESULTS: At 3 months, 88% (144 eyes) had uncorrected visual acuity of 20/40 or better; 86% (151 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and 10% (17 eyes) lost two or more lines of best-corrected visual acuity. At 12 months, 89% (122 eyes) achieved uncorrected visual acuity of 20/40 or better, 79% (115 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and 4% (6 eyes) lost two or more lines of best-corrected visual acuity. At 24 months, 92% (44 of 48 eyes) had uncorrected visual acuity of 20/40 or better, 86% (44 of 51 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and 5% (2 eyes) lost two or more lines of best-corrected visual acuity. At 36 months, 90% (9 eyes) achieved an uncorrected visual acuity of 20/40 or better, 90% (9 eyes) had corrected visual acuity to within +/- 1 diopter of intended correction, and no eyes lost two or more lines of best-corrected visual acuity. CONCLUSIONS: The results obtained with one procedure are within accepted standards of accuracy for refractive surgery, and there is the potential for refinement of the final optical correction. Complication rates are low and are not vision threatening. They included increased intraocular pressure, epithelial "map dot" changes, and recurrent corneal erosion syndrome, "central islands," and others. Photorefractive keratectomy appears to be a safe procedure over the short and medium term.

Adult↗
PubMed1993

A two-year experience with excimer laser photorefractive keratectomy for myopia.

PURPOSE: This report summarizes the authors' 2-year experience with excimer laser photorefractive keratectomy (PRK) on 160 eyes of 128 patients. METHODS: All eyes were treated with an excimer laser: fluence, 160 mJ/cm2; frequency, 5 Hz; ablation zone diameter, 5.0 to 5.5 mm; and depth per pulse, 0.21 to 0.27 microns. A suction fixation ring was used in all eyes either with nitrogen flow (79 eyes) or without nitrogen flow (81 eyes) across the cornea. Follow-up ranged from 1 month (152 eyes) to 24 months (12 eyes). RESULTS: At 3 months, 82% (139) of eyes achieved an uncorrected visual acuity of 20/40 or better; 83% were corrected to within +/- 1 diopter (D) of intended correction and 30% lost one line of best-corrected visual acuity. At 6 months, 88% (124) of eyes achieved an uncorrected visual acuity of 20/40 or better; 84% were corrected to within +/- 1 D of intended correction and 15% lost one line of best-corrected visual acuity. At 12 months, 91% (71) of eyes achieved an uncorrected visual acuity of 20/40 or better; 84% were corrected to within +/- 1 D of intended correction and 17% lost one line of best-corrected visual acuity. At 24 months, 100% (12) of eyes achieved an uncorrected visual acuity of 20/40 or better; 91.6% were within +/- 1 D of intended correction and 0% lost one line of best-corrected visual acuity. CONCLUSIONS: In eyes with a follow-up of 6 to 24 months, 77% to 100% achieved an uncorrected visual acuity of 20/40 or better and 84% to 92% were corrected to within +/- 1 D of the intended correction. The authors conclude that excimer laser PRK appears to be a safe procedure capable of correcting the eyes of patients with low to moderate myopia with approximately the same degree of accuracy as radial keratotomy.

Adult↗
PubMed1993

Penicillinase producing Neisseria gonorrhoeae from St Thomas' Hospital 1976-1990--the first fifteen years.

OBJECTIVE: To examine the penicillinase producing N. gonorrhoeae (PPNG) collected at St Thomas' Hospital from 1976-1990 and, by determination of antibiotic susceptibility pattern and application of three typing methods, examine the prevalence of different gonococcal types. Also to determine whether there is any relationship between antibiotic sensitivity, plasmid profile, auxotype and serovar. MATERIALS AND METHODS: A total of 665 isolates of PPNG from patients attending the Department of Genitourinary Medicine at St Thomas' Hospital were characterised by antibiotic MIC, plasmid profile, auxotyping and serotyping. RESULTS: Penicillin MICs for 85% of all isolates were between 0.25 and 32 mg/l. The MIC of tetracycline for 60-80% of the isolates was < 1 mg/l. A small number of isolates had tetracycline MICs of 32 mg/l but MICs > 32 mg/l were not seen. Over 90% of the isolates were sensitive to the remaining three antibiotics tested, erythromycin, cefuroxime and spectinomycin. The 3.2 or 4.4 MDa plasmid with or without the 24.5 MDa conjugal plasmid was seen in all isolates until 1989/90 when a 2.9 MDa beta-lactamase encoding plasmid and the 25.2 MDa plasmid mediating tetracycline resistance were also recognised. Ninety-nine percent of all isolates belonged to one of four auxotypes, prototrophic, arginine, proline or proline/arginine requiring. An initial predominance of isolates with the 1A outer membrane protein was reversed in 1982 and 1B has remained predominant. Thirty two different serovars were identified among the 665 isolates, 14 belonged to serogroup 1A and 18 to 1B, and the eight most common accounted for 83.9% (554) of all isolates. Analysis of the results of combined typing methods showed there was an association between antibiotic resistance, plasmid profile and serogroup. The number of auxotypes and serovars detected in the collection, indicates the possibility that PPNG have been introduced from abroad or outside our local population. CONCLUSION: Temporal trends in the distribution of auxotype/serovar classes show that the total population of PPNG isolates is formed by a heterogenous mixture in which certain auxotype/serovar classes appear, disappear and may re-emerge. Others were present throughout in small numbers.

Anti-Bacterial Agents↗
PubMed1992

Substrate specificity of human liver neutral alpha-mannosidase.

The digestion of radiolabelled natural oligosaccharide substrates by human liver neutral alpha-mannosidase has been studied by h.p.l.c. and h.p.t.l.c. The high-mannose oligosaccharides Man9GlcNAc and Man8GlcNAc are hydrolysed by the enzyme by two distinct non-random routes to a common product of composition Man6GlcNAc, which is then slowly converted into a unique Man5GlcNAc oligosaccharide, Man alpha(1----2)Man alpha(1----2)Man alpha(1----3)[Man alpha (1----6)] Man beta(1----4)GlcNAc. These pathways are different from the processing and lysosomal catabolic pathways for these structures. In particular, the alpha(1----2)-linked mannose residues attached to the core alpha(1----3)-linked mannose residue are resistant to hydrolysis. The key processing intermediate, Man alpha(1----3)[Man alpha(1----6)]Man alpha(1----6)[Man alpha(1----3)] Man beta(1----4)GlcNAc, is not produced in the digestion of high-mannose glycans by the neutral alpha-mannosidase, but it is hydrolysed by the enzyme by a non-random route to Man beta(1----4)GlcNAc via the core structure Man alpha(1----3)[Man alpha(1----6)]Man beta(1----4)GlcNAc. In contrast with its ready hydrolysis by lysosomal alpha-mannosidase, the core alpha(1----3)-mannosidic linkage is quite resistant to hydrolysis by neutral alpha-mannosidase. The precise specificity of neutral alpha-mannosidase towards high-mannose oligosaccharides suggests that it has a role in the modification of such structures in the cytosol.

Carbohydrate Conformation↗
PubMed1992

Activity of crystalline turkey egg white lysozyme.

Hexagonal crystals of turkey egg white lysozyme have been examined for activity in order to evaluate their potential for use in time-resolved X-ray crystallographic experiments. Substrates used in this study were hexa-N-acetylglucosamine (hexa-GlcNAc) and a modified analogue of hexa-GlcNAc where the terminal sugar ring was opened by reduction with tritiated sodium borohydride. This gave a labeled beta-N-acetylglucosaminitol unit at the sixth position of the sugar chain and allowed easy quantitation of enzymatic cleavage on TLC plates. Using these substrates, it has been shown that turkey egg white lysozyme is enzymatically active in the crystal. Enzyme dispersed in the buffer surrounding the crystal does not show detectable activity under conditions relevant to an X-ray experiment. Unmodified hexa-GlcNAc is hydrolyzed into di-, tri-, and tetrasaccharides in the crystal. This cleavage pattern is different from that obtained with hen egg white lysozyme in solution and likely causes of the differences are discussed. The reduced radiolabeled oligosaccharide has a unique cleavage pattern with trisaccharides as the products. The specific activity of the enzyme with the radiolabelled analogue was 9.8 (+/- 1.0) x 10(-7) mmol/min/mg protein at 22 degrees C in the crystal.

Animals↗
PubMed1992

Helicopter doctors?

All roadside procedures carried out by doctors of the Royal London Hospital Helicopter Emergency Medical Service were recorded. Of 100 injured patients treated consecutively, 68 patients required 73 treatments or procedures that were beyond the current training of the ambulance paramedic in the United Kingdom. Doctors are therefore an essential part of HEMS operations and allow earlier live-saving medical intervention in the prehospital phase of care.

Aircraft↗