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Biomedical subjects

A Barron

Publications and source records attributed to A Barron.

At least 19 recordsLinked to original sources

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗

Localized whole eye radiotherapy for retinoblastoma using a (125)I applicator, "claws".

PURPOSE: To treat children with retinoblastoma, who require whole eye radiotherapy, with a specially designed (125)I applicator that irradiates the eye while sparing the surrounding tissues. METHODS AND MATERIALS: Under general anesthesia, a pericorneal ring is attached to the 4 extraocular muscles, and 4 appendages, each loaded with (125)I seeds, are inserted beneath the conjunctiva in-between each pair of muscles and attached anteriorly to the ring. Twenty-nine eyes were treated. Eighteen received a median dose of 28 Gy during 91 hours and 11 received 40 Gy during 122 hours, when the relative biologic effectiveness was taken as 1 instead of 1.5. Six had received prior chemotherapy. RESULTS: Twenty-four eyes were followed up for 2-157 months (median 29). Although 22 eyes responded, local control was achieved in 13 patients, 3 of whom required additional treatment for new tumors; a further 3 required additional treatment for tumor recurrence as well as new tumors. One of these eyes was enucleated for neovascular glaucoma. All 6 Group I-III eyes and 6 of 18 Group V eyes were retained for 2-157 months (median 39), with good vision in 10 eyes. Three developed cataracts 7, 8, and 12 years later, 1 of which has been removed. CONCLUSIONS: This is a new way of irradiating the whole eye with a minimal dose to the surrounding tissues. The treatment time is only 5 days. It is effective in Groups I-III, but only 33% of Group V eyes retained vision. No late cosmetic defects occurred.

Antineoplastic Combined Chemotherapy Protocols↗

Trabeculectomy with mitomycin C in the treatment of post-traumatic angle recession glaucoma.

AIM: The presence of traumatic angle recession is a risk factor for failure of glaucoma filtration surgery and a previous study has suggested that antimetabolite treatment should be used in these patients. This study was undertaken to determine for the first time the mid term results of trabeculectomy with intraoperative application of mitomycin C in patients with post-traumatic angle recession glaucoma. METHODS: A retrospective analysis was made of 43 consecutive trabeculectomy procedures in 41 young black/mixed race patients followed for a mean period of 25 months (range 2-66 months). Mitomycin C 0.02% was applied between the sclera and conjunctiva for 1-5 minutes at the time of surgery. The intraocular pressure and visual acuity were measured postoperatively. The success of this technique was analysed by using a Kaplan-Meier cumulative survival curve. RESULTS: The intraocular pressure was successfully controlled at last follow up without topical treatment in 77% (33/43 eyes) and the visual acuity was the same or better in 81% (35/43 eyes). Cumulative probability of success was 85% at 1 year follow up, 81% at 2 years, and 66% at 3 years and thereafter. Hypotonous maculopathy occurred in one patient and no cases of late bleb infection were found. CONCLUSIONS: In medically uncontrolled post-traumatic angle recession glaucoma trabeculectomy with mitomycin C is an effective surgical procedure with an acceptable complication rate. Good intraocular pressure control and preservation of vision can be expected in most patients.

Adolescent↗

Auditing the introduction of a new product to a family planning service.

The audit aimed to develop a questionnaire to monitor how a new method od contraception is offered in service by identifying local demand and assessing levels of awareness of and interest in a new product (Mirena(R)) The audit also aimed to establish those suitable for Mirena and the numbers of Mirena fitted and characteristics of recipients.

Adolescent↗

Health over the phone.

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Computer Communication Networks↗

Electrophoresis of DNA in novel thermoreversible matrices.

We demonstrate the feasibility of temperature-sensitive polymers as novel matrices for capillary and slab electrophoresis of DNA. These matrices combine the case-of-use of agarose with resolution properties of polyacrylamide. Two classes of matrices are used: (i) aqueous suspensions of gel microspheres and (ii) solutions containing uncross-linked temperature-sensitive polymers. When heated, the viscosity of these solutions drops dramatically because of the phase transition behavior of these polymers, and therefore these formulations are easy to pour or load. Results are presented for separation of double-stranded DNA fragments (< 2000 bp) in capillary, tube, and slab electrophoresis. Preliminary results are also presented for separation of single-stranded sequencing fragments by capillary electrophoresis. In the tube format, good resolution was obtained for phi X174/HaeIII fragments. In the slab format, excellent resolution of double-stranded DNA was obtained, including simultaneous separation of a 10 bp ladder up to 150 base pairs. In the capillary format, pBR322/MspI fragments were completely resolved, and single-base resolution of sequencing fragments was obtained up to 150 bases. We believe that temperature-sensitive polymers represent a new and promising class of electrophoretic media.

DNA↗

Assessment of the palatability of antistaphylococcal antibiotics in pediatric volunteers.

OBJECTIVE: To evaluate the palatability of four commonly prescribed antistaphylococcal antibiotics, cloxacillin, cephalexin, erythromycin, and fusidic acid, in volunteer children. DESIGN: A single-blind taste test of four flavored antibiotic suspensions commonly used in the treatment of skin infections in pediatric patients. SETTING: University teaching hospital. PARTICIPANTS: Twenty healthy volunteer children with a mean age of 9.2 +/- 2.0 SD years (range 6-12). MAIN OUTCOME MEASURES: The taste of each antibiotic was rated by the children on a 10-cm visual analog scale incorporating a facial hedonic scale. The children were also asked which antibiotic they thought tasted the best and which tasted the worst. RESULTS: Taste scores were as follows: cloxacillin 1.4 +/- 1.8 cm, cephalexin 6.5 +/- 2.7 cm, erythromycin 6.8 +/- 3.0 cm, and fusidic acid 6.3 +/- 2.4 cm. The taste rating of cloxacillin was significantly lower compared with the other three antibiotics (p = 0.001). Cloxacillin was chosen as having the worst taste by a significant proportion of the children (18 of 20). None of the antibiotics was clearly best tasting. CONCLUSIONS: Given similar effectiveness, taste considerations may be important in the decision as to which antibiotic to prescribe. The perception that cloxacillin is poor tasting to children is supported by this study, which suggests that when compliance with oral medication is critical for successful treatment, prescription of cloxacillin suspension should be avoided.

Anti-Bacterial Agents↗

Hypertrophic cardiomyopathy associated with tacrolimus in paediatric transplant patients.

Reported side-effects of tacrolimus, a potent immunosuppressive agent, have not included cardiotoxicity. We describe 5 consecutive paediatric transplant recipients (3 small bowel with or without liver and 2 liver) who received tacrolimus. 2 developed congestive heart failure and hypertrophic obstructive cardiomyopathy which resolved after changing to cyclosporin. In the other 3 patients the cardiomyopathy regressed or improved with a lower dose of tacrolimus or after stopping the drug.

Blood Pressure↗

Surgical management of post-traumatic angle recession glaucoma.

PURPOSE: The purpose of this study is to compare the results of three different drainage procedures performed for uncontrolled post-traumatic angle recession glaucoma. METHODS: A retrospective analysis was undertaken of 87 drainage procedures performed on 65 patients over an 8-year period. The results of trabeculectomy (47 procedures), Molteno single-plate implantation (20 procedures), and trabeculectomy combined with antimetabolite (20 procedures) were compared. Of those treated with antimetabolite, 11 received postoperative subconjunctival injections of 5-fluorouracil and 9 received an intraoperative application of 0.02% mitomycin C to the trabeculectomy site. RESULTS: In the group undergoing trabeculectomy with antimetabolite therapy, the intraocular pressure (IOP) drop was significantly greater, the percentage of successful cases at 3 and 6 months postoperatively was significantly higher, and the number of postoperative glaucoma medications was significantly lower than the other two groups. No statistically significant differences were found between the groups undergoing trabeculectomy without antimetabolite therapy and Molteno implantation. Of concern were three cases of late bleb infection in the group that received postoperative antimetabolite therapy. CONCLUSION: In medically uncontrolled post-traumatic angle recession glaucoma, trabeculectomy with antimetabolite therapy is the most effective surgical procedure. However, late bleb infection is a significant risk.

Adolescent↗

Capacity of CD8+ T cells to reject immunogenic variants of a spontaneous murine carcinoma: lack of non-specific (NK1.1+) effector mechanisms.

Class I MHC-expressing (Ia-) immunogenic (imm +) variants, which elicit a strong syngeneic host immune rejection response, can be isolated following 5-azacytidine treatment from the MHC-negative non-immunogenic (imm-) murine carcinoma cell line SP1 (10.1 subclone). In the present study, we have shown that CD4-depleted CD8+ T cells are both necessary and sufficient for the rejection process. Treatment of semi-syngeneic B6 X CBA F1 mice with anti-NK1.1 antibodies had no effect on the rejection of immunogenic variants, although the splenic NK (natural killer) activity of recipients was fully abrogated. Thus NK1.1+ effectors, which include most NK and LAK (lymphokine activated killer) cells, are most likely not involved in the rejection process. This finding was supported by a complete lack of NK susceptibility of SP1 cells in vitro, although variable killing by LAK and poly-I: C-induced killer cells was observed. To assess the role of NK1.1-LAK and other non-T killers (e.g. cytolytic macrophages) in vivo, we determined the specificity of the rejection process. We examined the ability of immune animals to reject a mixture of non-immunogenic parent tumour cells (or cells of an unrelated syngeneic tumour) and of the variant tumour cells used for the initial immunization. Growth of the parent tumour cells was unaffected while the same animals rejected the immunogenic tumour cells. Our findings support a primary role of tumour-specific CD8+ T cells in the rejection of imm+ variants with no detectable involvement of non-specific effector cells in the tumour destruction process.

Adenocarcinoma↗

Purification and characterization of a glycine betaine binding protein from Escherichia coli.

A major component of the Escherichia coli response to elevated medium osmolarity is the synthesis of a periplasmic protein with an Mr of 31,000. The protein was absent in mutants with lambda placMu insertions in the proU region, a locus involved in transport of the osmoprotectant glycine betaine. This periplasmic protein has now been purified to homogeneity. Antibody directed against the purified periplasmic protein crossreacts with the fusion protein produced as a result of the lambda placMu insertion, indicating that proU is the structural gene specifying the 31-kDa protein. The purified protein binds glycine betaine with high affinity but has no affinity for either proline or choline, clarifying the role of proU in osmoprotectant transport. The amino-terminal sequence of the mature glycine betaine binding protein is Ala-Asp-Leu-Pro-Gly-Lys-Gly-Ile-Thr-Val-Asn-Pro.

Amino Acid Sequence↗

Regulation of envelope protein composition during adaptation to osmotic stress in Escherichia coli.

Adaptation to osmotic stress alters the amounts of several specific proteins in the Escherichia coli K-12 envelope. The most striking feature of the response to elevated osmolarity was the strong induction of a periplasmic protein with an Mr of 31,000. This protein was absent in mutants with lambda plac Mu insertions in an osmotically inducible locus mapping near 58 min. The insertions are likely to be in proU, a locus encoding a transport activity for the osmoprotectants glycine betaine and proline. Factors affecting the extent of proU induction were identified by direct examination of periplasmic proteins on sodium dodecyl sulfate gels and by measuring beta-galactosidase activity from proU-lac fusions. Expression was stimulated by increasing additions of salt or sucrose to minimal medium, up to a maximum at 0.5 M NaCl. Exogenous glycine betaine acted as an osmoregulatory signal; its addition to the high-osmolarity medium substantially repressed the expression of the 31,000-dalton periplasmic protein and the proU-lac+ fusions. Elevated osmolarity also caused the appearance of a second periplasmic protein (Mr = 16,000), and severe reduction in the amounts of two others. In the outer membrane, the well-characterized repression of OmpF by high osmolarity was observed and was reversed by glycine betaine. Additional changes in membrane composition were also responsive to glycine betaine regulation.

Adaptation, Physiological↗

Comparative stability and catalytic and chemical properties of the sulfate-activating enzymes from Penicillium chrysogenum (mesophile) and Penicillium duponti (thermophile).

ATP sulfurylases from Penicillium chrysogenum (a mesophile) and from Penicillium duponti (a thermophile) had a native molecular weight of about 440,000 and a subunit molecular weight of about 69,000. (The P. duponti subunit appeared to be a little smaller than the P. chrysogenum subunit.) The P. duponti enzyme was about 100 times more heat stable than the P. chrysogenum enzyme; k inact (the first-order rate constant for inactivation) at 65 degrees C = 3.3 X 10(-4) s-1 for P. duponti and 3.0 X 10(-2) s-1 for P. chrysogenum. The P. duponti enzyme was also more stable to low pH and urea at 30 degrees C. Rabbit serum antibodies to each enzyme showed heterologous cross-reaction. Amino acid analyses disclosed no major compositional differences between the two enzymes. The analogous Km and Ki values of the forward and reverse reactions were also essentially identical at 30 degrees C. At 30 degrees C, the physiologically important adenosine 5'-phosphosulfate (APS) synthesis activity of the P. duponti enzyme was 4 U mg of protein-1, which is about half that of the P. chrysogenum enzyme. The molybdolysis and ATP synthesis activities of the P. duponti enzyme at 30 degrees C were similar to those of the P. chrysogenum enzyme. At 50 degrees C, the APS synthesis activity of the P. duponti enzyme was 12 to 19 U mg of protein-1, which was higher than that of the P. chrysogenum enzyme at 30 degrees C (8 +/- 1 U mg of protein-1). Treatment of the P. chrysogenum enzyme with 5,5'-dithiobis(2-nitrobenzoate) (DTNB) at 30 degrees C under nondenaturing conditions modified one free sulfhydryl group per subunit. Vmax was not significantly altered, but the catalytic activity at low magnesium-ATP or SO4(2-) (or MoO4(2-)) was markedly reduced. Chemical modification with tetranitromethane had the same results on the kinetics. The native P. duponti enzyme was relatively unreactive toward DTNB or tetranitromethane at 30 degrees C and pH 8.0 or pH 9.0, but at 50 degrees C and pH 8.0, DTNB rapidly modified one SH group per subunit. APS kinase (the second sulfate-activating enzyme) of P. chrysogenum dissociated into inactive subunits at 42 degrees C. The P. duponti enzyme remained intact and active at 42 degrees C.

Amino Acids↗