Biomedical subjects
Publications and source records attributed to D Roberts.
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1. The fluorescent ATP analogue 1,N6-etheno-ATP is a good substrate and an efficient allosteric inhibitor of rabbit skeletal-muscle phosphofructokinase. 2. Fluorescence energy transfer occurs between bound 1,N6-etheno-ATP and phosphofructokinase. 1,N6-Etheno-ATP fluorescence is enhanced, intrinsic protein fluorescence is quenched, and the excitation spectrum of 1,N6-etheno-ATP fluorescence is characteristic of protein absorption. 3. The binding reaction of 1,N6-etheno-ATP observed by stopped-flow fluorimetry is biphasic. The fast phase results from binding to the catalytic site alone. The slow phase results from the allosteric transition of the R conformation into the T conformation induced by the binding of 1,N6-etheno-ATP to the regulatory site. 4. The fluorescence signal that allows the transition of the R conformation into the T conformation to be observed does not arise from 1,N6-etheno-ATP bound to the regulatory site. It arises instead from 1,N6-etheno-ATP bound to the catalytic site as a consequence of changes at the catalytic site caused by the transition of the R conformation into the T conformation. 5. In the presence of excess of Mg2+, the affinity of 1,N6-etheno-ATP for the regulatory site is very much greater in the T state than in the R state.
The method of Arons et al. (Cancer Res. 35:2033-2038, 1975) for assaying methotrexate (MTX) was used to monitor serum levels of the drug attained in 18 patients with osteosarcomas. The patients received either 100 mg or 200 mg of MTX/kg via a 6-hour infusion. With one fatal exception, unacceptable toxicity to MTX was prevented by leucovorin. Serum levels of the drug were assayed routinely at 6, 12, and 18 hours after termination of the infusion. Although significantly higher serum levels of MTX were observed at 6 hours after the infusion of 200 mg MTX/kg than after 100 mg/kg, the variation in rate of clearance of individual patients masked any subsequent dosage-related differences. The mean half-time for clearance of MTX was similar irrespective of the dosage of MTX and was 2.91 +/- 1.51 hr for 53 treatments. The single incidence of toxicity, requiring hospitalization, was accompanied with markedly higher serum levels of MTX at 18 hours, but not at either 6 or 12 hours after termination of the drug infusion, and by a slightly slower rate of clearance, 6.2 hours. Certain minor adaptations were incorporated in the original assay to simplify the analysis of data.
A study was made of the growth of three strains of non-cholera vibrio in a range of foodstuffs and of the effect of temperatures and pH on their ability to grow. Growth was tested at 4 degrees, 10 degrees, 22 degrees, 30 degrees, 37 degrees and 43 degrees C in a range of foods likely to be incorporated into cold hors d'oeuvres, e.g. egg, cream, rice, cold meat, seafood, aspic and mayonnaise. Non-cholera vibrios grew well in all these foods except mayonnaise, the rate of growth increasing with increased temperature of storage. At acid pH values the organisms died or grew very poorly but growth improved as the pH became more alkaline. None of the three strains showed any resistance to heat, an initial inoculum of greater than 10(7) organisms/g was reduced to less than 100 organisms/g in 2--3 min at 55 degrees C.
Two nutritionally poor bacteriological media, prepared from phosphate-buffered saline and from bronchial secretions, support the growth of Haemophilus influenzae only poorly. The presence of tobacco or pure nicotine in these media stimulates the growth of the organism, and the component(s) responsible appear(s) to be volatile.
Masticatory habit is a major factor determining the morphology of the craniofacial skeleton. The craniofacial skeleton essentially comprises a series of bony stress-bearing bridges forming a structural framework. The structural framework of the skull of dog has been described as a rigid trestle-like structure; it can be illustrated by mechanically removing nonresistant areas of bone. It is then found that a framework is produced which is partially rigid (cranium) and partly flexible (rostrum). It is postulated that the flexibility of the rostrum acts to absorb shock and it is suggested that the primate postorbital bar is developed in response to craniofacial morphology which increases compressive bite forces.
Sixty Carpentier-Edwards porcine valve bioprostheses stabilized with glutaraldehyde were implanted in 55 patients with acquired and congenital heart disease. The follow-up period ranged between 1 and 12 months. There were 3 hospital deaths (5%) and 2 late deaths (4%) in 24 mitral, 24 aortic, 5 mitral-aortic, 1 tricuspid and 1 pulmonary valve replacements. All patients were anticoagulated from the second postoperative day onwards for a period of 3 months after which those with sinus rhythm had their anticoagulants withdrawn. Paravalvular leakage led to re-operation in 3 cases (4%). No valve failure due to cusp rupture was encountered and no thromboembolic complications have occurred. Thirty-three patients were studied postoperatively by non-invasive methods and the results are presented.
Treatment with methotrexate (MTX) plus 1-beta-D-arabinofuranosylcytosine (ara-C) on Days 1, 4, and 7 after i.p. inoculation of L1210 ascites cells was more effective than treatment with one drug on Days 1, 4, and 7 followed by the second drug on Days 2, 5, and 8. Simultaneous treatment with both drugs was associated with a retention of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (ara-CTP) but no increase in the activity of deoxycytidine kinase in L1210 cells, whereas pretreatment with MTX 24 hr before the administration of ara-C was associated with approximately 2-fold increases in the level of ara-CTP and of deoxycytidine kinase in L1210 cells. However, from 5 hr after treatment with ara-C, higher levels of ara-CTP were observed in L1210 cells treated simultaneously with both drugs than in cells from animals pretreated with MTX 24 hr before treatment with ara-C. The superiority of simultaneous treatment over sequential treatment and the synergism between MTX and ara-C, previously reported for this schedule of simultaneous treatment, are attributed in part to the MTX-induced retention of ara-CTP and the increased exposure of L1210 cells to ara-CTP that results from the slower clearance of ara-CTP.
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Retention of a retromandibular space has necessitated developing a system of mandibular protrusion in hominid species. It is possible that mandibular protrusion can be effected by a single muscle-the lateral pterygoid-and the motion controlled by the excentrically placed mandibular suspensory ligaments. The elasticity of the ligaments produces an integrity maintenance force between the articular condyle and eminence which is normally of minimal size. Excessive craniofacial flexion, or the retention of a juvenile configuration of the mandible, could result in increasing this integrity maintenance force and cause crepitation and clicking. Ajustment of the ligaments could reduce these pathological manifestations.
The study comprises 375 patients who had received an endocardial pacemaker electrode primarily. A stylet electrode of the Medtronic type was used in 165 patients and of the Elema type in 79 patients. Elema's flexible electrode model 588 EMT was used in 131 patients. The total number of electrode complications was surprisingly high. In 92 out of the 375 patients, 141 serious episodes of pacing failure occurred during the observation period of from 6 to 42 months. The complication rate increased with pacemaker function time. The stylet electrodes gave the highest complication rate. The choice of vein for introducing the electrode into the heart seems not to affect the complication rate significantly. Nor did the initial threshold value of stimulation influence the complication rate to any marked degree. The pacemaker manufacturers have devoted much effort to producing long-life impulse generators but there is also a great need for well-functioning long-life electrodes.
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The inoculation of L1210 or L5178Y leukaemia cells decreased the platelet count of the recipient mouse before extensive infiltration of marrow was expected by either tumour line. The decrease was more pronounced after intravenous inoculation of L1210 leukaemia than after intraperitoneal inoculation. Inoculation of L5178Y cells by both routes caused an initial decrease but the count recovered to 80% of normal before becoming markedly depressed prior to death of the host. Implantation of diffusion chambers containing L1210 cells also decreased the platelet count, which later returned to normal.
Sera from chicken, turkey, pheasant, quail and their intergeneric hybrids were compared by their reactions in two-dimensional immunoelectrophorsis with homologous and heterologous antisera. As many as 44 antigenically distinguishable components were resolved in these sera by use of this technique. Sera from the intergeneric hybrids, when allowed to react with rabbit anti-White Leghorn antiserum, gave more precipitin peaks than did any of the parental sera in reaction with this same antiserum. Thus it appeared that intergeneric hybridization induced a propagation of avian serum antigens recognized by rabbit antiserum to a single parental serum. For example, all parental sera, in reaction with homologous or heterologous antisera, appeared to contain only one precipitin peak which migrated in the albumin area. Sera from the intergeneric hybrids of chicken X turkey, chicken X pheasant, and chicken X quail had two antigenetically distinguishable peaks in the albumin area. Sera from turkey X pheasant and pheasant X quail had only one peak in this region. These results agree with the observations obtained from polyacrylamide disc gel electrophoresis of the plasma proteins.
Combination of cyclophosphamide and adriamycin, encompassing a wide range of dosages, were administered on five different schedules to C57BL/6J X DBA/2J F1 female mice inoculated i.p. with L1210 ascites tumor cells. Among the resulting 85 treatment groups, the mean postinoculation survival of mice that died with tumor was 11.4 to 51.3 days; this represented increases of 62 to 628% over the survival of untreated controls. In some groups, tumor cells were eradicated in 9 of 10 treated mice. By contrast, neither drug given alone cured leukemic mice or extended their survival beyond controls by more than 96%. Adriamycin and cyclophosphamide were most effective when administered simultaneously on Day 1; additional treatment with adriamycin on Days 4 and 7 produced a significant increase in the survival of mice that died with tumor, but this regimen did not increase the incidence of cures. Combination therapy with these agents reduced the cytotoxic response of the host to subsequently inoculated L1210 cells. The pronounced therapeutic effectiveness of this drug combination is attributed to a true potentiation of the independent oncolytic action of each agent.
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