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Biomedical subjects

S Bryan

Publications and source records attributed to S Bryan.

64 records · Page 4Linked to original sources
PubMed1988

Alternate pathways of DNA replication in Escherichia coli.

We have described the pcbA1 mutation which enables E. coli cells to replicate DNA in the absence of a functional dnaE gene product if DNA polymerase I (the polA gene product) is present. The pcbA1 mutation phenotypically suppresses multiple dnaEts and dnaEam alleles. The pcbA1/PolI replication pathway differs from normal in sensitivity to certain DNA-damaging agents such as methylmethane sulfonate (MMS) and a lack of damage-directed mutagenesis. We report here cloning of the pcbA1 gene in a multicopy plasmid. The pcbA1 mutation is detected only in cis; therefore, cloning necessitated gene eviction. The pcbA1 gene lies closely- linked to gyrB. We have demonstrated the physical presence of DNA polymerase I in the replicating holoenzyme complex by immunoblotting using dnaEam strains. We conclude that E. coli has two alternate replisome structures: REP-A, in which DNA polymerase I is the functional synthetic subunit; and REP-E, in which the alpha-subunit, product of the dnaE gene, is functional. To investigate further the role of individual DNA polymerases in replication, we have isolated the polB gene on multicopy plasmids.

Alleles↗
PubMed1985

A randomized trial comparing mitoxantrone with doxorubicin in patients with stage IV breast cancer.

Mitoxantrone (Novantrone; dihydroxyanthracenedione) is an anthraquinone previously shown to be active in human breast cancer. It appears to have less toxicity than doxorubicin. Results of this phase II-III randomized cross-over trial to determine the relative efficacy and toxicity of mitoxantrone in comparison to doxorubicin, are presented. Patients with measurable, recurrent breast cancer with limited prior chemotherapy with or without radiotherapy for metastatic disease, and who had not been exposed to prior doxorubicin, were randomized to receive either mitoxantrone or doxorubicin every three weeks with cross-over on progression. Response rates, duration of remission, time to treatment failure, and drug toxicity, including cardiac toxicity evaluated with serial radionuclide angiocardiography, were evaluated. Differences in the response rates for the two groups were not statistically significant. Neither time to treatment failure nor duration of response are significantly different (p greater than 0.05). With respect to toxicity, mitoxantrone treated patients consistently exhibited a lower incidence and less severe drug toxicity as compared to their doxorubicin-treated counterparts. Cardiac toxicity was carefully monitored and thus four patients on doxorubicin have had drug related congestive heart failure, as compared to none on mitoxantrone. In summary, mitoxantrone appears to be as active as doxorubicin in patients with stage IV breast cancer previously treated with chemotherapy; however, mitoxantrone causes significantly less nausea, vomiting, stomatitis and alopecia at doses which induce equal or greater myelosuppression than doxorubicin, and appears to be less cardiotoxic.

Adult↗
PubMed1985

Mitoxantrone in malignant lymphoma.

Two phase II trials of mitoxantrone (Novantrone; dihydroxyanthracenedione) in refractory malignant lymphoma have been conducted. In the first of these, mitoxantrone, 5 mg/m2, was given weekly for six weeks and in the second, 14 mg/m2 was administered every three weeks. The first trial was conducted by the Southeastern Cancer Study Group (SECSG) and the second was a multicenter trial sponsored by Lederle Laboratories. Of the 51 patients entered in the SECSG trial, 28 could be evaluated for response and 43 for toxicity. WBC nadirs below 4.0 X 10(9)/litre were recorded in 25 patients. Three partial responses and no complete responses were obtained. These results contrast with those of the single dose every three weeks study in which 96 patients were entered and 69 of these were evaluated for response. Responses were obtained in 30 patients (4 complete, 26 partial). Side-effects on this three-weekly dose regimen were minimal. WBC nadirs below 4.0 X 10(9)/litre occurred in 85 patients. Twenty-three patients experienced at least mild nausea and vomiting and 15 had at least mild alopecia. These preliminary data indicate that mitoxantrone has significant activity in malignant lymphoma. All of the responding patients had received extensive prior therapy, many of them with anthracyclines in combination or as single agents. The higher response rate to mitoxantrone given at 14 mg/m2 every three weeks suggests that careful consideration should be given to dose schedule when this drug is examined further in phase III trials.

Alopecia↗
PubMed1982

Studies on two novel angiotensin II actions.

Animal data suggest that angiotensin II may directly affect renal sodium retention independent of aldosterone (4,6). Additionally there is evidence to suggest that the hormone can stimulate protein synthesis in a variety of tissues and that indeed it may be a vasculotoxin (5,7). We describe here experiments designed to elucidate the role of angiotensin II in renal sodium retention in normal man. Additionally we present preliminary evidence suggesting that unlike the rapid sodium retaining effect, some delayed (trophic) actions of the hormone may be generated by a hitherto unappreciated mechanism.

Adult↗
PubMed1976

Effect of oral contraceptives on rhythmic urinary metal excretion.

Thirteen women, six of whom were using oral contraceptive agents, between the ages of 23 and 34 years, free from illness, and without a previous clinical history of menstrual abnormality, were studied with chronobiological methods for circadian (about 24 hour) patterns of metal and creatinine excretinine excretion. Circadian rhythms were detected for the excretion of lithium, potassium, iron, sodium, copper, and creatinine. Statistically significant by lower 24 hour excretion (mesors) of lithium, potassium, and iron was detected for the subjects using oral contraceptive agents. Although all women adhered to nearly identical activity-rest (synchronization) schedules, the peak times (acrophases) of the metal excretory rhythms for oral contraceptive users were phase delayed by about two hours.

Adult↗
PubMedDate not supplied

The effect of PACS on the visualization of the lateral cervical spine and the management of patients presenting with trauma.

In patients presenting with trauma, early diagnosis of neck injuries is likely to affect long-term outcome. This paper reports a study that compared lateral images of the cervical spine produced by a Picture Archiving and Communication System (PACS) with the same images produced using computed radiography (CR). The study was undertaken at the Hammersmith Hospital, London. Data were collected on 100 patients who presented with trauma. Both soft copy (PACS) and hard copy (CR) images of the cervical spine were produced for each patient from the same radiographic exposure. The images were viewed by five clinical members of the Accident and Emergency Department. Data were collected on the level of the cervical spine that could be viewed, the clinical management following the viewing of the image and the use of PACS 'tools'. Overall no statistically significant differences between modalities were found in the level of visualization. Within viewer differences were found for three viewers: one indicating better visualization with PACS and two indicating better visualization with CR. The results relating to patient management indicate greater clinician confidence following the viewing of PACS images for two viewers. The use of PACS 'tools' improved visualization of the cervical spine for one viewer.

Adult↗