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Biomedical subjects

J Humphreys

Publications and source records attributed to J Humphreys.

At least 91 records · Page 5Linked to original sources

Bacteriostatic effect of human milk and bovine colostrum on Escherichia coli: importance of bicarbonate.

At pH 7.4 and in the presence of NaHCO3, human milk and bovine colostrum inhibited the growth of Escherichia coli O111. Adding sufficient iron to saturate the iron-binding capacity of the lactoferrin present in the milk or colostrum prevented bacteriostasis. At pH 6.8 neither molk nor colostrum inhibited E. coli 0111. Adjusting the pH to 7.4 with NaHCO3 resulted in the development of bacteriostatic activity. Adjusting the pH to 7.4 with NaOH was ineffective. Dialyzed colostrum and milk inhibited bacterial growth at pH 6.8 in the absence of added NaHCO3; addition of citrate or iron abolished bacteriostasis. The chromatographic elution profile of tyrosyl-transfer ribonucleic acid (tRNA) from iron-replete E. coli differs significantly from that of tyrosyl-tRNA from iron-deficient organisms. Examination of the elution profile tyrosyl-tRNA from E. coli 0111 growing in colostrum without added NaHCO3 showed that such bacteria were fully replete in iron. The nature of the elution profile of tyrosyl-tRNA also showed that iron was freely available to the bacteria when citrate was added to dialyzed colostrum but not available in its absence, even at pH 6.8. Results support the idea that the bacteriostatic action of milk and colostrum, due to the combined action of antibody and lactoferrin, depends on the addition of bicarbonate to counteract the iron-mobilizing effect of the citrate normally present in these secretions.

Animals↗

Sex hormone binding globulin in breast cancer.

Using a binding assay for sex hormone binding globulin, a Japanese group showed that they could select breast cancer patients more likely to be responsive to endocrine therapy, i.e. oestrogen receptor positive patients, by an increase in oestrogen binding capacity of the protein. We directly measured the levels of this protein using a specific antiserum to it, and the levels were not different from normal in any group of breast cancer patients whether or not oestrogen receptors were present. Both methods of measurement can detect a slight increase after a weak oestrogenic stimulus, indicating that they are as sensitive as each other.

Breast Neoplasms↗

Antibody-directed enzyme prodrug therapy with the T268G mutant of human carboxypeptidase A1: in vitro and in vivo studies with prodrugs of methotrexate and the thymidylate synthase inhibitors GW1031 and GW1843.

Antibody-directed enzyme prodrug therapy (ADEPT) is a technique to increase antitumor selectivity in cancer chemotherapy. Our approach to this technology has been to design a mutant of human carboxypeptidase A (hCPA1-T268G) which is capable of hydrolyzing in vivo stable prodrugs of MTX and targeting this enzyme to tumors on an Ep-CAM1-specific antibody, ING1. Through the use of this >99% human enzyme which is capable of catalyzing a completely nonhuman reaction, we hope to increase ADEPT selectivity while decreasing overall immunogenicity of the enzyme-antibody conjugate. In the current report, prodrugs of the thymidylate synthase inhibitors GW1031 and GW1843 and the dihydrofolate reductase inhibitor methotrexate were studied for their wild-type and mutant hCPA enzyme hydrolysis, their in vivo stability, and their use in therapy. Prodrugs with high kcat/Km ratios for mutated versus wild-type hCPA1 were examined in vitro for their stability in human pancreatic juice, and in vivo for their stability in mouse plasma and tissues. In addition, targeting and in vivo enzyme activity studies were performed with an ING1 antibody conjugate of the mutant enzyme (ING1-hCPA1-T268G). Finally, in vivo therapy studies were performed with LS174T tumors to demonstrate proof of principle. Results indicate that prodrugs can be synthesized that are selective and efficient substrates of hCPA1-T268G and not substrates of the endogenous CPA activities; this leads to excellent in vivo stability for these compounds. In vivo conjugate targeting studies showed that the antibody-enzyme conjugate was targeted to the tumor and enzyme was initially active in vivo at the site. Unfortunately therapeutic studies did not demonstrate tumor reduction. Experiments to determine reasons for the lack of antitumor activity showed that the enzyme activity decreased as a result of enzyme instability. The results offer encouragement for additional novel mutant enzyme improvements and additional in vivo studies on this unique approach to ADEPT.

Adenocarcinoma↗

Trauma history of sheltered battered women.

The purpose of this nursing research was to describe the trauma experience of sheltered battered women. Trauma history was operationalized as the participant's experience with traumatic life events in general (Trauma History Questionnaire [B. L. Green, 1995]) and with battering specifically (Conflict Tactics Scale, including a Physical Injury Severity scale). A convenience sample of 50 ethnically diverse women in the San Francisco Bay area was obtained from those residing in 2 shelters. Participants had experienced an average of 8.1 +/- 4.6 traumatic events (battering and nonbattering) over the course of their lives. Analysis of relationships between selected biopsychosocial and trauma history variables revealed the importance and beneficial effects of spiritual beliefs to many sheltered battered women.

Adolescent↗

Auditing audits: use and development of the Oxfordshire Medical Audit Advisory Group rating system.

OBJECTIVES: To assess the value of the Oxfordshire Medical Audit Advisory Group rating system in monitoring and stimulating audit activity, and to implement a development of the system. DESIGN: Use of the rating system for assessment of practice audits on three annual visits in Oxfordshire; development and use of an "audit grid" as a refinement of the system; questionnaire to all medical audit advisory groups in England and Wales. SETTING: All 85 general practices in Oxfordshire; all 95 medical audit advisory groups in England and Wales. MAIN OUTCOME MEASURES: Level of practices' audit activity as measured by rating scale and grid. Use of scale nationally together with perceptions of strengths and weaknesses as perceived by chairs of medical audit advisory groups. RESULTS: After one year Oxfordshire practices more than attained the target standards set in 1991, with 72% doing audit involving setting target standards or implementing change; by 1993 this had risen to 78%. Most audits were confined to chronic disease management, preventive care, and appointments. 38 of 92 medical audit advisory groups used the Oxfordshire group's rating scale. Its main weaknesses were insensitivity in assessing the quality of audits and failure to measure team involvement. CONCLUSIONS: The rating system is effective educationally in helping practices improve and summatively for providing feedback to family health service authorities. The grid showed up weakness in the breadth of audit topics studied. IMPLICATIONS AND ACTION: Oxfordshire practices achieved targets set for 1991-2 but need to broaden the scope of their audits and the topics studied. The advisory group's targets for 1994-5 are for 50% of practices to achieve an audit in each of the areas of clinical care, access, communication, and professional values and for 80% of audits to include setting targets or implementing change.

England↗

Regulating non-nursing healthcare workers.

This report looks at a comparative study of the changes in nurse education in the UK and Australia over the past decade. The aim is to examine the impact that a move towards a profession led by degree-qualified nurses might have on the profession's control of the workforce.

Australia↗

In the driving seat.

Explore the source record for details and available documents.

Family Practice↗

Children of battered women: worries about their mothers.

Children of battered women report a variety of worries about their mothers. In a study of 50 children (ages 10-17 years) from 5 battered women's shelters, children revealed worries about potential hazards and actual health hazards regarding their mothers. Nursing attention to worries provides information about the emotional lives of these children and helps them deal with expressed concerns.

Adolescent↗

Danazol treatment of advanced breast cancer.

Danazol, an effective agent in the treatment of benign breast disease, has been administrated to 41 patients with advanced breast cancer. These patients were treated with danazol for periods ranging from 1 to 40 weeks and responses were seen in seven of 41 (17%) patients. No responses were seen in the four premenopausal patients treated. Side effects were seen in nine of 41 (22%) patients, but in most patients these stopped when the dose of danazol was reduced. This preliminary study indicates that danazol may be an effective form of hormone treatment in patients with advanced breast cancer.

Adult↗