Biomedical subjects
Publications and source records attributed to P Morrison.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Benzoquinoid ansamycins, such as herbimycin A (HA) and geldanamycin (GA), are antibiotics that exhibit anti-tumor effects. These compounds have been shown to result in the intracellular depletion of important growth signaling molecules. Recently, GA has been shown to bind tightly to Hsp90, thereby implicating Hsp90 as a possible chaperone for those signaling molecules adversely affected by the benzoquinoid ansamycins. Here we have investigated the effects of HA and GA on the synthesis, maturation and stability of different protein tyrosine kinases. Exposing cells to either compound blocked normal maturation of the epidermal growth factor (EGF) receptor, platelet-derived growth factor (PDGF) receptor, and pp60(v-src). We show that only the nascent forms of the EGF and PDGF receptors are degraded under these conditions. Once the newly synthesized receptors had been translocated into the endoplasmic reticulum membrane, addition of the drugs no longer affected their stability. For the cytoplasmic tyrosine kinase, pp60(v-src), both the nascent as well as the mature forms of the protein were degraded in cells treated with the drugs. We discuss these observations as they pertain to the possible role of Hsp90 as a substrate-specific molecular chaperone, perhaps involved in the maturation and/or stability of proteins important for growth control.
All grades of nursing staff in a recently established interim secure forensic unit completed the Index of Work Satisfaction (IWS; n = 40). High levels of job satisfaction were achieved on four of the IWS subscales: (i) professional status; (ii) interaction; (iii) doctor-nurse relationship; and (iv) autonomy. Moderate levels of satisfaction were found on two of the subscales, task requirements and administration, while the salary subscale was the major area of dissatisfaction across the group. The high level of overall satisfaction in this area of psychiatric nursing may be regarded as a significant achievement in the development of new clinical services in what is regarded as a stressful area of nursing. Measures of job satisfaction may be useful benchmarks for evaluating future changes and developments in the service and for monitoring and improving the clinical work environment.
Explore the source record for details and available documents.
OBJECTIVE: The aim of this study is to identify patient and environmental characteristics associated with absconding behaviour, and to gain an understanding of the behaviour from the patients' perspective. METHOD: A prospective analysis of 77 consecutive incidents of absent-without-leave (AWOL) behaviour (n = 51 patients) was undertaken to develop a profile of patient and environmental characteristics associated with absconding behaviour. In addition, semi-structured interviews were carried out with a subsample of 14 patients within 24 h of returning to hospital from being AWOL. RESULTS: Those who absconded were male (58%), under 40 years of age (74%), admitted involuntarily (78%), and had a diagnosis of schizophrenia (42%). One-third of all AWOL incidents resulted from repeated absconding by the same individuals. The first 7 days post admission was a high-risk period for absconding behaviour. Issues raised in the interviews with patients identified a number of situational and environmental factors which are likely to increase the risk of absconding. CONCLUSIONS: Situational and environmental factors are more likely than patient characteristics to be predictive of absconding behaviour.
Explore the source record for details and available documents.
Demand for clinical services for familial breast cancer is continuing to rise across Europe. Service provision is far from uniform and, in most centres, its evolution has been determined by local conditions, specifically by local research interests, rather than by central planning. However, in a number of countries there is evidence of progress towards co-ordinated development and audit of clinics providing risk assessment, counselling, screening and, in some cases, prophylactic intervention. Much important information should emerge from continued observation and comparative assessment of these developments. In most countries for which relevant data are available, there is a distinct bias towards higher social class among those who avail themselves of clinic facilities (in line with findings from many other health-promotion initiatives). This should be addressed when considering future organisation of clinical services. Molecular genetic studies designed to identify the underlying mutations responsible for familial breast cancer are not generally regarded as part of the clinical service and are funded through research grants (if at all). Economic considerations suggest that there is a case for keeping this policy under review. Familial cancers throw into sharp relief certain ethical and legal issues that have received much recent attention from government advisory bodies, patients' representatives, professional commentators and the popular media. Two are of particular importance; first, the right to gain access to medical records of relatives, in order to provide accurate risk assessment for a given family member, versus the right to privacy in respect of personal medical information and, second, the obligation (or otherwise) to inform family members of their risk status if they have not actively sought that knowledge. The legal position seems to vary from country to country and, in many cases, is unclear. In view of pressures to establish uniform approaches to medical confidentiality across the EC, it is important to evaluate the experience of participants in this Demonstration Programme and to apply the principle of "non-malfeasance" in formulating regulations that should govern future practice in this field. Data on economic aspects of familial breast cancer are remarkably sparse and outdated. As evidence accrues on the influence of screening and intervention programmes on morbidity and mortality, there is a strong case for evaluating the cost-effectiveness of different models of service provision.
Increasingly women at high risk of breast cancer are opting for prophylactic surgery to reduce their risks. Data from 10 European centres that offer a risk counselling and screening service to women at risk show different approaches to the option of preventive surgery, although most centres adhere to a protocol including at least two risk counselling sessions and a psychological assessment. Thus far the combined centres have data on 174 women who have undergone prophylactic mastectomy with in excess of 400 women years of follow up. Operations were carried out on women with lifetime risks of 25-80%, with an average annual expected incidence rate of 1% per women. No breast cancers have occurred in this cohort. Long term follow up on an extended group of women will be necessary to truly address the risk of subsequent breast cancer and the psychological sequelae.
Oestrogen transdermal patches are now being used in the prophylaxis and treatment of post partum depression. Oestrogens are known to have potential adverse effects on breastfed infants. This case describes jaundice and poor weight gain in the child of a lactating mother prescribed oestrogen transdermal patches. There is a need for caution in the use of this therapy in breast feeding mothers and health professionals should be alert for problems.
The discovery of the human immunodeficiency virus (HIV) in breastmilk in 1985, and subsequent research, supports the hypothesis that breastfeeding provides a route of transmission to the nursing baby. Various routes of infection and relative rates of transmission have been studied in many parts of the world, leading to the blanket guideline that babies of HIV-infected mothers should not be breastfed, if a safe alternative can be provided. However, due to the limits inherent in various studies and various testing methods, the exact frequency of breastmilk transmission of HIV during the course of lactation remains unknown, and the conclusions drawn are thus conflicting and confusing. Replacement feeding of young babies with non-human milks and other foods may be hazardous in poverty-stricken populations in Africa and elsewhere, and still more research suggests that there are several properties in human milk that may provide specific protection to the baby of an infected mother. The possibility of providing the mother's own treated expressed breastmilk to the baby at risk of HIV infection via breastfeeding is an alternative which has yet to be fully explored and ways that this could be accomplished are examined. Those of us working with mothers and babies need more information before we can assist mothers living with HIV to make truly informed decisions about the safest way to feed their babies. Topics requiring urgent further attention are outlined.
The discovery of the human immunodeficiency virus (HIV) in breastmilk in 1985, and subsequent research, supports the hypothesis that breastfeeding provides a route of transmission to the nursing baby. Various routes of infection and relative rates of transmission have been studied in many parts of the world, leading to the blanket guideline that babies of HIV-infected mothers should not be breastfed, if a safe alternative can be provided. However, due to the limits inherent in various studies and various testing methods, the exact frequency of breastmilk transmission of HIV during the course of lactation remains unknown, and the conclusions drawn are thus conflicting and confusing. Replacement feeding of young babies with non-human milks and other foods may be hazardous in poverty-stricken populations in Africa and elsewhere, and still more research suggests that there are several properties in human milk that may provide specific protection to the baby of an infected mother. The possibility of providing the mother's own treated expressed breastmilk to the baby at risk of HIV infection via breastfeeding is an alternative which has yet to be fully explored and ways that this could be accomplished are examined. Those of us working with mothers and babies need more information before we can assist mothers living with HIV to make truly informed decisions about the safest way to feed their babies. Topics requiring urgent further attention are outlined.
In connective tissue, cell structure contributes to type I collagen expression. Differences in osteoblast microarchitecture may account for the two distinct cis elements regulating basal expression, in vivo and in vitro, of the rat type I collagen alpha1(I) polypeptide chain (COL1A1). The COL1A1 promoter conformation may be the penultimate culmination of osteoblast structure. Architectural transcription factors bind to the minor groove of AT-rich DNA and bend it, altering interactions between other trans-acting proteins. Similarly, nuclear matrix (NM) proteins bind to the minor groove of AT-rich matrix-attachment regions, regulating transcription by altering DNA structure. We propose that osteoblast NM architectural transcription factors link cell structure to promoter geometry and COL1A1 transcription. Our objective was to identify potential osteoblast NM architectural transcription factors near the in vitro and in vivo regulatory regions of the rat COL1A1 promoter. Nuclear protein-promoter interactions were analyzed by gel shift analysis and related techniques. NM extracts were derived from rat osteosarcoma cells and from rat bone. The NM protein, NMP4, and a soluble nuclear protein, NP, both bound to two homologous poly(dT) elements within the COL1A1 in vitro regulatory region and proximal to the in vivo regulatory element. These proteins bound within the minor groove and bent the DNA. Parathyroid hormone increased NP/NMP4 binding to both poly(dT) elements and decreased COL1A1 mRNA in the osteosarcoma cells. NP/NMP4-COL1A1 promoter interactions may represent a molecular pathway by which osteoblast structure is coupled to COL1A1 expression.
Explore the source record for details and available documents.
The recent isolation of breast cancer predisposing genes (BRCA1 and BRCA2) allows the identification of carriers within affected families. These carriers have a 50-85% risk of developing breast or ovarian cancer and need careful follow-up. The purpose of this study was to evaluate the management and screening protocols implemented in high risk families at various family cancer clinics in Europe. A questionnaire was mailed to the members of the European Familial Breast Cancer Collaborative Group (n = 30) requesting information on the following issues: indication for surveillance of breasts and ovaries, the recommended protocol, coordination of the screening examination, prophylactic surgery, the specific management of breast cancer in a mutation carrier and the use of oestrogen. 16 centres from nine countries responded. Most centres recommend surveillance of the breasts if the lifetime risk exceeds 15-20%. The surveillance protocol that is generally advised comprises monthly self breast examination, examination by a specialist every 6 months and annual mammography, all starting from an age between 25 and 35 years. Surveillance of the ovaries is recommended in BRCA1 and BRCA2-mutation carriers, in members from breast/ovarian cancer families and in some centres in 'breast cancer only' families with an early onset of breast cancer. The recommended protocol includes gynaecological examination, sonography and estimation of CA-125 at yearly intervals starting from the age 30-35 years. Prophylactic mastectomy is considered for proven mutation carriers in some centres. Most centres consider prophylactic oophorectomy in mutation carriers and some centres also consider it for members of breast/ovarian cancer families. This survey provides insight into the guidelines for surveillance and management of familial breast cancer used at various family cancer clinics in Europe; this insight may contribute to the appropriate management of these high risk women. It should be emphasised that most recommendations are based on experts' opinion rather than on any specific studies.
OBJECTIVE: Because head and neck tumors reside in a complex area, having a three-dimensional (3-D) model of the patient's unique anatomical features may assist in the delineation of pathology. The authors describe a new computer technique of 3-D anatomical reconstruction from two-dimensional computed tomography (CT) and magnetic resonance (MR) data and discuss how it represents a step forward in the continuing evolution of 3-D imaging. STUDY DESIGN: The authors selected three patients with solitary head and neck tumors and reconstructed their anatomy in a 3-D format for study. The tumors represented locations in the nose and central skull base (patient 1), temporal bone (patient 2), and neck (patient 3). MATERIALS AND METHODS: MR and CT images from the individual patients were electronically transferred to workstations in the Surgical Planning Laboratory of the authors' institution. Registration (or fusion) was carried out between the MR and CT images. The desired anatomic components underwent segmentation (identification and isolation). Assembly of the segmented images was performed and the resulting structures were integrated to produce a 3-D model. RESULTS: 3-D models of the following were constructed and displayed in an interactive format on high-capacity computer workstations: 1) a skull base sarcoma with extension into the nasopharynx and nose; 2) an acoustic neuroma with internal auditory canal involvement; and 3) a metastatic recurrence of a tongue base squamous cell carcinoma in the posterior triangle of the right side of the neck with extension to the skull base. CONCLUSION: The authors' Surgical Planning Laboratory has developed a 3-D reconstruction technique that has several new features. The models provided a very good 3-D interactive representation of the tumors and patient anatomy. The need now exists to develop this method of 3-D reconstruction of head and neck tumors for potential applications in treatment, research, and medical education.
In the first part of this paper we give a brief overview of the development of the different types of clinical assessment used in the UK. Some general problems related to the assessment of clinical practice are outlined. The second part of the paper focuses on the role of the external examiner in the clinical assessment of students. We outline some of the major problems we encountered as internal and external examiners on the same university-based course in which 'I-day' practical assessments were undertaken. We emphasize the particular problems of externally assessing the clinical practice component of the course in this manner and conclude that the continuous assessment model, while not without its own problems, is potentially a more effective approach to student assessment.
Anti-CD44 MoAb IM7 induced the loss of CD44 from mouse leucocytes thereby inhibiting leucocyte migration and joint inflammation in murine arthritis. Thus, targeting CD44 with MoAb may have potential for the treatment of patients with inflammatory joint diseases. Expression of CD44 by peripheral blood (PB) and synovial fluid (SF) leucocytes from rheumatoid arthritis (RA) patients was compared and the ability of IM7 to modulate this expression determined. RASF lymphocytes showed increased CD44 expression compared with those in PB indicative of an activated phenotype. As inflammatory SF did not up-regulate CD44 expression on PB lymphocytes, the increased CD44 expression by SF lymphocytes was a result of the selective homing of CD44(high) cells to the synovium rather than an effect of the synovial environment. RASF granulocytes showed reduced CD44 expression compared with those in PB, again indicative of an activated phenotype. However, this reduction could be induced on PB granulocytes following culture with inflammatory SF and was inhibited by anti-TNF-alpha MoAb, implying that soluble factors in inflammatory SF such as TNF-alpha induced granulocyte activation and CD44 loss. IM7 induced the loss of CD44 from lymphocytes (both from PB and SF) and granulocytes in vitro, but was subsequently re-expressed after 24 h culture in the absence of the MoAb. This loss of CD44 was blocked by serine- and metalloprotease inhibitors implying that IM7 induced the proteolytic cleavage of CD44 by a mechanism similar to that reported for the loss of CD44 from PMA-activated granulocytes. Furthermore, IM7-treated CD44(low) lymphocytes showed reduced adherence to both an endothelial cell line and RA synovial fibroblasts in vitro. The unique ability of IM7 to reduce CD44 expression by lymphocytes suggests that it could prevent lymphocyte extravasation and synovial infiltration in RA as previously reported in murine arthritis.