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Biomedical subjects

M Butler

Publications and source records attributed to M Butler.

At least 19 recordsLinked to original sources
PubMed1997

Unsaturated fatty acids enhance cell yields and perturb the energy metabolism of an antibody-secreting hybridoma.

Growth of the murine B-lymphocyte cell line CC9C10 and the myeloma SP2/0 was enhanced significantly by the presence of the unsaturated fatty acids, oleic and linoleic acids in serum-free culture. The cellular content of linoleic and oleic acids gradually increased during continuous culture passage, with no evidence of regulatory control. Over 10 culture passages in the presence of these fatty acids, the unsaturated/saturated fatty acid ratio of all cellular lipid fractions increased substantially. Most of the fatty acid accumulated in the polar lipid fraction (more than 74%) and only a small proportion was oxidized to CO2 (0.5%). Linoleic acid caused a decrease to one-eighth in the rate of metabolism of glutamine and a 1.4-fold increase in the rate of metabolism of glucose. There was no change in the relative flux of glucose through the pathways of glycolysis, pentose phosphate or the tricarboxylic acid cycle. The changes in energy metabolism were reversed when the cells were removed from fatty acid-supplemented medium. The most plausible explanation for these effects is the observed decrease in the rate of uptake of glutamine into cells loaded with linoleic acid. Growth of the CC9C10 cells in linoleic acid caused the Km of glutamine uptake to increase from 2.7 to 23 mM, whereas glucose uptake was unaffected.

Adaptation, Biological↗
PubMed1997

BCL-6 and other genomic alterations in non-Hodgkin's lymphoma (NHL).

This study reports on the frequency and disease association pattern of a number of gene rearrangements in a large panel of lymphoid tumours (n = 94). We detected the t(11;14) translocation, involving rearrangement of the BCL-1 locus, in 60% of mantle cell lymphomas. The BCL-2 gene, located at band 18q21, was rearranged in 42% of follicle centre lymphomas (FCL) and in 15% of diffuse large B-cell (DLBC) lymphomas. In this study, 80% of the c-MYC rearrangements were detected in aggressive diffuse lymphoma subsets but, interestingly, 9% of FCL showed involvement of t(8q24) translocation. In our study, rearrangements of the BCL-6 gene at band 3q27 were found in 31% of DLBC lymphomas. Interestingly, 50% of the BCL-6 rearrangement positive lymphoma cases had coexisting gene rearrangements involving all of the aforementioned gene loci. The molecular dissection of these genes will improve our understanding of the genesis of the diverse clinicopathological subtypes.

DNA-Binding Proteins↗
PubMed1997

Deregulation of MUM1/IRF4 by chromosomal translocation in multiple myeloma.

The pathogenesis of multiple myeloma (MM), an incurable tumour causing the deregulated proliferation of terminally differentiated B cells, is unknown. Chromosomal translocations (14q1) affecting band 14q32 and unidentified partner chromosomes are common in this tumour, suggesting that they may cause the activation of novel oncogenes. By cloning the chromosomal breakpoints in an MM cell line, we show that the 14q+ translocation represents a t(6;14)x(p25;q32) and that this aberration is recurrent in MM, as it was found in two of eleven MM cell lines. The translocation juxtaposes the immunoglobulin heavy-chain (IgH) locus to MUM1 (multiple myeloma oncogene 1)/IRF4 gene, a member of the interferon regulatory factor (IRF) family known to be active in the control of B-cell proliferation and differentiation. As a result, the MUM1/IRF4 gene is overexpressed--an event that may contribute to tumorigenesis, a MUM1/IRF4 has oncogenic activity in vitro. These findings identify a novel genetic alteration associated with MM, with implications for the pathogenesis and diagnostics of this tumour.

Animals↗
PubMed1997

Circumstances of falls resulting in hip fractures among older people.

OBJECTIVES: To describe the circumstances of falls resulting in hip fractures among older people and to determine whether the circumstances differ by gender, age, and residential status. DESIGN: Cross-sectional study. SETTING: Two hospitals in Auckland, New Zealand, in which all individuals aged 60 years or older with a fracture of the proximal femur are hospitalized. PARTICIPANTS: A total of 911 individuals (97% response rate) were hospitalized with fractures of the proximal femur; 77% were women, 66% were aged 80 years or older, and 58% were living in private homes at the time of fracture. MEASUREMENTS: Data were collected face-to-face by a trained interviewer using a standardized questionnaire. RESULTS: Ninety-six percent of the fractures were associated with a fall, with fewer that 2% of subjects reporting that their fractures occurred spontaneously before a fall. Sixteen percent of fractures were associated with an acute medical or physical condition. Although 85% of the fractures involving a fall occurred at home, only about 25% of these were associated with an environmental hazard, and only a proportion of these were likely to have been amenable to modification. The circumstances of falls differed significantly by age and residential status. CONCLUSION: Strategies aimed at preventing fall-related hip fractures among the old old and among institutionalized individuals should focus primarily on the modification of intrinsic factors. Modification of environmental hazards has the greatest potential for prevention among the young old and those living in private homes.

Accidental Falls↗
PubMed1996

The t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytoid lymphoma involves the PAX-5 gene.

The t(9;14)(p13;q32) translocation is associated with approximately 50% of lymphoplasmacytoid lymphoma (LPL), a subtype of B-cell non-Hodgkin's lymphoma (NHL). We cloned the chromosomal breakpoint of der (14) from an LPL case (1052) and showed that it involved a junction between 9p13 and the switch micro region of the Ig heavy chain locus (IgH) on 14q32. Using a YAC contig spanning 1.5 megabase (Mb), we determined that the 9p13 breakpoint in one case (1052) mapped within a 270-kb restriction fragment containing two previously reported 9p breakpoints associated with a alpha-heavy chain disease case (MAL) and KI-1 positive diffuse large cell lymphoma (DLCL) cell line (KIS-1). The same fragment also contained the PAX-5 gene which encodes a B-cell specific transcription factor involved in the control of B-cell proliferation and differentiation. The breakpoints of KIS-1 and 1052 were mapped within the 5' noncoding region of PAX-5, while the 9p13 breakpoint of MAL mapped 230 to 270 kb upstream to PAX-5. In all three cases, the translocation caused the juxtaposition of the PAX-5 gene to the IgH locus in the opposite direction of transcription. When compared with six other DLCL cell lines lacking t(9;14)(p13;q32), the KIS-1 cell line showed an 11-fold overexpression of PAX-5 mRNA and a significantly reduced expression of the p53 gene, which is normally regulated by PAX-5. Moreover, metaphase and interphase fluorescence in situ hybridization (FISH) analysis using a YAC clone spanning 1 Mb including the PAX-5 as a probe identified chromosomal translocations in 5 of 7 cases carrying 9p13 translocations. These findings suggest that the PAX-5 gene is the target of the t(9;14) in LPL whereby its expression may be deregulated by juxtaposition to IgH regulatory elements, thus contributing to lymphomagenesis.

Aged↗
PubMed1996

The effect of alternative carbohydrates on the growth and antibody production of a murine hybridoma.

A murine hybridoma (CC9C10) was adapted to grow in media containing alternative carbohydrates to glucose. Cell yields relative to the glucose-based culture decreased in order of the following supplements: glucose = maltose > galactose > fructose = sorbitol = xylitol, although significant yields (> 50% of glucose control) were observed in all cultures. In the absence of glucose, glutamine consumption rates were enhanced significantly. Antibody production was directly related to the viable cell concentration in each culture and was independent of the phase of culture. A high specific antibody productivity (qMab) was observed in the cultures containing the polyols, sorbitol, or xylitol, even though the cell yields and growth rates were lower than the glucose-based control. The measured qMab in the xylitol culture was 5.6 x that of the glucose culture and the volumetric yield of MAb was 29% higher.

Animals↗
PubMed1996

The study of biology as a cause of anxiety in student nurses undertaking the common foundation programme.

The subject of biology was identified as a cause of anxiety amongst student nurses on the common foundation programme (CFP), both verbally and in each of the written course evaluations, at a college of nursing and midwifery in the South of England. The aim of this study was to identify the major causes of anxiety and identify methods of reducing this anxiety in the present students, as well as minimizing anxiety in those students commencing their nurse education. Action research was considered the most appropriate design for this study. Student nurse participation was encouraged throughout the study (n = 66). A modified Delphi technique was used to identify and prioritize the causes of anxiety and a student quality circles group was formed for the purpose of problem solving by the students. This stimulated some of the biology teachers to form biology sub-groups to consider the students' proposals. Many changes were implemented. A focus group data collection method was used to evaluate the effectiveness of the relevant changes for the present students. The meeting was recorded and the tape examined for relevant data. The data indicated that although the students perceive biology as a subject that causes anxiety they did acknowledge that many of the changes made by the teachers were a positive step towards reducing the anxiety. Although the results were encouraging, it is noted that to gain a true understanding of the effect of the changes, further evaluation would need to be completed. The use of triangulation may be considered more appropriate to enhance the quality of the data obtained.

Anxiety↗
PubMed1996

The risks of hip fracture in older people from private homes and institutions.

This study aimed to determine whether the incidence of hip fracture is greater among those living in institutions compared with those living in private homes. Over two and a half years of surveillance, 1832 hip fractures were identified, of which 58% were sustained by those living in private homes and 42% by those living in institutions. The risks of hip fracture, unadjusted for age and sex, were 10.5 times greater for those living in institutions compared with those living in private homes. After adjusting for age and sex, these greatly increased risks were maintained, although for both men and women the risks decreased with age, such that at ages over 90 years the risks were not significantly different. Given these findings, hip fracture prevention strategies that focus particularly on individuals within institutions are highly commended.

Aged↗
PubMed1995

Hip fracture incidence among older people in Auckland: a population-based study.

AIM: To determine the incidence of hip fractures among those aged 60 years or older in the Auckland region. METHODS: Demographic data were obtained on all older people hospitalised with a fracture of the femoral neck in Auckland, between 8 July 1991 and 7 February 1994. Incidence rates were calculated using the 1991 census data. RESULTS: An average incidence of 733 hip fractures or 710 individuals sustaining hip fractures each year was observed. Age-adjusted incidence rates were 571.5 per 100,000 for women and 318.2 per 100,000 for men. 97.0% of the hip fractures were sustained by those identified in the records as European, with the rates for Maori and Pacific Island populations 25-50% lower than for Europeans. Among Maori and Pacific Island populations, incidence rates were similar for men and women. Overall, 41.8% of the hip fractures were sustained by those > or = 85 years, with 67.0% sustained by those > or = 80 years. Incidence rates increased with age, with the rates continuing to increase in those > or = 85 years. CONCLUSION: Among Europeans, hip fracture incidence rates in Auckland are similar to those found for other caucasian populations. However, the rates among Maori and Pacific Island populations are among the lowest internationally and are similar for men and women. The increase in incidence rates with age continues in those > or = 85 years.

Aged↗
PubMed1995

The effect of fatty acids on hybridoma cell growth and antibody productivity in serum-free cultures.

A murine B-lymphocyte hybridoma (CC9C10) was adapted for growth in a serum-free medium. Supplementation of the medium with cis-unsaturated fatty acids (10-50 microM) improved the cell yield in the order oleic/linoleic > linoleic > oleic. Initial supplementation with the fatty acids also caused a significant increase (58%) in the volumetric Mab titre. Continued growth of the cells in the fatty acid supplemented media over five culture passages resulted in a gradual deterioration of the Mab yield concomitant with the appearance of lipid inclusions in the cytosol. The higher Mab yield could be restored by a limited period of growth of the lipid-loaded cells in fatty acid-free medium. These effects were independent of growth rate. This suggests that the optimal intracellular lipid content is finely balanced between a reduced and an overloaded state. Specific glucose and glutamine utilisation rates were unaffected by the presence of fatty acids. Also, the optimal glucose and glutamine concentrations for growth were independent of the fatty acids.

Animals↗
PubMed1995

A service evaluation of stoma care nurses' practice.

Stoma care nurses aim to meet the physical, psychological, social and spiritual needs of patients. Development of stoma care nursing services has varied, as it has been the responsibility of each nurse, resulting in differences in the mode of delivery. This qualitative and quantitative study involved stoma care nurses from six areas in Essex, to assess patient perception of the service they received. Overall, the satisfaction level was high despite differences in delivery of care especially timing and frequency of visits at home.

Adolescent↗
PubMed1995

High-performance liquid chromatographic assay of plasma thalidomide: stabilization of specimens and determination of a tentative therapeutic range for chronic graft-versus-host disease.

Thalidomide is now widely used to treat chronic graft-versus-host disease, but its use is associated with non-teratogenic side effects such as peripheral neuropathy. To examine the value of monitoring plasma concentrations of the drug in such patients, we have developed a high-performance liquid chromatographic (HPLC) assay. The method uses 0.5 mL plasma, is linear to 10 mg/L and had a detection limit of 0.2 mg/L. Thalidomide in plasma specimens was unstable at physiological pH but could be stabilized for several weeks by simple acidification. We describe a protocol for monitoring patients treated with thalidomide which permits convenient transportation and storage of specimens and report, provisionally, that plasma concentrations in the range 1-7 mg/L are therapeutically effective in chronic graft-versus-host disease without adverse side effects.

Chromatography, High Pressure Liquid↗
PubMed1995

Prospective assessment of cholesterol embolization in patients with acute myocardial infarction treated with thrombolytic vs conservative therapy.

PURPOSE: To determine whether subclinical cholesterol embolization is a frequent sequela of thrombolytic therapy. Case reports of catastrophic cholesterol embolization temporally associated with thrombolytic therapy in 19 patients have suggested a causal relationship. PATIENTS AND METHODS: We prospectively followed 60 patients with acute myocardial infarction who underwent coronary bypass surgery within 1 month. Twenty-nine received thrombolytic therapy for myocardial infarction; 31 were treated conservatively. Two muscle biopsy specimens and one skin biopsy specimen were obtained from the vein harvest site at the time of bypass surgery. Paraffin block and frozen sections from each biopsy specimen were analyzed for evidence of cholesterol embolization. RESULTS: Cholesterol emboli were found in biopsy specimens from 4 of 29 patients who had undergone thrombolytic therapy (14%) and in 3 of 31 patients who had not undergone thrombolytic therapy (10%, p = NS). Clinical evidence of cholesterol embolization occurred in one patient. Cholesterol emboli were distributed inhomogeneously; they were not observed in any skin biopsy specimen and were never present in more than one muscle biopsy specimen from each patient. CONCLUSIONS: The prevalence of cholesterol embolization in patients with acute myocardial infarction treated with thrombolytic therapy is not significantly higher than in those treated without thrombolytic therapy. The cholesterol embolization seen in 12% of our patients was mostly subclinical and was probably spontaneous and/or catheterization induced. Isolated case reports of severe cholesterol embolization temporally associated with thrombolytic therapy do not represent a phenomenon that has widespread subclinical occurrence.

Aged↗
PubMed1995

Overuse injuries in classical ballet.

Successful management of classical ballet dancers with overuse injuries requires an understanding of the art form, precise knowledge of anatomy and awareness of certain conditions. Turnout is the single most fundamental physical attribute in classical ballet and 'forcing turnout' frequently contributes to overuse injuries. Common presenting conditions arising from the foot and ankle include problems at the first metatarsophalangeal joint, second metatarsal stress fractures, flexor hallucis longus tendinitis and anterior and posterior ankle impingement syndromes. Persistent shin pain in dancers is often due to chronic compartment syndrome, stress fracture of the posteromedial or anterior tibia. Knee pain can arise from patellofemoral syndrome, patellar tendon insertional pathologies, or a combination of both. Hip and back problems are also prevalent in dancers. To speed injury recovery of dancers, it is important for the sports medicine team to cooperate fully. This permits the dancer to benefit from accurate diagnosis, technique correction where necessary, the full range of manual therapies to joint and soft tissue, appropriate strengthening programmes and maintenance of dance fitness during any time out of class with Pilates-based exercises and nutrition advice. Most overuse ballet conditions respond well to a combination of conservative therapies. Those dancers that do require surgical management still depend heavily on ballet-specific rehabilitation for a complete recovery.

Ankle Injuries↗