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Biomedical subjects

M Butler

Publications and source records attributed to M Butler.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Glutamine-based dipeptides are utilized in mammalian cell culture by extracellular hydrolysis catalyzed by a specific peptidase.

A murine hybridoma (CC9C10) was grown in media containing alanyl-glutamine (ala-gln) or glycyl-glutamine (gly-gln) as a substitute for glutamine. High cell yields were obtained in the presence of 6 mM ala-gln or 20 mM gly-gln. The final cell yield in gly-gln was 14% higher than in gln. Monoclonal antibody productivity was comparable in gln, ala-gln or gly-gln. Substrate utilisation and metabolism was affected by the presence of the dipeptides, particularly with gly-gln. The specific consumption rates of glucose and six amino acids were reduced. Also the accumulation of ammonia and lactate was significantly lower. The higher concentration of gly-gln was necessary for cell growth because of the presence of a peptidase with a lower affinity for gly-gln. The peptidase activity of the basal medium and serum was low. However, a substantial peptidase activity was found in the cytosolic fraction of the cells with an apparent Km of 1.2 mM with respect to ala-gln and 14 mM with respect to gly-gln. It is proposed that the mechanism of dipeptide utilisation involves extracellular hydrolysis by this peptidase following its release into the culture medium.

Amino Acids↗
PubMed1994

A rat brain Sec1 homologue related to Rop and UNC18 interacts with syntaxin.

Sec1 is a hydrophilic protein that plays an essential role in exocytosis from the yeast Saccharomyces cerevisiae. Two high copy suppressors of mutations in the Sec1 gene, SSO1 and SSO2, were recently identified that encode proteins of the syntaxin family. Syntaxin (a T-SNARE), together with SNAP-25 and synaptobrevin/VAMP (a T- and a V-SNARE, respectively), is thought to form the core of the docking-fusion complex in synaptic vesicle exocytosis. Proteins that exhibit similarity to Sec1 were identified in the nervous system of Drosophila melanogaster (Rop) and Caenorhabditis elegans (UNC18). Based on the amino acid sequence alignment of Sec1, Rop, and UNC18, we have used a PCR-based approach to isolate a rat brain cDNA encoding a Sec1 homologue. The cDNA hybridizes to a 3.5-kb brain-specific mRNA by Northern blot analysis and encodes a protein of 593 amino acids (rbSec1). Antibodies raised against a central portion of rbSec1 recognize a 67.5-kDa protein in total homogenates of rat brain but not of nonneuronal tissues. When incubated with a Triton X-100 brain extract, rbSec1-glutathione S-transferase (GST) fusion protein, but not GST protein alone, specifically interacts with syntaxin but not with SNAP-25 or synaptobrevin/VAMP. We conclude that the function of proteins of the Sec1 family in membrane fusion involves an interaction with a T-SNARE.

Amino Acid Sequence↗
PubMed1994

Listeria monocytogenes and severe newborn respiratory failure supported with extracorporeal membrane oxygenation.

OBJECTIVE: To determine the efficacy of extracorporeal membrane oxygenation (ECMO) in newborn infants with early-onset Listeria monocytogenes infection, necrotizing pneumonia, and severe respiratory failure. DESIGN: Patient series. SETTING: ECMO referral centers. PARTICIPANTS: The Extracorporeal Life Support Organization Registry database of patients supported with ECMO between 1975 and 1991. INTERVENTION: ECMO. MEASUREMENTS AND RESULTS: Nine neonates were identified who were supported with ECMO for severe respiratory failure associated with L monocytogenes infection. Microbiologic studies demonstrated L monocytogenes organisms in the blood of all infants, and pneumonia was diagnosed by roentgenogram and/or isolation of L monocytogenes organisms in tracheobronchial secretions. All infants experienced progressive respiratory deterioration by age 36 hours and were placed on venoarterial bypass by 96 hours, having met institution-based criteria predictive of 80% to 90% mortality. The duration of ECMO for patients with Listeria infection (median, 210 hours; range, 137 to 454 hours) was prolonged compared with the duration of ECMO for neonates in all other registry diagnostic categories (median, 114 hours; range, 1 to 744 hours; N = 5146, P = .035). Six of the nine infants recovered completely. CONCLUSIONS: These data suggest that ECMO is efficacious in patients with severe respiratory failure secondary to Listeria sepsis. Prolonged time on bypass should be expected when Listeria sepsis is associated with severe necrotizing pneumonia.

Bacteremia↗
PubMed1994

Profile of energy metabolism in a murine hybridoma: glucose and glutamine utilization.

The antibody-secreting murine hybridoma, CC9C10, was grown in batch culture in a medium containing 20 mM glucose and 2 mM glutamine. After 2 days of exponential growth, the glutamine content of the medium was completely depleted, whereas the glucose content was reduced to 60% of the original concentration. The glucose and glutamine metabolism was analyzed at midexponential phase by use of radioactively labelled substrates. Glycolysis accounted for the metabolism of most of the glucose utilized (> 96%) with flux through the pentose phosphate pathway (3.6%) and the TCA cycle (0.6%) accounting for the remainder. Glutamine was partially oxidised via glutaminolysis to alanine (55%), aspartate (3%), glutamate (4%), lactate (9%), and CO2 (22%). Calculation of the theoretical ATP production from these pathways indicated that glucose could provide 59% and glutamine 41% of the energy requirement of the cells.

Adenosine Triphosphate↗
PubMed1994

Adaptation of mammalian cells to non-ammoniagenic media.

Although glutamine is used as a major substrate for the growth of mammalian cells in culture, it suffers from some disadvantages. Glutamine is deaminated through storage or by cellular metabolism, leading to the formation of ammonia which can result in growth inhibition. Non-ammoniagenic alternatives to glutamine have been investigated in an attempt to develop strategies for obtaining improved cell yields for ammonia sensitive cell lines. Glutamate is a suitable substitute for glutamine in some culture systems. A period of adaptation to glutamate is required during which the activity of glutamine synthetase and the rate of transport of glutamate both increase. The cell yield increases when the ammonia accumulation is decreased following culture supplementation with glutamate rather than glutamine. However some cell lines fail to adapt to growth in glutamate and this may be due to a low efficiency transport system. The glutamine-based dipeptides, ala-gln and gly-gln can substitute for glutamine in cultures of antibody-secreting hybridomas. The accumulation of ammonia in these cultures is less and cell yields in dipeptide-based media may be improved compared to glutamine-based controls. In murine hybridomas, a higher concentration of gly-gln is required to obtain comparable cell growth to ala-gln or gln-based cultures. This is attributed to a requirement for dipeptide hydrolysis catalyzed by an enzyme with higher affinity for ala-gln than gly-gln.

Adaptation, Physiological↗