Biomedical subjects
B Wilkins
Publications and source records attributed to B Wilkins.
Fatal disseminated fusarium infection in acute lymphoblastic leukaemia in complete remission.
Fusarium species are increasingly recognised as serious pathogens in the immunocompromised. The outcome in the context of persistent severe neutropenia has been almost universally fatal. However, there have been several case reports of successful treatment if neutrophil recovery can be achieved. This report presents the case of a fatality that occurred despite neutrophil recovery. A 67 year old man developed disseminated fusariosis during the neutropenic phase of induction chemotherapy for acute lymphoblastic leukaemia. Fusarium dimerum was isolated from blood cultures. This species is highly unusual and very few case reports exist in the literature. An initial response to amphotericin treatment coincided with neutrophil recovery but a subsequent relapse occurred, despite adequate neutrophil counts, which proved fatal. It is postulated that reseeding of the blood from an occult site, namely the right vitreum in this case, led to this secondary relapse despite achieving complete leukaemic remission.
Hepatic stellate cells express the low affinity nerve growth factor receptor p75 and undergo apoptosis in response to nerve growth factor stimulation.
We have examined the expression of p75, a member of the TNF receptor superfamily in hepatic stellate cells (HSC) and pancreatic stellate cells (PSC). Activated HSC and PSC were demonstrated by Western blot analysis to express p75. p75 was immunolocalized to cells with a myofibroblast-like morphology in the fibrotic bands of six fibrotic and cirrhotic liver biopsies and three biopsies of fibrotic human pancreas. Immunostaining of parallel sections indicated that these cells were alpha-smooth muscle actin-positive, identifying them as activated HSC and PSC, respectively. HSC apoptosis in tissue culture in the presence of serum was quantified after addition of 0.1 to 100 ng/ml of nerve growth factor (NGF) a ligand for p75, by in situ counting of apoptotic bodies after addition of acridine orange. HSC demonstrated a significant increase in apoptosis in response to 100 ng/ml NGF (0.05 > P by Wilcoxon's rank; n = 7) after 24 hours. NGF 100 ng/ml had no effect on HSC proliferation, but reduced total HSC DNA by 19% relative to control after 24 hours (n = 3). These data demonstrate that activated HSC express p75 and respond to NGF stimulation by undergoing apoptosis. We therefore report p75 as a novel marker of activated HSC and suggest that signaling via ligand binding to p75 may provide a mechanism for selective apoptosis of HSC.
Acute myeloblastic leukaemia with differentiation to myeloblasts and mast cell blasts.
Explore the source record for details and available documents.
Metabolic response during sport rock climbing and the effects of active versus passive recovery.
The objectives of this study were to 1) continuously assess oxygen uptake during and after difficult sport rock climbing and 2) to evaluate the effects of active versus passive recovery on post-climbing blood lactate and hand grip strength. Fifteen expert rock climbers attempted to climb (i.e., red point lead) a 20 m difficult route (5.12 b, YDS scale) set on an indoor climbing wall. Subjects were assigned to either active recovery (AR; n = 8), consisting of recumbent cycling at 25 Watts, or passive recovery (PR; n = 7). Expired air was analyzed during climbing and through a 10-minute recovery period by a lightweight battery-powered open circuit system. Oxygen uptake (VO2) and heart rate (HR) were measured continuously and averaged over 20-second intervals. These data were expressed as averages over the entire climb (VO2avg and HRavg) and as peak values. An estimated resting VO2 of 250 ml x min(-1) was subtracted from the interval VO2 values to provide net VO2 data which were subsequently converted to absolute VO2 values in liters for climbing (C - VO2net) and recovery (R - VO2net). Total net VO2 was calculated as the sum of C - VO2net plus R - VO2net. Blood samples were obtained via fingerprick at pre-climb and at 1-, 10-, 20-, and 30-minutes post-climb and analyzed for whole blood lactate. Handgrip strength was measured via dynamometry at pre-climb and at 1-, 10-, 20-, and 30-minutes post-climb. Mean climbing time was 2.57 +/- 0.41 min. During climbing, VO2avg and HRavg means were 1660 +/- 340 ml x min(-1) and 148 +/- 16 b x min(-1) respectively with mean peaks of 2147 +/- 413 ml x min(-1) and 162 +/- 17 b x min(-1). Relative VO2avg was 24.7 +/- 4.3 ml x kg(-1) x min(-1) with a mean peak value of 31.9 +/- 5.3 ml x kg(-1) x min(-1). Mean values for C - VO2net and R - VO2net were 4.009 +/- 0.929 L and 2.809 +/- 0.518 L respectively for the PR group with mean total net VO2 at 6.818 +/- 1.291 L. For the AR group mean values for C - VO2net and R - VO2net were 4.216 +/- 1.174 L and 7.691 +/- 3.154 L respectively with a mean total net VO2 of 11.906 +/- 4.172 L. There was no difference between the groups for C - VO2net, however R - VO2net and total net VO2 were significantly different (p < 0.05) between PR and AR. Blood lactate increased significantly with climbing in both AR and PR groups. Lactate remained elevated in the PR group until 30 minutes post-climb, but had returned to pre-climb level by 20 minutes in the AR group. Handgrip strength was significantly decreased at 1-minute post-climb for the AR group, but was not significantly changed for the PR group. Although climbers may be able to attain a plateau in VO2, the observed accumulation of lactate in the blood combined with the elevated recovery VO2 indicate a higher overall energy demand than indicated via the recorded VO2 during climbing. Low intensity active recovery appears to significantly reduce accumulated blood lactate within 20 minutes following difficult climbing, however further research is required to establish whether this strategy is advantageous for subsequent climbing performance.
A new in vivo and in vitro B cell lymphoma model, pi-BCL1.
We report a new variant of the BCL1 syngeneic mouse B-cell lymphoma model, which we have called pi-BCL1. pi-BCL1 can be established as a syngeneic tumor in BALB/c mice. Tumors can be removed, prepared and easily grown in liquid culture and subsequently transferred back successfully as syngeneic tumors. As a syngeneic tumor pi-BCL1 behave more like a lymphoma with solid tumor masses, than a chronic lymphocytic leukaemia of the original BCL1 model. The immunophenotype and the growth characteristics of the pi-BCL1 and BCL1 tumors appear very similar. Cytologically, pi-BCL1 appears to be a transformation from a small lymphocytic lymphoma to a more diffuse large cell centroblast-like higher-grade lymphoma. We are not aware of any previous reports of such transformation events in a syngeneic animal model of B cell lymphoma. We believe pi-BCL1 provides a useful new tool for the study of B cell lymphoma in vitro and in vivo and enables reduced numbers of tumor passage in mice.
Formic acid decalcification of bone marrow trephines degrades DNA: alternative use of EDTA allows the amplification and sequencing of relatively long PCR products.
Explore the source record for details and available documents.
The effect of wind speed and direction on the distribution of sewage-associated bacteria.
A study of the relationship between wind and the distribution of sewage-associated bacteria was undertaken at a location where the sewage was discharged into the sea adjacent to the mouth of a river. The numbers of presumptive Escherichia coli were determined in 149 sea-water samples taken from three locations at distances of 1.9, 2.4 and 4.3 km from the outfall. On each sampling occasion, data on the wind speed and direction in the 3 h prior to collection of the samples were also collected. Analysis of these data demonstrated a significant role for wind speed and direction. With respect to wind direction, the numbers of presumptive E. coli present in a sample were significantly higher when the sample site lay downwind of the outfall. Wind speed was shown to have an influence on the numbers of presumptive E. coli only when the sample site was downwind of the outfall. In an analysis of 61 samples, an inverse correlation (r2 = 0.73) between salinity and log presumptive E. coli numbers was demonstrated. These data demonstrate that wind speed and direction at the time of sampling significantly influence the numbers of presumptive E. coli detected in any sea-water sample. It is argued that failure to pay sufficient attention to these parameters in the design of monitoring programmes may result in the generation of data that could provide a seriously distorted picture of the microbiological status of a water body.
Metabolic and cardiovascular responses during work on a high ropes course.
BACKGROUND: High ropes course facilities are employed in adventure programs to promote self-esteem, stress management, and problem-solving skill development. Although the combination of fear, anxiety, and potentially high levels of physical exertion during such activity could yield situations of cardiac risk for certain individuals, no previous research has described the physiological nature of high ropes course work. The purpose of this study was to observe the metabolic and cardiovascular responses to a typical high ropes course experience. METHODS: Seventeen subjects gave informed consent to complete a 5-element sequence on an indoor high ropes course. The elements included step-swings (SS), swinging tires (ST), a 4-inch balance beam (B1), a vertical cargo net (CN), and a second beam (B2). These elements were positioned in series at a height of 20 feet above the floor. Expired air was analyzed continuously using a portable open circuit metabolic analyzer and heart rate (HR) was recorded at 5-second intervals via telemetry. Pre- and postcourse blood samples were obtained via finger-prick and analyzed for lactate (BL). Systolic (SBP) and diastolic (DBP) blood pressures were taken at an orientation session prior to each subject's test date and at pre-, mid-, and post course points during each test session. RESULTS: The mean ropes course work time was 11.2 +/- 2.9 min. Mean averaged/peak oxygen uptake (VO2), ventilation (VE), HR, and energy expenditure (EE) were 13.9 +/- 2.3/21.6 +/- 3.7 ml.kg-1.min-1, 36.4 +/- 8.1/49.6 +/- 10.3 l.min-1, 142 +/- 16/167 +/- 15 b.min-1, and 5.1 +/- 0.9/7.7 +/- 1.0 kcal.min-1 respectively. In descending order, mean EE was 6.2 +/- 1.1, 6.2 +/- 0.8, 5.4 +/- 1.0, 4.5 +/- 0.5, and 4.2 +/- 0.5 kcal +/- min-1 for the B2, ST, CN, B1, and SS elements respectively. Blood lactate increased (p < 0.05) from a pre course value of 1.9 +/- 0.6 mmol.l-1 to 5.0 +/- 1.1 mmol.l-1 post course. SBP values at pre- (136.7 +/- 16.0), mid-(169.8 +/- 19.7), and postcourse (154.1 +/- 19.2) were higher (p < 0.05) than the orientation SBP of 126.2 +/- 14.7 mmHg. Mid- and post course SBP means were significantly higher than the precourse mean. A significant difference was found for DBP between the midcourse (86.3 +/- 8.9) vs the orientation mean (79.1 +/- 6.8) only. CONCLUSIONS: Based upon the results of this study, average high ropes course work can be classified as aerobically moderate to heavy, at just over 4 METs with peak periods over 7 METs. Transient elevation in DBP may occur during elements with a high level of upper body work. High ropes course work does not present an unusually high physiological stress for healthy, physically fit individuals.
Radiological appearances of lymphomas arising from mucosa-associated lymphoid tissue (MALT) in the lung.
We review the radiological findings in 13 patients with histologically proven (n = 10) or clinically diagnosed (n = 3) lymphomas arising in mucosa-associated lymphoid tissue (MALT) of the lung. These rare B-cell lymphomas typically follow an indolent course, and many cases are still being incorrectly described in current radiological literature under the term pseudolymphoma. The patients frequently give a history of autoimmune disease involving the affected organ, and involvement of another mucosal site as part of a disseminated MALT lymphoma, is common. The radiographic patterns of pulmonary parenchymal involvement in lung MALT lymphomas have been reviewed, and correlation made with their clinical behaviour.
Hemorrhagic shock and encephalopathy syndrome. An unusual cause of sudden death in children.
Hemorrhagic shock and encephalopathy syndrome (HSES) is a sudden-onset symptom complex occurring in previously healthy infants and children. It was first described in 1983 in the United Kingdom in 10 infants. Subsequently, > 140 cases have been reported worldwide, although no cases have been previously reported in the forensic literature. Typically the child presents with fever, shock, encephalopathy with coma and seizures, evidence of hemorrhage, and diarrhea. Laboratory investigation reveals falling hemoglobin and platelet counts, renal impairment, evidence of disseminated intravascular coagulation, metabolic acidosis, and raised serum transaminases. Microbiological cultures are uniformly negative. The condition has a high mortality and morbidity. The etiology is unknown and may be multifactorial. However, hyperpyrexia appears to play a central role in pathogenesis. The diagnosis of HSES in the deceased child is one of exclusion and requires a careful antemortem history as well as a thorough autopsy with toxicological and microbiological investigations. A case of HSES is reported and the literature reviewed.
Head injury--abuse or accident?
Explore the source record for details and available documents.
Cerebral oedema after MDMA ("ecstasy") and unrestricted water intake. Hyponatraemia must be treated with low water input.
Explore the source record for details and available documents.
Evaluating zona pellucida structure and function using antibodies to rabbit 55 kDa ZP protein expressed in baculovirus expression system.
A cDNA encoding the rabbit 55 kDa ZP protein was expressed using a baculovirus expression system and was evaluated for its ability to elicit antibodies which may interfere with sperm-ZP interaction. The expressed glycosylated protein, BV55, was purified by wheat germ agglutinin lectin affinity chromatography. Antisera made in guinea pigs immunized with BV55 (GP-alpha-BV55) is specific for the 55 kDa rabbit ZP protein. Indirect immunofluorescence studies indicate that GP-alpha-BV55 localizes to a filamentous meshwork on the surface of the ZP of isolated rabbit eggs. Immunohistochemical analysis of rabbit ovaries demonstrated that this antigen is localized within the ZP of primary and more advanced stage ovarian follicles but is not detected in primordial follicles. In addition, the 55 kDa antigen was detected in the granulosa cells of secondary stage follicles but not in the oocyte. GP-alpha-BV55 effectively blocked the binding of rabbit sperm to rabbit eggs in vitro. However, Fab fragments generated from GP-alpha-BV55 failed to block sperm binding, suggesting that the inhibitory effect of GP-alpha-BV55 was due to stearic hindrance rather than specific blocking of a sperm receptor site. Although the Fab fragment did not inhibit sperm binding, additional studies demonstrated that biotinylated BV55 protein bound to rabbit sperm in the acrosomal region in a manner consistent with ligand activity in the sperm-ZP interaction, and that BV55 bound to rabbit sperm in a dose-dependent manner. These studies therefore demonstrate that antibodies against recombinant ZP proteins recognize the native intact ZP and inhibit sperm-ZP interaction. They also provide evidence that the rabbit 55 kDa ZP protein, which is the homolog of the pig ZP3 alpha sperm receptor protein, has sperm receptor activity.
Misleading Haemophilus influenzae type B antigenuria following immunization.
Explore the source record for details and available documents.
Molecular biology approaches to evaluate species variation in immunogenicity and antigenicity of zona pellucida proteins.
Immunocontraception using the glycoproteins of the mammalian zona pellucida (ZP) has held great promise because antibodies specific to ZP antigens would inhibit fertility and not be abortive. It has been shown, however, that some ZP proteins will elicit adverse effects since immunization may affect ovarian follicular development. These effects vary among different mammalian species as well as on the source of the ZP immunogen. Therefore, the use of molecular biology has been essential in identifying specific ZP protein(s) that inhibit fertility without altering ovarian follicular development and in defining the relationships of ZP proteins among different species. Use of recombinant ZP proteins has allowed us to begin to dissect antigenic domains of ZP proteins and to evaluate their potential roles in the fertilization process. Recent studies using recombinant rabbit ZP proteins to immunize cynomolgus monkeys (Macaca fascicularis) have shown that the 55 kDa ZP protein will elicit antibodies that inhibit sperm binding while not altering ovarian function, in contrast to immunization with a recombinant truncated protein of the 75 kDa ZP protein which causes ovarian dysgenesis. The rabbit 55 kDa protein is the homologue of the pig ZP3 alpha sperm receptor and the human ZPB protein but is distinct from the mouse ZP3 sperm receptor. Expression of this protein using the baculovirus expression system has further shown that the 55 kDa protein binds to capacitated rabbit spermatozoa over the acrosomal region and induces the acrosome reaction. Antibodies against this recombinant form of the ZP also inhibit rabbit spermatozoa from binding to rabbit egg in vitro. These studies demonstrate the need to determine the structure and function of ZP proteins of different mammalian species to evaluate their potential for contraceptive vaccines.
Effectiveness of HB2 (anti-CD7)--saporin immunotoxin in an in vivo model of human T-cell leukaemia developed in severe combined immunodeficient mice.
The transplantation of the human T-cell acute lymphoblastic leukaemia (T-ALL) cell line HSB-2 into severe combined immunodeficient (SCID) mice was found to produce a disseminated pattern of leukaemia similar to that seen in man. The intravenous injection of 10(7) HSB-2 cells was associated with a universally fatal leukaemia. Histopathological examination of animals revealed the spread of leukaemia initially from bone marrow to involve all major organs including the meninges. An immunotoxin (HB2-Sap) was constructed by conjugating the anti-CD7 MAb HB2 to the ribosome-inactivating protein saporin. An in vitro protein synthesis inhibition assay revealed specific delivery of HB2-Sap immunotoxin (IT) to CD7+ HSB-2 target cells with an IC50 of 4.5 pM. When SCID mice were injected with 10(6) HSB-2 cells and then treated 8 days later with a single intravenous dose of 10 micrograms of immunotoxin there was a significant therapeutic effect evidenced by the numbers of animals surviving in the therapy group compared with untreated controls (chi 2 = 5.348, P = 0.021). These results demonstrate the useful application of human leukaemia xenografts in SCID mice and the potential therapeutic effect of an anti-CD7 immunotoxin in human T-ALL.
The mammalian zona pellucida: its biochemistry, immunochemistry, molecular biology, and developmental expression.
Many studies of the molecular and biochemical aspects of mammalian fertilization have focused on the interaction of the spermatozoa with the zona pellucida (ZP). The zona pellucida, a unique extracellular matrix surrounding the mammalian oocyte, is formed during ovarian follicular development. Following ovulation of the mature ovum, the spermatozoa must bind to and penetrate this matrix before the fertilization process is completed and the male and female genetic information combine. Although numerous models for this interaction have been proposed, the complete process has yet to be elucidated. The precise mechanisms by which these interactions occur also vary markedly among different mammalian species, making it more difficult to establish a unified model. To a great extent, the study of the molecules involved in these interactions have been limited because small numbers of female gametes are available for these studies. The recent development of techniques to isolate large numbers of zonae pellucidae as well as advances in immunological and molecular biology techniques have permitted the detailed characterization of ZP proteins. Although there is a paucity of information on the post-translational modification and extracellular processing of these molecules which result in matrix formation, a number of properties have been elucidated allowing better correlation between the structure and function of different ZP proteins among species. This review reflects these studies in relation to protein nomenclature and the molecular complexity of ZP antigens.