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Biomedical subjects

M Burke

Publications and source records attributed to M Burke.

At least 91 records · Page 5Linked to original sources
PubMed1997

Primary biliary cirrhosis associated with antiphospholipid syndrome.

A 47-year-old female was admitted for severe pain of 1 month's duration in the third and fourth toes of the right foot, culminating in gangrene. Laboratory findings revealed liver enzyme abnormalities, and anti-mitochondrial, anti-phospholipid and antinuclear and doubtful anti-DNA antibodies. Systemic lupus erythematosus (SLE) was excluded on clinical grounds after a 6-year follow-up. Therefore, a diagnosis was made of the primary antiphospholipid syndrome, complicated by microvasculopathy, and associated with primary biliary cirrhosis.

Antiphospholipid Syndrome↗
PubMed1996

Chemomechanical transduction in the actomyosin molecular motor by 2',3'-dideoxydidehydro-ATP and characterization of its interaction with myosin subfragment 1 in the presence and absence of actin.

The effect of torsional freedom about the N-glycoside bond of ATP in the ability of the nucleoside triphosphate to support chemomechanical transduction (Takenaka et al., 1978) has been investigated by examining the ability of the nucleotide analogue 2',3'-dideoxy-2',3'-didehydro-ATP (1b, enf-ATP) to act as a substrate for myosin subfragment 1 in the presence and absence of actin and to support actin sliding in the standard in vitro motility assay. By converting the ribosyl ring of the natural substrate to the rigid and almost planar enofuranosyl ring, effects on torsional freedom about the N-glycoside bond due to changes in ribosyl ring pucker and/or by steric interferences of the protons attached to the 2' and 3' carbons are eliminated allowing for increased torsional freedom about the N-glycoside bond. The data indicate that this enofuranosyl analogue is an excellent substrate for subfragment 1 and actosubfragment 1 and produces actin sliding velocities which are twice as fast as those observed with ATP in the standard in vitro motility assay. The analogue diphosphate is trapped in S1 by the common P(i) analogues, but the rate of formation of the ternary complex formed with Vi is very slow compared to that observed with MgADP. Similar conformations of S1 are formed with Mg.enf-ATP and MgATP under steady-state conditions, but S1 with bound Mg.enf-ADP differs significantly from that observed with MgADP.

Actins↗
PubMed1996

Prognostic significance of BCL-2 expression and bcl-2 major breakpoint region rearrangement in diffuse large cell non-Hodgkin's lymphoma: a British National Lymphoma Investigation Study.

The Bcl-2 protein is capable of preventing apoptosis, and in vitro evidence suggests a role in drug resistance. It is expressed and the gene is rearranged in a proportion of cases of large-cell non-Hodgkin's lymphoma (NHL), but the clinical significance of these findings is controversial. The purpose of this study was to determine the influence of both Bcl-2 expression and major breakpoint region (MBR) bcl-2 rearrangement in a large cohort of prospectively accrued patients with intermediate-grade B-cell NHL treated in a standardized manner. All patients with Working Formulation F, G, or H NHL treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy in British National Lymphoma investigation studies between July 1974 and April 1992 were considered for this study if the appropriate paraffin blocks were available. Paraffin sections from the diagnostic specimen were analyzed for evidence of MBR rearrangement using a polymerase chain reaction-based method, and for Bcl-2 expression using immunohistochemistry. Failure to achieve complete remission (CR), relapse, death from NHL, and deaths from all causes were used as end points to measure CR rate, actuarial relapse rate, actuarial survival from NHL, and actuarial overall survival. One hundred sixty-one suitable patients were identified and tested for the bcl-2 MBR translocation, with 27 (17%) found to be positive; 153 of these patients were tested with immunocytochemistry, and 84 (55%) showed evidence of Bcl-2 expression. For patients who achieved CR from the initial treatment, the relapse rate was significantly higher in those with Bcl-2 expression than in those without. In addition, multivariate analysis identified Bcl-2 expression as the only factor significantly related to relapse rate in the subjects measured. The cause-specific survival for NHL in the series as a whole was significantly lower in patients with Bcl-2 expression than in those without. MBR status had no significant influence on any of the outcome measures, but the number of MBR-positive patients was relatively small, and larger studies are required. In conclusion, in Working Formulation F, G, and H NHL of B-cell type, expression of Bcl-2 protein predicted independently for relapse.

Adult↗
PubMed1996

Identification of myosin III as a protein kinase.

Drosophila ninaC gene encodes myosin homologous proteins which are classified as myosin III of the myosin superfamily, yet the physiological and biochemical function of myosin III has not characterized. We report here that myosin III does exhibit protein kinase activity. The kinase homologous domain (MYOIIIPK) of myosin III was expressed in the baculovirus expression system and purified to homogeneity. MYOIIIPK phosphorylated a number of proteins including myosin III p132 and smooth muscle myosin regulatory light chain (LC20), suggesting that myosin III is a multifunctional protein kinase. The phosphoamino acid analysis revealed that myosin III is a serine/threonine kinase but not a tyrosine kinase. The observation that MYOIIIPK phosphorylates myosin III suggests that the autophosphorylation might play a role for the regulation of myosin III function. This is the first direct demonstration of kinase activity for the myosin III class.

Adenosine Triphosphate↗
PubMed1996

Myosin subfragment 1 hydrophobicity changes associated with different nucleotide-induced conformations.

Myosin subfragment 1 hydrophobicity was found to be sensitive to the occupancy and nature of bound nucleotide at its active site, as shown by changes in elution behavior of unmodified and chemically modified S1 during phenyl hydrophobic chromatography. The elution properties of S1 were unaltered by alkylation of SH1 (Cys-707) with N-ethylmaleimide or by covalent bridging between SH1 and SH2 (Cys-697) with p-phenylenedimaleimide with trapping of MgADP. Although addition of MgADP or MgATP to the elution buffers had minimal effect on the elution properties of these modified S1 species, the presence of these nucleotides was found to produce differential effects with unmodified S1. With MgADP, where S1 is in the S1** MgADP state, the elution times were decreased slightly, whereas with MgATP, where S1 is primarily in the S1** MgADP.Pi state, the elution times were significantly lowered, indicating reduced accessibility for the immobilized phenyl ligand. Stable S1 ternary complexes, formed with MgADP and various Pi analogues, showed elution times similar to that for S1 in the buffers containing MgATP. Thus, two main classes of nucleotide-induced S1 conformations can be defined according to their interaction with immobilized phenyl. These nucleotide-induced changes in S1 hydrophobicity correlate well with reported changes in radius of gyration of S1 associated with different states of the bound nucleotide [Wakabayashi, K., Tokunga, M., Kohno, I., Sugimoto, Y.; Hamanaka, T., Takezawa, Y., Wakabayashi, T., & Amemiya, Y. (1992) Science 258, 443-447], suggesting that the observed hydrophobicity interaction may be measuring accessibility of the immobilized phenyl ligand into a hydrophobic crevice, and that this crevice is closed or tightened when S1 is in the S1** MgADP.Pi state.

Adenosine Diphosphate↗
PubMed1996

High-dose intravenous magnesium attenuates complement consumption after acute myocardial infarction treated by streptokinase.

OBJECTIVE: This study was designed to detect changes in complement levels following acute myocardial infarction and to test whether magnesium sulphate (MgSO4) administration interferes with the complement response that follows acute myocardial infarction. DESIGN: Twenty-nine patients with acute myocardial infarction treated with streptokinase were included and randomly assigned to three treatment groups. In groups A and B, a bolus of 1 g MgSO4 was infused intravenously followed by 4 g (group A) and 14 g (group B) MgSO4 for 24 h while normal saline was administered in group C (control). Blood samples for C3, C4 and CH-100 were obtained at baseline and repeatedly during the 48 h following the initiation of magnesium infusion. RESULTS: In groups A and C, a remarkable decrease in the levels of C3, C4 and CH-100 was observed when measured 1 h after the end of streptokinase infusion and thereafter for the ensuing 48 h compared to baseline values (P < 0.05). In group B, the decrease in these complement elements was attenuated, and a significant (P < 0.05) delayed decrease of C3 and C4 was observed only at 24 h and later up to 48 h. The mean level of CH-100 in group B was significantly depressed compared to baseline from 3 h and thereafter up to 48 h. Mean C3 values plotted against observation time differed between the three groups (P = 0.021). A similar trend was observed for C4 (P = 0.133) but not for CH-100 (P = 0.46). CONCLUSION: (1) Complement elements are being consumed following acute myocardial infarction treated by streptokinase. (2) High-dose intravenous magnesium attenuates the complement process following acute myocardial infarction. (3) These results might signify that magnesium modulates the inflammatory response that follows infarction.

Adult↗
PubMed1996

Organ-specific autoantibodies are possible markers for reproductive failure: a prospective study in an in-vitro fertilization-embryo transfer programme.

This study was conducted to investigate the usefulness of organ-specific autoantibodies as possible markers for reproductive failure. Antithyroid and antiovarian autoantibody concentrations were measured in 78 patients with mechanical or unexplained infertility that were enrolled in an in-vitro fertilization (IVF)/embryo transfer programme with follow-up of the outcome. In all, 16 patients (20.5%) were positive for antithyroid antibodies, nine (11.5%) were positive for antiovarian autoantibodies and two (2.6%) were positive for both autoantibodies. All 23 patients who were positive for either antithyroid or antiovarian autoantibodies, or both, were defined as the study group, and 55 who were negative for autoantibodies were considered as the control group. No statistical difference in the incidence of autoantibodies was found between the patients with mechanical infertility and those with unexplained infertility. No differences were found in the mean number of oocytes retrieved, fertilization rates or mean numbers of transferred embryos between the study and the control groups. The pregnancy rate per cycle was 10.8% (7/65) in the study group, compared with 25.0% (24/96) in the control group (P < 0.05). We conclude that organ-specific autoantibodies such as antithyroid and antiovarian antibodies may serve as possible markers for reproductive failure. Further investigation is required to understand the possible immunopathological mechanism for reproduction failure in patients with organ-specific autoantibodies.

Adult↗
PubMed1995

Reduction of cellular rejection and increase in longer-term survival after heart transplantation after HLA-DR matching.

HLA matching in cardiac transplants is perceived as being logistically difficult. We studied 1135 consecutive primary cardiac allografts between 1980 and 1994 to assess the effect of HLA mismatching on long-term graft survival and cellular rejection episodes within 3 months of transplantation. We found a significant association between HLA-DR mismatching and the number of episodes of rejection (no mismatch 0.80 [SE 0.13], one mismatch 1.22 [0.06], two mismatches 1.42 [0.06], p < 0.05). We found a similar correlation between the total number of biopsy specimens showing evidence of cellular rejection and HLA-DR mismatch. The time between operation and the first rejection episode shortened with increasing HLA-DR mismatch (no mismatch 85.5 [37.3] days, one mismatch 43.1 [8.1], two mismatches 24.1 [2.9], p < 0.05). Furthermore, the proportion of patients with no evidence of rejection correlated with HLA-DR incompatibility. A significant association between improved graft survival and HLA-DR mismatching was found over 1, 5, and 10 years after transplantation (no mismatch 1 year 92%, 5 years 83%, 10 years 76%, one mismatch 1 year 81%, 5 years 73%, 10 years 59%, and two mismatches 78% 1 year, 5 years 70%, and 10 years 52%, p = 0.02). Increased efforts to prospectively HLA match patients has resulted in 25% of patients transplanted between January and May 1995 (n = 13/52) receiving grafts matched for HLA-DR. HLA matching reduces the frequency and severity of acute cardiac allograft rejection and improves graft survival for up to 10 years. Our preliminary results suggest that it is possible to use HLA matching prospectively for our selection of recipients.

Actuarial Analysis↗
PubMed1995

Structural basis for actomyosin chemomechanical transduction by non-nucleoside triphosphate analogues.

Methylation of 2-[(2,4-dinitrophenyl)amino]ethyl triphosphate (dNOTP) was found to abolish its ability to support actin sliding in the in vitro motility assay. A comparative study of the interaction of myosin subfragment 1 (S1) and actoS1 with methylated (MdNOTP) and non-methylated dNOTP was undertaken. Both analogues were shown to be substrates for S1 NTPase in the presence of K+/EDTA, Ca2+, or Mg2+, although their rates of hydrolysis in the presence of the divalent cations were significantly greater than that occurring for ATP. However, actin had only a marginal effect on the rate of hydrolysis of MdNOTP, in sharp contrast to its effect on the hydrolysis of dNOTP and ATP which were quite similar. Moreover, while dNODP is able to form stable ternary S1 complexes with orthovanadate (Vi) or berylium fluoride (BeFx), whose formation results in increased thermal stability of S1, the methylated diphosphate analogue was unable to do so. These differences can be related to methylation-induced changes in the conformation of dNOTP indicated by molecular-modeling approaches. These studies suggest that methylation prevents the specific interaction of the aryl ring of dNOTP with S1 in the adenine binding region necessary for the formation of the force-producing intermediate (M. D. P*) during the S1 Mg(2+)-NTPase cycle.

Acid Anhydride Hydrolases↗
PubMed1995

Formation of stable inhibitory complexes of myosin subfragment 1 using fluoroscandium anions.

Evidence is presented that MgADP can be noncovalently trapped in myosin subfragment 1 in the presence of ScFx resulting in the concomitant loss of ATPase function. The rate of inactivation in the presence of MgCl2 at 25 degrees C is 8.7 M-1 s-1 which is too slow for a simple collisional mechanism and suggests that a subsequent slow isomerization step is responsible for formation of a stable tenary complex, S1.MgADP.ScFx in a manner analogous to that proposed for the Vi stabilized complex by Goodno (Goodno, C. C. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 2620-2624). It is also found that ADP can be trapped in subfragment 1 in the absence of MgCl2 indicating the formation of an S1.ADP.ScFx complex. The stability of these complexes at 4 degrees C was studied by following the loss of trapped [14C]ADP with a chase with ADP. The rate of nucleotide loss at 4 degrees C was biphasic for both complexes suggesting that the inhibitory complexes exist in two distinct states as previously proposed for the ternary complex stabilized by Vi (Mihashi, K., Ooi, A., and Hiratsuka, T. (1990) J. Biochem. (Tokyo) 107, 464-469). Formation of these complexes resulted in a marked enhancement of the intrinsic tryptophyl fluorescence suggesting that conformationally they may resemble the steady-state intermediate formed with MgATP. The failure to observe photolysis in the presence of excess Vi at sites associated with the ATP consensus sequence suggests that in these complexes ScFx occupies the site responsible for these cleavage reactions and that it is not displaced by the added Vi.

Actins↗
PubMed1995

The polymerase chain reaction in the demonstration of monoclonality in T cell lymphomas.

AIMS: To evaluate polymerase chain reaction (PCR) amplification of T cell receptor (TCR) beta and gamma chain genes as a means of demonstrating monoclonality in T cell lymphomas using histological samples; to compare the performance of PCR with Southern blot analysis. METHODS: TCR-beta, TCR-gamma and immunoglobulin heavy chain (IGH) genes were analysed using PCR in 55 cases of T cell lymphoma (28 frozen tissue and 27 paraffin wax embedded samples), diagnosed using morphological and immunohistochemical criteria. The 28 frozen samples were subjected to Southern blot analysis using TCR-beta, TCR-gamma and IGH gene probes. Twenty five B cell lymphomas and 21 non-neoplastic lymphoid tissue samples were used as controls. RESULTS: Using TCR-beta PCR, monoclonality was detected in 24 (44%) of 55 T cell lymphomas compared with 43 (78%) of 55 using TCR-gamma PCR and in 82% with both techniques. Five (9%) of 55 T cell lymphomas were IGH PCR positive. None of the non-neoplastic lymphoid control samples were PCR positive. All B cell lymphomas showed a polyclonal pattern with TCR-beta PCR while a single B cell lymphoma was positive using TCR-gamma primers. With TCR-beta PCR, a monoclonal result was seen in 12 (43%) of 28 frozen samples of T cell lymphoma, compared with 23 (82%) of 28 using Southern blot analysis. With TCR-gamma PCR, 19 (68%) of 28 frozen tissue samples were positive, compared with 26 (93%) of 28 using Southern blot analysis. A single case showed IGH rearrangement by Southern blot analysis. CONCLUSION: TCR-gamma PCR should be the method of choice for analysis of clonality in paraffin wax embedded sections of lymphoproliferative lesions, as TCR-beta PCR has a high false negative rate. Southern blot analysis remains the most successful technique when sufficient fresh tissue samples and resources are available.

Base Sequence↗
PubMed1995

Antipsychotic drug-induced dysphoria.

BACKGROUND: Dysphoric reactions to antipsychotic medication are well recognised in association with akathisia, but can also occur independently. METHOD: Fifty-one healthy volunteers were given haloperidol 5 mg in two consecutive pharmacokinetic studies. RESULTS: Dysphoria occurred in about 40% of the subjects on both occasions, but akathisia was only detected in 8% (first study) and 16% (second study). All adverse effects were transient and were abolished in nine of the ten subjects given procyclidine. CONCLUSIONS: While dysphoria is a well-recognized reaction in healthy volunteers, it is probably insufficiently recognised in patients, particularly if it occurs in the absence of akathisia. Better detection could improve compliance in patients.

Adult↗
PubMed1995

Doppler sonography of the inferior mesenteric artery: a preliminary study.

The purposes of this study were to look for the inferior mesenteric artery in patients undergoing abdominal sonography, to determine in what percentage of patients it is visible, and to characterize Doppler flow patterns of the inferior mesenteric artery in fasting patients without intestinal vascular disease. The inferior mesenteric artery was sought in 100 consecutive fasting adults (mean age, 54 years; 63 women, 37 men), as follows: the infrarenal aorta was scanned in a transverse plane; the origin of the inferior mesenteric artery was identified on the left anterolateral surface of the aorta; the inferior mesenteric artery was then traced caudally along the left side of the aorta. The inferior mesenteric artery and the superior mesenteric artery were studied with Doppler sonography in 50 different subjects without clinical or Doppler sonographic evidence of abdominal vascular disease (mean age, 44.9 years; 17 men, 33 women). Pulsed Doppler samples were taken within the inferior mesenteric artery in sagittal planes. The resistive index was calculated from the superior mesenteric artery and the inferior mesenteric artery. The inferior mesenteric artery was detected in all but eight patients (92%). In seven patients obesity prevented visualization. The eighth patient had undergone abdominal surgery on the previous day, limiting the sonographic examination. The diastolic flow in the inferior mesenteric artery was less than that in the superior mesenteric artery in all patients. The resistive index was 0.959 +/- 0.045 in the inferior mesenteric artery and 0.856 +/- 0.046 in the superior mesenteric artery (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗