Biomedical subjects
B Paul
Publications and source records attributed to B Paul.
Familial myelodysplasia: progressive disease associated with emergency of monosomy 7.
Two brothers developed hypoplastic anaemia with the development in one of refractory anaemia with excess blasts (RAEB) accompanied by emergence of monosomy 7. Both brothers have a constitutional inversion of chromosome 1. Neither shows the increased chromosomal fragility of Fanconi's anaemia or its variants. This family is the third reported in which monosomy 7 has been found when leukaemic or preleukaemic transformation has occurred in patients with familial hypoplastic anaemia.
Factor II, VII, IX and X concentrations in patients receiving long term warfarin.
Using standard one stage clotting assays the concentrations of factors II, VII, IX and X were determined in 37 patients stabilised on warfarin for between three months and 17 years. Contrary to popular belief, the concentrations were not equally depressed, with factor X the lowest, factor II at intermediate value, factors VII and IX the highest. Some 71% of the variance of the British corrected ratio (BCR) could be accounted for by measurement of the factors assayed. Analysis of this variance showed 91% of the explained variance attributable to factor II, 7% to factor VII, 1.6% to factor IX and 0.4% to factor X. With the sudden and recent withdrawal of human thromboplastin, investigation of the sensitivities of the animal thromboplastins to changes in vitamin K dependent factors in orally anticoagulated patients is needed to ensure that the potentially alarming falls in factors II and X in these patients are being adequately detected.
Effect of bacterial growth on the bursting pressure of fetal membranes in vitro.
By mounting a layer of chorioamniotic membrane on a specially designed reaction vessel, we studied the effect of Escherichia coli and/or group B streptococcus growing on the decidual surface of the membranes in tissue culture or bacteriologic medium. The organisms grew equally well in either medium. When growing in tissue culture medium, either organism significantly weakened the membranes as compared with controls (membranes incubated in the absence of either organism). Membranes derived from pregnancies delivered vaginally or abdominally responded similarly. When organisms were grown in bacteriologic medium, bursting pressures did not decrease. Addition of bacteriologic medium (20-60%) to tissue culture medium did not affect bacterial growth, but inhibited significantly the lowering of bursting pressures. Bacteriologic medium also inhibited the peroxidase-H2O2-halide system in vitro. Heat-killed bacteria and/or supernatants of culture medium previously inoculated with bacteria were not effective in weakening membranes. The results suggest that live bacteria in conjunction with active membrane metabolism lead to a weakening and eventual rupture of the membranes.
Suicide due to caustic soda--a case report with some unusual complications.
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[Effects of a single intra-articular injection of antibiotics on cartilage structure in rabbits].
Nebacetin, chloramphenicol, penicillin, and isotonic sodium chloride solution were injected once into 80 knee- and elbow-joints of rabbits. The histologic investigation of the hyaline cartilage after 2 respectively 5 months did not show any kind of lesions. The results of other authors in similar investigations and the indication for intra-articular application of antibiotics are discussed.
Aplastic anaemia in Zimbabweans.
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Functional and structural changes in m. vastus lateralis and m. vastus medialis in cases of meniscopathy and chondropathia patellae.
The skeletal muscle undergoes selective cellular changes in the sense of the myopathic and neurogeneous tissue syndrome, in the case of degenerative joint diseases. The occurring FT-fibre atrophy is coupled with a decrease of the glycolytic activity and of the LDH isoenzyme pattern. A neurogeneous component is under discussion.
[Analysis of the reasons for repeat arthrotomy of the knee joint].
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Acute lymphoblastic leukaemia in adults in the northern region of England--a study of 75 cases.
Over a ten-year period we have studied 75 cases of adult acute lymphoblastic leukaemia (ALL). Sixty of the cases were seen from 1979 to 1984 and represent an unselected series of all known cases in a region of 3 000 000 people. Study of these patients has given further insight into the heterogeneous, clinical and cytological nature of adult ALL. Three protocols have been used and results are presented indicating that conventional approaches to treatment in this disease are unsatisfactory. Not all patients could be entered on protocols but these patients are included to give the overall perspective of this disease in clinical practice. A new strategy is proposed which envisages abandoning traditional maintenance chemotherapy in favour of either allogeneic marrow transplant or autologous transplant in first remission in the post-consolidation phase. Preliminary results of this flexible approach are given.
Effect of pretreatment with alpha-difluoromethylornithine on the selectivity of methylglyoxal bis(guanylhydrazone) for tumor tissue in L1210 leukemic mice.
A number of studies have demonstrated that pretreatment of tumor-bearing animals with the inhibitor of polyamine biosynthesis, alpha-difluoromethylornithine (DFMO), potentiates the antitumor activity of methylglyoxal bis(guanylhydrazone) (MGBG). The present study examines whether this phenomenon is related to a DFMO-mediated increase in the selectivity of MGBG for tumor tissue. Specifically, the effect of DFMO pretreatment on the tissue distribution and content of MGBG was investigated in mice bearing ascites L1210 leukemia. At 3 and 18 h following a single i.v. injection of [14C]MGBG (50 mg/kg), L1210 cells and seven tissues from nonpretreated (control) and DFMO-pretreated (3% by drinking water for 3 days) animals were compared for their [14C]MGBG content. In control mice, the greatest amount of drug was found in L1210 cells, small intestine, and kidney (in decreasing order of magnitude) at both 3 and 18 h. This distribution was not altered following DFMO pretreatment, but the relative MGBG content of other tissues was shifted. On an average, DFMO pretreatment increased the accumulation of MGBG by 30% in normal tissues and 32% in tumor tissues at 3 h and 56% and 69%, respectively, at 18 h. Thus, pretreatment of leukemic mice with DFMO fails to improve the selectivity of MGBG for L1210 cells. It is possible that other tumor systems might demonstrate sufficient DFMO-mediated increases in MGBG uptake to enhance drug selectivity but not without significantly increasing MGBG uptake (and hence toxicity) in normal tissues.
Correlation of amniotic fluid optical density at 650 nm and lecithin/sphingomyelin ratios with phosphatidylglycerol.
In this study we have attempted to correlate amniotic fluid optical density measurements and lecithin/sphingomyelin (L/S) ratios with the presence of phosphatidylglycerol. An 85% correlation (126 of 148) of all three parameters was noted. When the assumption was made that phosphatidylglycerol is indicative of fetal pulmonary maturity, 93 of 94 fluid samples having an optical density at 650 nm greater than or equal to 0.15 had demonstrable phosphatidylglycerol for a 1% false positive rate. In 53 fluid samples having an optical density at 650 nm less than 0.15, phosphatidylglycerol was present in 11 and absent in 42, a 21% false negative rate. The same analyses with lecithin/sphingomyelin ratios showed a 5% false positive rate and a 31% false negative rate.
S-, N-, and O-glycosyl derivatives of 2-acetamido-2-deoxy-D-glucose with hydrophobic aglycons as potential chemotherapeutic agents and N-acetyl-beta-D-glucosaminidase inhibitors.
S-, N-, and O-Glycosyl derivatives of 2-acetamido-2-deoxy-D-glucose with hydrophobic aglycons have been obtained as potential, plasma-membrane active agents. 2-Acetamido-3,4,6-tri-O-acetyl-2-deoxy-1-thio-beta-D-glucopyranose (6) was converted into benzyl, diphenylmethyl, triphenylmethyl, and other thioglycosides. Acylation of 6 gave adamantoyl and haloacetyl derivatives. A similar series of N- and O-glycosyl derivatives was obtained from the corresponding NH2-1 and OH-1 analogs of 6, such as O- and N-dinitrophenyl, O- and N-adamantoyl, and N-4-methylbenzylidene derivatives. Several N- and S-glycosyl derivatives were found to inhibit mouse mammary adenocarcinoma (TA3) cells in vitro as well as N-acetyl-beta-D-glucosaminidase from beef liver.
Metabolism and binding of cyclophosphamide and its metabolite acrolein to rat hepatic microsomal cytochrome P-450.
The hepatic cytochrome P-450-mediated metabolism and metabolic activation of [chloroethyl-3H]cyclophosphamide [( chloroethyl-3H]CP) and [4-14C]cyclophosphamide [( 4-14C]CP) were investigated in vitro in the reconstituted system containing cytochrome P-450 isolated from phenobarbital-treated rats. In addition, hepatic microsomal binding and the hepatic microsome-mediated metabolism of [14C]acrolein, a metabolite of [4-14C]CP, were also investigated. The metabolism of [chloroethyl-3H]CP and [4-14C]CP to polar metabolites was found to depend on the presence of NADPH and showed concentration dependence with respect to cytochrome P-450 and NADPH:cytochrome P-450 reductase. Km and Vmax values were essentially similar (Km, 0.44 and 0.42 mM; Vmax, 4.8 and 7.0 nmol of polar metabolites formed/min/nmol of cytochrome P-450 for [4-14C]CP and [chloroethyl-3H]CP, respectively). The patterns of inhibition by microsomal mixed-function oxidase inhibitors, anti-cytochrome P-450 antibody, and heat denaturation of the cytochrome P-450 were essentially similar, with subtle differences between [4-14C]CP and [chloroethyl-3H]CP metabolism. The order of inhibition by various mixed-function oxidase inhibitors was SKF greater than alpha- and beta-naphthoflavones greater than metyrapone. The in vitro metabolic activation of CP in the reconstituted system demonstrated predominant binding of [chloroethyl-3H]CP to nucleic acids and almost exclusive binding of [4-14C]CP to proteins. Gel electrophoresis-fluorography of the proteins in the reconstituted system treated with [4-14C]CP demonstrated localization of the 14C label in the cytochrome P-450 region. To examine this association further, hepatic microsomes were modified with [14C]acrolein in the presence and the absence of NADPH. The results confirmed covalent association between [14C]acrolein and cytochrome P-450 in the microsomes and also demonstrated further metabolism of [14C]acrolein, apparently to an epoxide, which is capable of binding covalently to proteins. The results of these investigations not only confirm the significance of primary metabolism but also emphasize the potential role of the secondary metabolism of cyclophosphamide in some of its toxic manifestations.
Protection of ovarian function by continuous light in alloxan diabetic rats.
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Methicillin-resistant Staphylococcus aureus.
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Biotransformations of daunorubicin aglycones by rat liver microsomes.
Daunorubicin is biotransformed anaerobically by rat liver microsomes with a reduced nicotinamide adenine dinucleotide phosphate-generating system to form a series of aglycones. The first reaction, reductive cleavage of daunosamine (at C-7 in ring A) to form the 7- deoxyaglycone , is followed by reduction of the C-13 keto group. The 7- hydroxyaglycone may also form by hydrolytic cleavage of the amino sugar followed then by the same C-13 keto reduction. These reactions are not inhibited by beta- diethylaminoethyldiphenylpropyl acetate, whereas subsequent reactions in the D ring of the aglycones can be completely blocked by this cytochrome P-450 inhibitor: reductive and hydrolytic cleavage of the C-4 methoxy group. Thus, five reactions at three sites are described and theoretical pathways are proposed for the expected 12 aglycones from daunorubicin.