Biomedical subjects
Publications and source records attributed to H Lee.
P. falciparum grown in culture was used to immunize mice and to obtain hybridomas. Two hybrids were selected secreting high titers of monoclonal antibodies directed against the cytoplasm of erythrocytic forms of the Plasmodium and not against the membrane of normal or parasitized erythrocytes. Such antibodies are of potential value in the immuno-diagnosis of malaria.
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The effect of chronic alcohol administration on the structure and function of the rat liver plasma membranes has been investigated. Chronic alcohol administration did not affect the yield of these membranes using conventional isolation procedures. The extent of plasma membrane enrichment or contamination with other interior membranes was identical in the control and alcoholic preparations. The binding of 125I-labelled glucagon to these experimental liver plasma membranes was significantly decreased. Scatchard analysis of the high affinity sites showed a significant reduction (approximately equal to 35%) in receptor number rather than binding affinity, which was not altered. This anomaly persisted through 72-h withdrawal of alcohol. These data suggest that very stable changes were induced in these liver plasma membranes after prolonged alcohol ingestion.
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The effects of diazepam on the development of explanted stage 4 chick embryos were investigated. Diazepam, at 10-120 micrograms/ml, preferentially inhibited closure of the neural tube. This effect was reversible. Concentrations of 150-200 micrograms/ml inhibited not only neural tube closure but also blastodermal expansion, somite formation, and heart development in 52% of the embryos. Concentrations above 200 micrograms/ml were highly embryotoxic. Electron microscopy of affected neuroepithelial cells revealed that 1) apical surfaces were much smoother than usual and 2) apical filament bundles, which are generally thought to provide motive forces for uplifting of neural folds, were not well organized and often lacked alternating dark and light areas along their length. These findings and the fact that changes in cell surface topography reflect the contractile activities of underlying filament bundles suggest that the observed "smoothing" effect on apical cell surfaces and neural tube closure defects are due, at least in part, to the impaired ability of these filament bundles to contract.
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A series of ortho- and para-substituted L-phenylalanylpuromycin analogues were synthesized and evaluated as substrates for the peptidyltransferase reaction of Escherichia coli ribosomes. Kinetic results reveal that substitution of the p-methoxy group of the puromycin molecule alters the peptidyltransferase activity of the molecule with the following decreasing order of substrate efficiencies: p-NH2 greater than p-NHCOCH3 greater than p-NO2 = p-NHCO(CH2)2CH3 greater than p-NHCOCH2Br. However, the inability of the ribosome to tolerate a nitro group at the ortho position of the phenylalanine ring precluded the use of the photosensitive puromycin analogue, 2-nitro-4-azidophenylalanylpuromycin aminonucleoside (7a), as a photoaffinity label for the peptidyltransferase site.
A facile, two-step conversion of puromycin aminonucleoside (PAN) into 5'-deoxy-PAN (5) via 5'-chloro-5'-deoxy-PAN (1) was accomplished. Replacement of the 5'-OH group of PAN with H or Cl resulted in the elimination of kidney toxicity associated with the administration of PAN. The corresponding puromycin derivatives, 5'-chloro-5'-deoxypuromycin (4) and 5'-deoxypuromycin (6), derived from 1 and 5, respectively, were compared in a ribosomal peptidyltransferase assay. Both compounds were excellent substrates for the transpeptidation reaction, confirming our previous observations with 6 that the 5'-OH of puromycin is not essential for activity at the ribosomal level. Thus, 4 represents a new puromycin derivative that retains puromycin-like activity at the ribosomal site but is capable of releasing only a nonnephrotoxic aminonucleoside upon enzymatic release of the p-methoxyphenylalanyl side chain. The chloro derivative 4 exhibited significant antitrypanosomal activity in mice infected with Trypanosoma rhodesiense. The 5'-deoxy derivative 6 was inactive against trypanosomes.
We present a case of abdominal aortic aneurysm in which erosion and bleeding into the psoas muscle caused enlargement of that structure but remained confined within it until needle biopsy produced communication with the extraperitoneal space. This confirms the observation that separate compartmentalization of retrofascial and extraperitoneal spaces normally maintains.
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We have studied the fibrinogen binding to the platelets of four type I thrombasthenic two type II thrombasthenic patients and 15 normal subjects. The amount of [125I]fibrinogen bound to washed platelets in the presence or absence of 10 micrometers ADP was measured and the results expressed as the percentage of the total radioactivity added. The mean value for specific binding to the platelets of normal subjects was 3.7 (range 1--7.25) at 15 min after the addition of ADP. Type I thrombasthenic patients lack glycoproteins (GP) IIb and IIIa in the platelet membrane and intra-platelet fibrinogen. In all four patients studied, little or no specific fibrinogen binding was detected. Platelets of type II thrombasthenic patients contain detectable, although markedly reduced amounts of GP IIb and IIIa, and subnormal or normal levels of fibrinogen. In these platelets, significant specific fibrinogen binding was observed, the values being slightly below or at the lower end of the normal range. Fibrinogen binding to normal platelets was also measured after the addition of an IgG purified from the serum of a multi-transfused thrombasthenic type I patient. This antibody was previously shown to be directed against the GP IIb/IIIa complex as located by crossed immunoelectrophoresis. Specific fibrinogen-binding was blocked and the extent of the inhibition was directly proportional to the concentration of the antibody added.
The effect on platelet function of a monoclonal platelet antibody to platelet membrane glycoprotein I was tested. This antibody, AN51, inhibited ristocetin or bovine factor VIII-induced aggregation but did not modify ADP, collagen type I or type III, thrombin or arachidonic acid induced aggregations. Furthermore, the adhesion-aggregation of platelets induced by microfibrils was also inhibited by the antibody. Platelet adhesion to rabbit aorta subendothelium was impaired by the antibody. The persistent adhesion of platelets to collagenase-treated subendothelium was also inhibited. These findings strongly suggested that platelet membrane glycoprotein I could interact with a non-collagenic microfibrillar component of subendothelium. The binding of factor VIII/von Willebrand factor to platelet membrane in the presence of ristocetin was decreased in the binding site for factor VIII/von Willebrand factor to allow platelet adhesion to subendothelium.
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