Blood groups and lung cancer.
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ABO Blood-Group System↗
Biomedical subjects
R Lawson
Publications and source records attributed to R Lawson.
Evolutionary relationships of a "primitive" shark (Heterodontus) assessed by micro-complement fixation of serum transferrin.
The evolutionary relationships of six sharks were investigated by comparing their transferrins using the micro-complement fixation method. The immunological distances observed were used to build a tree that confirms that the squaloid and galeoid species examined belong to two separate groups and that Heterodontus, a genus of hitherto uncertain position, belongs with the galeoids. The divergence time estimated from the transferrin comparisons is roughly 240 +/- 65 million years between Heterodontus and galeoids.
Animals↗
Imidazole anticonvulsants: structure-activity relationships of [(biphenylyloxy)alkyl]imidazoles.
The [(biphenylyloxy)alkyl]imidazoles were found to be potent anticonvulsants. The most potent compound of the series, 1-[2- ([1,1'-biphenyl]-2-yloxy)ethyl]-1H-imidazole (4), had an ED50 of 15.5 mg/kg against maximal-electroshock-induced seizures in mice after oral administration; the horizontal screen ED50 was 320 mg/kg, revealing that the compound has a protective index of 21. Homologues bearing three- and four-carbon tethers between the imidazole and biphenylyloxy moieties were also active, but their potency was attenuated relative to 4. Congeners with the imidazolylalkoxy moiety at the meta or para positions of biphenyl were also less active. All these compounds were potent potentiators of hexobarbital-induced sleeping time in mice, presumably via the well-known imidazole-mediated inhibition of cytochrome P-450. The structural features governing the anticonvulsant and sleeping-time activities appear to be distinct, but a complete dissociation of these two effects has not been achieved. Thus, the potential of these compounds as clinically useful antiepileptic drugs would appear to be limited.
Animals↗
Discovery and anticonvulsant activity of the potent metabolic inhibitor 4-amino-N-(2,6-dimethylphenyl)-3,5-dimethylbenzamide.
Compound 2 [4-amino-N-(2,6-dimethylphenyl)benzamide] is an effective anticonvulsant in several animal models. For example, following oral administration to mice, it antagonized maximal electroshock (MES) induced seizures with an ED50 of 1.7 mg/kg. During drug disposition studies with 2, we found that it was rapidly metabolized by N-acetylation. Thirty minutes after oral administration of 1.7 mg/kg of 2 to mice, plasma concentrations of parent drug and the N-acetyl metabolite 5 were 1.09 and 0.41 microgram/mL, respectively. Six hours postadministration the concentrations were 0.23 and 0.22 microgram/mL, respectively. In order to sterically preclude or diminish the rate of metabolic N-acetylation, we synthesized analogues of 2 possessing either one (3) or two (4) methyl groups ortho to the 4-amino substituent. Both compounds antagonized MES-induced seizures after administration to mice; oral ED50 values for 3 and 4 were 3.5 and 5.6 mg/kg, respectively. Compound 3 was rapidly metabolized by N-acetylation. However, 4 provided exceptionally high and long-lived plasma concentrations of parent drug; no N-acetyl metabolite could be detected. While 2 and 3 had no pharmacologically relevant effects on hexobarbital-induced sleeping time in mice, 4 was a potent, dose-dependent potentiator of sleeping time. Oral administration of 375 micrograms/kg led to a 61% increase in sleeping time relative to control values. Thus, 4 represents one of the most potent potentiators of hexobarbital-induced sleeping time described to date.
Acetylation↗
Purine nucleotide metabolism: the discovery of a major new oligomeric adenosine tetraphosphate derivative in rat heart.
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Adenosine Diphosphate↗
Superoxide dismutase and catalase in Toxoplasma gondii.
Catalase and superoxide dismutase detected in both RH and C strain Toxoplasma gondii tachyzoites were distinctly different in electrophoretic mobility from host cell enzymes. Catalase and superoxide dismutase activity levels were similar in both Toxoplasma strains and showed narrow pH optima around 8.0. Toxoplasma superoxide dismutase was resistant to cyanide but inhibited by azide or peroxide, consistent with an iron-containing enzyme typical of protozoan parasites. These enzymes may play a role in intracellular survival; however, they do not appear to be the basis for differences in virulence to mice.
Animals↗
Severe colitis induced by soap enemas.
A patient had severe colitis after soap enemas for five days. Elimination of the soap enemas resulted in resolution of the colitis. We suggest that soap enemas be avoided.
Colitis↗
Ecdysterone selectively stimulates the expression of a 23000-Da heat-shock protein-beta-galactosidase hybrid gene in cultured Drosophila cells.
To study the regulated expression of cloned heat-shock genes in homologous cells, hybrid Drosophila heat-shock-Escherichia coli beta-galactosidase genes were constructed. Segments of the ecdysterone-inducible 23,000-Da heat-shock protein (hsp23) gene and of two other hsp genes (hsp84 and 70), which are not hormone regulated, were functionally linked to the bacterial coding sequence, and the resulting hybrid genes were introduced into cultured, hormone-responsive Drosophila cells by transfection. All hybrid genes directed the synthesis of E. coli-specific beta-galactosidase in heat-treated cells. hsp23 hybrid gene expression was stimulated strongly by ecdysterone, while the activities of the other hybrid genes were not affected at all by the hormone. A hybrid gene with only 147 bp of hsp23 promoter sequence could not be activated by either heat or ecdysterone treatment. Thus, far upstream sequences contain signals required for the regulated expression of the hsp23 gene in Drosophila cells.
Animals↗
The heat shock consensus sequence is not sufficient for hsp70 gene expression in Drosophila melanogaster.
A hybrid gene in which the expression of an Escherichia coli beta-galactosidase gene was placed under the control of a Drosophila melanogaster 70,000-dalton heat shock protein (hsp70) gene promoter was constructed. Mutant derivatives of this hybrid gene which contained promoter sequences of different lengths were prepared, and their heat-induced expression was examined in D. melanogaster and COS-1 (African green monkey kidney) cells. Mutants with 5' nontranscribed sequences of at least 90 and up to 1,140 base pairs were expressed strongly in both cell types. Mutants with shorter 5' extensions (of at least 63 base pairs) were transcribed and translated efficiently in COS-1 but not at all in D. melanogaster cells. Thus, in contrast to the situation in COS-1 cells, the previously defined heat shock consensus sequence which is located between nucleotides 62 and 48 of the hsp70 gene 5' nontranscribed DNA segment is not sufficient for the expression of the D. melanogaster gene in homologous cells. A second consensus-like element 69 to 85 nucleotides upstream from the cap site is postulated to be also involved in the heat-induced expression of the hsp70 gene in D. melanogaster cells.
Animals↗
False-positive Hemoccult reaction caused by Betadine.
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False Positive Reactions↗
Evidence that the mitochondrial activator of phosphorylated branched-chain 2-oxoacid dehydrogenase complex is the dissociated E1 component of the complex.
Branched-chain 2-oxoacid dehydrogenase complex is inactivated by phosphorylation of the alpha-subunit of the E1 component of the complex. High-speed supernatant from rat liver mitochondria contains an activator protein which can restore activity to the phosphorylated complex without concomitant dephosphorylation [(1982) FEBS Lett. 147, 35-39]. We report here several lines of evidence which indicate that activator is the dissociated non-phosphorylated form of the E1 component.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Expression of heat shock-beta-galactosidase hybrid genes in cultured Drosophila cells.
Derivatives of Drosophila 70,000 dalton heat shock protein (hsp70) genes were constructed in which all of the hsp70 coding sequence but for the first seven codons had been substituted by a DNA segment coding for E. coli beta-galactosidase. The constructs were capable of directing the synthesis of active beta-galactosidase in COS1 (SV40 transformed African Green Monkey Kidney) cells. The hybrid genes were then used to develop a procedure permitting the introduction of genes and their transient expression in cultured cells of Drosophila melanogaster. Introduction of hybrid genes was achieved by DEAE-dextran-mediated transfection. Substantial gene activity was observed in heat-treated cells only 4 h, maximal activity 24 h after transfection. Various parameters of the transfection/transient expression system including the effects of different 3'nontranslated sequences on hybrid gene expression were investigated in an attempt to provide a useful procedure for studies of the expression of other genes in D. melanogaster cells. To show that promoters which are weaker than that of the hsp70 gene direct the synthesis of easily measurable amounts of beta-galactosidase in D. melanogaster cells, the expression of a hsp84-beta-galactosidase hybrid gene was also examined. Expression of the hsp70 hybrid gene occurs during heat shock, at temperatures at which other proteins are not made, and decreases sharply after heat treatment. The expression of the transfected gene therefore closely follows that of the endogenous hsp70 genes. This result suggests that a short hsp70 gene segment consisting of 195 base pairs of upstream sequence and a complete RNA leader region contain all the information required for the induced synthesis of proteins during heat shock.
Animals↗
Amino acid sequence at the major phosphorylation site on bovine kidney branched-chain 2-oxoacid dehydrogenase complex.
Inactivation of branched-chain 2-oxoacid dehydrogenase complex correlates with phosphorylation at one site on the alpha subunit of the E1 component. The amino acid sequence surrounding this phosphorylated serine residue has now been determined. This sequence shows certain similarities with the sequence surrounding phosphorylated residue(s) on pyruvate dehydrogenase complex.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Multi-site phosphorylation of branched-chain 2-oxoacid dehydrogenase complex within mitochondria isolated from rat liver, kidney and heart.
The alpha subunit of the E1 component of branched-chain 2-oxoacid dehydrogenase complex becomes rapidly phosphorylated in rat liver, kidney and heart mitochondria incubated in the presence of succinate and [32P]phosphate. Peptide mapping of tryptic digests of the phosphorylated alpha subunit indicates that 3 distinct sites are phosphorylated, as has been reported previously by us for phosphorylation in vitro of highly purified complex.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Rapid purification of bovine kidney branched-chain 2-oxoacid dehydrogenase complex containing endogenous kinase activity.
Branched-chain 2-oxoacid dehydrogenase complex has been purified to near homogeneity by a simple, rapid procedure. The final product contains endogenous kinase activity capable of phosphorylating and inactivating the complex. Phosphorylation continues after complete inactivation, indicating the possibility of several phosphorylatable sites.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Multi-site phosphorylation of bovine kidney branched-chain 2-oxoacid dehydrogenase complex.
The alpha-subunit of the E1 component of branched-chain 2-oxoacid dehydrogenase is phosphorylated at 3 sites by an endogenous kinase. Inactivation of the complex correlates with rapid phosphorylation of one of these sites. The similarities with the covalent regulation of pyruvate dehydrogenase complex are discussed.
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗
Lymphadenopathy associated with diphenylhydantoin therapy.
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Adult↗
Anomalous uncrossed retinal projections fail to activate superior colliculus neurons in rabbits unilaterally enucleated by fetal surgery.
Previous studies have shown that unilateral enucleation of rabbit pups produces an aberrant uncrossed retinotectal projection. These fibers failed to drive collicular units when stimulated with either light or electric shock. The present study attempts to assess the possibility that enucleation at earlier stages of development would lead to a greater degree of morphological and physiological reorganization in the uncrossed retinotectal projection. Rabbit fetuses were unilaterally enucleated at day 20 or 25 of gestation. Birth is at day 31. After 3 months, the degree of reorganization of the uncrossed retinotectal projection was assessed using the following techniques: (1) autoradiographic demonstration of the projection from the remaining eye, (2) electrophysiological recording of collicular unit activity, and (3) a combination of these methods. Autoradiographic data indicated a much greater expansion of the anomalous uncrossed projection in fetally enucleated animals than in those enucleated at birth. Labelled terminals were found to occupy more than the anterior third of the ipsilateral colliculus and were distributed to the entire depth of the stratum griseum superficiale and stratum opticum. Electrode penetrations within the boundaries of the expanded projection failed to locate collicular units which could be driven by either light stimulation of the eye or electric shock of the optic nerve. Only a few cells encountered in the lateral border area, receiving the normal uncrossed retinal projection, could be driven by light stimulation. These negative findings are in contrast to the data reported for the rat and hamster where anomalous retinal projections are capable of forming functional connections. Further comparative studies of reorganization are needed.
Animals↗