Biomedical subjects
Publications and source records attributed to R S Johnson.
A case of extreme, recurrent epistaxis secondary to a ruptured aneurysm of the sphenopalatine artery is reported and diagnosis of the condition by angiography and its treatment by Gianturco coil embolization is discussed.
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The technique of resonance Raman spectroscopy has been used to investigate the interaction of the antibiotic rifampicin with Escherichia coli RNA polymerase. Spectra were analyzed by generating the first derivative of each recorded spectrum using the Savitsky-Golay algorithm. The only band that shifted significantly in the resonance Raman spectrum of rifampicin upon the formation of the drug-core polymerase complex was the amide III band. It underwent an 8 cm-1 shift from 1306 cm-1 in aqueous solution to 1314 cm-1. A comparable shift was observed for the rifampicin-holoenzyme complex. Thus, the interaction of the sigma subunit with the core polymerase does not significantly alter the manner in which rifampicin interacts with RNA polymerase. The nature of this shift has been analyzed further by recording the resonance Raman spectrum of rifampicin in a variety of solvents with different hydrogen-bonding solvents (benzene and carbon disulfide) the amide III band was observed at approximately 1220 cm-1; in dimethyl sulfoxide, a weak hydrogen-bond acceptor, 1274 cm-1; in water, a strong hydrogen-bonding solvent, 1306 cm-1; and finally, in triethylamine, a stronger hydrogen-bonding solvent than water, it was observed at 1314 cm-1. Thus, as the hydrogen-bonding ability of the solvent increased, the amide III band shifted to higher frequency. Based on these results, the rifampicin binding site in RNA polymerase provides a stronger hydrogen-bonding environment for the amidic proton of rifampicin than is encountered when rifampicin is free in aqueous solution.
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Three Collies with a skin disorder, 6 progeny from a breeding of 2 of the Collies (incross litter), and the 4 progeny from the breeding of an affected Collie male and a normal Labrador Retriever female (outcross litter) were examined. By 7 to 11 weeks of age, all 6 dogs in the incross litter developed a qualitatively similar, but variably severe, dermatitis of the ears, face, lips, tip of the tail, and over bony prominences of limbs. Later, myopathic signs characterized by bilaterally symmetrical skeletal muscle atrophy of the head, neck, trunk, and extremities; facial palsy; decreased jaw tone; stiff gait; and hyperreflexia were observed in the dogs more severely affected by the dermatitis. Of the 4 dogs in the outcross litter, 3 had similar, but milder, clinical manifestations of the dermatitis and myopathy. Cutaneous lesions consisted of intraepidermal and subepidermal vesicles or pustules with intradermal infiltration by leukocytes. Muscle lesions included myositis; myofiber degeneration, regeneration, and atrophy; and fibrosis. A generalized myopathy in the severely affected dogs was indicated by abnormal readings on needle electromyograms and normal motor nerve conduction velocities. Spontaneous needle electromyogram abnormalities were fibrillation potentials, positive sharp waves, and bizarre high-frequency discharges. Retrospective and prospective genetic analyses disclosed a definite familial tendency and indicated the condition has an autosomal dominant component.
From a consecutive series of 105 patients undergoing bipolar tubal sterilization (BPS), ten pregnancies were reported, and a tubal patency rate of 16% was found at hysterosalpingography. There were no significant clinical variables separating the BPS failure patients from those with successful sterilization. Ninety percent of the BPS failures were intrauterine, and 90% occurred within three cycles of BPS. The results of this investigation suggest that (1) BPS tubal occlusion may be associated with an increased failure (pregnancy and tubal patency) rate; (2) the majority of BPS failures are intrauterine gestations; (3) delayed fibrosis, rather than immediate tubal destruction, may be the mechanism of BPS tubal occlusion; (4) for maximum effectiveness, patients undergoing BPS should use alternative contraception for two to three cycles; and (5) surgeons employing BPS require precise training in the application of this modality of female sterilization.
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The cooperativity with respect to substrates exhibited by allosteric enzymes as well as their inhibition and activation by effectors is mediated through the propagation of conformational changes from the site of ligand binding on one polypeptide chain to other, unliganded chains. This "communication" between subunits in the enzyme is achieved in part by changes at the intersubunit bonding domains as the oligomeric enzymes are converted from the low affinity state to a conformation of high affinity. Structural alterations at the bonding domains between the catalytic and regulatory subunits of aspartate transcarbamoylase from Escherichia coli were detected in derivatives containing either nickel or cobalt in place of the endogenous zinc ion bound to each of the six regulatory chains. These metal-substituted derivatives exhibited physical-chemical and allosteric properties identical to those of the native enzyme. Spectral analyses indicated that both nickel and cobalt are bound to the enzyme in a distorted tetrahedral environment. With the nickel ions serving as spectral probes for structural alterations at the intersubunit bonding domains, it was observed that the substrate, carbamoyl phosphate, and the bisubstrate ligand, N-(phosphonacetyl)-L-aspartate caused different changes. The substrate analog, succinate, alone had no effect. However, the combination of both carbamoyl phosphate and succinate produced the same spectral change as that caused by the bisubstrate analog. Circular dichroism measurements on the nickel derivative showed that the perturbation at 360 nm was directly proportional to the extent of occupancy of the six active sites by the bisubstrate ligand. In contrast, the changes at 406 and 460 nm coincided with the gross conformational change measured by the decrease in the sedimentation coefficient of the enzyme. These latter changes in the circular dichroism and the alterations in the absorption spectrum were complete even though about one-third of the active sites were unliganded.
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Although the importance of ligand-promoted conformational changes in allosteric enzymes has been recognized, it often has been difficult to determine whether the effects of binding are propagated to remote positions in different chains. Efforts were made, therefore, to demonstrate that changes due to ligand binding to the catalytic chains of aspartate transcarbamoylase (carbamoylphosphate:L-aspartate carbamoyltransferase, EC 2.1.3.2) of Escherichia coli are "communicated" to the regulatory chains. For these studies the endogenous zinc in the latter chains was replaced by nickel, which served as a discriminating spectral probe. The Ni(II)-enzyme was constructed by dissociating the native enzyme, separating the catalytic and regulatory subunits, removing Zn(II) from the latter, replacing it with Ni(II), and reconstituting the enzyme from native catalytic and Ni(II)-containing regulatory subunits. Ni(II) derivatives containing either six Ni(II) or five Ni(II) and one Zn(II) possess the allosteric properties of the native enzyme and exhibit absorption bands at 360 and 440 nm due to charge transfer transitions. Smaller bands were also observed at 665 and 720 nm from d-d transitions, which are consistent with tetrahedral geometry in the coordination sphere of nickel. Binding of the bisubstrate ligand N-(phosphonacetyl)-L-aspartate to the catalytic subunit of Ni(II)-aspartate transcarbamoylase perturbed the Ni(II) chromophore, giving rise to two difference spectral bands (at 390 and 465 nm). Spectral titrations showed that the conformational changes at the metal-ion-binding sites were complete even though about one-third of the active sites were unoccupied. This propagation of conformational changes is in accord with other evidence indicating that the allosteric transition in aspartate transcarbamoylase is concerted.
Water and sediment samples collected during 1977-78 from the Indian River lagoon between Vero Beach, Indian River County, and Fort Pierce, Saint Lucie County, Florida were analyzed for PCBs and DDT. Sample locations were chosen on the basis of proximity to major tributaries, sewage outfalls, or municipal area. Concentrations in water samples were below 0.01 ppb sigma DDT and 0.5 ppb PCBs. Small amounts of PCBs and DDT were found in most sediment samples, ranging from less than 1.0 ppb to 0.63 ppm Aroclor 1254 and from less than 0.1 ppb to 0.081 ppm sigma DDT. Samples from the Taylor Creek tributary and from the Fort Pierce power plant and municipal docking area contained higher PCB concentrations then did samples from other locations. DDT and PCB levels in most samples indicate little contamination by these compounds of the Indian River Waterway between Vero Beach and Fort Pierce.