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Biomedical subjects

R M Sweet

Publications and source records attributed to R M Sweet.

At least 55 records · Page 3Linked to original sources
PubMed1992

Lesions of the nasal radix in pediatric patients: diagnosis and management.

Lesions involving the nasal radix are not extremely uncommon in the pediatric population. Such lesions may represent inflammatory or infectious processes, neoplasia, traumatic sequelae, or developmental anomalies, but faulty embryogenesis is considered the most common cause. During my surgical experience, I have encountered nasal dermoids, nasal gliomas, and nasal encephaloceles resulting in lesions at the root of the nose. Each of these has unique features that will affect therapy.

Adult↗
PubMed1991

X-ray structure of trypanothione reductase from Crithidia fasciculata at 2.4-A resolution.

Trypanosomes and related protozoan parasites lack glutathione reductase and possess instead a closely related enzyme that serves as the reductant of a bis(glutathione)-spermidine conjugate, trypanothione. The human and parasite enzymes have mutually exclusive substrate specificities, providing a route for the design of therapeutic agents by specific inhibition of the parasite enzyme. We report here the three-dimensional structure of trypanothione reductase from Crithidia fasciculata and show that it closely resembles the structure of human glutathione reductase. In particular, the core structure surrounding the catalytic machinery is almost identical in the two enzymes. However, significant differences are found at the substrate binding sites. A cluster of basic residues in glutathione reductase is replaced by neutral, hydrophobic, or acidic residues in trypanothione reductase, consistent with the nature of the spermidine linkage and the change in overall charge of the substrate from -2 to +1, respectively. The binding site is more open in trypanothione reductase due to rotations of about 4 degrees in the domains that form the site, with relative shifts of as much as 2-3 A in residue positions. These results provide a detailed view of the residues that can interact with potential inhibitors and complement previous modeling and mutagenesis studies on the two enzymes.

Amino Acid Sequence↗
PubMed1991

Crystallization and a preliminary X-ray crystallographic study of alpha-amylase from Bacillus licheniformis.

alpha-Amylase from Bacillus licheniformis has been crystallized by the hanging-drop vapor diffusion method in the presence of calcium ions using ammonium sulfate as precipitant. The crystals are tetragonal, belonging to the space group P4(1)2(1)2 (or P4(3)2(1)2), with unit cell dimensions of a = 119.9 and c = 85.4 A. The asymmetric unit contains one molecule of alpha-amylase, with a crystal volume per protein mass (VM) of 2.78 A3/Da. The crystals diffract to better than 2.0 A Bragg spacing when exposed to synchrotron X-rays and they are reasonably stable in the X-ray beam. Thus the crystals are suitable for structure determination at high resolution by X-ray methods.

Bacillus↗
PubMed1990

Structure of an acyl-enzyme intermediate during catalysis: (guanidinobenzoyl)trypsin.

The crystal and molecular structure of trypsin at a transiently stable intermediate step during catalysis has been determined by X-ray diffraction methods. Bovine trypsin cleaved the substrate p-nitrophenyl p-guanidinobenzoate during crystallization under conditions in which the acyl-enzyme intermediate, (guanidinobenzoyl)trypsin, was stable. Orthorhombic crystals formed in space group P2(1)2(1)2(1), with a = 63.74, b = 63.54, and c = 68.93 A. This is a crystal form of bovine trypsin for which a molecular structure has not been reported. Diffraction data were measured with a FAST (Enraf Nonius) diffractometer. The structure was refined to a crystallographic residual of R = 0.16 for data in the resolution range 7.0-2.0 A. The refined model of (guanidinobenzoyl)trypsin provides insight into the structural basis for its slow rate of deacylation, which in solution at 25 degrees C and pH 7.4 exhibits a t1/2 of 12 h. In addition to the rotation of the Ser-195 hydroxyl away from His-157, C beta of Ser-195 moves 0.7 A toward Asp-189 at the bottom of the active site, with respect to the native structure. This allows formation of energetically favorable H bonds and an ion pair between the carboxylate of Asp-189 and the guanidino group of the substrate. This movement is dictated by the rigidity of the aromatic ring in guanidinobenzoate--model-building indicates that this should not occur when arginine, with its more flexible aliphatic backbone, forms the ester bond with Ser-195. As a consequence, highly ordered water molecules in the active site are no longer close enough to the scissile ester bond to serve as potential nucleophiles for hydrolysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Crystallization of the globular domain of histone H5.

The globular domain of histone H1/H5 binds to the nucleosome and is crucial for the formation of chromatin higher order structure. We have expressed in Escherichia coli a gene that codes for the globular domain of H5. The protein produced in E. coli is functional in nucleosome binding assays. We have obtained crystals of the protein that diffract to beyond 2.5 A (1 A = 0.1 nm) resolution. The crystals are orthorhombic with unit cell dimensions of a = 80.1 A, b = 67.5 A and c = 38.0 A.

Crystallization↗
PubMed1990

Molecular characteristics of recombinant human CD4 as deduced from polymorphic crystals.

We have grown crystals of a soluble recombinant form of human CD4, a transmembrane glycoprotein found predominantly on the surface of helper T cells. Crystals composed of the entire extracellular portion of CD4 exhibit extensive polymorphism. Of the five crystal types that have been grown, the best diffracts to Bragg spacings of 4.9 A. Symmetry considerations and characterization of the asymmetric unit by volume-specific amino acid analysis lead to the suggestion that a tetramer is the fundamental unit of crystallization. The characterization also showed that several of the crystal types have unusually high solvent contents. Because high solvent content and weak diffraction are indicative of an extended flexible structure, we examined the molecular shape of the recombinant CD4 with ultracentrifugation and found that it has an axial ratio of roughly 6, when modeled as a prolate ellipsoid. These results, combined with crystal packing constraints, suggest dimensions of approximately 25 x 25 x 125 A for a monomer. The structural features deduced here may be relevant to the biological function of CD4 as a receptor mediating cell-cell and cell-virus interactions.

Amino Acids↗
PubMed1989

Structural consequences of a one atom mutation on aspartate transcarbamylase from E. coli.

Tyr-240 of the catalytic chain of aspartate transcarbamylase from E. coli has been substituted by Phe using site-directed mutagenesis. The regulatory mechanisms of the mutant enzyme have been shown to be slightly less effective than the wild-type enzyme. A study of the structural consequences of the mutation using solution X-ray scattering and computer simulations is reported here. No significant change from the wild-type enzyme is detectable in the quaternary structure. Simulations suggest that the only effect of the mutation is an increased mobility of the mutated side chain.

Allosteric Regulation↗
PubMed1985

Mass distribution of a probable tail-length-determining protein in bacteriophage T4.

Analysis of dark-field scanning transmission electron micrographs of unstained freeze-dried specimens established that the interior of the intact bacteriophage T4 tail tube contains extra density that is missing in tubes artificially emptied by treatment with 3 M guanidine hydrochloride. The mass of the tail tube is 3.1 X 10(6) daltons, and the central channel is 3.2 nm in diameter. Quantitative analysis of the density data is consistent with the presence of up to six strands of a protein molecule in the central channel that could serve as the template or ruler structure that determines the length of the bacteriophage tail and that could be injected into the cell with the phage DNA.

Escherichia coli↗
PubMed1983

Correlation of sequence hydrophobicities measures similarity in three-dimensional protein structure.

The degree of similarity in the three-dimensional structures of two proteins can be examined by comparing the patterns of hydrophobicity found in their amino acid sequences. Each type of amino acid residue is assigned a numerical hydrophobicity, and the correlation coefficient rH is computed between all pairs of residues in the two sequences. In tests on sequences from two properly aligned proteins of similar three-dimensional structures, rH is found in the range 0.3 to 0.7. Improperly aligned sequences or unrelated sequences give rH near zero. By considering the observed frequency of amino acid replacements among related structures, a set of optimal matching hydrophobicities (OMHs) was derived. With this set of OMHs, significant correlation coefficients are calculated for similar three-dimensional structures, even though the two sequences contain few identical residues. An example is the two similar folding domains of rhodanese (rH = 0.5). Predictions are made of similar three-dimensional structures for the alpha and beta chains of the various phycobiliproteins, and for delta hemolysin and melittin.

Amino Acid Sequence↗
PubMed1983

Eosinophilic granuloma of the temporal bone: medical and surgical management in the pediatric patient.

Eosinophilic granuloma is frequently confused with infectious diseases or neoplastic conditions of the temporal bone. It is one of a spectrum of diseases classically known as histiocytosis X. Eosinophilic granuloma usually takes a benign clinical course; however, progression of disease has frequently been documented in the pediatric age group. Our interest in eosinophilic granuloma was generated by a 2-year-old white boy who presented with a large postauricular mass, aural discharge, and posterior-canal-wall granulation tissue. We present this patient's clinical course and a review of the literature concerning diagnosis, treatment, and prognosis of eosinophilic granuloma of the temporal bone.

Bone Diseases↗
PubMed1983

Regulation of Nostoc sp. phycobilisome structure by light and temperature.

Nostoc sp. strain MAC cyanobacteria were green in color when grown in white light at 30 degrees C and contained phycobilisomes that had phycoerythrin and phycocyanin in a molar ratio of 1:1. Cells grown for 4 to 5 days in green light at 30 degrees C or white light at 39 degrees C turned brown and contained phycoerythrin and phycocyanin in a molar ratio of greater than 2:1. In addition to the change in pigment composition, phycobilisomes from brown cells were missing a 34.5-kilodalton, rod-associated peptide that was present in green cells. The green light-induced changes were typical of the chromatic adaptation response in cyanobacteria, but the induction of a similar response by growth at 39 degrees C was a new observation. Phycobilisomes isolated in 0.65 M phosphate buffer (pH 7) dissociate when the ionic strength or pH is decreased. Analysis of the dissociation products from Nostoc sp. phycobilisomes suggested that the cells contained two types of rod structures: a phycocyanin-rich structure that contained the 34.5-kilodalton peptide and a larger phycoerythrin-rich complex. Brown Nostoc sp. cells that lacked the 34.5-kilodalton peptide also lacked the phycocyanin-rich rod structures in their phycobilisomes. These changes in phycobilisome structure were indistinguishable between cells cultured at 39 degrees C in white light and those cultured at 30 degrees C in green light. A potential role is discussed for rod heterogeneity in the chromatic adaptation response.

Adaptation, Physiological↗
PubMed1983

Surgical considerations for dacryocystorhinostomy with special emphasis on hemostatic techniques.

Thirty patients were treated. All surgical procedures were carried out without technical difficulty. Estimated blood loss varied between 5 ml and 25 ml. In no case did bleeding obscure the operative field. Two patients did experience transient hypertension after injection of lidocaine with epinephrine. This was easily controlled by the anesthesiologist. After follow-up periods ranging from one year to five years, all patients have achieved a satisfactory result. No recurrent epiphora or infection has been noted. The technique described in this communication involves drugs, instruments, and equipment which have made our dacryocystorhinostomy rapid (35 to 45 minutes), controlled, and predictable. Surgical morbidity is negligible. Hemorrhage is no longer a fearsome problem. Exposure is always adequate. And, above all, uniform success has been very gratifying to surgical patients and surgeons.

Adolescent↗
PubMed1981

Squamous carcinoma of the uvula.

From a study of the clinical courses of nine patients with squamous carcinoma of the uvula and a review of the clinical literature involving such lesions, we have concluded that these tumors have a very poor prognosis when metastases occur, despite seemingly adequate initial therapy to the primary tumor. Consequently, we believe that more aggressive treatment (which may include irradiation of even subclinically involved neck nodes) should be considered.

Carcinoma, Squamous Cell↗
PubMed1981

Recurrent cementifying fibroma of the jaws.

The cementifying fibroma is a benign fibro-osseous tumor of the jaws, and is generally believed to originate from the periodontal ligament. The tumor commonly presents as an asymptomatic mass lesion, and is usually well-circumscribed clinically so that conservative excisions have been the treatment of choice. From 1970-1980, 94 cases of cementifying fibromas involving either the maxilla or the mandible were accessioned by the Tumor Registry of the Armed Forces Institute of Pathology. Recurrences were found in 11 of these cases, of which 6 involved the mandible. Experiences with these cases are described, as well as experiences with two patients who were managed at the National Naval Medical Center and National Institutes of Health. Conclusions indicate that preferred management for most recurrent cementifying fibromas involves conservative removals which attempt to preserve form and function of the affected site. Residual disease when unavoidable often remains quiescent for extended periods of time without compromise to the patient involved.

Adolescent↗