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Biomedical subjects

W T Miller

Publications and source records attributed to W T Miller.

At least 19 recordsLinked to original sources
PubMed1992

A retroviral-like metal binding motif in an aminoacyl-tRNA synthetase is important for tRNA recognition.

The gag genes of retroviruses encode nucleocapsid proteins that package genomic RNA and are essential for viral infectivity. These RNA binding proteins have a Cys-Xaa2-Cys-Xaa4-His-Xaa4-Cys zinc binding motif that is distinct from the typical zinc-finger motif Cys-Xaa2-Cys-Xaa12-14-His-Xaa2-His that is found in some transcriptional activators. Escherichia coli alanyl-tRNA synthetase contains a zinc-binding Cys-Xaa2-Cys-Xaa6-His-Xaa2-His motif that resembles that of retroviral nucleic acid binding proteins. We show here that, for alanyl-tRNA synthetase, the metal bound at the retroviral-like metal binding motif is important specifically for tRNA recognition and not for amino acid activation. Moreover, the enzyme-tRNA interaction is strongly dependent on the geometry of metal coordination to the protein. These and additional experiments collectively suggest a role for the retroviral-like metal binding motif in RNA recognition and, further, raise the possibility that the protein-bound metal itself participates in an RNA interaction.

Alanine-tRNA Ligase↗
PubMed1992

Rounded atelectasis: diagnosis by fine-needle aspiration cytology.

Rounded atelectasis, a rare, benign mass lesion, is most often seen in association with asbestos-related pleural changes. Often a presumptive diagnosis can be made on the basis of characteristic CT and chest radiographic findings. However, not infrequently radiographic imaging fails to differentiate rounded atelectasis from primary bronchogenic carcinoma, a disease which is seen with increased frequency in patients with asbestos exposure. We describe two cases where the diagnosis of rounded atelectasis was made by fine-needle aspiration (FNA) cytology. The cytologic features included abundant pulmonary parenchymal material with thickened alveolar walls containing pulmonary macrophages and connective tissue. It is important to realize that this is a useful positive finding indicating rounded atelectasis, rather than a negative finding suggesting the absence of neoplasm. Needles with a cutting action may be necessary to obtain sufficient material to make the diagnosis of rounded atelectasis.

Aged↗
PubMed1992

Asbestos-related chest diseases: plain radiographic findings.

In summary, there are a wide range of pulmonary manifestations seen in asbestos-exposed individuals from pleural and parenchymal fibrosis to pleural and parenchymal malignancy. The chest roentgenogram has assumed an important role in the detection and surveillance of asbestos-related pleural and parenchymal changes.

Asbestos↗
PubMed1992

A metal-binding motif implicated in RNA recognition by an aminoacyl-tRNA synthetase and by a retroviral gene product.

A randomly generated mutation in Escherichia coli alanine tRNA synthetase compensates for a mutation in its cognate tRNA. The enzyme's mutation occurs next to a Cys-X2-Cys-X6-His-X2-His metal-binding motif that is distinct from the zinc finger motif found in some DNA-binding proteins. Instead, the synthetase's metal binding domain resembles the Cys-X2-Cys-X4-His-X4-Cys metal-binding domain of the gag gene product of retroviruses. For Ala-tRNA synthetase, the metal bound at the Cys-His motif is important specifically for the tRNA-dependent step of catalysis, and the enzyme-tRNA interaction is dependent on the geometry of metal co-ordination to the enzyme. These data, and the demonstrated sensitivity of RNA packaging to mutations in the metal-binding domain of the gag gene product of retroviruses, suggest that an aminoacyl-tRNA synthetase and retroviruses have adopted a related metal-binding motif for RNA recognition.

Alanine-tRNA Ligase↗
PubMed1992

Thymoma mimicking a thyroid mass.

Two cases of ectopic cervical thymoma are presented. These cases both manifested as mass lesions at the thoracic inlet, displacing the trachea, and were originally misdiagnosed as thyroid masses. The masses had clinical features similar to those previously reported for cervical thymoma: preponderance in women, benign clinical course, and absence of myasthenic symptoms.

Aged↗
PubMed1992

Thymoma--report of 71 cases and a review.

Of the 71 cases of thymoma reviewed, 31 were benign and 40 were malignant. Associated syndromes were common--myasthenia gravis 51% (36/71), red cell aplasia 3%, hypogammaglobulinemia 4%, mucocutaneous candidiasis 1%, and a number of other autoimmune diseases and neoplasms. These were almost equally distributed among benign and malignant tumors. A plain radiograph showing diffuse involvement of the mediastinum always indicates invasive (malignant) thymoma, while a localized pattern usually suggests a benign lesion (25 of 39 cases). Computerized tomography or MRI often gives additional information. An optimistic approach and aggressive radiotherapy are indicated in patients whose only metastatic disease is to one pleural space; prolonged survival is frequent in this group.

Adolescent↗
PubMed1991

Evidence for a "cysteine-histidine box" metal-binding site in an Escherichia coli aminoacyl-tRNA synthetase.

Escherichia coli alanyl-tRNA synthetase contains the sequence Cys-X2-Cys-X6-His-X2-His. This motif is distinct from the zinc fingers of DNA-binding proteins but has some similarity to the Cys-X2-Cys-X4-His-X4-Cys zinc-binding motif of retroviral gag proteins, where it has a role in RNA packaging. In Ala-tRNA synthetase, this sequence is located in an amino-terminal domain which has the site for docking the acceptor end of the tRNA near the bound aminoacyl adenylate and is immediately adjacent in the sequence to the location of a mutation that affects the specificity of tRNA recognition. We show here that Ala-tRNA synthetase contains approximately 1 mol of zinc/mol of polypeptide and that addition of the zinc chelator 1,10-phenanthroline inhibits its aminoacylation activity. Conservative mutations of specific cysteine or histidine residues in the "Cys-His box" destabilize and inactivate the enzyme, whereas mutations of intervening amino acids do not inactivate. The possibility that this motif can bind zinc (or cobalt) was demonstrated with a synthetic 22 amino acid peptide that is based on the sequence of the alanine enzyme. The peptide-cobalt complex has the spectral characteristics of tetrahedral coordination geometry. The results establish that the Cys-His box motif of Ala-tRNA synthetase has the potential to form a specific complex with zinc (at least in the context of a synthetic peptide analogue) and suggest that this motif is important for enzyme stability/activity.

Alanine-tRNA Ligase↗
PubMed1991

Mutant aminoacyl-tRNA synthetase that compensates for a mutation in the major identity determinant of its tRNA.

A single G3.U70 base pair in the acceptor helix is the major determinant for the identity of alanine transfer RNAs (Hou & Schimmel, 1988). Introduction of this base pair into foreign tRNA sequences confers alanine acceptance on them. Moreover, small RNA helices with as few as seven base pairs can be aminoacylated with alanine, provided that they encode the critical base pair (Francklyn & Schimmel, 1989). Alteration of G3.U70 to G3.C70 abolishes aminoacylation with alanine in vivo and in vitro. We describe here the mutagenesis and selection of a single point mutation in Escherichia coli Ala-tRNA synthetase that compensates for a G3.C70 mutation in tRNAAla. The mutation maps to a region previously implicated as proximal to the acceptor end of the bound tRNA. In contrast to the wild-type enzyme, the mutant charges small RNA helices that encode a G3.C70 base pair. However, the mutant enzyme retains specificity for alanine tRNA and can serve as the sole source of Ala-tRNA synthetase in vivo. The results demonstrate the capacity of an aminoacyl-tRNA synthetase to compensate through a single amino acid substitution for mutations in the major determinant of its cognate tRNA.

Amino Acyl-tRNA Synthetases↗
PubMed1991

Drug-related pleural and mediastinal disorders.

The full range of mediastinal and pleural toxic effects of various drugs is reviewed. The importance of clinical information in suggesting the diagnosis of drug-induced disorders is emphasized. A separate section on the pleural and mediastinal toxic effects of illicit drugs is included.

Humans↗
PubMed1990

Synthetic peptide model of an essential region of an aminoacyl-tRNA synthetase.

A 40 amino acid sequence of the unsolved structure of Escherichia coli alanine-tRNA synthetase is essential for tRNA binding and encodes an immunological determinant that cross-reacts with antibodies raised against a eukaryote (insect Bombyx mori) alanine enzyme. The secondary structure of this sequence is predicted to be an amphiphilic alpha-helix that includes one aspartyl and eight glutamyl side chain carboxyl groups. The antibody reactivity and the conformation of a synthetic peptide model of this region (Glu346 to Ser385) were investigated. In addition, double Arg----Gln and Leu----Ala substitutions were separately placed in the enzyme on the hydrophilic and hydrophobic face, respectively, of the predicted helix. These mutations conserve the polar/nonpolar character of each face and retain the potential for helix formation. Circular dichroism spectra of the synthetic peptide model demonstrate the potential for amphiphilic helix formation for the segment from Glu346 to Ser385. The behavior of the mutations in the enzyme, together with earlier data and immunological assays presented here, suggests that one face of the putative helix is an antigenic region of the surface of the enzyme where it contributes to the interaction with alanine tRNA and that the specific sequence of the helix is an important determinant of enzyme stability.

Alanine-tRNA Ligase↗
PubMed1990

Supplemental emergent chest computed tomography in the management of blunt torso trauma.

The efficacy of conventional chest X-ray (CXR) in comparison to chest computed tomography (CCT) in acutely injured blunt trauma patients was examined. Over a 21-month period, 50 patients underwent CXR and CCT according to a standard protocol, and their films and records were reviewed retrospectively. Hemo- and/or pneumothorax (HPTX) was noted in 12 patients (five by CXR, 12 by CCT). Pulmonary contusion (PC) was identified in ten patients (four by CXR, ten by CCT). Three additional false positive PC were diagnosed by CXR. Therapy changes based upon CCT findings occurred in seven of seven HPTX and five of six PC. The two imaging techniques were complementary in detecting fractures. Atelectasis was a common CCT finding (58% incidence). Chest X-ray is less sensitive than chest computed tomography in the detection of HPTX (42% vs. 100%) and PC (40% vs. 100%). Emergent chest computed tomography is recommended in stable patients with: 1) blunt high-energy torso trauma, 2) "cross-body" injury pattern, and/or 3) a mechanism of injury suggestive of chest trauma.

Adult↗
PubMed1990

Cryptococcal pulmonary infection in patients with AIDS: radiographic appearance.

The clinical, laboratory, and radiographic findings in seven patients with acquired immunodeficiency syndrome (AIDS) and cryptococcal pulmonary infections were reviewed. The infection was most commonly seen on radiographs as lymphadenopathy, interstitial infiltrates, or both. Interstitial infiltrates were commonly nodular. Large nodules or alveolar infiltrates, the most common findings at presentation in both immunocompetent patients and immunocompromised patients without AIDS, were not present in our series. Isolated pleural effusion was seen as the only radiographic finding in one case. Meningitis was present in six of seven cases and was neurologically silent in five of six cases. Cryptococcal pneumonia in AIDS patients should prompt a search for neurologically silent cryptococcal meningitis.

Acquired Immunodeficiency Syndrome↗