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Biomedical subjects

W T Miller

Publications and source records attributed to W T Miller.

At least 55 records · Page 3Linked to original sources
PubMed1999

Advanced emphysema: preoperative chest radiographic findings as predictors of outcome following lung volume reduction surgery.

PURPOSE: To determine whether preoperative chest radiographic findings alone can reliably predict which patients will achieve the best functional outcome of lung volume reduction surgery. MATERIALS AND METHODS: The preoperative chest radiographs obtained in 57 patients who had undergone lung volume reduction surgery were retrospectively scored by five blinded readers for severity and distribution of emphysema, evidence of lung compression, disease heterogeneity, and other features. Comparisons were made with the 3-6-month postoperative functional outcome for each patient. RESULTS: High disease heterogeneity (score > 2) and unequivocal lung compression (score 1) both were 100% predictive of a favorable outcome (FEV1 increase, > or = 30%). Low heterogeneity (score < 1) was 94% predictive of an unfavorable outcome (FEV1 increase < 30%), as was a lack of lung compression, which was 92% predictive of an unfavorable outcome. These two features also correlated with an improved 6-minute walk test result, although this correlation was weaker. CONCLUSION: Chest radiography alone may be sufficient for initial screening. High disease heterogeneity and lung compression on chest radiographs are highly predictive of a favorable functional outcome.

Aged↗
PubMed1999

Acute biliary disease: initial CT and follow-up US versus initial US and follow-up CT.

PURPOSE: To evaluate the utility of ultrasonography (US) versus that of computed tomography (CT) for assessment of acute biliary disease. MATERIALS AND METHODS: Radiologic reports and clinical charts were reviewed in all patients who underwent US and CT within 48 hours of each other for evaluation of acute right upper quadrant pain. Radiologic findings and clinical outcome were correlated. RESULTS: CT was the initial imaging study in 57 patients, and CT findings resulted in underdiagnosis or misdiagnosis of acute biliary disease in eight of 11 patients. Follow-up US results were suggestive of the correct diagnosis and provided additional clinical information in seven of these eight patients. US findings resulted in altered clinical treatment in six of 11 patients with acute biliary disease. US was the initial study in 66 patients, and US findings were suggestive of biliary disease or the correct diagnosis in seven of seven patients with acute biliary disease. Follow-up CT did not result in changes in clinical treatment in any patient with acute biliary disease. CONCLUSION: Initial US is better than initial CT in patients suspected of having acute biliary disease. Follow-up CT provides no additional information regarding the biliary system, and its use should be limited to those patients with a wider differential diagnosis or with confusing clinical symptoms and signs.

Acute Disease↗
PubMed1998

Intramolecular regulatory interactions in the Src family kinase Hck probed by mutagenesis of a conserved tryptophan residue.

Intramolecular interactions between the Src homology domains (SH2 and SH3) and the catalytic domains of Src family kinases result in repression of catalytic activity. The crystal structure of the Src family kinase Hck, with its regulatory domains intact, has been solved. It predicts that a conserved residue, Trp260, at the end of the linker between the SH2 and the catalytic domains plays an important role in regulation by the SH3 and SH2 domains. We have mutated this residue and compared the activities of C-terminally phosphorylated wild type Hck and W260A Hck. The W260A mutant has a higher specific activity than wild type Hck. The W260A mutant requires autophosphorylation at Tyr416 for full activity, but it is not activated by ligand binding to the SH3 or SH2 domains. This mutation also changes the accessibility of the SH2 and SH3 domains to their cognate peptide ligands. Our results indicate that Trp260 plays a critical role in the coupling of the regulatory domains to the catalytic domain, as well as in positioning the ligand binding surfaces.

Amino Acid Sequence↗
PubMed1998

Phosphorylation and activation of cGMP-dependent protein kinase by Src.

Using information obtained from experiments with peptide substrates of v-Src, a motif within the cGMP-binding domain of cGMP-dependent protein kinase (cGK) was identified as a potential phosphorylation site for v-Src. Here we show that the purified Ialpha isozyme of cGK is phosphorylated stoichiometrically and in a time-dependent manner by purified Src in vitro. The kinase activity of cGK is elevated approximately 4-fold (relative to autophosphorylated cGK) or 10-fold (relative to unphosphorylated cGK) upon tyrosine phosphorylation by Src. Phosphorylation of cGK by v-Src produces modest effects on the cGMP-binding properties and dissociation rates of cGK, and reduces the kact for cGMP. We hypothesize that the mechanism of activation may involve coupling of the cGMP binding domain to the catalytic domain.

Cyclic GMP↗
PubMed1998

Enhanced phosphorylation of Src family kinase substrates containing SH2 domain binding sites.

Src family protein-tyrosine kinases possess several modular domains important for regulation of catalytic activity and interaction with potential substrates. Here, we explore interactions between the SH2 domain of Hck, a Src family kinase, and substrates containing SH2 domain-binding sites. We have synthesized a series of peptide substrates containing a high affinity SH2 domain binding site, (phospho)Tyr-Glu-Glu-Ile. We show that the presence of this sequence in a peptide results in a dramatic increase in the phosphorylation rate of a second tyrosine located at the N terminus. Enhanced phosphorylation is not a consequence of stimulation of enzymatic activity by C-terminal tail displacement but is imparted instead by a 10-fold reduction in the Km of the phosphotyrosine-containing peptide when compared with a control. The isolated catalytic domain of the non-receptor tyrosine kinase Abl does not show a preference for the pYEEI motif-containing peptide; however, the preference is restored when the SH2 domain of Src is introduced into Abl. Furthermore, enhanced phosphorylation is dependent on the distance between SH2 domain-binding site and phosphorylatable tyrosine, with the minimum distance requirement being seven amino acids. Reversing the orientation of the pYEEI motif with respect to the substrate sequence decreases phosphorylation by down-regulated Hck, but both orientations are utilized equally well by activated Hck. We discuss the possible implications of these results for processive phosphorylation of substrates in vivo by Src family kinases.

Amino Acid Sequence↗
PubMed1998

Reperfusion edema after thromboendarterectomy: radiographic patterns of disease.

In patients with chronic pulmonary embolism, pulmonary thromboendarterectomy may result in a unique form of noncardiogenic pulmonary edema termed reperfusion edema. This report reviews the authors' experience after pulmonary thromboendarterectomy with particular emphasis on the radiographic manifestations of reperfusion edema. The clinical and radiographic record of 25 patients who underwent pulmonary thromboendarterectomy at the University of Pennsylvania from 1985 through 1995 were reviewed. The zonal distribution of radiographic opacity, time to maximal opacity, and the time to clearance of reperfusion edema were determined. The relationship of these radiographic manifestations to clinical severity of disease and clinical outcome was examined. Reperfusion edema, characterized by patchy bilateral perihilar alveolar opacities, occurred in all but one patient. There is a lower lung zone predominance of opacities, but in individual cases, striking unilateral or haphazard arrangements of opacities may be seen. In this small sample of patients, no association between preoperative pulmonary arterial pressures and radiographic appearance or clinical outcome was found. However, severity of radiographic opacities, as measured by the extent of involved lung, correlated with disease severity, as measured by time to extubation and time to discharge. Pneumonia, defined as a radiographic opacity that evolves discordantly with the reperfusion edema opacities, occurred in 20% of cases. Reperfusion edema is a common consequence of pulmonary thromboendarterectomy. The severity of radiographic manifestations and clinical severity of disease are related. This characteristically appears as perihilar alveolar opacities.

Adult↗
PubMed1998

Mycobacterial infection in immunocompromised patients.

Mycobacterial infection, including both tuberculosis and nontuberculous mycobacterial infection, is an important cause of morbidity and mortality in immunocompromised patients, particularly those who are infected with the human immunodeficiency virus. When these patients have active tuberculosis, apical, often cavitary, opacities characteristic of postprimary tuberculosis remain among the more common radiographic presentations. However, unusual radiographic manifestations of tuberculosis are more common in immunocompromised patients than in the general population. Nontuberculous mycobacterial infection in immunocompromised patients is frequently hematogenously disseminated, and the appearance on chest radiography is varied. Among patients infected with the human immunodeficiency virus, unifocal or multifocal alveolar infiltrates and mediastinal lymphadenopathy are the most common manifestations.

AIDS-Related Opportunistic Infections↗
PubMed1998

Thoracic CT in the intensive care unit: assessment of clinical usefulness.

PURPOSE: To determine the clinical usefulness of thoracic computed tomography (CT) in patients in a general intensive care unit (ICU). MATERIALS AND METHODS: Images obtained in 108 consecutive thoracic CT examinations and the associated bedside chest radiographs and medical records in 85 patients (55 men, 30 women; age range, 19-92 years) in the ICU of an institution were retrospectively reviewed. CT findings were compared with concurrent bedside chest radiographic findings. The clinical importance of each CT finding was determined by reviewing the clinical record. RESULTS: Of the 232 chest radiographic findings, 199 (86%) were confirmed at CT; when disagreement about mild congestive heart failure was excluded, there was a 93% agreement (199 of 213 findings). However, only CT demonstrated 250 (52%) of the 482 total findings (232 + 250 findings). Although many of these new findings were not clinically important, 32 (30%) of the 108 CT examinations had at least one new clinically important finding. These important new findings most often were (a) abscesses or postoperative fluid collections in the mediastinum, chest wall, or retroperitoneum; (b) malignancies that were detected, staged, or evaluated; (c) unsuspected pneumonia; or (d) pleural effusions. The CT findings resulted in changes in clinical management in 24 (22%) of the 108 examinations. CONCLUSION: CT of the thorax is clinically useful in selected situation in patients in ICUs.

Case-Control Studies↗
PubMed1998

The right inferior supraazygous recess: a cause of upper esophageal pseudomass on double-contrast esophagography.

OBJECTIVE: Our purpose was to characterize the radiographic features of a pseudomass impression on the upper thoracic esophagus, to determine the frequency of such a pseudomass both on double-contrast esophagography and on CT, and to elucidate the anatomic basis for this finding. MATERIALS AND METHODS: Our study group consisted of 135 patients whose double-contrast esophagograms were reviewed retrospectively for the presence or absence of an extrinsic indentation on the right posterolateral wall of the upper thoracic esophagus. In another patient group, 50 CT scans of the chest were also reviewed for the presence or absence of a prominent right inferior supraazygous recess and an associated indentation on the upper thoracic esophagus. RESULTS: Thirteen (9.6%) of the 135 barium studies revealed a smooth, gently sloping indentation on the right posterolateral wall of the upper thoracic esophagus. The indentations ranged from 5 to 10 cm in length and extended inferiorly from the thoracic inlet to or just below the aortic arch. Twenty-four (48%) of the 50 CT scans revealed a prominent right inferior supraazygous recess projecting behind the esophagus. In five cases (10%), this recess also caused a smooth indentation on the upper thoracic esophagus. CONCLUSION: A pseudomass impression was seen on double-contrast radiography as a smooth, gently sloping indentation on the right posterolateral wall of the upper thoracic esophagus in approximately 10% of patients. The indentation probably represents a normal anatomic variant (i.e., an unusually prominent right inferior supraazygous recess) that should not be mistaken for adenopathy or other masses in the mediastinum impinging on the esophagus.

Contrast Media↗
PubMed1997

Activation of the Src-family tyrosine kinase Hck by SH3 domain displacement.

The protein Hck is a member of the Src family of non-receptor tyrosine kinases which is preferentially expressed in haematopoietic cells of the myeloid and B-lymphoid lineages. Src kinases are inhibited by tyrosine-phosphorylation at a carboxy-terminal site. The SH2 domains of these enzymes play an essential role in this regulation by binding to the tyrosine-phosphorylated tail. The crystal structure of the downregulated form of Hck has been determined and reveals that the SH2 domain regulates enzymatic activity indirectly; intramolecular interactions between the SH3 and catalytic domains appear to stabilize an inactive form of the kinase. Here we compare the roles of the SH2 and SH3 domains in modulating the activity of Hck in an investigation of the C-terminally phosphorylated form of the enzyme. We show that addition of the HIV-1 Nef protein, which is a high-affinity ligand for the Hck SH3 domain, to either the downregulated or activated form of Hck causes a large increase in Hck catalytic activity. The intact SH3-binding motif in Nef is crucial for Hck activation. Our results indicate that binding of the Hck SH3 domain by Nef causes a more marked activation of the enzyme than does binding of the SH2 domain, suggesting a new mechanism for regulation of the activity of tyrosine kinases.

Amino Acid Sequence↗