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Biomedical subjects

T A Morris

Publications and source records attributed to T A Morris.

34 records · Page 2Linked to original sources

Degree of polymer organization decreases the binding of a monoclonal antibody raised against the beta-chain amino terminus of fibrin.

UNLABELLED: Accurate non-invasive diagnosis of deep venous thrombosis and pulmonary embolism remains an elusive goal. Radiolabeled antibodies specific for the epitope exposed on the beta-chain of fibrin after fibrino-peptide B release (anti-beta) enabled in situ imaging of thrombi in experimental subjects with nuclear medicine techniques. When used in patients anticoagulated for thrombo-embolic disease, however, the antibody was unable to reliably image the thrombi. We postulated that the neoepitope on the beta-chain of fibrin is covered up as fibrin organizes into a polymer network and is therefore exposed to the antibody only during active incorporation of fibrin subunits. We determined the equilibrium binding kinetics of an anti-beta monoclonal antibody to fibrin in various stages of organization. The concentration of exposed epitopes on immobilized fibrin monomers was equal to the molar concentration of fibrin beta-chains. The percentage of beta-chains exposed to the antibodies markedly decreased as the fibrin network was allowed to organize, a process catalyzed by calcium. CONCLUSIONS: The beta-chain amino terminus of fibrin is exposed transiently as subunits are added to the enlarging fibrin network. Anti-beta antibodies bind preferentially to actively enlarging fibrin polymers.

Antibodies, Monoclonal↗

Parenchymal scarring is associated with restrictive spirometric defects in patients with chronic thromboembolic pulmonary hypertension.

UNLABELLED: The finding of a restrictive pulmonary defect may divert clinicians from considering the diagnosis of chronic thromboembolic pulmonary hypertension because lung volumes are usually normal in this disorder. We have, however, encountered a significant number of these patients with reduced lung volumes. Furthermore, we have observed many patients who have developed parenchymal scars and/or pleural thickening. To determine whether such findings are associated with lung volume restriction, we analyzed patients evaluated at our institution for chronic thromboembolic pulmonary hypertension over a 20-month period in whom thoracic high-resolution CT scans and pulmonary function testing had been performed. Patients with obstructive or restrictive lung disease from another cause were excluded. We compared the presence of lung restriction (total lung capacity below 80% of predicted) with the extent of parenchymal scarring, pleural thickening, and pulmonary artery diameter on CT scans. Of 191 patients evaluated, 51 met criteria for entry. Eleven patients (22%) had lung restriction. Parenchymal scarring was highly associated with lung restriction (p = 0.01). Neither pleural thickening (p = 0.08) nor pulmonary artery diameter (p = 0.80) was associated with lung restriction. CONCLUSIONS: A significant number of patients with chronic thromboembolic pulmonary hypertension may have restrictive lung defects. The restriction may be due to parenchymal scarring.

Adult↗

Preliminary evidence that augmentation therapy diminishes degradation of cross-linked elastin in alpha-1-antitrypsin-deficient humans.

It is hypothesized that emphysema develops in some severely alpha 1-antitrypsin (AAT)-deficient persons because endogenous elastases are not adequately controlled by AAT, and accelerated elastin degradation occurs. It is not known whether augmentation therapy with AAT diminishes degradation of lung elastin in severely deficient persons with lung disease. Two severely deficient, PiZ patients were studied, a 63-year-old never-smoking woman with bronchiectasis and a 41-year-old smoking man with emphysema. Urinary desmosine (DES) was determined before and after augmentation therapy with AAT, 260 mg/kg/month. Mean +/- SEM pretreatment urinary DES was elevated in both patients, 19.7 +/- 0.9 (n = 2) and 10.8 +/- 0.2 (n = 2) micrograms/g creatinine, respectively, compared to normal values of 7.5 +/- 0.3 (n = 22) micrograms/g creatinine. Following augmentation therapy, urinary DES values decreased 40 and 36%, respectively, to 11.9 +/- 0.3 (n = 8) and 6.9 +/- 0.4 (n = 7) microgram/g creatinine (p < 0.05). We conclude that monthly AAT augmentation therapy decreased DES excretion in the urine of these PiZ patients. We speculate that since there was lung disease in both patients, a decrease in degradation of lung elastin is the most likely explanation for this observation.

Adult↗

Intravascular bronchioloalveolar tumor of the lung presenting as pulmonary thromboembolic disease and pulmonary hypertension.

Intravascular bronchioloalveolar tumor, the pulmonary counterpart of epithelioid hemangioendothelioma, typically presents as bilateral pulmonary nodules in young women. We report a case of intravascular bronchioloalveolar tumor that clinically mimicked acute pulmonary thromboembolic disease initially and was subsequently proven to have pulmonary hypertension with right ventricular dysfunction by angiography. The diagnosis of intravascular bronchioloalveolar tumor was confirmed by immunohistochemical and ultrastructural studies after it was suspected on routine histologic examination. In addition, the tumor cells expressed glycoprotein cell adhesion molecule CD44, which has been implicated in increased tumor invasiveness and metastasis in various carcinomas and several aggressive non-Hodgkin's lymphomas.

Carrier Proteins↗

Characterization of the gene encoding human cone transducin alpha-subunit (GNAT2).

The human cone transducin alpha-subunit (GNAT2) gene has been completely characterized. The human GNAT2 transcription unit is 9967-bp in length and consists of eight exons with seven introns. The eight exons are identical to the reported cDNA sequence (Lerea et al., 1989). Northern blot analysis of RNA from human retinas and a retinoblastoma cell line, WERI-RB1, reveals a 1.7-kb transcript for GNAT2. Multiple transcription initiation sites were mapped for human retina and WERI-RB1 RNA by primer extension and S1 nuclease protection assays. This gene has seven initiation sites spanning 31 bp. The sequence upstream of the GNAT2 gene shows a TATA box consensus sequence at -29, a CCAAT box consensus sequence at -58 (reverse orientation), and a sequence (CCATAT) similar to the CCAAT box consensus at -76. The GNAT2 upstream sequence shows no significant identity with the upstream region of the human rod transducin alpha-subunit gene (GNAT1) or with the upstream regions of the color visual pigment genes, indicating that the expression of GNAT2 may be regulated differently than these other rod- and cone-specific proteins.

Amino Acid Sequence↗

Characterization and comparative structural features of the gene for human interstitial retinol-binding protein.

We have cloned the gene for human interstitial retinol-binding protein (IRBP) and compared its nucleotide sequence with that of the corresponding cloned cDNA. The human IRBP gene is approximately 9.5 kilobase pairs (kbp) in length and consists of four exons separated by three introns. The introns are 1.6-1.9 kbp long. The gene is transcribed by photoreceptor and retinoblastoma cells into an approximately 4.3-kilobase mRNA that is translated and processed into a glycosylated protein of 135,000 Da. The amino acid sequence of human IRBP can be divided into four contiguous homology domains with 33-38% identity, suggesting a series of gene duplication events. In the gene, the boundaries of these domains are not defined by exon-intron junctions, as might have been expected. The first three homology domains and part of the fourth are all encoded by the first large exon, which is 3,180 base pairs long. The remainder of the fourth domain is encoded in the last three exons, which are 191, 143, and approximately 740 base pairs long, respectively. This unusual structure is shared with the bovine IRBP gene. A large (1.7 kbp) fragment appears to have been lost from the 3'-noncoding region of the last human exon. We conclude that the human and bovine genes have similar evolutionary histories.

Amino Acid Sequence↗

Management of lone star ticks (Acari: Ixodidae) in recreational areas with acaricide applications, vegetative management, and exclusion of white-tailed deer.

A project on management of lone star ticks, Amblyomma americanum (L.), at Land Between the Lakes, a Tennessee Valley Authority recreational area in Kentucky-Tennessee, during 1984-1988, demonstrated the effectiveness and economics of three control technologies. Acaricide applications (chlorpyrifos at 0.28 kg [AI]/ha), vegetative management (mowing and removal of 40% overstory and 90-100% of midstory, understory, and leaf litter), and host management (white-tailed deer exclusion from a 71-ha campground with a single-line fence) provided 75, 70, and 64% mean controls of all life stages of the lone star tick, respectively. Combinations of acaricide applications + vegetative management, acaricide applications + host management, and acaricide applications + vegetative management + host management produced 94, 89, and 96% mean control of all life stages, respectively. The costs of acaricide applications (two per year), vegetative management (two mowings per year), and white-tailed deer exclusion (single-line fence) were $45, $150, and $30/ha/yr, respectively. Results of this project are used to design management strategies that could be considered for use against lone star ticks in recreational areas.

Analysis of Variance↗

Diffusing capacity is not measurably affected by routine lung perfusion scanning.

Lung scanning with radiolabeled macroaggregated albumin (MAA) has caused cardiovascular collapse and death in patients with extensive pulmonary vascular disease. These adverse reactions have been suggested to be secondary to MAA embolic occlusion of a significant portion of the remaining pulmonary circulation. The single breath diffusing capacity for carbon monoxide (SBDLCO) is heavily dependent on the status of the pulmonary microcirculation and is reduced in clinical pulmonary embolism. The effect of MAA particles on the lung microcirculation was measured by SBDLCO in 11 patients undergoing clinically indicated lung perfusion scanning. SBDLCO was measured before and immediately after injection of 256,000 to 448,000 20-40 micron particles of [99mTc]MAA. Mean SBDLCO prior to injection was 18.9 +/- 1.7 (s.e.m.) and immediately after injection was unchanged at 19.0 +/- 1.6 ml/min/mmHg. The lowest pre-injection SBDLCO values were 11.5 and 6.2 ml/min/mmHg (54% and 28% of predicted, respectively); in neither of these patients was there a detectable change in SBDLCO measured after injection of MAA. Thus occlusion of as many as 448,000 20-40 micron pulmonary vessels by MAA is without detectable impact on the transfer of carbon monoxide even in patients with sufficient pulmonary disease to lower the SBDLCO to 28% of predicted.

Adolescent↗

Tinidazole or pivampicillin in third molar surgery.

There is an increasing body of evidence implicating oral anaerobic bacteria in the aetiology of post-surgical dentoalveolar infections. This information has lead to several studies demonstrating the usefulness of specific anaerobicidal drugs in the prevention and treatment of dento-alveolar infection. One such study utilised a single 2 g preoperative oral dose of tinidazole which was found to be significantly better than placebo in preventing infective sequelae after removal of impacted mandibular third molars. The present study was designed to compare a high-dose short-term broad spectrum penicillin, (pivampicillin), with the previously described regimen, using tinidazole in order to discern the existence or otherwise of any practical difference between an anaerobicidal and a broad spectrum antibiotic when local infection was considered.

Adolescent↗

Pigment gallstone composition in cirrhotic and noncirrhotic subjects.

The composition of pigment gallstones from patients with and without cirrhosis was compared. Carbonate-containing pigment stones were distinguished from noncarbonate stones by infrared spectroscopy. Calcium was the major cation of each stone group. The major anion in noncarbonate pigment stones was bilirubinate or phosphate, but was carbonate in carbonate stones. The composition of pigment stones from cirrhotic and noncirrhotic patients was similar except that significantly less carbonate was present in carbonate stones, and less pigment (bilirubinate) was present in noncarbonate stones from noncirrhotics. These data suggest that irrespective of the presence of cirrhosis, the formation of noncarbonate pigment stones involves the selective precipitation of calcium bilirubinate and phosphate, whereas carbonate stone formation involves the selective precipitation of calcium carbonate.

Age Factors↗

Pigment versus cholesterol cholelithiasis: identification and quantification by infrared spectroscopy.

We previously reported that 27% of 92 cholecystectomized patients had pigment stones (Am J Dig Dis 19:585-590, 1974). Using standard biochemical methods, we found that cholesterol accounted for an average of 77% of the dry weight of cholesterol stones, but that unconjugated bilirubin represented a mean of only 7% of pigment stones. This quantitation of pigment stones was limited because approximately 66% of their weight was insoluble. To characterize pigment and cholesterol stone composition further, we used infrared spectroscopy--a technique requiring neither crystallinity nor solubilization--to quantitate pigment, carbonate, and cholesterol in gallstones. Other organic and inorganic components of stones were measured by standard methods. By infrared spectroscopy, two types of pigment stones were identified: carbonate-containing and noncarbonate pigment stones. Carbonate pigment stones contained significantly more calcium, carbonate, and phosphate, but less pigment than noncarbonate stones. Compared to our initial report, the total measured components of all pigment stones were increased 6-fold from 10 to 63%. Cholesterol was the major component of cholesterol stones by chemical assay or infrared spectroscopy. Among five cholesterol stones with limited solubility, 80% of the insoluble residue was identified as cholesterol by infrared spectroscopy. This study extends our knowledge of pigment stone and cholesterol stone composition by the use of quantitative infrared spectroscopy in conjunction with standard biochemical methods; furthermore, it confirms that pigment and cholesterol stones differ in composition and form by different mechanisms.

Carbonates↗

Evaluation of radiographic lucency or opaqueness of gallstones as a means of identifying cholesterol or pigment stones. Correlation of lucency or opaqueness with calcium and mineral.

A major criterion for the selection of patients with gallstones for treatment with chenodeoxycholic acid is the radiographic demonstration of lucent gallstones. In this study, we sought to evaluate the degree of selectivity of that criterion for distinguishing patients with cholesterol stones from those with pigment stones and to define the determinants of stone lucency or opaqueness. Of 92 lucent stones, 14% were pigment stones; and of 18 of opaque stones, 33% were cholesterol. Thus, the criterion of stone lucency allows inclusion of a significant number of subjects (14%) with lucent pigment stones, which may account for about one-half of the reported 33% incidence of treatment failures with chenodeoxycholic acid. Conversely, of patients with opaque stones, the one-third with cholesterol stones would be excluded from chenodeoxycholic acid treatment. Calcium is the major metal of both types of stones. However, opaque stones contain 6 times more calcium than lucent stones, which accounts for the difference in radiographic appearance.

Bile Pigments↗

Approaching equity in consumer health information delivery: NetWellness.

The growing public interest in health and wellness information stems from many sources, including social changes related to consumers' rights and women's health movements, and economic changes brought about by the managed health care revolution. Public, hospital, and medical center libraries have been ill-equipped to meet the increasing need for consumer-oriented materials, even though a few notable programs have been established. The "Information Superhighway" could be an effective tool for sharing health information if access to telecomputing equipment and training were available to those with an information need. The University of Cincinnati Medical Center, with its libraries in the leading role, is delivering NetWellness, an electronic consumer health library service, to residents of 29 counties in three midwestern states. Users connect directly through the Internet, through regional Free-Nets, and by visiting one of 43 public access sites where networked workstations have been installed. The continued success of the project depends on developing partnerships, providing quality content and maintaining fair access.

Community-Institutional Relations↗

The structure of medical informatics journal literature.

OBJECTIVE: Medical informatics is an emergent interdisciplinary field described as drawing upon and contributing to both the health sciences and information sciences. The authors elucidate the disciplinary nature and internal structure of the field. DESIGN: To better understand the field's disciplinary nature, the authors examine the intercitation relationships of its journal literature. To determine its internal structure, they examined its journal cocitation patterns. MEASUREMENTS: The authors used data from the Science Citation Index (SCI) and Social Science Citation Index (SSCI) to perform intercitation studies among productive journal titles, and software routines from SPSS to perform multivariate data analyses on cocitation data for proposed core journals. RESULTS: Intercitation network analysis suggests that a core literature exists, one mark of a separate discipline. Multivariate analyses of cocitation data suggest that major focus areas within the field include biomedical engineering, biomedical computing, decision support, and education. The interpretable dimensions of multidimensional scaling maps differed for the SCI and SSCI data sets. Strong links to information science literature were not found. CONCLUSION: The authors saw indications of a core literature and of several major research fronts. The field appears to be viewed differently by authors writing in journals indexed by SCI from those writing in journals indexed by SSCI, with more emphasis placed on computers and engineering versus decision making by the former and more emphasis on theory versus application (clinical practice) by the latter.

Abstracting and Indexing↗