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Biomedical subjects

R L Weiss

Publications and source records attributed to R L Weiss.

At least 37 records · Page 2Linked to original sources

Acetylglutamate synthase from Neurospora crassa: structure and regulation of expression.

A DNA clone which complemented an arg-14 mutation of Neurospora crassa was isolated by sib selection from a cosmid library (pMOcosX). Southern and restriction-fragment-length polymorphism (RFLP) analysis confirmed that the cloned DNA contained the arg-14 gene. The arg-14 gene was identified as the structural gene for acetylglutamate synthase by immunodepletion of enzyme activity with antibodies prepared against an arg-14 fusion protein and by the thermal instability of acetylglutamate synthase in a temperature-sensitive arg-14 mutant. The fungai acetylglutamate synthase has little sequence homology to its bacterial counterpart, unlike other arginine biosynthetic enzymes. Expression of the arg-14 gene is regulated by cross-pathway control similar to many amino acid biosynthetic genes. However, expression of acetylglutamate synthase occurs throughout the developmental growth cycle, unlike other arginine biosynthetic enzymes.

Arginine↗

The usefulness of transesophageal echocardiography in diagnosing cardiac contusions.

OBJECTIVES: To assess the usefulness of transesophageal echocardiography in diagnosing cardiac contusions in patients with blunt trauma. BACKGROUND: For more than a decade, noninvasive tests, including ECGs, cardiac enzymes, nuclear studies, and transthoracic echocardiography have been utilized in an attempt to identify trauma patients with cardiac injuries. These tests have been imperfect in identifying the patients at high risk for mortality. METHODS: We retrospectively reviewed the charts in 22 patients with transesophageal echocardiographically diagnosed cardiac contusions noting age, race, sex, transthoracic echocardiographic examinations, study quality, and outcome. We also noted the Injury Severity Score, which is a measure of the severity of illness in trauma patients. Higher scores correlate more severe injury and higher mortality. We defined cardiac contusions as presence of wall motion abnormality, including either or both ventricles, in the absence of transmural myocardial infarction on ECG following nonpenetrating chest trauma. RESULTS: Over a 30-month period, 81 transesophageal echocardiographic examinations were performed on trauma patients. Among this group, 22 patients were diagnosed as having cardiac contusions. There were 15 patients with right ventricular contusions, 7 patients with left ventricular contusions, and 2 patients with both ventricles involved. We compared this group with all ICU trauma patients admitted to the hospital during this time period. Overall, the contusion patients had an average Injury Severity Score of 27 and a mortality of 27% compared with the overall trauma group with an Injury Severity Score of 33 and a corresponding mortality of 9% (p < 0.001). Corresponding ECGs were nondiagnostic in 73% of patients with cardiac contusion. There were no complications related to the transesophageal examinations. CONCLUSIONS: Transesophageal echocardiographically diagnosed cardiac contusion in trauma patients carries a high mortality rate. Transesophageal examinations are safe and provide excellent quality images where transthoracic examinations were inadequate. Right ventricular contusions are approximately twice as common as left ventricular contusions.

Adolescent↗

Marital interaction coding system: revision and empirical evaluation.

Given the vast amount of codeable information in marital interactions, observational coding systems must emphasize particular classes of behavior. The most widely used marital coding scheme, the Marital Interaction Coding System (MICS), like many older behavioral coding systems, emphasizes verbal content over affect. Changes made to the MICS between versions III and IV are described; they were intended to increase the system's use of coded affect and to decrease autodependence in sequential analysis. We used an archival data set of 994 couples' videotaped conflict negotiations coded with the MICS. As intended, the MICS-IV, relative to the MICS-III, was found to have the advantage of capturing more non-verbal affect expressed during marital interactions, which resulted in stronger interactional contingencies (e.g. Wife Blame-->Husband Blame, Husband Facilitation-->Wife Facilitation). The MICS-IV also yielded significantly lower levels of spurious autodependence.

Adult↗

Reversible uridylylation of the Escherichia coli PII signal transduction protein regulates its ability to stimulate the dephosphorylation of the transcription factor nitrogen regulator I (NRI or NtrC).

We have reconstituted the signal transduction system responsible for the negative regulation of the transcription of the Escherichia coli glnA gene, encoding glutamine synthetase, by glutamine. This signal transduction system consists of four proteins: the transcription factor NRI (NtrC), which activates glnA transcription when it is phosphorylated, the kinase/phosphatase protein NRII (NtrB) that directly controls the extent of NRI phosphorylation, the PII signal transduction protein that controls the phosphatase activity of NRII, and the uridylyltransferase/uridylyl-removing (UTase/UR) enzyme that is regulated by glutamine and controls the activity of PII. In the reconstituted system, the removal of uridylyl groups from the PII protein, catalyzed by the UTase/UR protein in the presence of glutamine, resulted in the stimulation of NRI approximately P dephosphorylation. In contrast, the uridylylated form of the PII protein had no discernible effect on NRI phosphorylation. The uridylylation of the trimeric PII protein by the monomeric UTase/UR protein is a non-cooperative reaction in which the partially modified species accumulated and were readily observed. Partially modified PII trimers were partially active in stimulating the dephosphorylation of NRI approximately P. Thus, both the PII-UTase/UR and PII-NRII interactions display the continuous variability characteristic of rheostats as opposed to the binary variability characteristic of toggle switches.

Bacterial Proteins↗

A polyprotein precursor of two mitochondrial enzymes in Neurospora crassa. Gene structure and precursor processing.

N-Acetylglutamate kinase (AGK) and N-acetyl-gamma-glutamyl-phosphate reductase (AGPR) function as two separate mitochondrial enzymes, but are encoded by a single nuclear gene in several fungi. The Neurospora crassa arg-6 gene encoding these enzymes has been cloned and sequenced, and the enzymes responsible for processing the polyprotein precursor have been identified. The 871-amino acid precursor contains a normal N-terminal mitochondrial targeting sequence, an internal connecting region (approximately 200 amino acids) upstream of the distal reductase domain, and coding regions with N-terminal amino acid sequences identical with those of purified N-acetylglutamate kinase and N-acetyl-gamma-glutamyl-phosphate reductase. Sequence comparisons of the coding regions indicate high levels of conservation between prokaryotic and fungal proteins. Regions suggesting ancestral relationships to N-acetylglutamate synthase and aspartate beta-semialdehyde dehydrogenase have been identified. Both the N-terminal targeting sequence and the connecting region contain consensus sites for cleavage by the mitochondrial processing peptidase and processing enhancing protein. In vitro processing assays with intact mitochondria, solubilized mitochondria, and purified enzymes have shown that the mitochondrial processing peptidase and processing enhancing protein cleave not only the N-terminal mitochondrial targeting sequence but also process the polyprotein precursor into the two mature enzymes.

Aldehyde Oxidoreductases↗

Management of the thyroid isthmus in tracheostomy: a prospective and retrospective study.

The thyroid isthmus is often encountered while a tracheostomy is being performed. This study details retrospective and prospective comparison of electrocautery division of the isthmus with older techniques. In this study, electrocautery division of the thyroid isthmus during tracheostomy is faster and as safe as other techniques with respect to blood loss, perioperative complications, and airway outcome.

Blood Loss, Surgical↗

Malignant thymoma. A complicated triad of SVC syndrome, cardiac tamponade, and DIC.

A patient presented with multisystem disease due to a very aggressive malignant thymoma. The case was complicated by the triad of cardiac tamponade, superior vena cava (SVC) syndrome, and disseminated intravascular coagulation (DIC). A review of the English literature reveals this to be a unique constellation of clinical symptoms and that DIC was heretofore unreported.

Adult↗

Impact of the incidental diagnosis of clinically unsuspected central pulmonary artery thromboembolism in treatment of critically ill patients.

Mortality is high in unrecognized pulmonary embolism (PE), but the diagnosis is difficult to establish, especially in patients with coexisting cardiopulmonary disorders. We describe a group of 14 patients with pulmonary thromboemboli in whom transesophageal echocardiography (TEE) performed for coexisting cardiopulmonary conditions established the clinical diagnosis of PE not suspected prior to TEE. The patients had initial clinical diagnoses of heart failure (eight patients), cardiogenic shock (two patients), atrial septal defect (two patients), aortic dissection (one patient), and pneumonia (one patient). Thirteen patients had risk factors for PE. Transthoracic echocardiography (TTE) demonstrated right heart strain in eight patients but did not visualize PE in any of the patients. The TEE diagnosis of occult central pulmonary artery thromboembolism changed treatment in all 14 patients. Ten of the 14 patients were successfully discharged from the hospital. We conclude that occult central pulmonary artery thromboemboli are not uncommon in patients presenting with acute cardiopulmonary disorders and the presence of risk factors for PE and right heart strain on TTE should alert the physician to suspect PE. If and when TEE is performed in patients with acute cardiopulmonary disorders with risk factors for PE and right heart strain, the physician should evaluate the main pulmonary artery and its branches for central pulmonary artery thromboemboli.

Adult↗

Improvement in circulatory and oxygenation status by perflubron emulsion (Oxygent HT) in a canine model of surgical hemodilution.

To examine the effect of a low dose of Oxygent HT on hemodynamics and oxygen transport variables in a canine model of profound surgical hemodilution, two groups of adult anesthetized splenectomized beagles were hemodiluted with Ringer's solution to Hb 7 g/dL. The treated group received 1 mL/kg Oxygent HT (90% w/v perflubron emulsion [perfluorooctyl bromide], Alliance Pharmaceutical Corp.) and both groups (7 controls and 10 treated) were further hemodiluted using 6% hydroxyethyl starch until cardiorespiratory decompensation occurred. Pulmonary artery catheterization data and oxygen transport variables were recorded at Hb decrements of 1 g/dL breathing room air. There was no difference among groups during initial hemodilution. However, in the Oxygent HT group there was a statistically significant improvement in mean arterial pressure, CVP, cardiac output, PvO2, SvO2, DO2, and pulmonary venous admixture shunt during profound hemodilution to Hb levels of 6, 5, and 4 g/dL. A low dose of Oxygent HT offered benefit in improving hemodynamics and oxygen transport parameters even under air breathing conditions in a model of surgical hemodilution. This effect was most apparent at lower levels of Hb.

Animals↗

Arginine transport in mitochondria of Neurospora crassa.

Transport of arginine into mitochondria of Neurospora crassa has been studied. Arginine transport was found to be saturable (Km = 6.5 mM) and to have a pH optimum of pH 7.5. Mitochondrial arginine transport appeared to be facilitated transport rather than active transport because: (i) the arginine concentration within the mitochondrial matrix after transport was similar to that of the reaction medium, and (ii) uncouplers and substrates of oxidative phosphorylation did not affect the transport rate. The basic amino acids ornithine, lysine, and D-arginine inhibited arginine transport. The arginine transport system could be irreversibly blocked by treating mitochondria with the reactive arginine derivative, N-nitrobenzyloxycarbonyl-arginyl diazomethane.

Amino Acids↗

Ornithine decarboxylase activity in tumor and normal tissue of head and neck cancer patients.

Tumorigenesis requires increased biosynthesis of polyamines and elevated levels of ornithine decarboxylase, which is the rate-limiting enzyme in the polyamine synthesis pathway. Previous animal studies have noted a marked increase in ornithine decarboxylase after exposure to tumorigenic stimuli and that pretreatment with vitamins A and E provides protection against the carcinogenic action. However, studies of ornithine decarboxylase activity in human oral cavity carcinoma have not been as specific. The goal of this study was to determine whether a specific difference in ornithine decarboxylase activity occurs in tumor versus adjacent normal tissue in head and neck squamous cell carcinoma patients. Ornithine decarboxylase activity was measured in 30 consecutive head and neck cancer patients undergoing surgical therapy. Ornithine decarboxylase levels were found to be significantly elevated in tumor tissue samples when compared to adjacent normal mucosa samples (P less than .004). This finding confirms the previous findings noted in animal models and implies that the protective effects of vitamins A and E will extend to human head and neck cancers.

Carcinoma, Squamous Cell↗

A clinical laboratory management elective for pathology residents.

Many practicing pathologists, particularly those in private settings, function as managers. Their responsibilities may not only involve directing the successful activities of laboratory personnel, but often require a level of accountability to hospital administrators or business managers. Traditional training programs focus on technical competency and devote little time, if any, to preparing their graduates for the management aspects of their careers. In response to this need, a 1-month elective was designed for senior pathology residents at the University of Utah, Salt Lake City. The cumulative experiences of a large academic pathology department and its successful commercial laboratory venture provided a real-world supplement to a curriculum founded in basic business management principles.

Curriculum↗

Diagnosis of cytomegalovirus pneumonitis on bronchoalveolar lavage fluid: comparison of cytology, immunofluorescence, and in situ hybridization with viral isolation.

Forty-three bronchoalveolar lavage (BAL) specimens from 40 immunocompromised patients were studied for the presence of cytomegalovirus (CMV) by rapid diagnostic methods. DNA in situ hybridization, cytology, and immunofluorescence were compared to conventional cell culture. Eleven (25%) of the 43 BAL samples grew CMV in culture. In situ hybridization detected 6 of these 11 for sensitivity, specificity, and predictive values of positive and negative of 55%, 94%, 75%, and 86%, respectively. Cytology had a sensitivity of 73% and specificity of 100%. Six Papanicolaou-stained cytospins were screened cytologically versus one hybridization cytospin, and the higher sensitivity of cytology may reflect this extensive sampling. The immunofluorescent method had a sensitivity equal to that of cytology (73%): however, the specificity (72%) was significantly less than that of either the probe or cytology. These data suggest that although in situ hybridization can be a rapid, useful method for detecting CMV in BAL specimens, cytology appears to be a more sensitive method.

Bronchoalveolar Lavage Fluid↗