Recognition of depressed affect in hospitalized psychiatric patients: staff and patient perceptions

A comparison of self-report vs. observer rating of depressed mood in a heterogenous inpatient population revealed wide variations in concordance among diagnostic groups. Patients diagnosed as having Affective Psychosis and "Other' illnesses showed the highest correlation between four self-report scales and an observer rating scale. Patients with a diagnosis of depressive Neurosis showed only modest correlation, while Schizophrenics revealed no significant correlation, on these instruments, suggesting inconsistent communication of affect from Schizophrenic patients to observers. In contrast, when self-report scales were intercorrelated, patients in all four diagnostic categories showed highly significant correlations, indicating that they were consistently reporting their affective state on these instruments. The implications of these findings for future research as well as for practical clinical management are discussed.     

Time to clinical stability in patients hospitalized with community-acquired pneumonia: implications for practice guidelines

CONTEXT: Many groups have developed guidelines to shorten hospital length of stay in pneumonia in order to decrease costs, but the length of time until a patient hospitalized with pneumonia becomes clinically stable has not been established. OBJECTIVE: To describe the time to resolution of abnormalities in vital signs, ability to eat, and mental status in patients with community-acquired pneumonia and assess clinical outcomes after achieving stability. DESIGN: Prospective, multicenter, observational cohort study. SETTING: Three university and 1 community teaching hospital in Boston, Mass, Pittsburgh, Pa, and Halifax, Nova Scotia. PATIENTS: Six hundred eighty-six adults hospitalized with community-acquired pneumonia. MAIN OUTCOME MEASURES: Time to resolution of vital signs, ability to eat, mental status, hospital length of stay, and admission to an intensive care, coronary care, or telemetry unit. RESULTS: The median time to stability was 2 days for heart rate (< or =100 beats/min) and systolic blood pressure (> or =90 mm Hg), and 3 days for respiratory rate (< or =24 breaths/min), oxygen saturation (> or =90%), and temperature (< or =37.2 degrees C [99 degrees F]). The median time to overall clinical stability was 3 days for the most lenient definition of stability and 7 days for the most conservative definition. Patients with more severe cases of pneumonia at presentation took longer to reach stability. Once stability was achieved, clinical deterioration requiring intensive care, coronary care, or telemetry monitoring occurred in 1% of cases or fewer. Between 65% to 86% of patients stayed in the hospital more than 1 day after reaching stability, and fewer than 29% to 46% were converted to oral antibiotics within 1 day of stability, depending on the definition of stability. CONCLUSIONS: Our estimates of time to stability in pneumonia and explicit criteria for defining stability can provide an evidence-based estimate of optimal length of stay, and outline a clinically sensible approach to improving the efficiency of inpatient management.     

Apoptotic induction in transformed follicular lymphoma cells by Bcl-2 downregulation

The roles of Bcl-2 protein and the protein ratio of Bcl-2/Bax in regulating cell growth in various lymphoma cell lines were examined. A dose-dependent decrease in Bcl-2 protein expression was observed in the different lymphomas incubated with lipid-incorporated bcl-2 antisense oligonucleotides (L-bcl-2). Growth inhibition was observed in a transformed follicular lymphoma (FL) cell line, which has the t(14;18) translocation and Bcl-2 protein overexpression. One of the mechanisms by which L-bcl-2 growth inhibition is mediated in these transformed FL cells might be through apoptotic induction, because the treated cells had an increased apoptotic index and showed the typical DNA fragmentation. These studies indicate that Bcl-2 protein is critical in the growth regulation of transformed FL cells. L-bcl-2 did not induce growth inhibition in lymphoma cells not expressing Bcl-2 or Bax protein. Thus, the protein ratio of Bcl-2/Bax may also be important in regulating the growth of these lymphomas.     

Protein thermostability above 100 degreesC: a key role for ionic interactions

The discovery of hyperthermophilic microorganisms and the analysis of hyperthermostable enzymes has established the fact that multisubunit enzymes can survive for prolonged periods at temperatures above 100 degreesC. We have carried out homology-based modeling and direct structure comparison on the hexameric glutamate dehydrogenases from the hyperthermophiles Pyrococcus furiosus and Thermococcus litoralis whose optimal growth temperatures are 100 degreesC and 88 degreesC, respectively, to determine key stabilizing features. These enzymes, which are 87% homologous, differ 16-fold in thermal stability at 104 degreesC. We observed that an intersubunit ion-pair network was substantially reduced in the less stable enzyme from T. litoralis, and two residues were then altered to restore these interactions. The single mutations both had adverse effects on the thermostability of the protein. However, with both mutations in place, we observed a fourfold improvement of stability at 104 degreesC over the wild-type enzyme. The catalytic properties of the enzymes were unaffected by the mutations. These results suggest that extensive ion-pair networks may provide a general strategy for manipulating enzyme thermostability of multisubunit enzymes. However, this study emphasizes the importance of the exact local environment of a residue in determining its effects on stability.     

The Homothorax homeoprotein activates the nuclear localization of another homeoprotein, extradenticle, and suppresses eye development in Drosophila

The Extradenticle (Exd) protein in Drosophila acts as a cofactor to homeotic proteins. Its nuclear localization is regulated. We report the cloning of the Drosophila homothorax (hth) gene, a homolog of the mouse Meis1 proto-oncogene that has a homeobox related to that of exd. Comparison with Meis1 finds two regions of high homology: a novel MH domain and the homeodomain. In imaginal discs, hth expression coincides with nuclear Exd. hth and exd also have virtually identical, mutant clonal phenotypes in adults. These results suggest that hth and exd function in the same pathway. We show that hth acts upstream of exd and is required and sufficient for Exd protein nuclear localization. We also show that hth and exd are both negative regulators of eye development; their mutant clones caused ectopic eye formation. Targeted expression of hth, but not of exd, in the eye disc abolished eye development completely. We suggest that hth acts with exd to delimit the eye field and prevent inappropriate eye development.     

Structural and functional analogy between pneumolysin and proaerolysin

Pneumolysin and proaerolysin are bacterial toxins that form pores in host cells by oligomerization. We propose that they may have similar structures despite a poor sequence identity. The crystal structure of proaerolysin reveals a protein composed of four domains, arranged in the shape of an elongated comma. Electron microscopy of the pneumolysin monomer shows a similar arrangement of domains. The sequence of pneumolysin recognizes the template of proaerolysin from a library of protein folds. A three-dimensional model of pneumolysin has been constructed by the comparative approach using the structure of proaerolysin. This model, together with results on the activity of site- specific mutants and the positions of antigenic sites, has been used to propose functional roles of individual domains.      

Production of human normal adult and fetal hemoglobins in Escherichia coli

A hemoglobin expression system in Escherichia coli is described. In order to produce authentic human hemoglobin, we need to co-express both methionine aminopeptidase and globin genes under the control of a strong promoter. We have constructed three plasmids, pHE2, pHE4 and pHE7, for the expression of human normal adult hemoglobin and a plasmid, pHE9, for the expression of human fetal hemoglobin, in high yields. The globin genes can be derived from either synthetic genes or human globin cDNAs. The extra amino-terminal methionine residues of the expressed globins can be removed by the co-expressed methionine aminopeptidase. The heme is inserted correctly into the expressed alpha- globin from our expression plasmids. A fraction (approximately 25%) of the heme is not inserted correctly into the expressed beta- or gamma- globin. However, the incorrectly inserted hemes can be converted into the correct conformation by carrying out a simple oxidation-reduction process on the purified hemoglobin molecule. We have investigated the functional properties of the expressed hemoglobins by measuring their oxygen-binding properties and their structural features by obtaining their 1H-NMR spectra. Our results show that authentic human normal adult and fetal hemoglobins can be produced from our expression plasmids in E. coli and in high yields. Our expression system allows us to design and to produce any recombinant hemoglobins needed for our research on the structure-function relationship in hemoglobin.      

Bilateral femoral neck fractures as a complication of myelography

This paper discusses two cases of bilateral subcapital fracture of the proximal femur as a complication of myelography with Conray 60. The literature is reviewed.