The association between histopathologic effects and liver weight changes induced in mice and rats by chemical exposures: An analysis of the data from Toxicity Reference Database (ToxRefDB).

Absolute (ALW) and relative (RLW) liver weight changes are sensitive endpoints in repeat-dose rodent toxicity studies, and their changes are often used for quantitative assessment of health effects induced by hepatotoxic chemicals using the benchmark dose-response modeling (BMD) approach. To find biologically relevant liver weight changes to chemical exposures, we evaluated all data available for liver weight changes and associated liver histopathologic findings from the Toxicity Reference Database (ToxRefDB). Our analysis of 389 subchronic mouse and rat studies for 273 chemicals found significant differences in treatment-related ALW and RLW changes between dose groups with and without liver histopathologic changes. In addition, we demonstrate that chemical treatment-induced ALW and RLW changes can predict the presence of histopathologic findings and inform the selection of biologically relevant liver weight changes for BMD modeling and derivation of toxicity values.

Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells. Adult AIDS Clinical Trials Group 285 Study Team.

Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1-infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 microg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/microL for 6 subjects, 200 to 500/microL for 6 subjects, and <200/microL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log(10)) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)

Trypanosoma brucei: identification of an internal region of phosphoglycerate kinase required for targeting to glycosomal microbodies.

Among the microbodies found in eukaryotes are the glycosomes of Trypanosoma brucei, thought to be closely related to peroxisomes. Two types of targeting signals for glycosomes have been identified thus far: type 1 at the C-terminus and type 2 at the N-terminus. In this report, we use an epitope-tagging system to characterize the targeting signal found on the minor glycosomal isozyme of phosphoglycerate kinase, 56PGK. No type 1 or 2 signal was found; rather, the topogenic information was found to be internal. Chimeric molecules formed with the cytoplasmic phosphoglycerate kinase isozyme indicate that a region between amino acids 24 and 91 of 56PGK is essential for glycosomal targeting. No homology was found between this region and peroxisomal proteins containing internal targeting signals.

Health care utilization of patients with psychogenic nonepileptic seizures.

Medical records were reviewed for 94 consecutive inpatients diagnosed with nonepileptic seizures. A 122-item follow-up questionnaire was returned by 71 patients (76%). The majority of the subjects reported fewer seizures (73%), their general health as "very good" (20%) or "good" (37), and "improved" quality of life (55%). Many patients had either discontinued (50%) or reduced (17%) use of anticonvulsant medications. The patients most often sought care from primary care providers (46%), followed by psychiatrists/psychologists (41%) and neurologists (31%). Of the 57 patients (80%) advised to seek psychiatric care, 27 individuals (47%) followed this recommendation.

Psychiatric implications of surgical treatment of epilepsy.

Clinicians must consider the psychiatric issues relevant to patients undergoing neurosurgical procedures for epilepsy. Obtaining the patient's psychiatric history can facilitate stabilizing the patient's condition before operative intervention. Preoperatively, depressive and anxiety disorders are the most common psychiatric conditions diagnosed in candidates for surgical treatment of epilepsy. Although psychotic disorders occur infrequently, they demand attention because symptoms may interfere with patient compliance with follow-up care. Patients with chronic psychotic symptoms who have ongoing seizures postoperatively and bilateral seizure foci are at higher risk for a poor outcome and postoperative psychosis. When psychiatric disorders are present, surgical management is not contraindicated, but preoperative psychiatric intervention may be warranted. Most patients have a favorable outcome with the elimination of seizures, which simplifies the subsequent treatment of a psychiatric disorder.

A major tyrosine-phosphorylated protein of Trypanosoma brucei is a nucleolar RNA-binding protein.

We have previously identified a set of tyrosine-phosphorylated proteins with apparent molecular masses of 44-46 kDa as some of the major tyrosine phosphorylated species in the protozoan parasite Trypanosoma brucei. We now show that these molecules, herein named Nopp44/46, are localized in the nucleolus. Using monoclonal antibodies, we have isolated Nopp44/46 cDNA clones from expression libraries. Sequence analysis reveals that the predicted amino acid sequence of the molecule is composed of an N-terminal unique region, an internal acidic region, and C-terminal repeat region. Analysis of the cDNA clones and genomic Southern analysis indicated that Nopp44/46 belongs to a multigene family in which different gene copies are very similar but vary in the number of repeats. Interestingly, the repetitive amino acid sequence motif contains multiple RGG (Arg-Gly-Gly) boxes characteristic of RNA-binding proteins. In vitro binding experiments demonstrated that Nopp44/46 is indeed capable of binding nucleic acids. Competition experiments with different RNA homopolymers demonstrated that Nopp44/46 preferentially binds to poly(U). These studies suggest that Nopp44/46 may play a role in RNA metabolism in trypanosomes and raise the possibility that tyrosine phosphorylation may regulate the process.

Chronic inflammatory meningoencephalitis should not be mistaken for Alzheimer's disease.

We describe two patients with a chronic encephalopathy that clinically resembled dementia but that resolved after oral administration of high-dose corticosteroid therapy. Both patients had serologically documented Sjögren's syndrome, a diagnosis that was further supported by biopsy of a salivary gland in one. Neither patient had radiologic evidence of vasculitis of the central nervous system. In one patient, meningeal and brain biopsy specimens showed perivascular inflammatory lymphocytic infiltrates. Chronic inflammatory meningoencephalitis is a treatable cause of chronic encephalopathy that should be clinically distinguished from dementia associated with Alzheimer's disease.

Characterization of a Trypanosoma brucei nuclear gene encoding a protein homologous to a subunit of bovine NADH:ubiquinone oxidoreductase (complex I).

A Trypanosoma brucei gene has been identified that encodes a protein predicted to be a component of the trypanosome homologue of mitochondrial NADH:ubiquinone oxidoreductase (complex I). High homology was found to a 20-kDa component of the iron-sulfur protein fraction of bovine mitochondrial NADH:ubiquinone oxidoreductase and the products of the ndhK locus of Paramecium tetraurelia mitochondria and the NQO6 locus of Paracoccus denitrificans. The homology extends to several other proteins predicted to function as part of electron transport systems, including the psbG/ndhK gene products of chloroplast and cyanobacterial genomes which are thought to be subunits of a NADH:plastoquinone oxidoreductase involved in chlororespiration. The T. brucei ndhK counterpart is nuclearly encoded. An extended amino terminus of the T. brucei ndhK with structural similarity to mitochondrial presequences indicates that its transfer into mitochondria is likely. Stumpy and slender bloodforms and procyclic forms all possess similar levels of ndhK transcripts despite previous reports of stage-regulated expression of complex I-like activity.

Electroconvulsive Therapy for Depression After Temporal Lobectomy for Epilepsy.

Electroconvulsive therapy (ECT) was administered to a 25-year-old woman with major depression with psychotic features who had undergone a left temporal lobectomy for medically intractable partial epilepsy 1 year earlier. Her depressive illness responded to ECT without ill effects to her seizure disorder.

Status epilepticus as a complication of concurrent electroconvulsive and theophylline therapy.

Status epilepticus that occurs after electroconvulsive therapy is a rarely reported event. Seizures associated with use of theophylline usually result from severe toxicity. We report a case in which status epilepticus occurred after electroconvulsive therapy in a patient who had a theophylline level above the accepted therapeutic range but below that generally associated with seizures. Caution should be exercised in the concurrent administration of electroconvulsive therapy and theophylline preparations.

Psychiatric aspects of chronic organic brain syndrome.

In chronic organic brain syndrome, or dementia, the patient generally retreats to simple, familiar situations and resists involvement in others. The symptoms represent both organic deficits due to brain damage and psychologic reactions to the deficits. Some causes are treatable. Because of progressive change in the total behavior of the patient, major rearrangement of life-style is often necessary. The physician should guide both patient and family in this process. Medication may also be helpful.