Rat leukocyte interferons: production of an acid-labile interferon after induction with Newcastle disease virus

Rat leukocytes produce three interferon species after infection with Newcastle disease virus. Two of the three interferon species (22-24,000 and 30,000 daltons) were acid and heat stable, protected rat and mouse cells from virus-mediated cytopathic effect (CPE), and were neutralized by antisera to mouse L-cell (alpha/beta) interferon. The third, 30,000-dalton interferon species was heat and acid labile; protected rat, mouse, human, and bovine cells from virus-mediated CPE; and was neutralized by antisera to mouse L-cell interferon and human leukocyte interferon. Thus, the rat leukocyte interferon system is similar to the human system in the kinetics of interferon production, the production of multiple interferons, heterologous antiviral activity, molecular weight, and in the production of an acid-labile species. The rat leukocyte interferon system therefore represents an important model for examining the normal production and action of acid-labile interferons and their possible role in the regulation of leukocyte function and cellular differentiation.     

Lymphoid subpopulation changes after thermal injury and thermal injury with infection in an experimental model.

Subpopulation analysis of peripheral blood lymphocytes is a frequently used measure of immunocompetence. Yet, little is known about the lymphocyte subpopulations in the circulation and lymphoid organs after severe trauma. Blood, spleen, and lymph node (LN) subpopulations were compared in a rat model of burn injury (B) and burn injury with infection (BI). B and BI rats received 30% total body surface scald burns. Infection was induced by seeding wounds with Pseudomonas aeruginosa. Subpopulations were identified by flow cytometry 48 hours after burn. Helper lymphocytes were selectively depleted from the circulation of BI but not B animals, which caused the ratio of helper to suppressor cells (HSR) in BI animals to decrease significantly compared with the unburned controls. Both LN helper and suppressor cells were decreased in BI animals and the HSR was unchanged, but a selective reduction in suppressor cells in B LN increased the HSR relative to unburned controls. Spleen subpopulations were unchanged for both B and BI groups. Subpopulation changes after trauma and infection were different for each tissue examined.     

Transjugular hepatic vein cannulation in rats with nonisotopic in vivo verification

A simple, rapid and relatively atraumatic method for transjugular cannulation of the hepatic vein and for repeated sampling of hepatic venous blood in the rat is described. Preliminary in vivo verification of the cannula's position is proposed, either by using the glucose differential between consecutive samples of the hepatic venous blood and inferior vena cava blood, or more practically, by using the glucose differential between the hepatic venous blood and tail blood obtained simultaneously. The latter procedure is favored because of its technical simplicity.     

Differential gene expression in ovarian carcinoma: identification of potential biomarkers

Ovarian cancer remains the fifth leading cause of cancer death for women in the United States. In this study, the gene expression of 20 ovarian carcinomas, 17 ovarian carcinomas metastatic to the omentum, and 50 normal ovaries was determined by Gene Logic Inc. using Affymetrix GeneChip HU_95 arrays containing approximately 12,000 known genes. Differences in gene expression were quantified as fold changes in gene expression in ovarian carcinomas compared to normal ovaries and ovarian carcinoma metastases. Genes up-regulated in ovarian carcinoma tissue samples compared to more than 300 other normal and diseased tissue samples were identified. Seven genes were selected for further screening by immunohistochemistry to determine the presence and localization of the proteins. These seven genes were: the beta8 integrin subunit, bone morphogenetic protein-7, claudin-4, collagen type IX alpha2, cellular retinoic acid binding protein-1, forkhead box J1, and S100 calcium-binding protein A1. Statistical analyses showed that the beta8 integrin subunit, claudin-4, and S100A1 provided the best distinction between ovarian carcinoma and normal ovary tissues, and may serve as the best candidate tumor markers among the seven genes studied. These results suggest that further exploration into other up-regulated genes may identify novel diagnostic, therapeutic, and/or prognostic biomarkers in ovarian carcinoma.     

Differentiating major depressive disorder in youths with attention deficit hyperactivity disorder

BACKGROUND: Youths with attention deficit hyperactivity disorders (ADHD) frequently have comorbid major depressive disorders (MDD) sharing overlapping symptoms. Our objective was to examine which depressive symptoms best discriminate MDD among youths with ADHD. METHODS: One-hundred-eleven youths with ADHD (5.2-17.8 years old) and their parents completed interviews with the K-SADS-PL and respective versions of the child or the parent Mood and Feelings Questionnaire (MFQ-C, MFQ-P). Controlling for group differences, logistic regression was used to calculate odds ratios reflecting the accuracy with which various depressive symptoms on the MFQ-C or MFQ-P discriminated MDD. Stepwise logistic regression then identified depressive symptoms that best discriminated the groups with and without MDD, using cross-validated misclassification rate as the criterion. RESULTS: Symptoms that discriminated youths with MDD (n=18) from those without MDD (n=93) were 4 of 6 mood/anhedonia symptoms, all 14 depressed cognition symptoms, and only 3 of 11 physical/vegetative symptoms. Mild irritability, miserable/unhappy moods, and symptoms related to sleep, appetite, energy levels and concentration did not discriminate MDD. A stepwise logistic regression correctly classified 89% of the comorbid MDD subjects, with only age, anhedonia at school, thoughts about killing self, thoughts that bad things would happen, and talking more slowly remaining in the final model. LIMITATIONS: Results of this study may not generalize to community samples because subjects were drawn largely from a university-based outpatient psychiatric clinic. CONCLUSIONS: These findings stress the importance of social withdrawal, anhedonia, depressive cognitions, suicidal thoughts, and psychomotor retardation when trying to identify MDD among ADHD youths.     

The effect of diabetes mellitus on endodontic treatment outcome: data from an electronic patient record

BACKGROUND: The authors used a custom-built electronic record system to investigate endodontic diagnostic and treatment outcome data in patients with and without diabetes. METHODS: The medical histories and endodontic treatment data for nonsurgical endodontic patients treated in predoctoral and postgraduate specialty clinics were entered into an electronic record system. A total of 5,494 cases (including 284 cases in patients with diabetes) were treated, and 540 cases (including 73 cases in patients with diabetes) had follow-up data two years or more postoperatively. The authors performed univariate and multivariate analyses to determine important factors affecting endodontic diagnosis and treatment outcome. RESULTS: Patients with diabetes had increased periodontal disease of teeth with endodontic involvment compared with patients who did not have diabetes. There was a trend toward increased symptomatic periradicular disease in patients with diabetes who received insulin, as well as flareups in all patients with diabetes. Two years or longer postoperatively, 68 percent of cases followed were successful. Older age, the absence of preoperative lesions, the presence of permanent restorations and longer postoperative evaluation periods all were associated with a successful outcome. A multivariate analysis showed that in cases with preoperative periradicular lesions, a history of diabetes was associated with a significantly reduced successful outcome. CONCLUSIONS: Patients with diabetes have increased periodontal disease in teeth involved endodontically and have a reduced likelihood of success of endodontic treatment in cases with preoperative periradicular lesions. CLINICAL IMPLICATIONS: Patients with diabetes who are treated endodontically should be assessed carefully and be treated with effective antimicrobial root canal regimens, particularly in cases with preoperative lesions.     

Early growth response gene 1 (EGR1) is deleted in estrogen receptor-negative human breast carcinoma

BACKGROUND: Patients with estrogen receptor (ER)-positive and ER-negative breast carcinomas differ in terms of disease progression, treatment regimens, and prognosis. The mechanism underlying the biologic differences of the two groups is understood poorly. Array comparative genome hybridization (CGH) on breast carcinoma subtypes demonstrated a consistent association between loss in regions of chromosome 5q and ER-negative tumors. It was shown previously that early growth response gene 1 (EGR1) on 5q acts like a tumor-suppressor gene, with its expression repressed in breast carcinomas. METHODS: To test the hypothesis that EGR1 is deleted differentially in ER-negative versus ER-positive breast carcinomas, fluorescence in situ hybridization was employed in this study to determine the EGR1 deletion status in 50 breast carcinoma specimens. Deletion status was measured by the signal ratio of EGR1/chromosome 5. Linear regression was used to assess the results. RESULTS: The mean EGR1/chromosome 5 ratio for the ER-negative group was significantly lower compared with the same ratio for the ER-positive group (P < 0.001). Although grade alone was not significant for predicting the ratio, the interaction between ER status and grade was significant (P < 0.01): For ER-negative specimens, the higher the grade, the lower the EGR1/chromosome 5 ratio. CONCLUSIONS: The EGR1 gene appeared to be deleted in ER-negative human breast carcinomas. Egr-1 may contribute to the pathogenesis of ER-negative breast carcinomas versus ER-positive breast carcinomas.     

Steady-state pharmacokinetics of bupropion SR in juvenile patients

OBJECTIVE: To examine the steady-state pharmacokinetic properties of bupropion sustained release (SR) and their potential developmental differences in youths. METHOD: Eleven boys and eight girls aged 11 to 17 years old were prescribed bupropion SR monotherapy for attention-deficit/hyperactivity disorder (n = 16) and/or depressive disorders (n = 16). Bupropion SR was given in morning doses of 100 mg/day (n = 11) or 200 mg/day (n = 8) for 14 days or less, with five subjects studied on both doses. All subjects had blood draws from an intravenous port every 1 to 3 hours for 24 hours after their usual morning doses. Pharmacokinetic variables were determined by noncompartmental and compartmental analyses for bupropion and metabolites, respectively. RESULTS: Bupropion and its metabolites exhibited linear pharmacokinetics. Areas under the concentration curves for the hydroxybupropion, threohydrobupropion, and erythrohydrobupropion were 20, 12, and 2.7 times higher, respectively, than for bupropion. Relative to adults, the mean half-lives of bupropion (12.1 hours) and threohydrobupropion (26.3 hours) were significantly shorter, and areas under the concentration curve ratios of metabolites to bupropion were 19% to 80% higher. CONCLUSIONS: Youths metabolize bupropion SR faster to hydroxybupropion and other active metabolites than adults. Until the clinical importance of bupropion's metabolites is clarified, bupropion SR should be given in divided doses to youths, as the manufacturer recommends for adults taking higher doses.