Targeting T cells against brain tumors with a bispecific ligand-antibody conjugate

Haemophilus influenzae is a bacterium of medical interest of which the entire genome has been sequenced. The proteome of the microorganism has been analyzed by two-dimensional gel electrophoresis, during which immobilized pH 3-10 gradient strips were used and approximately 300 proteins were identified. In order to detect additional, basic proteins, we analyzed the soluble protein fraction of H. influenzae and the proteins of fractions collected from affinity chromatography on heparin, by two-dimensional gel electrophoresis, using for the first-dimensional separation immobilized pH gradient strips comprising the pH region of 6-11. The protein spots were analyzed by matrix-assisted laser desorption ionization-mass spectrometry. One hundred and two proteins were identified, of which 58 were identified for the first time. A large percentage of the basic proteins represent nucleic acid binding and, in particular, ribosomal proteins. The locations of the identified basic proteins of H. influenzae are indicated in a two-dimensional map.     

The effects of instructional match and content overlap on generalized reading performance

This study examined the effects of instructional match and content overlap on students' ability to generalize from passage reading instruction. Four students with mild disabilities served as participants. Using a multielement design, students were instructed with passages at two levels of text difficulty (instructionally matched vs. instructionally mismatched), and generalization was assessed with passages at two levels of similarity to those instructed (low vs. high content overlap). Results indicated that students' oral reading accuracy and fluency showed the greatest degree of generalization when instructional materials were matched to the students' skill level and assessment materials were similar to those used during instruction. Moreover, these results were maintained at 1-month follow-up. The implications of these findings for classroom reading instruction and the assessment of students' reading skills are discussed.     

Esophagitis in Sprague-Dawley rats is mediated by free radicals

Free radical-mediated esophagitis was studied during duodenogastroesophageal reflux (mixed reflux) or acid reflux in rats. The influence of reflux on esophageal glutathione levels was also examined. Mixed reflux caused more gross mucosal injury than acid reflux. Gross mucosal injury occurred in the mid-esophagus. Total glutathione (GSH) in the esophageal mucosa of control rats was highest in the distal esophagus. The time course of esophageal GSH in rats treated by mixed reflux showed a significant decrease 4 hr after initiation of reflux, followed by a significant increase from the 12th hour on. Mucosal GSH was increased in both reflux groups after 24 hr but significantly more so in the mixed than in the acid reflux group. The free radical scavenger superoxide dismutase (SOD) prevented esophagitis and was associated with decreased GSH levels. GSH depletion by buthionine sulfoximine (BSO) prevented esophagitis and stimulated SOD production in the esophageal mucosa. It is concluded that gastroesophageal reflux is associated with oxidative stress in the esophageal mucosa. The lower GSH levels in the mid-esophagus may predispose to damage in this area. Duodenogastroesophageal reflux causes more damage than pure acid reflux. Oxidative stress leads to GSH depletion of the esophageal mucosa in the first few hours following damage but then stimulates GSH production. GSH depletion by BSO does not worsen esophagitis since it increases the esophageal SOD concentration.     

Geographic variations in the composition of ivory of the African elephant (Loxodonta africana)

OBJECTIVES: The purpose of the present study was to compare the inclination of the occlusal plane with occlusal guidance as a contributing factor to masticatory movement. METHODS: Masticatory movements of 41 young adults were measured using a 3-D mandibular movement analysing system. The inclination of the occlusal plane was measured in the sagittal plane using a 3-D digitizer. The contribution of the occlusal guidance and the inclination of the occlusal plane to the direction of the masticatory path of closure was evaluated at various closing levels. RESULTS: The masticatory path of closure outside the intercuspal range was influenced mainly by the inclination of the occlusal plane, and the masticatory path of closure near the intercuspal range was only influenced by occlusal guidance. The so-called gliding type masticatory pattern was observed predominantly in subjects with a posteriorly inclined occlusal plane. In contrast, a chopping type masticatory pattern was observed predominantly in subjects with an anteriorly inclined occlusal plane. CONCLUSIONS: The contribution of the inclination of the occlusal plane to masticatory movement was greater than that of occlusal guidance throughout the closing phase except near the intercuspal range.     

Ethical evaluation of hypnosis research: a survey of investigators and their institutional review boards

We surveyed hypnosis researchers and Institutional Review Boards (IRBs) with regard to the ethical evaluation of research protocols. Researchers and IRB administrators were independently surveyed within the same institutions. Both objective and free response items were used to address substantive issues such as deception and at-risk populations, as well as practical matters such as paperwork. Parallel questions allowed a point-counterpoint between researchers and IRBs. Overall, the results suggest that IRBs do not treat hypnosis research differently than other types of research. We end with recommendations for facilitating interactions between hypnosis researchers and their IRBs.     

Replication and integration of a Vibrio cholerae cryptic plasmid linked to the CTX prophage

We identified a 4.7kb cryptic plasmid in all ctxAB+ Vibrio cholerae strains we tested. An isolate of the V. cholerae classical biotype strain 0395 that harbours the cryptic plasmid at high copy number was found. Hybridization analysis demonstrated that sequences highly related or identical to this plasmid exist in all toxigenic strains of V. cholerae but were notably absent in all non-toxigenic environmental isolates that lacked the genes for toxin-co-regulated pili and the filamentous CTX prophage. Accordingly, we have named the cryptic plasmid pTLC for toxin-linked cryptic. The complete nucleotide sequence of pTLC from the high-copy-number isolate was determined. The largest open reading frame in the plasmid is predicted to encode a protein similar to the replication initiation protein (pII) of Escherichia coli F-specific filamentous phages. The nucleotide sequence of pTLC also facilitated the structural characterization of the DNA homologous to pTLC in other strains of V. cholerae. pTLC-related DNA exists in these strains as both low-copy-number, covalently closed circular DNA and tandemly duplicated, chromosomally integrated DNA. Remarkably, the chromosomally integrated form of pTLC is adjacent to the CTX prophage. The strain distribution, chromosomal location and DNA sequence of pTLC suggests that it may be a genetic element that plays some role in the biology of CTXphi, perhaps facilitating either its acquisition or its replication.     

Life events and post-traumatic stress: the development of a new measure for children and adolescents

BACKGROUND: A new interview measure of life events and post-traumatic stress disorder (PTSD) has been developed for children and adolescents aged 9 through 17, for use in both epidemiological and clinical studies. It includes 'high magnitude' events associated with PTSD as well as other 'low magnitude' events. METHOD: The interview is designed as a module of the Child and Adolescent Psychiatric Assessment, an interviewer-based interview conducted with parent and child separately by trained lay interviewers. The module includes: (1) questions about a wide range of events; (2) a screen for key PTSD symptoms (painful recall, avoidance, hypervigilance); and (3) a detailed interview on all PTSD symptoms, including onset, duration, severity and co-morbidity. A test-retest reliability study was conducted with 58 parents and children, who were interviewed twice by different interviewers. RESULTS: Intraclass correlations were 0.72 (child) and 0.83 (parent) for high magnitude events, and 0.62 (child) and 0.58 (parent) for low magnitude events. Kappa coefficients ranged from high for violence and sexual abuse to low for child reports of serious accidents and natural disasters. The reliability of the PTSD screen symptoms was fair to excellent (kappa = 0.40-0.79), and reliability of PTSD symptoms in those who passed the screen was excellent (ICC = 0.94-0.99). Compared with a general population sample (N = 1015), the clinic-referred subjects and their parents were twice as likely to report a traumatic event and, depending on the event, up to 25 times as likely to report symptoms of PTSD. CONCLUSIONS: The results support the reliability and discriminant validity of the measure.     

A randomized controlled trial of filgrastim during remission induction and consolidation chemotherapy for adults with acute lymphoblastic leukemia: CALGB study 9111

Recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) shortens the time to neutrophil recovery after intensive chemotherapy, but its role in the treatment of adults with acute lymphoblastic leukemia (ALL) is uncertain. We randomly assigned 198 adults with untreated ALL (median age, 35 years; range, 16 to 83) to receive either placebo or G-CSF (5 microgram/kg/d) subcutaneously, beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was >/=1, 000/microL for 2 days. The study assignment was unblinded as individual patients achieved a complete remission (CR). Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy. Patients assigned to placebo received no further study drug. The median time to recover neutrophils >/=1,000/microL during the remission induction course was 16 days (interquartile range [IQR], 15 to 18 days) for the patients assigned to receive G-CSF and 22 days (IQR, 19 to 29 days) for the patients assigned to placebo (P < .001). Patients in the G-CSF group had significantly shorter durations of neutropenia (<1, 000/microL) and thrombocytopenia (<50,000/microL) and fewer days in the hospital (median, 22 days v 28 days; P = .02) compared with patients receiving placebo. The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo (P = .04 by the chi-square test for trend). During Courses IIA and IIB of consolidation treatment, patients in the G-CSF group had significantly more rapid recovery of neutrophils >/=1,000/microL than did the control group by approximately 6 to 9 days. However, the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group. Overall toxicity was not lessened by the use of G-CSF. After a median follow-up of 4. 7 years, there were no significant differences in either the disease-free survival (P = .53) or the overall survival (P = .25) for the patients assigned to G-CSF (medians, 2.3 years and 2.4 years, respectively) compared with those assigned to placebo (medians, 1.7 and 1.8 years, respectively). Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment, but its use did not markedly affect the ultimate outcome.