Apolipoprotein D is down-regulated during malignant transformation of neurofibromas

Apolipoprotein D (apoD) expression was studied in nonneoplastic peripheral nerve, neurofibromas (NFs), and malignant peripheral nerve sheath tumors (MPNSTs) by quantitative polymerase chain reaction, in situ hybridization, and immunohistochemistry. Multiplex quantitative polymerase chain reaction for messenger RNA was performed on a series of formalin-fixed and paraffin-embedded specimens that included 9 MPNSTs, 12 NFs, and 4 normal peripheral nerves. The average apoD expression was 108-fold decreased (DeltaCt = -7.3) in the MPNSTs compared with the NFs (P < .05). ApoD expression levels were 3.0-fold elevated (DeltaCt = 1.7) in the NFs compared with nonneoplastic peripheral nerve (P < .05). In situ hybridization for apoD RNA was performed on a separate series of 10 cases in which each microscopic section included both MPNST and the NF from which it arose. These studies confirmed elevated apoD expression in NFs compared with MPNSTs and demonstrated that this expression was variable among individual cells within the NFs. Differential expression by immunohistochemistry could only be demonstrated in selected areas, most likely because apoD protein is a small molecule that is secreted out of the cell into the extracellular space and plasma. ApoD expression initially increases a small amount with the formation of NFs from nonneoplastic peripheral nerve and subsequently decreases markedly as NFs transform into MPNSTs. This expression pattern may serve as a marker for cell cycle inhibition during peripheral nerve tumorigenesis.     

Effect of unilateral and bilateral auditory cortex lesions on the discrimination of vocalizations by Japanese macaques

Ten Japanese macaques were trained to discriminate between two types of Japanese macaque coo vocalizations before and after auditory cortex ablation. Five of the animals were tested following left unilateral ablation, whereas the other five were tested following right unilateral ablation. After postoperative testing, symmetrical lesions were made in the remaining hemisphere in two animals from each group and the effect of bilateral lesions was assessed. The animals were tested using a shock avoidance procedure. Unilateral ablation of left auditory cortex consistently resulted in an initial impairment in the ability to discriminate between the vocalizations with the animals regaining normal performance in 5-15 sessions. In contrast, right unilateral ablation had no detectable effect on the discrimination. Bilateral auditory cortex ablation rendered the animals permanently unable to discriminate between the coos. Although the monkeys could learn to discriminate the coos from noise and from 2- and 4-kHz tones, they had great difficulty in discriminating between the coos and tones in the same frequency range as the coos (i.e., 500 Hz and 1 kHz). The initial impairment following left unilateral lesions indicates that the ability to perceive species-specific vocalizations is lateralized to the left hemisphere. The observation that bilateral lesions abolish the discrimination indicates that the recovery in the left lesion cases was the result of the right hemisphere mediating the discrimination.     

HLA-B*35-Restricted CD8+-T-Cell Epitope in Mycobacterium tuberculosis Rv2903c

Few human CD8(+) T-cell epitopes in mycobacterial antigens have been described to date. Here we have identified a novel HLA-B*35-restricted CD8(+) T-cell epitope in Mycobacterium tuberculosis Rv2903c based on a reverse immunogenetics approach. Peptide-specific CD8 T cells were able to kill M. tuberculosis-infected macrophages and produce gamma interferon and tumor necrosis factor alpha.     

Treatment of parkinsonian tremor with clozapine

Summary After preliminary obsevations on 5 psychotic and 7 nonpsychotic parkinsonian patients had shown unexpected impressive beneficial effects of the atypical neuroleptic clozapine on tremor, an open clinical study including 12 patients was started. Under a dosage-range 25–50 mg/day significant reduction of tremor intensity and tremor related functional disability (CURS, Sweet's scale) was achieved. Akinesia was not deteriorated, initial fatigue disappeared spontaneously. Pharmacological mode of action of clozapine's antitremor effect remains unclear. Its broad receptor binding spectrum with strong antiserotonergic properties might here play a major role.     

Violence in the Schools: Clinical Issues and Case Analysis for High-Risk Children

School violence in rural communities has gained considerable attention nationally. Examined are theoretical considerations involving escape theory, the risk and protective factors for school violence, case analyses of recent case studies, and discussion of recent school violence involving fatal injuries to others. Also discussed are diagnostic issues in understanding children who are at-risk for school violence and ways school violence maybe managed in the schools. Suggestions and recommendations including recommendations provided by the National School Safety Center for school personnel are offered, as are steps to be taken in creating a safe school environment. This information may be helpful to child psychiatry and clinical personnel who provide services to school aged children.     

Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma

Bortezomib, a proteasome inhibitor with efficacy in multiple myeloma, is associated with thrombocytopenia, the cause and kinetics of which are different from those of standard cytotoxic agents. We assessed the frequency, kinetics, and mechanism of thrombocytopenia following treatment with bortezomib 1.3 mg/m2 in 228 patients with relapsed and/or refractory myeloma in 2 phase 2 trials. The mean platelet count decreased by approximately 60% during treatment but recovered rapidly between treatments in a cyclic fashion. Among responders, the pretreatment platelet count increased significantly during subsequent cycles of therapy. The mean percent reduction in platelets was independent of baseline platelet count, M-protein concentration, and marrow plasmacytosis. Plasma thrombopoietin levels inversely correlated with platelet count. Murine studies demonstrated a reduction in peripheral platelet count following a single bortezomib dose without negative effects on megakaryocytic cellularity, ploidy, or morphology. These data suggest that bortezomib-induced thrombocytopenia is due to a reversible effect on megakaryocytic function rather than a direct cytotoxic effect on megakaryocytes or their progenitors. The exact mechanism underlying bortezomib-induced thrombocytopenia remains unknown but it is unlikely to be related to marrow injury or decreased thrombopoietin production.     

Cardiac Genetic Predisposition in Sudden Infant Death Syndrome

Background

Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality. Genetic heart diseases (GHDs) underlie some cases of SIDS.