40 Hz Auditory Steady-State Response: The Impact of Handedness and Gender

The 40 Hz auditory steady-state response (ASSR) is a periodic response to a periodic stimulation. Its sources are located in the primary auditory cortex and the asymmetry of the planum temporale has previously been associated with hand preference and gender-related differences; thus subject’s handedness and gender could potentially influence ASSRs. Nevertheless, electrophysiological studies of ASSRs are mainly dominated by right-handed participants and the observed findings can only be generalized to the right-handed populations. However, for a potential use of 40 Hz ASSR as a translational biomarker of neuropsychiatric disorders, it is important to investigate the response in association to handedness and gender. We included an equal number of left-handed and right-handed males and females and recorded EEG responses during left-ear, right-ear and both ears stimulation. The results of the study suggest that the processing of 40 Hz auditory stimulation depends on the subjects’ gender and handedness: significantly lower phase-locking and strength of 40 Hz ASSRs were observed in left-handed females as compared to left-handed males, but right-handers did not differ in 40 Hz ASSRs. Our observation of the opposite impact of gender in the examined handedness groups stresses the importance of careful consideration of handedness and gender factors when evaluating the determinants of inter individual variability of 40 Hz ASSRs. This finding is of particular importance for clinical studies in psychiatry and neurology.     

Legionella pneumophila contamination of a hospital humidifier. Demonstration of aerosol transmission and subsequent subclinical infection in exposed guinea pigs

Water from a humidifier located in the hospital was found to be contaminated with Legionella pneumophila, serogroup 1. The source of water for the humidifier was the hospital potable water system. Exposure of culture mediums to the humidifier aerosols yielded L. pneumophila, serogroup 1. Exposure of guinea pigs to humidifier aerosols produced a subclinical infection as demonstrated by seroconversion to L. pneumophila. Seroconversion rate of guinea pigs to L. pneumophila was higher when greater quantities of L. pneumophila were present in the water; a corresponding increase in recovery of the organism from culture mediums exposed to aerosols was also seen. This report shows that mechanically created aerosols of Legionella-contaminated potable water might be the vehicle of transmission of Legionnaires' disease, especially in the hospital setting.     

Immunoprofile of the adenomatoid odontogenic tumor

This study was focused on the immunohistochemical profile of the adenomatoid odontogenic tumor. A Pub/Medline search revealed a number of immunohistochemical studies including cytokeratin profiles, extracellular matrix proteins, Integrins, ameloblast‐associated proteins resorption regulators (RANK, RANKL), p53, PCNA, MDM2 protein, cyclin D1, Ki‐67, Bcl‐2 metallothionein, metalloproteinases, D56 hepatocyte growth factor, c‐met, DNA methyltransferase, podoplanin, TGF‐βI, Smad‐2/3, Smad‐I‐5/‐8, Smad 4, beta‐ catenin, calretinin, and clonality. Careful interpretation of the findings indicates that the adenomatoid odontogenic tumor may be more of a hamartomatous than neoplastic nature.     

Regulation of manganese superoxide dismutase and other antioxidant genes in normal and leukemic hematopoietic cells and their relationship to cytotoxicity by tumor necrosis factor

Myeloid cells are a major source of superoxide and other oxygen metabolites. As a protective mechanism, cells express antioxidant enzymes including manganese superoxide dismutase (Mn-SOD), copper-zinc SOD (Cu/Zn-SOD), and glutathione peroxidase (GSX-PX). Even though hematopoietic cells are a major source of oxidants, little is known of their expression of antioxidants. We found that seven myeloid leukemic cell lines blocked at different stages of differentiation constitutively expressed Mn-SOD, Cu/Zn-SOD, and GSX-PX RNAs. Level of Mn-SOD activities paralleled levels of Mn-SOD RNA. Terminal differentiation of native HL-60 cells to either granulocytes or macrophages did not alter levels of Mn-SOD RNA but markedly decreased cell division. Myeloid leukemic lines sensitive to cytotoxic effects of tumor necrosis factor (TNF) as well as normal peripheral blood lymphocytes and monocytes, dramatically increased their levels of Mn- SOD RNA in the presence of TNF. In contrast, Cu/Zn-SOD and GSX-PX RNA levels did not increase in these same cells. TNF-resistant leukemic lines had higher constitutive levels of Mn-SOD RNA and activity; and these levels did not change in the presence of TNF. Antisense but not random oligonucleotides to Mn-SOD markedly increased the sensitivity to the inhibitory effects of TNF for both the native HL-60 (TNF-sensitive) and K562 (TNF-resistant) cell lines. Further studies showed that the antisense oligonucleotides entered the cells and resulted in decreased levels of Mn-SOD RNA. The data suggest that Mn-SOD may provide protection against cytotoxicity of TNF in hematopoietic cells.     

Community-acquired pneumonia caused by Legionella dumoffii in a patient with hairy cell leukemia

Summary A case of community-acquired pneumonia caused byLegionella dumoffii in a patient with hairy cell leukemia is described. Diagnosis was confirmed by isolation by culture of sputum and broncho-alveolar lavage specimens, positive direct fluorescent antibody stains, and antibody seroconversion from 1 : 16 (acute) to 1 : 4096 (six months). The blue white autofluorescence of theL. dumoffii colonies when viewed under ultraviolet light was particularly useful in preliminary identification. The patient recovered from his pneumonia after administration of erythromycin and rifampin. Legionella have been shown to multiply in monocytes and cell-mediated immunity appears to be the primary mechanism of host defense in man. Hairy cell leukemia is characterized by monocyte dysfunction and such patients have a predilection for infection by microbes that are controlled by cell-mediated defenses. We review other cases of community-acquiredL. dumoffii pneumonia as well as other cases of Legionella infection in patients with hairy cell leukemia.

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Nicht nosokomiale Pneumonie durch Legionella dumoffii bei einem Patienten mit Haarzell-Leukämie

Zusammenfassung Bei einem Patienten mit Haarzell-Leukämie wurde eine nicht nosokomialeLegionella dumoffii — Pneumonie beobachtet. Die Diagnose wurde gesichert durch kulturellen Erregernachweis aus Sputum und Bronchoalveolar-Lavageflüssigkeit, eine positive direkte Antikörper-Fluoreszenz und einen Antikörperanstieg im Serum mit einem Titer von 1 : 16 im Akutstadium auf 1 : 4096 nach sechs Monaten. Für die vorläufige Erregeridentifizierung war die weiße Autofluoreszenz derL. dumoffii-Kulturen unter ultraviolettem Licht besonders hilfreich. Nach Behandlung mit Erythromycin und Rifampicin heilte die Pneumonie ab. Es wurde nachgewiesen, daß sich Legionella in Monozyten vermehrt. Beim Menschen ist die zellvermittelte Immunität offensichtlich der primäre Abwehrmechanismus. Bei Haarzell-Leukämie besteht typischerweise eine Monozytenfunktionsstörung. Die Patienten sind besonders anfällig für Infektionen durch Erreger, die unter der Kontrolle der zellvermittelten Abwehr stehen. Wir geben eine Übersicht über andere Fälle vonL. dumoffii Pneumonie und andere Fälle von Legionella-Infektionen bei Patienten mit Haarzell-Leukämie.

     

Somatic cell hybrid analyses of hematopoietic differentiation

A differentiated cell expresses an entire set of specialized features. Somatic cell hybridization provides a method to examine control of gene regulation. We studied the expression of tissue-specific features in hybrids between human promyelocytes (HL-60) and human Burkitt's lymphoma cells (P3HR-1). Two hybrid lines, HP-1 and HP-2, and 18 hybrid clones were established and confirmed by karyotype, isozyme, and surface antigen analyses. The hybrids extinguished the 10 myeloid (HL- 60) features that we examined including myeloid morphology, histochemistry, and functions that included response to colony- stimulating factor and ability to differentiate to granulocytes or macrophages. In contrast, the hybrids synthesized immunoglobulin and expressed Epstein-Barr nuclear, early, and viral capsid antigens similar to the P3HR-1 lymphoid parental line. Results are contrasted to the findings when P3HR-1 lymphocytes are fused to human erythroid- myeloid cells (K562). Taken together, our results suggest that phenotypic differences between human myeloid and lymphoid cells in the hematopoietic lineage involve mutually exclusive programs and may possibly be mediated by the activity of diffusible, transacting molecules.     

Mutation and protein expression of p53 in acquired immunodeficiency syndrome-related lymphomas

p53 mutations are found in a variety of neoplasia. B-immunoblastic lymphoma (BIBL) is a rapidly progressive, aggressive lymphoma. As patients with acquired immunodeficiency syndrome (AIDS) live longer, BIBL is becoming an increasing problem. We asked three questions in our study. What is the frequency of p53 mutations in BIBL? Is it more frequent in patients with AIDS? Can immunohistochemical staining of lymph nodes for expression of p53 substitute for mutational analysis of p53 to detect lymphomas with mutated p53? Exons 5, 6, 7, 8 of the p53 gene (hot-spots for mutations) were amplified and examined for mutations by single-strand conformation polymorphism (SSCP) analysis. Altered migration was observed in 7 of 52 BIBL samples. Of these, 4 of 25 were from individuals infected with human immunodeficiency virus (HIV) and 3 of 27 were not infected with HIV. Direct sequencing of amplified material confirmed the presence of mutations in exons 5, 7, 8 of p53. A total of 26 BIBL as well as other lymphoma/leukemia samples, stained strongly by immunohistochemistry with three antibodies directed against human p53. Five of 6 BIBL samples with p53 mutations stained strongly for p53, but 20 lymphoma samples with no detectable p53 mutations also stained strongly for p53. Of note, however, 10 hyperplastic, nonmalignant lymph nodes from individuals either infected or not infected with HIV had negligible staining for p53 protein. In conclusion, p53 mutations occur in about 14% BIBL samples; the frequency of p53 mutations in BIBL in individuals with and without AIDS was similar. Positive p53 immunohistochemistry did not correlate with detectable p53 mutations in the same tissue, but positive immunohistochemical staining for p53 was only found in neoplastic lymph nodes. This latter finding provides a strong warning that p53 immunochemistry with available reagents cannot be used to determine which tumors have mutations of p53.     

An undifferentiated variant derived from the human acute myelogenous leukemia cell line (KG-1)

A variant subline (KG-1a) of the human acute myelogenous leukemia (AML) cell line (KG-1) has been isolated. The cells retain the same constitutive markers as the parent line, including HLA antigens, isoenzymes, and karyotype. The cells from the subline are morphologically and histochemically undifferentiated blast cells, while the parent cells and several of its clones are at the myeloblast and promyelocyte stages of development. The variant cells do not respond to colony-stimulating factor (CSF), and they do not express the human la antigen, nor a recently characterized AML antigen. The parent KG-1 cells are stimulated to proliferate in the presence of CSF and the cells express the la and AML antigen. Variant AML cell lines, such as KG-1a, will be useful in vitro models for investigating cellular response to CSF and for studying antigen expression in leukemic cells.     

Randomized study of 13-cis retinoic acid v placebo in the myelodysplastic disorders

A double-blind, placebo-controlled randomized trial of 13-cis retinoic acid was performed to determine if the drug has a therapeutic effect in patients with myelodysplastic syndromes (MDS). Sixty-eight evaluable patients with MDS were randomized to receive a single, daily oral dose of either 13-cis retinoic acid (13-CRA, 100 mg/m2) or matching placebo. Treatment was continued, when possible, for a period of 6 months. Determination of response to treatment was based on clinical course, repeat bone marrow biopsies, and aspirates and blood counts (CBC) with WBC differential, platelet, and reticulocyte numbers at specified intervals. No significant difference was noted between the two treatment groups in response to test drug (P = .66). One patient (3%) in the 13-CRA group and two patients (6%) in the placebo group had a minor response. Approximately 30% of patients in both groups had progression of their disease, and progression-free survival was nearly identical. Greater than 90% of the patients receiving 13-CRA developed mild or moderate skin toxicity that was reversible with decreasing or discontinuing the drug. Our study did not find that 13-CRA exerts a beneficial therapeutic effect in patients with MDS.