Assignment of gene coding for cell surface glycoprotein with a molecular weight of 75,000 to human chromosome 11

The gene for a cell surface glycoprotein recognized by a mouse monoclonal antibody (Mab 4), has been assigned to human chromosome 11 by the study of mouse-human lymphocyte hybrids. The antigen is present on all human peripheral blood leukocytes, on human fibroblasts, and on human lymphoid and erythroid cell lines, but not on erythrocytes. Immunoprecipitation and polyacrylamide slab gel electrophoresis of both human cells and mouse-human hybrid clones carrying human chromosome 11 show that the apparent molecular weight of this glycoprotein is 75,000.     

Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry

The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype.     

Differential expression of p53 gene family members p63 and p73 in head and neck squamous tumorigenesis

p73 and p63 are recently cloned genes that share considerable structural and functional homologies with the p53 tumor suppressor gene. These genes, unlike p53, express multiple mRNA isoforms with variable biologic functions, and their suppressor nature has yet to be confirmed. To determine the interrelationship between these genes in the tumorigenesis of head and neck squamous carcinoma (HNSC), we performed immunohistochemical analyses of their protein products and compared the data with clinicopathologic parameters in 38 patients. In histologically normal epithelium, p53 and p73 showed similar basal and/or parabasal expression, but that of p53 was weaker and discontinuous. p63 staining was noted in more suprabasal cellular layers and was stronger. In dysplasias, all three markers manifested variable but gradual increase in extent and intensity of cellular expression with histologic progression. In carcinomas, p63 was the most frequently expressed (94.7%), followed by p73 (68.4%) and p53 (52.6%). Significant statistical correlation was noted only between p63 and p73 expressions (P =.04). Although no statistical correlation was found between p53 and p63 or p73, p53-negative tumors overexpressed either p63 or p73. p73 expression was associated with distant metastasis and perineural/vascular invasion. Our study indicates that (1) p63 and p73 expression may represent an early event in HNSC tumorigenesis, (2) the lack of correlation between p73 or p63 and p53 expression suggests an independent and/or compensatory functional role, (3) p73 expression may play a part in HNSC progression, and (4) p73 and p63 may function as oncogenes in the development of these tumors.     

Ultrastructural study of characteristic organelles (paired organelles,micronemes, micropores) of sporozoa and related organisms

Summary By means of electron microscopy a study has been made of different developmental stages of Eimeria callospermophili, E. falciformis, Toxoplasma gondii, Frenkelia spec. (= M-organism), Babesia bigemina, and B. ovis. Major emphasis was given to the analysis of some characteristic organelles of the motile stages of the sporozoans. These organelles were the paired organelle, the micronemes and the micropores.Supported by the Deutsche Forschungsgemeinschaft.     

Light and electron microscope studies on the Sarcocystis of Rattus fuscipes,an Australian rat

Summary Light and electron microscope studies on the Sarcocystis of Rattus fuscipes showed that sarcocysts of two types occurred in this rat. These types could be distinguished from each other on the morphology of their cyst walls, on the size and micromorphology of their zoites, as well as by the changes they induced in the host cell. On the basis of these differences, it was concluded that the two sarcocyst types belonged to distinct Sarcocystis species. The possible life histories of the infections occurring in the rats were considered.Abbreviations A Amylopectin - C Conoid - CF Connected Tissue Fibres - CP Capillary - CW Cyst Wall - DC Daughter Cell - DCA Daughter Cell Anlagen - E Erythrocyte - FE Fibrillar Elements - GA Golgi Adjunct - GO Golgi Apparatus - GS Ground Substance - HC Host Cell - HCN Host Cell Nucleus - I Invagination - M Metrocyte - ME Merozoite - MI Mitochondrion - MIH Host Cell Mitochondrion - MN Micronemes - N Nucleus - NE Nucleus of Endothelial Cell - NR Neck Region - NU Nucleolus - OG Osmiophilic Granules - P Papilla - PI Pellicular Invagination - PR Projections - PW Primary Wall - RH Rhoptries - S Septum - SP Sarcoplasm - TS Thread-like Structures - Z Zoites Visiting DAAD Research Fellow from the Department of Parasitology, University of Queensland, AustraliaSupported by the Deutsche Forschungsgemeinschaft     

Magnetic carbohydrate nanoparticles for affinity cell separation

Magnetically responsive nanoparticles were prepared from enzymatically hydrolysed starch and magnetite. Two different monoclonal antibodies were covalently coupled to the particles. The antibody-coupled particles were in the size range of 100-300 nm and had an iron content of about 60%. Using 100 micrograms of magnetic particles (coupled with monoclonal mouse anti-rat Ig kappa light chain antibody) a very high depletion of surface Ig positive cells (mostly B-cells) from one million rat peripheral blood mononuclear cells could be achieved. The separation efficiency was evaluated by flow cytofluorometric analysis. This technique permits the detection of a small number of surface Ig positive cells among 10,000 negative cells.     

Die Bedeutung der Glutathionkonzentration der Erythrocyten für die Diagnose der Osteomyelofibrose

Zusammenfassung Bei 16 von 17 Patienten mit Osteomyelofibrose wurden in den Erythrocyten erhöhte Konzentrationen an reduziertem Glutathion nachgewiesen. Die Bestimmung des Glutathions kann als differentialdiagnostisch wertvolles Kriterium für die Charakterisierung der Osteomyelofibrose angesehen werden.

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Summary In 16 of 17 patients with osteomyelofibrosis the concentration of erythrocyte reduced glutathione was increased. It is concluded that the determination of erythrocyte glutathione is of differential diagnostic value in the characterization of osteomyelofibrosis.

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

An IFN-beta-albumin fusion protein that displays improved pharmacokinetic and pharmacodynamic properties in nonhuman primates.

The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy.     

Die Gattung Knemidocoptes (Acari,Sarcoptoidea)

Zusammenfassung Es wird vorgeschlagen, die Gattung Knemidocoptes Fürstenberg, 1870, auf Grund zahlreicher charakteristischer Merkmale als eigene Familie in der Überfamilie Sarcoptoidea Dubinin, 1951, zu führen. Die Familie Knemidocoptidae besitzt nur eine Gattung mit 9 verschiedenen Arten: K. glaberrimus, K. philomelae, K. fossor, K. mutans, K. jamaicensis, K. pilae, K. laevis, K. gallinae, K. prolificus. Von jeder Species wird eine ausführliche Darstellung gegeben und soweit bekannt ihre Biologie und Pathogenität besprochen. Das bisher noch nicht beobachtete Männchen von K. jamaicensis wird beschrieben. Ein Bestimmungsschlüssel der Gattung Knemidocoptes wird angeführt.Mit 20 Textabbildungen