Treatment-outcome for synchronous head-and-neck and oesophageal squamous cell carcinoma.

Background And Purpose: Although head & neck and oesophageal carcinomas occur synchronously in up to 12%, almost no data on feasibility and outcome after radiotherapy are available.

Materials And Methods: From 1989 to 2002, 24 patients were treated at Tuebingen University and Fulda hospital with a radiation based, curative approach. These were analyzed retrospectively.

Therapy and prophylaxis of Ebola virus infections.

The first cases of Ebola hemorrhagic fever were reported from Sudan and Zaire (now Democratic Republic of the Congo) in 1976, but the virus has only received significant attention since 1995. Until recently, the development of therapeutics or vaccines was not considered a priority. The knowledge gained during the past decade on the biology and pathogenesis of Ebola virus has led to the development of therapeutic strategies that are currently being investigated.

The role of reverse genetics systems in studying viral hemorrhagic fevers.

Viral hemorrhagic fever (VHF) is an infectious syndrome in humans often associated with high fatality rates. For most VHFs there are no specific and effective therapies or vaccines available and, in general, there is a lack of knowledge regarding the biology and pathogenesis of the causative agents. Therefore, a more detailed understanding of the molecular basis of VHF pathogenesis, including the identification of viral virulence determinants and host interactions and responses, will be important to enhance our ability to control VHF infections.

Effects of Ebola virus glycoproteins on endothelial cell activation and barrier function.

Ebola virus causes severe hemorrhagic fever with high mortality rates in humans and nonhuman primates. Vascular instability and dysregulation are disease-decisive symptoms during severe infection. While the transmembrane glycoprotein GP(1,2) has been shown to cause endothelial cell destruction, the role of the soluble glycoproteins in pathogenesis is largely unknown; however, they are hypothesized to be of biological relevance in terms of target cell activation and/or increase of endothelial permeability.

Ebola virus VP40 late domains are not essential for viral replication in cell culture.

Ebola virus particle formation and budding are mediated by the VP40 protein, which possesses overlapping PTAP and PPXY late domain motifs (7-PTAPPXY-13). These late domain motifs have also been found in the Gag proteins of retroviruses and the matrix proteins of rhabdo- and arenaviruses. While in vitro studies suggest a critical role for late domain motifs in the budding of these viruses, including Ebola virus, it remains unclear as to whether the VP40 late domains play a role in Ebola virus replication.

Simplified methods of implant treatment in the edentulous lower jaw: a 3-year follow-up report of a controlled prospective study of one-stage versus two-stage surgery and early loading.

Background: Interest in the use of one-stage surgery and immediate loading of oral implants has lately been increasing.

Purpose: The aim of this study was to compare the 3-year results of one-stage surgery versus two-stage surgery, early loading versus loading after a 3-month healing period, and the use of one-piece implants versus the use of two-piece implants.

Materials And Methods: The study included 108 patients with edentulous mandibles.

Development of a new vaccine for the prevention of Lassa fever.

Background: Recent importation of Lassa fever into Germany, the Netherlands, the United Kingdom, and the United States by travelers on commercial airlines from Africa underscores the public health challenge of emerging viruses. Currently, there are no licensed vaccines for Lassa fever, and no experimental vaccine has completely protected nonhuman primates against a lethal challenge.

Methods And Findings: We developed a replication-competent vaccine against Lassa virus based on attenuated recombinant vesicular stomatitis virus vectors expressing the Lassa viral glycoprotein.

[A historic case of Wegener's granulomatosis: the physicist who discovered the electromagnetic waves: Heinrich Hertz].

Summary: A diary and an extensive correspondence of Heinrich Hertz and his family provide a meticulous documentation of his life, made available by Albrecht Folsing in 1997 through a carefully investigated biography, which permit the conclusion that H. Hertz died of Wegener's granulomatosis, 45 years before this disease had been explored. WEGENER'S GRANULOMATOSIS: The symptoms of the granulomatosis, that was first described by Friedrich Wegener in 1936 and 1939 are presented in short with literal quotations of the author: It begins with a refractory cold that will last until the end, then follow involvement of the paranasal sinuses, ears, mucous lining of mouth and pharynx, slight fever, weakness, in the final phase dissemination with nephritis, septic fever, arthritis, myalgia, paralyses leading to total immobility, exitus.

Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marburg viruses.

Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein. A single intramuscular injection of the EBOV or MARV vaccine elicited completely protective immune responses in nonhuman primates against lethal EBOV or MARV challenges.

Intracellular localization of Crimean-Congo Hemorrhagic Fever (CCHF) virus glycoproteins.

Background: Crimean-Congo Hemorrhagic Fever virus (CCHFV), a member of the genus Nairovirus, family Bunyaviridae, is a tick-borne pathogen causing severe disease in humans. To better understand the CCHFV life cycle and explore potential intervention strategies, we studied the biosynthesis and intracellular targeting of the glycoproteins, which are encoded by the M genome segment.

Results: Following determination of the complete genome sequence of the CCHFV reference strain IbAr10200, we generated expression plasmids for the individual expression of the glycoproteins GN and GC, using CMV- and chicken beta-actin-driven promoters.

RNA polymerase I-driven minigenome system for Ebola viruses.

In general, Ebola viruses are well known for their ability to cause severe hemorrhagic fever in both human and nonhuman primates. However, despite substantial sequence homology to other members of the family Filoviridae, Reston ebolavirus displays reduced pathogenicity for nonhuman primates and has never been demonstrated to cause clinical disease in humans, despite its ability to cause infection. In order to develop a tool to explore potential roles for transcription and replication in the reduced pathogenicity of Reston ebolavirus, we developed an RNA polymerase I (Pol I)-driven minigenome system.

Establishment of conventional and fluorescence resonance energy transfer-based real-time PCR assays for detection of pathogenic New World arenaviruses.

Background: Five of the known arenaviruses cause viral hemorrhagic fever in humans and are classified as biosafety level 4 pathogens. Four of the viruses, namely Junin, Guanarito, Machupo, and Sabia, belong to clade B of New World arenaviruses that also comprises the nonpathogenic viruses Tacaribe, Cupixi, and Amapari.

Objectives: To establish real-time reverse transcription (RT)-PCR assays for Junin and Guanarito virus based on fluorescence resonance energy transfer (FRET) probes, and a universal RT-PCR assay for all known clade B viruses with conventional read-out.

Epidemiology of Hoffmeister's genetically determined predisposition to disturbed development of the dentition in patients with true skeletal class III malocclusion.

Aim: The prevalence of symptoms of Hoffmeister's "genetically determined predisposition to disturbed development of the dentition" as studied in patients with true skeletal Class III malocclusion; results of the study were compared with those found in the scientific literature regarding samples from the normal population and from orthodontic patients.

Patients And Methods: The prevalence of 20 defined symptoms was evaluated in 120 patients with true skeletal Class III malocclusion. The patients were selected on the basis of a positive family history and on the presentation of typical characteristics of a skeletal Class III morphology in a lateral cephalogram.

Role of Ebola virus secreted glycoproteins and virus-like particles in activation of human macrophages.

Ebola virus, a member of the family Filoviridae, causes one of the most severe forms of viral hemorrhagic fever. In the terminal stages of disease, symptoms progress to hypotension, coagulation disorders, and hemorrhages, and there is prominent involvement of the mononuclear phagocytic and reticuloendothelial systems. Cells of the mononuclear phagocytic system are primary target cells and producers of inflammatory mediators.

Simplified methods of implant treatment in the edentulous lower jaw. Part II: Early loading.

Background: Most implant treatment is performed with a two-stage surgical procedure. A disadvantage of these implant treatments is that they are time-consuming.

Purpose: The aim of the present study was to evaluate the results of early loading in the edentulous mandible and to compare those results with treatment results of one-stage surgery followed by a healing period and with two-stage surgery.

An animal model for the tickborne flavivirus--Omsk hemorrhagic fever virus.

The tickborne encephalitis (TBE) serocomplex of flaviviruses consists primarily of viruses that cause neurologic disease; these viruses include Omsk hemorrhagic fever virus (OHFV), a virus that is genetically related to other TBE serocomplex viruses but that circulates in an ecologically distinct niche and causes markedly different human disease. The objective of this study was to examine a potential small-animal model for OHFV and to compare the pathology of infection with that of the neurotropic tickborne flavivirus, Powassan virus (POWV). POWV-infected BALB/c mice demonstrated typical arboviral encephalitis, characterized by paresis and paralysis before death, and viral infection of the cerebrum, characterized by inflammation and necrosis.

[200 years testing hearing disorders with speech, 50 years german speech audiometry -- a review].

Unlabelled: FROM THE BEGINNIGS TO CLASSICAL SPEECH TESTS: The need for classification of different degrees of hearing disorders first arose when it seemed possible to treat deafness. Grapengiesser in Berlin 1801 had applied galvanic current to the ears of deaf children and reported some success. Pfingsten in Kiel in 1804 using this method was the first to use speech in diagnosing different degrees of deafness.

Rescue of Ebola virus from cDNA using heterologous support proteins.

Using the infectious clone for Zaire ebolavirus, the functional specificity of viral proteins of the ribonucleoprotein complex in transcription/replication was investigated by substituting them with heterologous proteins derived from closely (Reston ebolavirus) and distantly related filoviruses (Marburgvirus). The data clearly demonstrated that transcription/replication are neither strictly species-specific nor genus-specific. Protein interactions between the nucleoprotein NP and the virion protein VP35 and the polymerase L and VP35 seemed to be the most critical steps.

Functional analysis of the noncoding regions of the Uukuniemi virus (Bunyaviridae) RNA segments.

The role of the variable portion of the noncoding regions (NCRs) of the three Bunyaviridae RNA segments (L, M, S) in transcription, replication, and packaging was studied using the recently developed plasmid-driven RNA polymerase I minigenome system for Uukuniemi (UUK) virus, genus Phlebovirus (11), as a model. Comparison of the different segments showed that all NCRs were sufficient to mediate transcription/replication of a minigenome but demonstrated decreased promoter strength in the order M > L > S. Chimeric minigenomes with flanking NCRs from different genome segments revealed that the number of total base pairs within the inverted, partially complementary ends was important for transcription and replication.

Enhanced virulence of influenza A viruses with the haemagglutinin of the 1918 pandemic virus.

The 'Spanish' influenza pandemic of 1918-19 was the most devastating outbreak of infectious disease in recorded history. At least 20 million people died from their illness, which was characterized by an unusually severe and rapid clinical course. The complete sequencing of several genes of the 1918 influenza virus has made it possible to study the functions of the proteins encoded by these genes in viruses generated by reverse genetics, a technique that permits the generation of infectious viruses entirely from cloned complementary DNA.

Resolution of primary severe acute respiratory syndrome-associated coronavirus infection requires Stat1.

Intranasal inhalation of the severe acute respiratory syndrome coronavirus (SARS CoV) in the immunocompetent mouse strain 129SvEv resulted in infection of conducting airway epithelial cells followed by rapid clearance of virus from the lungs and the development of self-limited bronchiolitis. Animals resistant to the effects of interferons by virtue of a deficiency in Stat1 demonstrated a markedly different course following intranasal inhalation of SARS CoV, one characterized by replication of virus in lungs and progressively worsening pulmonary disease with inflammation of small airways and alveoli and systemic spread of the virus to livers and spleens.