The fourth genus in the Orthomyxoviridae: sequence analyses of two Thogoto virus polymerase proteins and comparison with influenza viruses

The tick-borne Thogoto virus (THOV) is the type species of a newly recognized fourth genus, Thogotovirus, in the family Orthomyxoviridae. Because of the distant relationship of THOV with the influenza viruses, determination of its genomic information can potentially be used to identify important domains in influenza virus proteins. We have determined the complete nucleotide sequence of the second longest RNA segment of THOV. The molecule comprises 2212 nucleotides with a single large open reading frame encoding a protein of 710 amino acids, estimated M_r 81 284. The protein shares 77% amino acid similarity with the PB1-like protein of Dhori virus, a related tick-borne virus, and 50–53% with the PB1 polymerase proteins of influenza virus A, B and C. All the motifs characteristic of RNA-dependent polymerases were identified including the SSDD motif common to all RNA-dependant RNA polymerases, indicating that the THOV protein is functionally analogous to the influenza virus PB1 proteins and involved in chain elongation. We also report the corrected sequence of the third longest RNA segment of THOV, encoding a protein which shares 44–47% amino acid similarity with the PA-like polymerase proteins of influenza virus A, B and C. The biological significance of conserved domains in these orthomyxovirid proteins is discussed.     

Das kleinzellige Bronchialkarzinom – neue Entwicklungen nach ASCO 2007

Wiener Medizinische Wochenschrift - Aggressives Tumorwachstum, frühe Metastasierung und hohe Assoziation mit intensivem Nikotinkonsum sind die Charakteristika des kleinzelligen...     

A transient granulocyte killing defect secondary to a varicella infection

A varicella infection in a previously healthy young girl was complicated by bacterial sepsis, arthritis, and osteomyelitis in multiple locations. This secondary complication caused by Staphylococcus aureus was associated with a transient defect in granulocyte function and an alteration in the representation of CD4 and CD8 positive lymphocyte subpopulation. The mechanism responsible for secondary bacterial infections following varicella may be due to transient defects in granulocyte function.     

T-Cell receptor αβ and γδ T cells in rat and human skin — are they equivalent?

In the not-so-distant past the skin was generally viewed as a passive target for immune-mediated injury. Over the last decade, however, concepts of a previously unrecognized role for the skin have unfolded, whereby resident bone marrow-derived leukocytes (e.g. Langerhans cells and T cells) initiate and regulate the immune responses that protect it. Their combination with other immunomodulatory resident cells (e.g. keratinocytes, melanocytes, endothelial cells, fibroblasts) led to the idea that the skin may function as a self-sustaining lymphoid tissue. Although T lymphocytes or, at least, certain subpopulations thereof have the general propensity to populate epithelial tissues, there exist major species differences regarding the phenotype of intraepidermal T cells. The purpose of this review is to fill gaps in our understanding of the relationship of rodent skin T cells to T cells identified in human skin and the normal physiologic and pathologic role(s) of these cells.     

Untersuchung zur Morbidität der indigenen Volksgruppen der Chiquitanos im südlichen Amazonasgebiet

The Chiquitano-tribe lives in the southern Amazonas region in Bolivia, remote from larger towns. A study (n=1514) on morbidity over an one year period (April 1995 till March 1996) and its relation to general and social medicine is given. Most frequently, childreh under 15 years and women in parity age (15–45 years) sought consultation (34,1 %, 42,7 %). Gastrointestinal, respiratoral and gynecological-obstetric diseases were predominant (22,4 %, 16,2 % and 15,7 %). In the dry season, common colds and respiratoral infections represented the major health problem. In the rainy season, infectious diarrhea diseases caused by polluted water as a consequence of extended floods were most frequent. Typical tropical diseases (malaria, Dengue fever, Chagas’ disease, leprosy a.o.) and socially caused diseases (AIDS, dependencies on drugs and alcohol, consequencies of crime) were rarely seen. With respect to severity, 55,8 % of the patients showed mild disorders. More serious diseases were observed in 39, 8 %. 4,6 % of the patients were diagnosed severly ill and needed hospitalization. Epidemiological data on general and social medicine of minorities in developing countries and their actual degree of medical care are important in a shrinking world. The data are useful to estimate medical needs and plan improvements to the health care system especially in rural areas.     

Rapid chemical kinetic techniques for investigations of neurotransmitter receptors expressed in Xenopus oocytes

Xenopus laevis oocytes have been used extensively during the past decade to express and study neurotransmitter receptors of various origins and subunit composition and also to express and study receptors altered by site-specific mutations. Interpretations of the effects of structural differences on receptor mechanisms were, however, hampered by a lack of rapid chemical reaction techniques suitable for use with oocytes. Here we describe flow and photolysis techniques, with 2-ms and 100-μs time resolution, respectively, for studying neurotransmitter receptors in giant (≈20-μm diameter) patches of oocyte membranes, using muscle and neuronal acetylcholine receptors as examples. With these techniques, we find that the muscle receptor in BC₃H1 cells and the same receptor expressed in oocytes have comparable kinetic properties. This finding is in contrast to previous studies and raises questions regarding the interpretations of the many studies of receptors expressed in oocytes in which an insufficient time resolution was available. The results obtained indicate that the rapid reaction techniques described here, in conjunction with the oocyte expression system, will be useful in answering many outstanding questions regarding the structure and function of diverse neurotransmitter receptors.     

Cotinine determination by immunoassays may be influenced by other nicotine metabolites

Polyclonal rabbit anticotinine antiserum, which can be used for biomonitoring nicotine uptake by the determination of cotinine in body fluids, was checked by a competitive ELISA for its cross-reactivity with nine nicotine metabolites. The highest percentage of relative crossreactivity (about 30%) was observed with trans-3-hydroxycotinine, a metabolite which is known to be excreted in 3-fold higher amounts than cotinine in the urine of human smokers. Therefore, it is possible that cotinine determinations performed by immunochemical methods — especially in urine — may yield overestimated cotinine concentrations.     

Low T3 syndrome and chronic inflammatory rheumatism

For the clarification of pathogenesis and clinical relevance of decreases of the triiodothyronine (T3) level in patients with chronic inflammatory rheumatism in a group of 63 patients with clinically, paraclinically and roentgenologically diagnosed rheumatoid arthritis (59 times) and with SLE (4 times), respectively, parallel were determined parameters of the thyroid gland function and of the rheumatic activity as well as a subtile drug anamnesis for the medication of antirheumatic drugs was established. In 33 of the 63 patients who were included into the study decreases and low normal values, respectively, for the total T3 (TT3 less than 1.5 nmol/l) were found. In comparison to the remaining 30 patients with normal TT3 a typical constellation of paraclinical parameters of the thyroid gland with distinct reduction of TT3 and free T3 (FT3), low normal total T4 (TT4), slight increase of the reverse T3 (rT3), moderate decrease of the basal and stimulated TSH and an only very small restriction of the binding capacity of the thyroid hormone (TBG) were found. A clinically relevant hypothyroidism is thus to be excluded with certainty. Antirheumatic drugs, in particular steroidal ones (glucocorticoids) may on principle also induce such paraclinical constellations, related to the thyroid gland. In our investigations a therapy with antirheumatic drugs is causally scarcely considered, since both in the group of patients with decrease of T3 and without decrease comparable quantities of antirheumatic drugs including glucocorticoids were administered and the cortisol values in the plasma do not differ. The investigations confirm our already formerly expressed supposition that also in rheumatics a "low-T3-syndrome" is existing as it is otherwise described in consumptive extrathyroidal diseases (NTI).(ABSTRACT TRUNCATED AT 250 WORDS)     

CGP 6809 — A new nitrosoureido-sugar derivative with activity in human tumor xenografts

Summary CGP 6809 [ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)--d-glucofuranoside] is a new methylnitrosoureido-sugar derivative that has been shown to be active against a broad spectrum of transplantable tumours in mice and rats [14]. We investigated the anti-tumour effect of CGP 6809 in ten selected, human tumour xenograft lines growing s. c. in nude mice. The p. o. administration of 125 mg/kg per day for 10–15 days was less toxic (lethality 12% in tumour-bearing nude mice) than the i. p. injection of 62.5 mg/kg per day (lethality 22%). The anti-tumour effect was similar for both application routes; two large bowel cancers responded to treatment with CGP 6809, rectal cancer CXF 158 showed a remission, and the rapidly growing, undifferentiated colonic cancer CXF 280 exhibited a transient no-change. Furthermore, remissions were observed in the epidermoid lung cancer LXF 322 and in thyroid cancer 117. Tumour progression was found in another epidermoid lung cancer and in three stomach cancers, one melanoma, and one soft tissure sarcoma. CGP 6809 is a promising new agent for clinical trials, especially for large bowel and epidermoid lung cancer.Supported in part by grant PTB 8467 from the Bundesminister für Forschung und Technologie, Bonn, FRG