Semliki Forest virus-induced polykaryocyte formation is an ATP-dependent event

Summary Infection of Aedes albopictus cells with Semliki Forest virus (SFV) leads to polykaryocyte formation below pH 6.2. This syncytium formation is accompanied by a decrease of the cellular ATP level. Addition of inhibitors of oxidative phosphorylation leads to a rapid, total depletion of ATP in infected cells at pH 6 and results in an inhibition of polykaryocyte formation. However, when cells were exposed for only a few minutes to pH 6 in the presence of the inhibitors and then kept at pH 7.2, the ATP level partially recovered to values sufficient for syncytium formation. Similar results were obtained after ATP depletion induced by 2-deoxyglucose. Thus, it can be concluded that SFV-induced syncytium formation is an ATP-dependent event.With 6 Figures     

Pooling of clinical specimens prior to testing for Chlamydia trachomatis by PCR is accurate and cost saving

The accuracy and cost savings of pooling specimens prior to testing for Chlamydia trachomatis by PCR were evaluated with genital and urine specimens (n = 2,600). There was a 60% reduction in tests without significant loss of accuracy. The efficiency of pooling vaginal swabs is demonstrated for the first time.     

Apparent superiority of H2-receptor stimulation and simultaneousβ-blockade over conventional treatment withβ-sympathomimetic drugs in post-acute myocardial infarction: Cardiac effects of impromidine — a new specific H2-receptor agonist — in the surviving catecholamine-insensitive myocardium

Left ventricular infarction (AMI) was produced in experimental animals and the contractile response to -adrenergic and H₂-histaminergic stimulation by isoproterenol and impromidine tested in the isolated perfused heart preparation. Adenylate cyclase activity as well as binding characteristics of [³H]-dihydroalprenolol ([³H]-DHA), [³H]-methyl-tiotidine ([³H]-TIOT) and [³H]-quinuclidinyl benzilate ([³H]-QNB) to cardiac ₁-, H₂- and cholinergic muscarinic receptors were determined in sarcolemmal membrane preparations of the right ventricle of the same hearts. In addition, an attempt was made to elucidate the therapeutic value of post-AMI treatment with impromidine in the presence and absence of-sympathomimetic, in contrast to administration of prenalterol and the conventional therapy with -sympathomimetic drugs, e.g. dobutamine. Three days post-AMI the dose-response curve for isoproterenol of right ventriculardP/dt _max was significantly depressed, while the inotropic effect of impromidine was not impaired. Stimulation of adenylate cyclase activity by isoproterenol was reduced by 80% whereas impromidine and NaF stimulation rates were unaltered. Receptor-binding studies indicated a 90% loss and 10-times lowered affinity (K _D) of the remaining -receptors while specific [³H]-TIOT- and [³H]-QNB-binding was unchanged.Administration of dobutamine increased mortality rates and extension of infarct size, led to a further decrease in contractile response to isoproterenol, induced complete insensitivity of adenylate cyclase to isoproterenol stimulation and caused pronounced additional reduction of number and affinity of [³H]-DHA-binding sites. In contrast, all above alterations were prevented by treatment with either prenalterol or combined administration of impromidine plus metoprolol. It is concluded, that these alterations in the non-ischemic, uninvolved myocardium post-AMI are the result of catecholamine-induced specific damage of sarcolemmal -receptors. Furthermore, treatment with H₂-agonists in combination with -blocking agents may have beneficial effects, whereas conventional therapy with -sympathomimetic drugs tends to worsen the already depressed function of the -adrenergic stimulation mechanism.Supported by grants Ba 666/1 and Ba 666/2-2 from the Deutsche Forschungsgemeinschaft (DFG).Data presented in this paper are part of a doctoral thesis by Dr S.B. Felix.     

Gastrointestinal mesenchymal tumors - immunophenotypic classification and survival analysis

The current definition of gastrointestinal tumors (GIST) as CD117-positive mesenchymal tumors of uncertain malignant potential fails to include a number of cases with similar histology. In an attempt to improve the classification of these neoplasms, we conducted an immunohistochemical analysis of 244 mesenchymal tumors with histological features of GIST. According to their immunophenotype, the tumors were classified as GISTs, which are characterized by CD117 (c-kit) expression; gastrointestinal CD117-negative CD34 positive stromal tumors (GINST); alpha-smooth muscle actin and/or desmin positive gastrointestinal leiomyogenic tumors (GILT); S-100 and glial fibrillary acidic protein positive gastrointestinal glial/schwannian tumors (GIGT); gastrointestinal neuronal/glial tumors (GINT), which are positive for S-100/glial fibrillary acidic protein plus neuronal/glial markers; and gastrointestinal fibrous tumors (GIFT), which are only vimentin positive. The most common type of tumors were GIST, followed in order of frequency by GINST, GILT, GIGT, GIFT, and GINT. GISTs did not show any preferential location, whereas GINSTs occurred almost exclusively in the stomach and duodenum, and GILTs preferentially in the large intestine. Over a median follow-up period of 71 months, malignant behavior, i.e., metastatic spread, was observed in all tumor types except GINTs. Malignancy was associated with distal gut location, high mitotic activity, large tumor size, and nuclear pleomorphism, though none of these criteria alone discriminated between benign and malignant. Kaplan-Meier analysis of disease-specific survival showed significant differences in the long-term outcome of the newly defined subgroups. We conclude that, despite strong morphological similarities, gastrointestinal mesenchymal tumors are heterogeneous in their immunophenotype and biology.     

Enhanced MYCN expression and lsochromosome 17q in pineoblastoma cell lines

We have established two cell lines, PER-452 and PER-453, from an 8-month-old girl with an extensive pineoblastoma. Characterization of these lines revealed that the proto-oncogenes MYC and MYCN were not amplified, but both cell lines showed MYCN expression comparable to a cell line with 200-fold MYCN amplification. Both cell lines contained an i( 17q). These results support the concept that pineoblastomas belong to a larger group of primitive neuroectodermal tumors of the central nervous system. These two cell lines provide a unique opportunity to investigate the molecular genetic mechanisms underlying these neoplasms further. Genes Chrom Cancer 9:129-135 (1994).© 1994 Wiley-Liss, Inc.     

Molecular and cytogenetic characterization of a non-mosaic isodicentric Y chromosome in a patient with Klinefelter syndrome

We report on an adult male with Klinefelter phenotype and an isodicentric Y chromosome (47,XX,+idic(Y)(q12)), a combination which has to the best of our knowledge not been reported before. The patient was hospitalized in forensic psychiatry because of repeated delinquency, aggressive, aberrant and inappropriate behavior, and borderline intelligence. Molecular cytogenetic studies (FISH) showed that the SRY gene was present on both ends of the idicY, while there was only one signal for the Yq subtelomere probe. Molecular investigations by multiplex PCR, using STS markers covering the short and long arm of the Y chromosome did not indicate a deletion of Y chromosomal material. Molecular investigations of STR markers located on Xp22.3 and Xq28 indicated paternal origin of the additional X chromosome and an error in paternal meiosis I. Results of FISH analysis and molecular investigations are compatible with a phenotype as described for individuals with a 48,XXYY karyotype and support the findings that isodicentric Y chromosomes are frequently accompanied by other sex chromosomal abnormalities.     

Red cell hemoglobin,hydrogen ion and electrolyte concentrations during exercise in trained and untrained subjects

Summary Red cell concentrations of hemoglobin (MCHC), H⁺, Na⁺, K⁺, Mg⁺⁺, Cl^– were measured in femoral venous blood of six untrained (UT), six endurance trained (TR) and three semitrained (ST) subjects during graded increasing work (4, 8, 12, 18 and 24 mkp/s, 10–15 min on each step) on a bicycle ergometer. Before exercise no significant differences were detected for the measured variables when comparing UT and TR. During exercise MCHC, [Na⁺], [K⁺] and [Mg⁺⁺] remained constant indicating lack of water shift into the erythrocytes in spite of a marked acidosis (lowest pH_Blood value 7.225). This lack resulted from an elevated extracellular osmolality. [H⁺]_Ery and [Cl^–]_Ery maximally increased by 2.0×10^–8 eq/kg H₂O and 10 meq/l, respectively. The change was markedly greater in UT than in TR at equal load. However, if [H⁺]_Ery and [Cl^–]_Ery were related to pH of whole blood, differences between groups almost disappeared and the ions were distributed as predictable from in vitro experiments (Fitzsimmons and Sendroy, 1961). Behaviour of H⁺ and Cl^– may be of importance for oxygen dissociation under in vivo conditions.Supported by Bundesinstitut für Sportwissenschaften, Köln     

Studies on the serum proteins of chimeras: III. Detection of donor-type C′5 in allogeneic and congenic post-irradiation chimeras

Allogeneic and congenic post-irradiation chimeras were produced by bone marrow transfer from C′5 active donor mice into C′5 defective recipients. During the first 4 weeks after transfer many of the chimeras contained haemolytic complement activity in their sera. B6AF₁→A chimeras developed higher levels of activity than did B10D2 (new line)→ B10D2 (old line).

Spleen tissue, but not liver tissue, taken from the chimeric animals during this time period incorporated [¹⁴C]amino acid into MuB1 as demonstrated by autoradiography of immunoelectrophoretic patterns, suggesting localization of the active donor cells in the spleen rather than in the liver. Formation of donor-type IgG remained demonstrable for a more extended period after induction of chimerism than formation of MuB1.

A transplantable hepatoma in C57L/J, a C′5 active mouse strain, also incorporated [¹⁴C]amino acid into MuB1.

     

Effect of desloratadine versus placebo on nasal airflow and subjective measures of nasal obstruction in subjects with grass pollen-induced allergic rhinitis in an allergen-exposure unit

BACKGROUND: Unlike many antihistamines, desloratadine can reduce nasal congestion in patients with seasonal allergic rhinitis (SAR). OBJECTIVE: We compared the effects of 5 mg of desloratadine and placebo on nasal airflow and SAR symptoms, including nasal congestion, in response to grass pollen in an allergen-exposure unit. METHODS: In a randomized, double-blind, placebo-controlled, crossover trial, 47 subjects with histories of SAR received desloratadine or placebo every morning for 7 days and, after a 10-day washout period, were crossed over to the other treatment arm for 7 days. Subjects underwent a 6-hour allergen exposure on day 7 of each treatment period. Nasal airflow and nasal secretion weights were measured before and every 30 minutes during allergen exposure; SAR symptoms (including nasal congestion) were scored before exposure and every 15 minutes thereafter. RESULTS: Nasal obstruction, as measured by nasal airflow, was less severe with desloratadine than with placebo (P <.02). Individual and combined SAR symptom severity scores, including nasal congestion and sneezing, were significantly lower with desloratadine than with placebo (all P < or =.003). Within 30 minutes of allergen exposure, less severely decreased nasal airflow (P <.02), less nasal secretions (P <.001), and less severe symptoms, including nasal congestion (P <.002), rhinorrhea, and sneezing, occurred with desloratadine compared with placebo, and this continued throughout (0-6 hours) allergen exposure. Desloratadine was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSION: In subjects with allergen-induced SAR symptoms, desloratadine significantly reduced the severity of nasal obstruction and accompanying complaints of nasal congestion and other SAR symptoms compared with the effects of placebo.     

Predicting the development of infant emotionality from maternal characteristics

Few studies have examined the associations between environmental conditions and developing infant emotionality or the differential susceptibility to those conditions. The present longitudinal study aims to make a contribution to close that gap. We analyzed whether positive emotionality, negative emotionality/irritability, and withdrawal/fear at the end of the first year of life are predictable from preceding caregiver's depression/anxiety, social support, and sensitivity in the interaction with the infant while controlling for antecedent states of emotionality. Furthermore, the question of whether associations between maternal characteristics and subsequent fear are stronger in the subgroup of infants high in irritability as opposed to those who are low in irritability was investigated. Subjects were 101 healthy firstborn infants and their primary caregivers. Assessments were conducted at infant ages of 4, 8, and 12 months. Depression, anxiety, and the social support of the caregiver were assessed by questionnaire. Sensitivity in the caregiver-infant interaction was assessed by behavior observations within the scope of home visits. Temperament characteristics were observed in standardized laboratory episodes. Whereas negative emotionality and withdrawal/fear were significantly predictable from the maternal characteristics, no predictability could be shown for developing positive emotionality. There were indications of a stronger association between the maternal characteristics and developing withdrawal/fear in irritable infants.