Long-term reduction of vasopressin excretion induced by the central injection of an immunoconjugate (antibody to vasopressin linked to ricin a chain)

We have previously demonstrated that vasopressin-producing neurons are the target of monoclonal antibodies to vasopressin microinjected into the brain tissue. At the same time, this central microinjection of vasopressin-monoclonal antibody into the supraoptic nuclei produced hydro-osmotic disorders mimicking the effects of a central diabetes insipidus. In order to investigate the increase in both duration and amplitude of the biological effects seen after the injection of vasopressin-monoclonal antibody, an immunoconjugate was constructed with the vasopressin-monoclonal antibody IgG1k isotype and the cytotoxic part of the ricin molecule, the ricin A chain. The biological parameters, such as diuresis and urine osmolality which are directly regulated by vasopressin, and vasopressin excretion, were measured after the central injection of this immunotoxin/immunoconjugate. The consequences of immunotoxin injection were also studied when immunotoxin was co-injected with monensin (50 nM) which has been shown to decrease the intracellular degradation of immunotoxin, and plasma complement, which has been shown to increase the neuronal uptake of immunotoxin. Single injection of immunotoxin near the hypothalamic supraoptic nuclei significantly increased diuresis and decreased vasopressin excretion. However, these effects were only transient and disappeared 24 h later. Four successive injections of immunotoxin (one per day) with monensin induced a decrease of vasopressin excretion which was still observed after a resting period of four days after the fourth injection. The long-term reduction of vasopressin excretion was induced in rats receiving four successive injections of a mixture consisting of immunotoxin with monensin and plasma complement. In such experiments, the vasopressin content of urine remained low (55% under the baseline value), two weeks after the fourth injection of immunotoxin. At the same time, the diuresis was increased (80% above the baseline value) and urine osmolality lowered (45% under the baseline value). When non-specific IgG replaced specific antibody, vasopressin excretion, diuresis as well as urine osmolality were unchanged.

The results of this study demonstrated that the use of a specific immunotoxin results in a local interference with the vasopressinergic neurons and induces a long-term reduction of vasopressin secretion.     

Modulating parameters of excitability during and after transcranial direct current stimulation of the human motor cortex

Weak transcranial direct current stimulation (tDCS) of the human motor cortex results in excitability shifts which occur during and after stimulation. These excitability shifts are polarity-specific with anodal tDCS enhancing excitability, and cathodal reducing it. To explore the origin of this excitability modulation in more detail, we measured the input–output curve and motor thresholds as global parameters of cortico-spinal excitability, and determined intracortical inhibition and facilitation, as well as facilitatory indirect wave (I-wave) interactions. Measurements were performed during short-term tDCS, which elicits no after-effects, and during other tDCS protocols which do elicit short- and long-lasting after-effects. Resting and active motor thresholds remained stable during and after tDCS. The slope of the input–output curve was increased by anodal tDCS and decreased by cathodal tDCS. Anodal tDCS of the primary motor cortex reduced intracortical inhibition and enhanced facilitation after tDCS but not during tDCS. Cathodal tDCS reduced facilitation during, and additionally increased inhibition after its administration. During tDCS, I-wave facilitation was not influenced but, for the after-effects, anodal tDCS increased I-wave facilitation, while cathodal tDCS had only minor effects. These results suggest that the effect of tDCS on cortico-spinal excitability during a short period of stimulation (which does not induce after-effects) primarily depends on subthreshold resting membrane potential changes, which are able to modulate the input-output curve, but not motor thresholds. In contrast, the after-effects of tDCS are due to shifts in intracortical inhibition and facilitation, and at least partly also to facilitatory I-wave interaction, which is controlled by synaptic activity.     

The emergence of national electronic health record architectures in the United States and Australia: models, costs, and questions

Emerging electronic health record models present numerous challenges to health care systems, physicians, and regulators. This article provides explanation of some of the reasons driving the development of the electronic health record, describes two national electronic health record models (currently developing in the United States and Australia) and one distributed, personal model. The US and Australian models are contrasted in their different architectures ("pull" versus "push") and their different approaches to patient autonomy, privacy, and confidentiality. The article also discusses some of the professional, practical, and legal challenges that health care providers potentially face both during and after electronic health record implementation.     

Monosomy 9q and trisomy 16q in a case of congenital solitary infantile myofibromatosis

Although infantile myofibromatosis (IM) is the most common fibrous proliferation of infancy, many aspects of this benign lesion have not been explored. IM histogenesis is still poorly understood, despite immunohistochemical staining and ultrastructural features that suggest a myofibroblastic origin. IM diagnosis is often made difficult by the predominance of small primitive spindle cells over myofibrobasts and the presence of intravascular growth. Genetic information is scarce, with only one karyotyped case. Here we describe a case of solitary IM discovered at birth in an otherwise healthy girl. The tumor was well circumscribed, arranged in nodules and made up of ovoid cells without atypia, in a myxoid background. Immunohistochemical evaluation indicated a myofibroblastic differentiation. The cytogenetic and fluorescence in situ hybridization analyses revealed an abnormal chromosome 9, derived from an unbalanced whole-arm translocation between chromosomes 9 and 16. On both chromosomes, the breakpoints were located in the pericentric heterochromatic region. This clonal abnormality has not been reported in other tumors and is different from the chromosome 6q deletion reported in the single previous reported IM karyotype.     

Pregnancy outcome after blastocyst transfer as compared to early cleavage stage embryo transfer

BACKGROUND: Retrospective cohort study to evaluate differences in outcome when embryo transfer was performed either on day 2-3 (cleavage stage, CS-group) or on day 4-5 (blastocyst stage, BS-group). METHODS: A total of 1259 consecutive cycles yielding 500 live born babies performed at a single centre in Bregenz, Austria, were included. Main outcome measures were implantation and (multiple) pregnancy rates and neonatal outcome including birth defects. RESULTS: Total Pregnancy rate was 44% vs 28% (P < 0.001) and the total 'take home baby rate' was 37% vs 22% in the BS-group and the CS-group, respectively. Rate of multiple gestations (34% vs 17%, P = 0.001) was significantly higher among the BS-group, resulting in a higher rate of preterm deliveries < 36 weeks (26% vs 17%, P = 0.045). Female factor causing infertility (40% vs 21%, P < 0.001) was significantly higher among the BS-group. For the CS-group, rate of singleton pregnancies (83% vs 66%, P = 0.001) and idiopathic cause of infertility (34% vs 22%, P = 0.012) were significantly higher. No statistically significant differences were found in sex, Caesarean section rate, Apgar score and umbilical artery pH-values, total mean birth weight, admission rate to intensive care unit, days of hospitalization and number of minor and major birth defects. CONCLUSIONS: Our data suggest that blastocyst transfer may lead to a higher pregnancy rate with an overall better take-home baby rate (THBR) at the cost of higher rates of multiples and preterm deliveries.     

Multiple transformation phenotypes among revertants of temperature-sensitive mutants in the type 5 adenovirus DNA-binding protein

Seven independently isolated revertants of temperature-sensitive mutants in the 72K protein of Ad5 were tested for the ability to transform rat cells under a variety of conditions. Using the continuous cell line designated CREF, at 36° the range of transformation phenotypes of the different revertants included a frequency characteristic of WT and also the elevated frequency associated with the parental temperature-sensitive alleles. Transformation frequency did not correlate with other phenotypes, such as plaque size or plaquing efficiency on HeLa cells at 38.5°–39°. Therefore, although it is likely that the 72K protein modulates transformation, it is possible to dissociate genetically this regulatory function of the protein from its replicative function in permissive infection.     

Effect of sensory stimulus on striatal dopamine release in humans and cats: a [(11)C]raclopride PET study

BACKGROUND: Sensory stimulation of the forelimb extremities constitutes a well-established experimental model that has consistently shown to activate dopamine (DA) neurotransmission in the mammals' forebrain. OBJECTIVES: To visualize in vivo this modification of striatal DA release in healthy human volunteers using Positron Emission Tomography (PET) and [(11)C]raclopride. Experiments in humans were paralleled by experiments in anesthetized cats. Changes in endogenous DA release were assessed through its competition with [(11)C]raclopride binding (BP(raclo)), a radioligand probing DA D2-receptors. RESULTS: In humans no significant difference of BP(raclo) in caudate (with sensory stimulation: 2.0 +/- 0.3 versus without sensory stimulation: 2.2 +/- 0.3; P = 0.3) or putamen (2.6 +/- 0.3 versus 2.6 +/- 0.2; P = 0.9) ipsilateral to the stimulus was disclosed as a result of sensory stimulation. Similarly, no change of BP(raclo) was observed contralaterally to the stimulation in the caudate nucleus (with sensory stimulation: 2.0 +/- 0.4 versus without sensory stimulation: 2.1 +/- 0.2; P = 0.5) and the putamen (2.5 +/- 0.4 versus 2.6 +/- 0.2; P = 0.4). In cats the same results were obtained in the ipsilateral to stimulation striatum (with sensory stimulation: 2.5 +/- 0.03 versus without sensory stimulation: 2.4 +/- 0.05; P = 0.7). No change was also observed contralaterally to the stimulation (2.4 +/- 0.04 versus 2.5 +/- 0.06; P = 0.6). The [(11)C]raclopride binding remained unchanged by sensory stimuli in both humans and cats. CONCLUSION: This suggests that the DA release induced by sensory stimulus is mostly extrasynaptic whereas the synaptic DA release is probably small, which fits well with the absence of [(11)C]raclopride displacement. The mechanism of this extrasynaptic DA release could be related to a local action of glutamate on dopaminergic terminals via a thalamo-cortico-striatal loop. Present results also underline homology between cat and human responses to sensory stimuli and validate the use of cat brain to find physiological concepts in humans.     

Morphologic, biometric, and isoenzyme characterization of Trichuris suis

Trichuris suis isolates were collected from the cecum of Sus scrofa domestica (pig) and S. s. scrofa (wild boar). Morphology and biometry studies were carried out. Morphology studies showed the existence of typical caudal papillae in males of T. suis from wild boars, but no other difference was observed in the biometric parameters (total length, esophageal length, posterior-portion body length, and spicular length) of T. suis isolated from either host. Individual extracts were subjected to malate dehydrogenase (MDH), malic enzyme (ME), glucose 6-phosphate dehydrogenase (G6PD), lactate dehydrogenase (LDH), and superoxide dismutase (SOD) isoenzyme analysis following starch-gel electrophoresis, and the isoenzyme patterns were compared with those obtained from other species of trichurids. MDH, ME, G6PD, LDH, and SOD isoenzyme patterns were identical for T. suis from both hosts. MDH isoenzyme patterns were characterized by the presence of one cathodic isoenzyme. ME, G6PD, and LDH isoenzyme patterns indicated the presence of three phenotypes, whereas the SOD isoenzyme pattern showed only one phenotype characterized by the existence of two (anodic and cathodic) bands. Different LDH and SOD isoenzyme patterns observed for T. suis, T. ovis, and T. skrjabini confirm once more that isoenzyme patterns have potential as a diagnostic tool for differentiation of different species of Trichuris. Received: 21 October 1997 / Accepted: 2 December 1997     

Restriction fragment pattern analysis of genomes from French isolates of suis herpes virus 1 (Aujeszky's disease virus)

Summary Purified DNA from 45 isolates of suis herpes virus 1 (SHV1) collected between 1980 and 1987 from clinical outbreaks of Aujeszky's disease on French farms was compared by restriction fragment pattern (RFP) analysis. The BamHI generated RFPs were found to be distinguishable, confirming RFP analysis as a potential epidemiological tool. The RFP could be assigned to two established major electrophoretic types and different subtypes. The RFP analysis indicated that the majority of outbreaks were caused by ADV with a central European genome type. The heterogeneity of RFPs among PRV isolates recovered from the central nervous system, lung, and foetus was not restricted specifically to one clinical entity. Variations in the virulence of the 45 isolates studied in mice, chicks, or piglets were unrelated to the RFP subtypes. One unusual RFP has been described for one strain of low virulence.     

Altersspezifische Trends des risikoreichen Alkoholkonsums in Deutschland: Parallele oder unterschiedliche Verläufe?

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Nach der Collectivity-of-Drinking-Cultures-Theorie von Skog finden Veränderungen des Alkoholkonsums in allen...