Infants at risk for schizophrenia: sequelae of a genetic neurointegrative defect. A review and replication analysis of pandysmaturation in the Jerusalem Infant Development Study.

A 1975 report stated that a schizophrenic genotype may be manifested in infants by a neurointegrative defect called pandysmaturation. Recent evidence supports this: (1) 12 studies found delayed development in schizophrenics' infants and in preschizophrenics; (2) "blind" psychometric evaluations favored an adult schizotypal disorder in four to six of seven high-risk subjects with pandysmaturation in the New York study; and (3) finally, in a partial replication of this method using the Jerusalem data, blind diagnoses of "probable" and "possible" pandysmaturation were significantly related to a parental diagnosis of schizophrenia and to cognitive and motor neurointegrative deficits at 10 years. Obstetrical complications were unrelated to diagnosis, pandysmaturation, or outcome in the overall sample. However, we found a small subgroup of schizophrenic offspring in whom the most severe motor deficits at follow-up were related to obstetrical complications, pandysmaturation, and low birth weight.     

Individual differences in adult human sleep and wakefulness: Leitmotif for a research agenda

This paper reviews the literature on interindividual variability in human sleep parameters, sleepiness, responses to sleep deprivation, and manifestations of sleep disorders. Variability among individuals in sleep/wake biology and behavior is pervasive. The magnitude of such individual differences is often considerable and comparable to the effect sizes of many experimental and clinical interventions. Evidence is accumulating that certain aspects of sleep/wake-related variability--such as sleep duration, daytime sleepiness, and vulnerability to the effects of sleep loss--involve trait characteristics in healthy populations and among sleep-disordered patients. Establishing the trait-specific nature of variability in sleep/wake parameters is a prerequisite for elucidating the corresponding neurophysiologic and/or genetic mechanisms. At present, it remains largely unknown what underlies or predicts sleep/wake-related traits, what relationships these traits may have to each other, and what functional significance may be associated with specific traits. Scientific studies addressing these issues are warranted, as understanding the basis of trait variability may yield new insights into sleep/wake regulation and sleep pathology. Understanding individual differences in sleep and wakefulness may also have provocative but important implications for health economics and clinical care, as well as for safety, productivity, and general well-being. This paper gives suggestions for a research agenda focusing on individual differences in sleep research and sleep medicine.     

Hemocompatibility of medical connectors with biopassive or bioactive surface coatings

Although medical connectors compose very small parts of the extracorporeal circulation (ECC) system they represent a critical localization where early thromboembolic processes can manifest. In the present study we modified an in vitro closed-loop model with fresh human whole blood for the preclinical evaluation of the hemocompatibility of three types of medical connectors: non-coated (control); with silicone-, and heparin-coating. Each single loop consists of five polycarbonate connectors joined together by five pieces of silicone tubes. Thrombin-antithrombin-III, beta-thromboglobulin (beta-TG), PMN-Elastase, terminal complement complex, CD 11b expression, and surface-absorbed fibrinogen were measured. After 1 and 2 h recirculation, platelet loss, release of beta-TG, and adsorption of fibrinogen were significantly higher (p<0.05) within the non-coated connectors compared to the silicone- and heparin-coated groups. Following this experiment, the connectors were filled again with fresh heparinized whole blood from the same donor to evaluate the influence of prior blood contact. Here, the activation of platelets and coagulation was dependent on the duration of the blood preincubation period. Probably, the coated surfaces possess a reduced, or selective adsorption of plasma proteins, which in turn leads to a faster creation of a blood-friendly secondary superficial membrane, and prevents a further denaturation and hence activation of the adsorbed proteins.     

Expression and regulation of connexins in cultured ventricular myocytes isolated from adult rat hearts

Gap junctions were assayed during re-differentiation of adult rat cardiomyocytes in long-term culture to gain insight into the processes of remodeling. Double immunostaining allowed the localization of connexins Cx40, Cx43, and Cx45 between myocytes and demonstrated co-expression and co-localization in individual cells and gap junction plaques, respectively. Immunoblots showed differential time-dependent changes in connexin expression and phosphorylation. The total amount of connexins and the ratio of phosphorylated/non-phosphorylated isoforms gradually increased during the re-establishment of intercellular communication. Dual voltage-clamp studies showed the involvement of several types of gap junction channels. Multichannel currents yielded diverse spectra of g(j,inst)=f( V(j)) and g(j,ss)=f( V(j)) relationships ( g(j,inst): instantaneous gap junction conductance; g(j,ss): conductance at steady state; V(j): transjunctional voltage), indicative of homotypic and heterotypic channels. Single-channel currents revealed two prominent conductances reflecting gamma(j,main) and gamma(j,residual). The histograms of gamma(j,main) showed four discrete peaks (41-44, 59-61, 70-76, and 100-107 pS) attributable to a combination of Cx45-Cx45, Cx40-Cx45 and Cx43-Cx45 channels (1st peak), Cx43-Cx43 and Cx40-Cx43 channels (2nd peak), Cx43-Cx43 channels (3rd peak) and Cx40-Cx40 and Cx40-Cx43 channels (4th peak). However, the presence of heteromeric channels cannot be excluded. The data are consistent with an up-regulation of Cx45 and Cx43 during re-differentiation.     

Decreased prefrontal 5-HT2A receptor binding in subjects at enhanced risk for schizophrenia

The brain serotonin-2A receptor (5-HT_2AR) has been implicated in both the pathology of schizophrenia and the therapeutic action of atypical antipsychotics. However, little is known about the 5-HT_2AR status before the onset of schizophrenia and before the exposure to antipsychotics. We used [¹⁸F] altanserin and positron emission tomography (PET) in a pilot study of 6 individuals suspected to be at elevated risk for schizophrenia and seven age-matched controls to test the hypothesis that regional 5-HT_2AR binding is altered in the prodromal stages of schizophrenia. Distribution volume ratios (DVRs) as a proxy for 5-HT_2AR availability were significantly reduced in prefrontal cortex regions of at-risk subjects, implicating early abnormalities of serotonergic neurotransmission that antecede the onset of schizophrenia.     

Die Ausbildung der Haptoglobintypen im Säuglingsalter

Zusammenfassung Das gesunde Neugeborene bildet seinen eigenen Haptoglobintyp innerhalb der 1. Lebenswoche aus. Unreife (Frühgeborene) und starke Hämolyse können das Auftreten verzögern. Am Ende des 3. Monats war der eigene Typ bei allen untersuchten Säuglingen (865) nachweisbar.     

Einige Befunde zur Sinnesphysiologie der Kaltblüterzecke Amblyomma testudinis

Zusammenfassung Aus eigener Zucht stammende Larven, Nymphen und Imagines von Amblyomma testudinis wurden auf ihre Sinnesleistungen hinsichtlich Phototaxis, Thermotaxis, Geotaxis und Chemotaxis untersucht. Es ergab sich ein entwicklungsabhängiger Wandel im phototaktischen Verhalten von anfangs positiver Phototaxis bei den Larven über indifferente Phototaxis bei vollgesogenen Larven und nüchternen Nymphen zu negativer Phototaxis bei vollgesogenen Nympen sowie - und -Imagines. Sämtliche Entwicklungsstadien mit Ausnahme der -Imagines verhalten sich temperaturindifferent vor dem Kontakt mit einem Wirt; vollgesogene Larven und Nymphen dagegen bevorzugen niedrige Temperaturen. Nymphen und Imagines, die noch nicht gesogen haben, reagieren negativ geotaktisch. Sie erklettern vermutlich in der Natur die Spitzen von Pflanzen und Steinen, um dort das Vorbeikriechen eines Wirtes abzuwarten. Imagines von Amblyomma testudinis reagieren mit einer positiven Chemotaxis auf Schlangen stärker als auf Kröten. Auch Substrat aus Schlangenbehältern enthält mindestens für 30 Std nach der Entfernung der Schlangen chemotaktisch wirksame Stoffe.

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Contributions to sensory physiology of the tick Amblyomma testudinis

Summary Phototaxis, thermotaxis, geotaxis and chemotaxis of larvae, nymphs and adults of Amblyomma testudinis from own breedings were studied. The phototactic behaviour changed according to the different stages of development: unfed larvae were positively phototactic, fed larvae and unfed nymphs were indifferent, fed nymphs but also the adults showed a negative phototaxis.—All stages of development besides the females reacted without any preference for a distinct temperature, whereas larvae and nymphs after feeding prefered lower temperatures.—Unfed nymphs and adults were negatively geotactic which corresponds to their natural behaviour of climbing plants for catching hosts.—Adults of Amblyomma testudinis showed a higher rate of chemotaxis for snakes than for toads; substrate from snake cages containes chemotaxis inducing substances for more than 30 hours after elimination of the snakes.

     

Neoglycoprotein binding to colorectal tumour cells: Comparison between primary and secondary lesions

Summary Biotinylated neoglycoproteins are useful to determine the expression of sugar receptors (lectins) histochemically in routinely processed tissue sections. Assessment of the presence of distinct receptor classes with specificity to-galactosides and to- or-N-acetylgalactosamine, selected on the basis of their potential relevance for recognition processes within the metastatic cascade in murine model systems, was performed for a common human tumour type, colorectal cancer. The four different types of neoglycoproteins, derived from covalent attachment of commercially available derivatives of-N-acetylgalactosamine, differed only quantitatively in their capacity to detect specific binding on cultured cells and tissue sections, thus posing no major restriction on the choice of synthetic process for histochemical efficiency of the product. Glycocytological application revealed specific probe binding and a regulation of level of receptor expression for a human colon carcinoma cell line primarily forN-acetylgalactosamine-specific receptors upon retinoic acid-induced differentiation. Monitoring of sections of the 12 cases of primary and secondary colorectal lesions invariably disclosed the presence of the respective receptors, the extent of cell labelling in primary tumours and metastases being similar. Establishment of metastases, even in different target organs, is apparently not followed by a major phenotypic variation in this feature.