Disconjugated binocular eye movements at onset of multiple sleep latency test in childhood narcolepsy

In four of six subjects with narcolepsy, multiple sleep latency tests-examined disconjugated binocular eye movements were observed in the very beginning of multiple sleep latency test recordings. The eye movements appeared before disappearance of alpha and decrease of chin electromyography. All subjects with disconjugated eye movements had also rapid eye movement sleep without atonia and symptoms of rapid eye movement behavior disorder in their past history. Three of them (all children) had post-vaccination narcolepsy. It is not known whether such eye movements are seen in most narcoleptic subjects or whether they are more common in autoimmune/inflammatory narcolepsy with involvement of the structures that coordinate eye movements.

     

Aint/Tacc3 is highly expressed in proliferating mouse tissues during development, spermatogenesis, and oogenesis.

Aint was originally identified on the basis of its interaction in vitro with the aryl hydrocarbon nuclear receptor translocator (Arnt). Arnt is a common heterodimerization partner in the basic helix-loop-helix (bHLH)-PER-ARNT-SIM (PAS) protein family and is involved in diverse biological functions. These include xenobiotic metabolism, hypoxic response, and circadian rhythm. In addition, Arnt has a crucial role during development. Aint is a member of a growing family of transforming acidic coiled-coil (TACC) proteins and is the murine homologue of human TACC3. Here we report the spatiotemporal expression of Tacc3 mRNA and protein in embryonic, postnatally developing, and adult mouse tissues using in situ hybridization and immunocytochemistry. Tacc3 mRNA was highly expressed in proliferating cells of several organs during murine development. However, the only adult tissues expressing high levels were testis and ovary. Immunocytochemistry revealed that Tacc3 is a nuclear protein. Our results suggest that Tacc3 has an important role in murine development, spermatogenesis, and oogenesis.     

Use of Wishart Prior and Simple Extensions for Sparse Precision Matrix Estimation

A conjugate Wishart prior is used to present a simple and rapid procedure for computing the analytic posterior (mode and uncertainty) of the precision matrix elements of a Gaussian distribution. An interpretation of covariance estimates in terms of eigenvalues is presented, along with a simple decision-rule step to improve the performance of the estimation of sparse precision matrices and associated graphs. In this, elements of the estimated precision matrix that are zero or near zero can be detected and shrunk to zero. Simulated data sets are used to compare posterior estimation with decision-rule with two other Wishart-based approaches and with graphical lasso. Furthermore, an empirical Bayes procedure is used to select prior hyperparameters in high dimensional cases with extension to sparsity.     

Leukoregulin, a T-cell derived cytokine, upregulates stromelysin-1 gene expression in human dermal fibroblasts: evidence for the role of AP-1 in transcriptional activation.

Leukoregulin (LR), a product of activated T-cells, has been recently shown to modulate the metabolism of extracellular matrix components in human skin fibroblast cultures (Mauviel et al., J Cell Biol 113:1455-1462, 1991). In this study we focused our attention on the effects of LR on the expression of stromelysin-1 gene. This matrix metalloprotease has a broad spectrum of degradative activity and it is also required for maximal activation of interstitial collagenase. Incubation of skin fibroblast cultures with LR resulted in a dose- and time-dependent elevation of stromelysin-1 mRNA levels, the maximum enhancement being up to approximately sevenfold. This effect was abolished by cycloheximide, suggesting a requirement for ongoing protein synthesis. Transient cell transfections with a promoter/reporter gene construct containing 1.3 kb of 5' flanking DNA of the human stromelysin-1 gene linked to the chloramphenicol acetyl transferase (CAT) gene, indicated enhancement of promoter activity by LR. This enhancement was abolished by a single base substitution in the AP-1 binding site of the promoter. Furthermore, gel mobility shift assays demonstrated enhanced AP-1 binding activity in nuclear extracts from cells incubated with LR. However, LR did not alter the activity of a construct containing three AP-1 sequences in front of the thymidine kinase promoter linked to the CAT gene. These results collectively suggest that activation of stromelysin-1 gene expression by LR is mediated by AP-1 regulatory elements which are necessary, but not sufficient, for gene response.     

Oncofetal antigens as tumor markers in the cytologic diagnosis of effusions

To test the value of oncofetal antigens in the cytologic diagnosis of effusions, immunoperoxidase staining with antisera to carcinoembryonic antigen (CEA), alpha fetoprotein (AFP), pregnancy-specific beta 1-glycoprotein (SP1) and placental alkaline phosphatase (PLAP) was carried out on pleural and peritoneal fluids from 72 cases. Sections of formalin-fixed, paraffin-embedded cell blocks were used in most cases; cytocentrifuge preparations were used in some. Reactions were negative with all antisera in 23 of 24 nonmalignant effusions as well as in all 7 cases of malignant mesothelioma and 4 cases of malignant lymphoma. In 24 of 36 confirmed carcinomatous effusions, staining was positive with one or more antisera, including anti-CEA positivity in 23 of the 24 cases. In 5 of the 24 cases with positive staining, a confident diagnosis of malignancy had not been made on routine cytologic preparations. Immunoperoxidase staining for CEA appears to be of supportive value in the cytologic diagnosis of malignancy in effusions.     

Evolution of collagen IV genes from a 54-base pair exon: A role for introns in gene evolution

The exon structure of the collagen IV gene provides a striking example for collagen evolution and the role of introns in gene evolution. Collagen IV, a major component of basement membranes, differs from the fibrillar collagens in that it contains numerous interruptions in the triple helical Gly-X-Y repeat domain. We have characterized all 47 exons in the mouse alpha 2(IV) collagen gene and find two 36-, two 45-, and one 54-bp exons as well as one 99- and three 108-bp exons encoding the Gly-X-Y repeat sequence. All these exons sizes are also found in the fibrillar collagen genes. Strikingly, of the 24 interruption sequences present in the alpha 2-chain of mouse collagen IV, 11 are encoded at the exon/intron borders of the gene, part of one interruption sequence is encoded by an exon of its own, and the remaining interruptions are encoded within the body of exons. In such "fusion exons" the Gly-X-Y encoding domain is also derived from 36-, 45-, or 54-bp sequence elements. These data support the idea that collagen IV genes evolved from a primordial 54-bp coding unit. We furthermore interpret these data to suggest that the interruption sequences in collagen IV may have evolved from introns, presumably by inactivation of splice site signals, following which intronic sequences could have been recruited into exons. We speculated that this mechanism could provide a role for introns in gene evolution in general.     

Cardiovascular, ventilatory and total activity responses of brown trout to handling stress

Changes in total activity, heart and ventilation rates were observed in 2-year-old brown trout, following handling stress, using non-contact bioelectronic monitoring equipment. Experiments were carried out in laboratory conditions at water temperatures below 4° C, Transfer between tanks as well as 5 min restraint stress increased the total activity of fish for 24 to 48 h, after which it declined to near the pre-stress level. The transfer and struggle both elevated the heart rate for 3 to 4 days. Ventilation rate was elevated to a maximum of about 30% above the nominal level and recovered within 3 to 4 days. Both heart and ventilation rates were higher in feeding fish relative to fasting fish after stress and rates remained higher throughout a 7 day period of recovery. A diel rhythm of lower rates during the night appeared in both heart and ventilation rates within 3 to 4 days after handling stress.     

Stroke research in GenomEUtwin.

Stroke is one of the leading causes of severe disability and death in the world. In the present article we outline possibilities and limitations for future stroke research within the GenomEUtwin. The combined sample of twins born before 1958 from Denmark, Finland, and Sweden, and available for follow-up into the second millennium for non-fatal and fatal stroke events through national inpatient and death registers exceeds 70,000 twin pairs. This sample size will enable the study of genetic influences on stroke and major stroke subtypes. Large samples of twins in GenomEUtwin have been followed up repeatedly through interviews and questionnaires concerning a variety of exposures and potential risk factors for stroke. We briefly outline how this information can be combined with the health register information for epidemiologic and genetic epidemiologic studies of stroke. We also present the number of twin pairs concordant and discordant for stroke in Denmark, Finland and Sweden, and time lags between events for twins concordant for stroke. This information illustrates that the number of affected sib pairs for linkage studies is relatively limited, but the sample sizes are promising for association studies.