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The karyotype of D. elongatus was investigated by means of C-banding, silver staining, and mithramycinand quinacrine fluorescent staining. The diploid chromosome number is 2n = 50. C-banding shows pericentromerically localized constitutive heterochromatin in every chromosome. Two of the chromosome pairs carry two telomeric nucleolus organizer regions each. No heteromorphic sex chromosomes were found.
Motoneuron diseases represent a m&jor challenge to modern neurology, yet their clinical manifestations ware first described more than hundred years ago, and despite many studies the etiology of these diseases ramd,ns obscure with no effective treatments having been reported. Although progress has been made in establishing genetic linkage in the rare inherited for.ms of these diseases such as familial amyotrophic lateral scleriosisl , spinal mDscular atrophy and X-linked bulbo-spinal-mDscular atrophy, this new information has not yet affected therapeutic techniques. During the last few years several important steps have been taken concerning the physiological mechanisms involved in motoneuron survival during development, after lesion and in animal models of degenerative diseases, the molecular clOning of several new neurotrophic factors (brain-derived neurotrophic factor (BDNP), neurotrophin-3 and-4 (NT-3 and NT-4) and ciliary neurotrophic factor (CNTP)); the identification of a gene family of receptor molecules for same of these factors, progress in the understanding of the effects of polypeptide growth factors on muscle cell differentiation, neuronal sprouting (insulin-like growth factor-I and -11 (IGF-I and IGF-II), and in vitro motoneuronal survival (CNTF, IGF-I and -II and basic FGF). These findings have raised new hopes in that they could lead to a better understanding of the pathophysiological processes underlying these diseases, and that the pharmacological use of same of these newly characterized neurotrophic factors could present new possibilities for the treatment of these diseases.
The structure of the rat ciliary neurotrophic factor (CNTF) gene and the regulation ofCNTF mRNA levels in cultured glial cells were investigated. The rat mRNA is encoded by a simple two-exon transcription unit. Sequence analysis of the region upstream of the transcription start-site did not reveal a typical TATA-box consensus sequence. Low levels of CNTF mRNA were detected in cultured Schwann cells, and CNTF mRNA was not increased by a variety of treatments. Three-week-old astrocyteenriched cell cultures from new-born rat brain contained easily detectable CNTF mRNA. In astrocyte-enriched cultures, upregulation of CNTF mRNA levels was observed after treatment with IFN-gamma. CNTF mRNA levels were down-regulated in these cells by treatments that elevate intracellular cyclic AMP and by members of the fibroblast growth factor (FGF) family. The implications of these results for potential in vivo functions of CNTF are discussed.
CNTF is a cytosolic molecule expressed postnatally in myelinating Schwann cells and in a subpopulation of astrocytes. Although CNTF administration prevents lesion-mediated and genetically determined motor neuron degeneration, its physiological function remained elusive. Here it is reported that abolition of CNTF gene expression by homologous recombination results in a progressive atrophy and loss of motor neurons in adult mice, which is functionally reflected by a small but significant reduction in muscle strength.
Die Kupfer-Zink-Lagerstätte von Kupferberg-Neufang im Bereich der Münchberger Deckenstruktur besteht aus einem etwa 4 km langen Zug einzelner stratiformer Vererzungslinsen, der in NW-SE-Richtung vom anchimetamorphen Paläozoikum "Bayerischer" Faziesentwicklung in die Prasinit-Phyllit-Serie hinüberzieht. Bisherige lagerstättenkundliche Untersuchimgen interpretierten die gesamte Lagerstätte als einheitliche, submarin-exhalativ entstandene stratiforme Bildung in Zusammenhang mit ordovizischem basischem Vulkanismus, der in den Rahmengesteinen der Lagerstätte durch die Diabase der anchimetamorphen Randschieferserie bzw. die Prasinite der Prasinit-Phyllit-Serie dokumentiert ist. Diese Vorstellung steht jedoch in deutlichem Widerspruch zu den Ergebnissen neuerer geochemischer und biostratigraphischer Untersuchungen, die für die Diabase und Prasinite eine völlig unterschiedliche Zusammensetzung ergaben und die zeigten, daß die Prasinit-Phyllit-Serie schon im Oberproterozoikum, die erzführenden Schichten im anchimetamorphen Paläozoikum aber erst im Unterdevon sedimentiert wurden. Für eine Klärung der Situation sind weitere Untersuchungen im Bereich der Lagerstätte erforderlich.
Transforming growth factor \(\beta\) (TGF-\(\beta\)) has a growth-inhibitory effect on numerous different cell types of the immune system, including T lymphocytes. We show in this study that the inhibitory action of TGF-\(\beta\) on T lymphocytes is accompanied by a block of interleukin 2 (IL-2) gene expression which is mediated, at least in part, by inhibition of IL-2 promoter/enhancer activity. The functional analysis of cis-regulatory (protoenhancer) elements of the IL-2 enhancer/promoter region showed that the most TGF-\(\beta\)-responsive element maps to its so-called upstream promoter site. The proto-enhancer activity of the upstream promoter site element is also inhibited by cyclosporin A. The upstream promoter site DNA harbors two noncanonical, closely linked binding sequences for octamer and AP-1-like factors. Both sites are involved in the establishment of IL-2 enhancer activity. Since the activity of genuine octamer sites but not that of AP-1-binding sites is also impaired by TGF-\(\beta\) and cyclosporin A in E14 T lymphoma cells, we conclude that both immunosuppressives interfere with the activity but not the DNA binding of octamer factors in T lymphocytes.
Phenotypic and functional changes in lymphocytes from rhesus monkeys (Macaca mulatta) were investigated during the first 6 months after infection with SIVmac 32H. Animals preimmunized with keyhole limpet hemocyanin (KLH) were sacrificed l, 3, 6, 12, and 24 weeks post infection. Subset composition and function of lymphocytes from blood, spleen, lymph node and thymus were analysed. In addition to a rapid decline in CD4/CD8 ratios, a massive reduction in CD29+CD4+ cells was seen in the periphery. Although depletion of this subset was observed throughout the course of this experiment, the loss of proliferative T cell responses was most pronounced very early after infection and partially recovered after Month 3. Polyclonal cytotoxic responses were only slightly affected. In the thymus, a gradual, but moderate loss of CD4 + CD8 + immature thymocytes, and a relative increase in both CD4 + and CD8 + mature subsets was observed. Infectious virus was readily recovered from homogenates of lymph node and spleen, but not of thymus tissue. Interestingly, however, virus was detected in thymocytes from all infected animals by cocultivation with a simian immunodeficiency virus (SIV) susceptible cell line.
Effects of smoking on thermal pain threshold in deprived and minimally-deprived habitual smokers
(1993)
This study examined the antinociceptive effects of smoking in nine habitual smokers under deprived (12 h) and minimally-deprived (< 30min) conditions. Pain threshold for thermal stimuli, heart rate, blood pressure and ratings of mood, arousal, dominance and well-being were assessed before and after smoking a cigarette. Overall, smoking affected all measured variables in the expected direction, leading to increased physiological activity, elevated pain threshold and improved mood. However, most of these effects depended on the deprivation status of the subjects, such that smoking after deprivation increased pain threshold whereas smoking after minimal deprivation did not. Pain threshold before smoking was the same for both groups. Deprived subjects had lower pre-smoke diastolic blood pressure, heart rate, and arousal levels, which rose to equal minimally-deprived subjects scores after smoking.
The relation between hypochondriacal attitudes, thermal pain threshold, and attentional bias toward pain was examined in a non-clinical population (N = 28). Attentional bias was operationalized with a concentration-performance test, which subjects performed while connected to a pain stimulator. Subjects were informed that they would receive a painful stimulus during the second part of the test, while the first part was introduced as pain-free. The pain stimulus was never applied during the test phase. The expectancy of a forthcoming pain stimulus reduced the performance of high hypochondriacal subjects in both parts of the test. Low hypochondriacal subjects, on the other hand, displayed significantly better performance in the first, pain-free compared to the second, pain-related part of the test. Thermal pain thresholds were assessed at four measuring sites (thenar, neck, collar-bone, abdomen), but no relations with hypochondriasis sum scores and locus of pain stimulation were found. A stepwise multiple regression of pain threshold by individual Illness Attitude Scales (IAS) led to 66% of the variance being explained by the scales ‘concern about pain’, ‘worry about illness’, and ‘disease phobia’. Results are discussed in terms of amplifying somatic style, preoccupation with or attentional bias toward bodily symptoms, and experimental induction of a hypochondriacal state.
In distance geometry problems and many other applications, we are faced with the optimization of high-dimensional quadratic functions subject to linear equality constraints. A new approach is presented that projects the constraints, preserving sparsity properties of the original quadratic form such that well-known preconditioning techniques for the conjugate gradient method remain applicable. Very-largescale cell placement problems in chip design have been solved successfully with diagonal and incomplete Cholesky preconditioning. Numerical results produced by a FORTRAN 77 program illustrate the good behaviour of the algorithm.