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The major macromolecule on the surface o/Leishmania majorpromastigotes is a lipophosphoglycan (LPG). This glycoconjugate plays a key role in determining infectivity and survival of para-sites in the mammalian host cell. In addition, L. major LPG is able to induce a host-protective immune response. In this article, we summarise the evidence for recognition of highly purified LPG by T cells and we discuss the potential mechanisms of T-cell Stimulation by this non-protein antigen.
Ten monoclonal antibodies (McAbs) raised to Schistosoma japonicum eggs could be assigned using several serological and immunochemical techniques to 3 groups. The McAbs, termed A, B and C-McAbs, apparently recognize carbohydrate epitopes that can be located on the same antigen molecule. The antibodies, generally of IgM isotype, are idiotypically related. They are distinct from another IgM McAb (Group D-McAb) the carbohydrate target epitope of which can also be associated with the epitopes of A. B and C-McAbs. The McAbs produce large vacuolated bleb reactions in the circumoval precipitin test (COPT) and target epitopes have different representations in various life cycle stages such as immature and mature eggs, male and female worms (including S. mansoni). Antigens affinity purified on columns containing A, B, C and D-McAbs stimulate proliferation of T cells from egg-sensitized mice and elicit DTH reactions in such mice. This raises the possibility that the target antigens of these carbohydrate-reactive monoclonal antibodies are immunopathologic and involved in egg-induced granuloma formation.
Leishmanien besitzen eine Vielzahl von Mechanismen, die humorale und zelluläre Immunabwehr effektiv zu unterlaufen. Diese hängen eng mit der Expression von hauptsächlich zwei Glykokonjugaten auf der Parasitenoberfläche zusammen, dem gp63 und dem Lipophosphoglykan. Die Parasiten sind einerseits schlechte Aktivatoren des alternativen Komplementweges und umgehen damit ihre eigene extrazelluläre Lyse. Oberflächengebundene Komplementfaktoren fördern andererseits die Aufnahme der Leishmanien durch Makrophagen. Solange diese nicht durch T-Zellen aktiviert sind, dienen sie den Parasiten als "Refugium". Dies gilt insbesondere, als Leishmanien in der Lage sind, 1. den "oxidative burst" zu hemmen; 2. toxische Sauerstoffmetaboliten zu entgiften; 3. abbauende lysosomale Enzyme zu hemmen und 4. das saure Milieu in den Lysosomen für ihren eigenen Metabolismus auszunutzen. Schließlich unterlaufen Leishmanien die zelluläre Immunabwehr des Wirts, indem sie die Aktivierung von T-Lymphozyten hemmen und die Expansion von T-Zell-Sub-populationen bewirken, die für ihr eigenes Überleben nützlich sind.
Hyperolius viridiflavus nitidulus inhabits parts of the seasonally very hot and dry West African savanna. During the long lasting dry season, the small frog is sitting unhidden on mostly dry plants and has to deal with high solar radiation load (SRL), evaporative water loss (EWL) and small energy reserves. It seems to be very badly equipped to survive such harsh climatic conditions (unfavorable surface to volume ratio, very limited capacity to störe energy and water). Therefore, it must have developed extraordinary efficient mechanisms to solve the mentioned Problems. Some of these mechanisms are to be looked for within the skin of the animal (e.g. protection against fast desiccation, deleterious effects of UV radiation and over-heating). The morphology of the wet season skin is, in most aspects, that of a "normal" anuran skin. It differs in the Organization of the processes of the melanophores and in the arrangement of the chromatophores in the Stratum spongiosum, forming no "Dermal Chromatophore Unit". During the adaptation to dry season conditions the number of iridophores in dorsal and ventral skin is increased 4-6 times compared to wet season skin. This increase is accompanied by a very conspicuous change of the wet season color pattern. Now, at air temperatures below 35° C the color becomes brownish white or grey and changes to a brilliant white at air temperatures near and over 40° C. Thus, in dry season State the frog retains its ability for rapid color change. In wet season State the platelets of the iridophores are irregularly distributed. In dry season State many platelets become arranged almost parallel to the surface. These purine crystals probably act as quarter-wave-length interference reflectors, reducing SRL by reflecting a considerable amount of the radiated energy input. EWL is as low as that of much larger xeric reptilians. The impermeability of the skin seems to be the result of several mechanisms (ground substance, iridophores, lipids, mucus) supplementing each other. The light red skin at the pelvic region and inner sides of the limbs is specialized for rapid uptake of water allowing the frog to replenish the unavoidable EWL by using single drops of dew or rain, available for only very short periods.
Natural changes in the transcription of rRNA genes were studied in nucleoli from three oogenic stages of the newt Triturus alpestris with electron microscope, autoradiographic, and biochemical techniques. From determinations of the uridine triphosphate pool sizes and [3H]uridine uptake, phosphorylation, and incorporation into 28S and 18S rRNAs in vivo it was estimated that the rate of rRNA synthesis was about 0.01% in previtellogenic oocytes and 13% in mature oocytes when compared to midvitellogenesis. Spread preparations of nucleoli showed significant morphological changes in the transcriptional complexes. The total number of lateral fibrils, i.e., ribonucleoproteins containing the nascent rRNA precursor, were drastically decreased in stages of reduced synthetic activity. This indicates that rRNA synthesis is regulated primarily at the level of transcription. The resulting patterns of fibril coverage of the nucleolar chromatin axes revealed a marked heterogeneity. On the same nucleolar axis occurred matrix units that were completely devoid of lateral fibrils, matrix units that were almost fully covered with lateral fibrils, and various forms of matrix units with a range of lateral fibril densities intermediate between the two extremes. Granular particles that were tentatively identified as RNA polymerase molecules were not restricted to the transcription l complexes. They were observed, although less regularly and separated by greater distances, in untranscribed spacer regions as well as in untranscribed gene intercepts. The results show that the pattern of transcriptional control of rRNA genes differs widely in different genes, even in the same genetic unit.
The minor form of vallne tBNA from baker's yeaat - tRNA\(^{Val}_{2b}\) - purified by column chromatography was completely digesteft with guanylo-BNase and pancreatic ENase. The products of these digestions were separated by a combination of thin-layer chromatography on cellulose and high voltage electrophoresis on DEAE-paper and then identified. The halves of tRNA Val 2b were prepared by partial digestion with pancreatic Mass and their complete guanylo-BNase and pancreatic ENase, digests were analysed. Basing on the obtained data the primary structure of baker1s yeast tRNA\(^{Val}_{2b}\) was reconstructed.
The arrangement of transcriptional units in the loops of lampbrush chromosomes from oocyte nuclei of urodele amphibia and from primary nuclei of the green alga Acetabularia have been studied in the electron microscope using spread preparations. Loops with different patterns of arrangement of matrix units (i.e. to a first approximation, transcriptional units) can be distinguished: (i) loops consisting of one active transcriptional unit; (ii) loops containing one active transcriptional unit plus additional fibril-free, i.e. apparently untranscribed, intercepts that may include 'spacer' regions; (iii) loops containing two or more transcriptional units arranged in identical or changing polarities, with or without interspersed apparent spacer regions. Morphological details of the transcriptional complexes are described. The observations are not compatible with the concept that one loop reflects one and only one transcriptional unit but, rather, lead to a classification of loop types according to the arrangement of their transcriptional units. We propose that the lampbrush chromosome loop can represent a unit for the coordinate transcription of either one gene or a set of several (different) genes.
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.
Crystals of the R, S diastereoisomer of [Cp(CO)\(_2\)-FeSiCH\(_3\)F]\(_2\)O are monoclinic, space group ndc (No. 14), with a = 846.0(3) [836.4(1»), b = 768.0(3) [757.1(1»), c = 1548.5(4) [1522.3(2)] pm, {3 = 97.34(3t [97.47(3t] at 300 K [120 K] with Z = 2. Even at 120 K the Si-O-Si fragment is found to be strictly linear due to crystallographically imposed symmetry. To explain the unusual electron distribution derived from the X-ray data collected, several types of possible disorders are discussed, none of which leads to a satisfying explanation. Retaining the Ci symmetry (linear Si-O-Si fragment in the final model) the important bond lengths are Fe-Si 226.7(1) [226.5(1)] pm, Si-F 160.9(2) [161.8(2)] pm, Si-O 160.3(1) [161.1(1)] pm, Si-C 185.0(3) [185.6(3)] pm. The electronic features of this compound were probed via molecular orbital calculations of the extended Hiickel type. It was found that the lone pairs on the siloxane oxygen were tipped away from cylindrical symmetry. The tipping was directed toward the fluorine substituents on the silicon atoms and away from the CpFe(CO)\(_2\) units. A pertubational approach was utilized to rationalize this effect.
Man erhält Dimethyl-tellur-bis(alkylxanthogenate) des Typs R2Te(S2COR'lz mit R = CH3, sowie R' = CHs, C2Hs, i-CsH7 durch Umsetzung von Dimethyltellur-diiodid mit den stöchiometrischen Mengen der jeweiligen Natriumxanthogenate. Ebemalls führt eine Einschiebung von CS2 in die Te-O-Bindung von Dimethyl-tellur-bis(alkoxyden) zu den Dimethyl-tellur-bis(alkylxanthogenaten). Die Röntgenstrukturanalyse von (CH3hTe(S2COCH3)2 zeigt, daß das Molekül im Kristall als V'-pentagonale Bipyramide vorliegt.
Methyldixanthogenatostibane
(1983)
Methyldixanthogenatostibane CH\(_3\)Sb(S\(_2\)COR)\(_2\) erhält man entweder durch Reaktion von Methyldibromstiban mit entsprechenden Natriumxanthogenaten bei tiefen Temperaturen (-78°C) oder durch Einschiebung von CS\(_2\) in Methyldialkoxistibane. Die Röntgenstrukturanalyse von CH\(_3\)Sb(S\(_2\)COC\(_2\)H\(_5\))\(_2\) zeigt, daß im Kristall die Chelatliganden das Antimonatom intraund intermolekular koordinieren, so daß eine pentagonal-pyramidale bzw. unter Einbezug des freien Elektronenpaars pentagonal-bipyramidale Koordination am Antimon vorliegt.
Although evidence obtained with the PC12 cell line has suggested a role for the ras oncogene proteins in the signal transduction of nerve growth factor-mediated fiber outgrowth, little is known about the signal transduction mechanisms involved in the neuronal response to neurotrophic factors in nontransformed cells. We report here that the oncogene protein T24-ras, when introduced into the cytoplasm of freshly dissociated chick embryonic neurons, promotes the in vitro survival and neurite outgrowth of nerve growth factor-responsive dorsal rootganglion neurons, brain-derived neurotrophic factor-responsive nodose ganglion neurons, and ciliary neuronotrophic factor-responsive ciliary ganglion neurons. The proto-oncogene product c-Ha-ras also promotes neuronal survival, albeit less strongly. No effect could be observed with truncated counterparts of T24-ras and c-Ha-ras lacking the 23 C-terminal amino acids including the membrane-an-choring, palmityl-accepting cysteine. These results sug-gest a generalized involvement of ras or ras-like proteins in the intracellular signal transduction pathway for neurotrophic factors.
The period of natural cell death in the development of rodent motor neurons is followed by a period of sensitivity to axonal injury1-3. In the rat this early postnatal period of vulnerability coincides with that of very low ciliary neurotrophic factor (CNTF) levels in the sciatic nerve before CNTF increases to the high, adult levels4. The developmental time course of CNTF expression, its regional tissue distribution and its cytosolic localization (as suggested by its primary structure)4*5 favour a role for CNTF as a lesion factor rather than a target-derived neurotrophic molecule like nerve growth factor. Nevertheless CNTF exhibits neurotrophic activity in vitro on different populations of embryonic neurons6. To determine whether the vulnerability of motor neurons to axotomy in the early postnatal phase is due to insufficient availability of CNTF, we transected the axons of newborn rat motor neurons and demonstrated that iocal application of CNTF prevents the degeneration of the corresponding cell bodies.
The occurrence of stacked annulate tamellae is documented for a plant cell system, namely for pollen mother cells and developing pollen grains of Canna generalis. Their structural subarchiteeture and relationship to endoplasmie reticulum (ER) and nuclear envelope cisternae is described in detail. The results demonstrate structural homology between plant and animal annulate lamellae and are compatible with, though do not prove, the view that annulate lamcllar cisternae may originate as a degenerative form of endoplasmic retieulum.
Electron microscopic spread preparations of oocyte nucleoli (lampbrush stage) of various amphibians are quantitatively evaluated and the length distributions of repeat-, matrix-, and spacer-units along the rRNA cistron containing axes are given. The correlation of the matrix unit data with the gel electrophoretic pattern of labelled nuclear RNA from the same oocytes is examined. The mean value of the matrix unit corresponds fairly well to a 2.6 million D peak of pre-rRNA but the distribution of both matrix units and labelled pre-rRNAs shows an asymmetrical heterogeneity indicating the existence of some larger primary transcription products of rDNA. Novel structural aspects are described in the spacer regions which suggest that transcription does also take place in DNP regions between the matrix units. A special "prelude piece" coding for approx. 0.5 million D of RNA is frequently visualized in the spacer segments at the beginning of a matrix unit. Possible artifacts resulting from the preparation, the relative congruence between the data obtained using both methods, and the functional meaning of the findings are discussed against the background of current concepts of structural organization and transcription products of nucleolar DNA.
Segregation of the nucleolar components is described in the differentiated nucleus of the generative cell in the growing Clivia and Lilium pollen tubes. This finding of a natural nucleolar segregation is discussed against the background of current views of the correlations of nucleolar morphology and transcriptional activity.
No abstract available
No abstract available
The influenza virus H1N1 (the A/USSR/90/77 strain) that reappeared in 1977 after the H1N1 influenza viruses had disappeared from the human population, is compared with the A/FM/1/47 and the A/FW/1/50 influenza viruses by the method of oligonucleotide mapping of individual segments of the viral RNAs. Seven genes of the A/USSR/90/77 virus appear to be very similar to the corresponding genes of the A/FW/1/50 virus, whereas the gene coding for the M protein displays considerable homology to the corresponding gene of the A/FM/1/47 virus. The data demonstrate that the A/USSR/90/77 strain is a recombinant virus.
Barley stripe mosaic virus (BSMV) RNA which was previously reported to contain poly(A) sequences (Agranovsky et al., 1978) can be specifically esterified with tyrosine in vitro in the presence of an aminoacyl-tRNA synthetase fraction from wheat embryos. All the three RNA components of the BSMV strain with a three-component genome (Norwich) and both RNA components of a two-component strain (Russian) can be tyrosylated. The poly(A)-containing (bound to oligo(dT)-cellulose) and poly(A)-deficient(not bound to oligo(dT)-cellulose) fractions of BSMV RNA display a similar amino acidaccepting ability. The nucleotide sequence which accepts tyrosine is coupled with the intact genomic polyadenylated BSMV RNA. The viral RNA isolated after sucrose density gradient centrifugation under drastic denaturing conditions retains its aminoacylating activity, which suggests that this activity is not due to the presence in a BSMV RNA preparation of a tyrosine tRNA associated with BSMV RNA. Inhibition of aminoacylation of the 3’-oxidized (treated with sodium metaperiodate) BSMV RNA suggests that the tyrosine-accepting structure is localized at the 3’ terminus of BSMV RNA molecules. It is shown that segments of different lengths obtained upon random fragmentation can be tyrosylated. The 3’-terminal (tyrosine-accepting) poly(A)+ segments can be isolated. The shortest segments of viral RNA capable of being aminoacylated [i.e., containing both tRNA-like structure and poly(A)] consists of approximately 150-200 nucleotides. The analysis of the oligonucleotides derived from individual BSMV RNA components labeled with 32P at the 3’ end revealed two types of 3’-terminal sequences different from poly(A). It is suggested that a poly(A) sequence is intercalated between a 3’-terminal tyrosineaccepting structure and the 5’-terminal portion of poly(A)+ BSMV RNA.
The gene encoding the human homologue of the guinea pig uterine bombesm receptor [( 1992) Eur. J. Biochem. 208,405] was isolated from a genomic lambda library by the PCR/homology screening approach. The gene spans more than 4 kb and consists of 3 exons and 2 introns. The deduced amino acid sequence shows about 86% identity to that of guinea pig bombesin receptor. This subtype of bombesin receptor is expressed in the pregnant uterus and in two human tumour cell lines, T47D (ductal breast carcinoma) and A431 (epidermal carcinoma). PCR analysis of genomic DNA from human-mouse cell hybrids allows the cloned gene to be localized to the region q26q28 on chromosome X.
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.
No abstract available
No abstract available