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The effect of measles virus (MV) infection on mRNA expression and protein synthesis of cytokines in human malignant glioma celllines (0-54 and U-251) was investigated. Primary MV infections led in both celllines to the induction of interleukin-1 fJ (ll-1 (3), interleukin-6 (IL-6), interferon-(3 (IFN-fJ), and tumor necrosis factor-a (TNF-a). ln contrast, persistently infected astrocytoma lines continually produced IL-6 (two out of 12 lines high Ievels) and IFN-ß, whereas only 1 out of 121ines synthesized TNF-a and none IL-1ß. The pathways for induction of IL-1fJ and TNF-a expression were not suppressed by the persistent MV infection, since IL-1ß and TNF-a could be induced by external stimuli Jike diacylglycerol analog plus calcium ionophore. lnterestingly, persistently infected astrocytoma cells synthesized considerably higher Ievels of ll-1ß and TNF-a than uninfected cells afteradditional external induction. These results suggest that in the centrat nervous system (CNS) of SSPE patients a percentage of persistently infected astrocytes may continually synthesize IL-6 and IFN-ß, and in the presence of additional external stimuli, as possibly provided by activated lymphocytes, might ovarexpress the inflammatory cytokines IL-1 ß and TNF-a. This may be of pathogenetic significance in CNS diseases associated with persistent MV infections.
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.
The direct involvment of the Wilm's tumor suppressor gene (WTl) in Denys-Drash syndrome through mutations within exons 8 or 9 has recently been established. The absence of such alterations in three patients with Frasier syndrome provides a molecular basis for distinguishing these two syndromes that are associated with streak gonads, pseudohermaphroditism and renal failure.
'lbe mouse skin tumor model was used to investigate whether the Ievel of DNA 8dducts and/or the rate of cell division in the epidermis are indicators of the risk of cancer formation for an individual in an outbred animal popul8tion. A high risk was considered to be reftected by 8 short latency period for the 8ppearance of 8 papilloma. Fernale NMRI mice were treated twice weekly with 2.5 nmol 7 ,12-dimethylbenz[a]antbracene (DMBA) and 3 nmoi12-0-tetradecanoylphorbol-13- 8cetate (TPA) and the appearance of papillomas was registered. The first papilloma 8ppeared after 7.5 weeks. After 17 weeks, when 12 of 14 mice bad 8t least one papilloma, an osmotic minipump deliverlog 5-bromo-2'deoxyuridine (BrdU) was implanted into eacb mouse for 24 h. The mice were killed after 24 h ~d the epidermis was analyzed for D:MBA-nucleotide 8dducts by 32p.postlabeling, for the cell number per unit skin length, and for the labeling index for DNA synthesls. Unexpectedly, D:MBA-nucleotide 8dduct Ievels were highest in those anima1s wbich showed the Iongest latency periods. Adduct Ievels were negatively correlated with the 18beling index, indicating that dilution of adducts by cell division was a predominant factor in determining average adduct concentrations. Individual tumor-latency time was not corTelated with either cell ntunber or labeling index. This could be due to the fact that the measurements only provided 8veraged data and gave no infonnation on the specific situation in clones of premalignant cells. Under the conditions of tbis assay, therefore, neither DNA adduct Ievels nor information on the average kinetics of cell division bad a predidive value for the individual amcer risk withln a group of outbred animals receiving the same treatment
[7-3H)Styrene 7,8-oxide was administered by oral gavage to male CD rats at a dose of 1.3 mg/kg. After 4 h, the forestomach was excised, DNA was isolated, purified to constant specific radioactivity and degraded nzymatically to the 3 '-nucleotides. Highperformance liquid chromatography fractions with the normal nucleotides contained most of the radiolabel, but a minute level of adduct label was also detccted. Using the units of the covalent binding index (micromoles adduct per mole DNA nucleotide)/(millimole chemical administered per kilogram body weight), a DNA binding potency of 1.0 was derived. A comparison of the covalent binding indices and carcinogenic potencies of other genotoxic forestarnach carcinogens showed that the tumorigenic activity of styrene oxide is unlikely to be purely genotoxic. Therefore, styrene oxide was compared with 3-tbutylhydroxyanisole (BHA) with respect to stimulation of cell proliferation in the forestomach. Male Fischer 344 rats were treated for four weeks at three dose levels of styrene oxide (0, 137, 275 and 550 mg/kg, three times per week by oral gavage) and BHA (0, 0.5, 1 and 2% in the diet); the highest doses had been reported to result in 84% and 22% carcinomas in the forestomach, respectively. Cell proliferation was assessed by incorporation of bromodeoxyuridine into DNA and immunohistochemical analysis. An increase in the lablling indexwas found in a11 treated animals. In the prefundic region of the forestomach, the labeHing index increased significantly, from 42% (controls) to 54% with styrene oxide and from 41 to 55% with BHA. Rats treated with BHA also had severe hyperplastic lesions in the prefundic region, i.e., at the location of BHA-induced forestomach carcinomas. The number of cells per millimetre of section length was increased up to 19 fold. Hyperplastic lesions were not seen with styrene oxide, despite the higher tumour incidence reported with this compound. We conclude that the carcinogenicity of styrene oxide to the forestomach most probably involves a mechanism in which marginal genotoxicity is combined with promotion by increased cell proliferation.
Wben irradiated at 360 nm, furocoumarins with a hydroperoxide group in a side chain effciently give rise to a type of DNA damage that can best be explained by a photoinduced generation of hydroxyl radicals from the excited pbotosensitizers. The observed DNA damage profiles, i.e. the ratios of single-strand breaks, sites of base loss (AP sites) and base modifications sensitive to fonnamidopyrimidine-DNA glycosylase (FPG protein) and endonuclease m, are similar to the DNA damage profile produced by hydroxyl radicals generated by lonizing radiation or by xanthine and xanthine oxidase in the presence of Fe(III)-EDTA. No such damage is observed with the corresponding furocoumarin alcohols or in the absence of near-UV radiation. The damage caused by the photo-excited hydroperoxides is not influenced by superoxide dismutase (SOD) or catalase or by D2O as solvent. The presence of t-butanol, however, reduces both the formation of single-strand breaks and of base odifications sensitive to FPG protein. The cytotoxicity caused by one of the hydroperoxides in L5178Y mome lymphoma cells is found to be dependent on the near-UV irradiation and to be much higher than that of the corresponding alcohol. Therefore the new type of photoinduced damage occurs inside cells. Intercalating photosensitizers with an attached hydroperoxide group might represent a novel and versatile class of DNA damaging agents, e.g. for phototherapy.
In somatic cells DNA topoisomerase II (topo II) is thought to be involved in the domain Organization of the genome by anchoring the basis of chromatin loops to a chromosomal scafFold. Lampbrush chromosomes of am-phibian oocytes directly display this radial loop Organization in cytological preparations. In order to find out whether topo II may play a role in the Organization of these meiotic chromosomes, we performed immunofluorescence studies using antibodies against Xenopus topo II. Our results indicate that topo II is apparently absent from lampbrush chromosomes and is hence unlikely to act as a "fastener" of the numerous lateral chromosomal loops. Topo II was, however, enriched in the amplified nucleoli of Xenopus oocytes.
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.
No abstract available
When bovine or human growth hormones (GH) were injected into 6 months old (about 10 g) gilthead seabream, the growth rate of the fish, as measured by changes in their weight, increased by only about 15% compared with the saline-injected control. No effect or even slight inhibition of the growth rate was obtained when chicken or porcine GHs were injected. In a preliminary experiment, it was found that injection ofthe native GH increased the growth rate ofthe fish by about 20% after treatment for only 2 weeks. An expression vector, using the pRE1 plasmid and transformation into MZl cells, produced the gilthead seabream GH, providing a supply for further experiments on the effect of the homologaus GH on growth. Two reporter genes, ß-galactosidase (lacZ) and melanoma oncogene of Xiphophorus (mrk YY), were microinjected into fertilized eggs of S. aurata. Expression of these two genes could be demonstrated in 2-day-old embryos, the lacZ gene by staining of its enzymatic product, and the mrk YY gene by its phenotypic expression.
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.
In leishmaniasis, macrophages are known to play a central role as modulators of the specific immune activity. In this article, Heidrun Moll presents evidence for the critical involvement of another component of the skin immune system, the epidermal Langerhans cell. She proposes that Langerhans cells take up parasites in the skin and transport them to the draining lymph node for presentation to T cells and initiation of the specific immune response.
Als Newcomer im Kreise der Anwender IIOn Molecular Modelling Software sieht man sich mit einer verwirrenden und ständig wachsenden Vielfalt von einschlägigen Programmen konfrontiert. die alle viel versprechen. Oie meisten bieten Grafik 110m Feinsten und eine beeindruckende Benutzeroberfläche. Unterschiede gibt es in der Funlctionalität, der Fehlerhäufigkeit, beim Support und natürlich im Preis. Seit ca. einem Jahr haben wir MOLEK 9000 auf einer IRIS 40351G im Einsatz. Hier ein erster Erfahrungsbericht.
Der vorliegende Beitrag faßt den derzeitigen Stand der Untersuchungen von Hangrutschungen im Bereich der Frankenhöhe, die im Rahmen des EPOCH-Programmes durchgeführt wurden, zusammen. Nach einer Inventarisierung der regionalen Rutschungsereignisse wird die Rutschung bei Obergailnau in einer geomorphologischen Detailkartierung vorgestellt. Für die Auslösung der Rutschung kommen mehrere Faktoren in Betracht: neben einer erhöhten Rutschungsanfälligkeit aufgrund der geologisch-tektonischen Verhältnisse muß v.a. auch eine Einflußnahme durch die Landnutzung mit berücksichtigt werden. Dazu zählen Steinbrucharbeiten in unmittelbarer Nähe der Rutschung, aber auch Wasserbaumaßnahmen am Schloßberg. In diesem potentielllabilisierten Gebiet kam es nach überdurchschnittlichen Niederschlägen Anfang 1958 zu einer Überschreitung der Belastungsgrenze des Hanges, die sich in einer großflächigen Rutschung äußerte. Die weiteren Untersuchungen sollen zeigen, ob sich die für Obergailnau herausgestellten Faktorenkomplexe im regionalen Rahmen verifizieren lassen.
We examined the potential role of fibroblast growth factor 5 (FGF-5) as a target-derived trophic factor for spinal motoneurons. Northern analysis of total RNA from rat skeletal muscle revealed an FGF-5 mRNA transcript both during the period of embryonic motoneuron death and in the adult. Recombinant human FGF-5 supported the survival of highly enriched cultures of embryonic chick motoneurons. Significant proportions of the motoneuron survival activity of rat skeletal muscle extracts could be immunoprecipitated using an antiserum to FGF-5. The immunoprecipitable activity was present in soluble and matrix-bound forms in embryonic muscle, but bound exclusively to the extracellular matrix in adult muscle. These results, along with the secretory nature of FGF-5, suggest that FGF-5 may act as a target-derived trophic factor for motoneurons.
The human foamy virus (HFV) bel-l transactivator protein was expressed in insect cells by a recombinant baculovirus. For the generation of the recombinant baculovirus, Acbel-1, the bel-l gene of an HFV mutant was used, that bears truncations in the bel-l overlapping bel-2 open reading frame. Acbel-1 infected Sf9 cells produced high amounts of recombinant protein of the same electrophoretic mobility (36 kD) as bel-l expressed in mammalian cells. The baculovirus expressed bel-l proteinwas readily identified by a polyclonal rabbit serum directed against bel-1 in immunoblot assay. As in mammalian cells, bel-l was predominantly localized to the nucleus of Acbel-1 infected insect cells. The baculovirus expressed bel-1 proteinwill be of use to determine the action of this novel viral transactivator more precisely.
The effect of 6-chloro-2,3,4,5-tetrahydro-3-methyi-1-H-3-benzazepine (SKF 86466), a selectlve nonimldazoline alpha-2 adrenoceptor antagonlst, on hippocampal re1ease of norepinephrine and dopamlne in conscious rats was lnvestigated by /n vlvo mlcrodialysis and high-pressure liquid chromatography. Additionally, extracellular concentrations of hippocampal dopamine (DA) and norepinephrtne (NE), durtng Infusion of selective monoamine uptake Inhibitors, were determined in freely moving rats. The basal concentration of NE in the dialysate was 4.9 ± 0.3 pg/20 pl. lntravenous admlnistratlon of 5 or 10 mgJkg of SKF 86466 was associated wlth a transierlt inc:rease (30 min) of 2-fold (12 ± 1 pg/20 ,d; p < .05) and 8-fold (39 ± 3 pg/20 pl; p < .05), respectlvely, in dlalysate NE, whereas a 1-mgfkg dose had no effect. DA was not detected in basal dlalysates, but after the adminlstratlon of 5 or 10 mgJkg of SKF 86466, 3.9 ± 0.4 and 6.4 ± 0.6 pg/20 pl, respectlvely, was present in the dialysates. The rnaxlmum increase in dialysate DA was reached 60 to 90 min after SKF 86466. The DA was not derived from plasma because plasma NE was elevated after the 5 mgJkg dose of SKF 86466 whereas no plasma DA was detected. ln order to determlne whether DA was present in noradrenergic nerve termlnals, the dopamine ß-hydroxylase Inhibitor SKF 1 02698 was administered (50 mgJkg i.p.). The Inhibitor decreased dialysate NE but DA was stin not detected in the dialysate. When SKF 86466 (5 mgJkg t.v.) was adminlstered 4 hr after SKF 102698, DA appeared in the dialysate but there was no lncrease in dialysate NE. Administration through the dialysis probe of the DA uptake Inhibitor, GBR-12909 (0.1 and 1 pM), dose-dependently lnaeased DA Ieveis to 5.7 ± 1.2 and 9.6 ± 2.8 pg/20 pl, respectively. GBR-12909 had no effect on hippocampal NE. Desipramine (5 and 10 pM) lncreased dose-dependently dialysate NE and lncreased DA concentrations to detectable Ieveis (2.7 ± 0.5 and 3.5 ± 0.7 pg/20 ,d, respectively). These results suggest that the a/pha-2 adrenoceptors modulate both NE and DA release in the rat hlppocampus and that DA detected in the hlppocampal dialysate might be released from dopaminergic neurons.
The mineralogical and chemical characteristics of fulgurites ( = natural glasses forrned by lightning strikes to the ground) from the southern Centrat Sahara (Niger) are presented. The fulgurites are indicators of thunderstorms. The northernmost important fulgurite formation in the study area reached up to about l8°N, with decreasing fulgurite concentration from south to north. Their distribution pattern and the relative dating of their formation in relation to Iandscape history from the Late Pleistocene onwards (e.g., palaeolakes, palaeosols), and to Neolithic settlement reveals their value as palaeoenvironmental indicators. They indicate: (1) local palaeoenvironmental conditions depending on the topographical situation in a complex dune relief; (2) climatic change during the mid-Holocene from northerly rains to southerly rains; and (3) the northernmost Iimit of important thunderstorrns and rainfall activity since this time in the southern Centrat Sahara.
When human neutrophils become desensitized to formyl peptide chemoattractants, the receptors (FPR) for these peptides are converted to a high affinity, GTP-insensitive form that is associated with the Triton X-1 00- insoluble membrane skeleton from surface membrane domains. These domains are actin and fodrin-rich, but G protein-depfeted suggesting that FPR shuttling between G protein-enriched and depleted domains may control signal transduction. Todetermine the molecular basis for FPR interaction with the membrane skeleton, neutrophil subcellular fractions were screened for molecules that could bind photoaffinity-radioiodinated FPR solubilized in Triton X-1 00. These receptors showed a propensity to bind to a 41- to43-kDa proteinband on nitrocelluloseoverlays of SOS-PAGE-separated cytosol and plasma membrane fractions of neutrophils. This binding, as weil as FPR binding to purified neutrophil actin, was inhibited 50% by 0.6 \(\mu\)M free neutrophil cytosolic actin. Addition of greater than 1 \(\mu\)M G-actin to crude or lectin-purified Triton X-1 00 extracts of FPR from neutrophil membranes increased the sedimentationrate of a significant fraction of FPR two to three fold as measured by velocity sedimentation in Triton X-1 00-containing linear sucrose density gradients. Addition of anti-actin antibodies to FPR extracts caused a concentration-dependent immunoprecipitation of at least 65% of the FPR. More than 40% of the immunoprecipitated FPR was specifically retained on protein A affinity matrices. Membrane actin was stabilized to alkaline washing when membranes were photoaffinity labeled. Conversely, when purified neutrophil cytosolic actinwas added to membranes or their digitonin extracts, after prior depletion of actin by an alkaline membrane wash, photoaffinity labeling of FPR was increased two- to fourfold with an EC\(_{50}\) of approximately 0.1 \(\mu\)M actin. We conclude that FPR from human neutrophils may interact with actin in membranes to form Triton X-1 00-stable physical complexes. These complexes can accept additional G-actin monomers to form higher order molecular complexes. Formation of FPR-actin complexes in the neutrophil may play a role in the regulation of chemoattractantinduced activation or actin polymerization.
No abstract available.
1.2-Dioxetanes, very reactive and high energy molecules. are involved as labile intermediates in dioxygenase- activated aerobic metabolism and in physiological processes. Various toxico1ogica1 tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonucleasesensitive sites, most of them are FPG protein-sensitive base modifications (8-hydroxyguanine, fonnamidopyrimidines). Pyrimidinedimersand sites ofbase loss (AP sites) which were probed by UV endonuclease and exonuclease 111 are minor lesions in this system. While the alky1-substituted dioxetanes do not show any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetanes such as benzofuran and furocoumarin dioxetanes are strongly mutagenic in S. typhimurium strain TA I 00. DNA adducts formed with an intermediary alkyJating agent appear to be responsible for the mutagenic activity of benzofuran dioxetane. We assume that the benzofuran epoxides, generated in situ from benzofuran dioxetanes by deoxygenation are the ultimate mutagens of the latter. since benzofuran epoxides are highly mutagenic in the S. typhimurium strain TAIOO and they form DNA adducts. as detected by the 212Ppostlabelling technique. Our results imply that the type of D NA darnage promoted by dioxetanes is dependent on the structural feature of dioxetanes. Furthermore, the direct photochemical DNA darnage by energy transfer. i.e., pyrimidine dimers, plays a minor role in the genotoxicity of dioxetanes. Instead, photooxidation dominates in isolated DNA. while radical darnage and alkylation prevail in the cellular system.
We report on the growth of the compound semiconductor MgTe as weil as the ternary alloy Cd\(_{l-x}\)Mg, Te by molecular hcam cpitaxy. This is to our knowkdgc thc first time that this material has heen grown by any epitaxial technique. Bulk MgTe, which is hygroscopic, has a band gap of 3.0 eV and crystallizcs usually in thc wurtzite structure. Pseudomorphic films were grown on zincblende Cd Te suhstrates for a MgTe thickness helow a critical layer thickncss of approximately 500 nm. In addition, Cd\(_{l_x}\),Mg\(_x\)Te epilayers were grown with a Mg concentration between 0 and 68%, which corresponds to a band gap betwcen 1.5 and 2.5 eV at room temperature. The crystalline quality of thc layers is comparabk to CdTc thin films as long as they are fully strained. The lauice constant of zincblende MgTe is slightly smaller than that of CdTe, and the lattice mismatch is as low as O.7%. In addition highly n-type CdMgTe layers were fabricatcd by hromine doping. The tunability of the band gap as weil as the rather good laUice match with CdTc makes the matcrial interesting for optoelectronic device applications for the entire visible range.
No abstract available
Since systematic hematological studies on blood and bone marrow changes after treatment with 15-Deoxyspergualin (DOS) are lacking, a quantitative assessment was performed fourteen or twenty eight days after intraperitoneal application of DOS to rats. Further observations done 7 and 14 days after discontinuation of DOS administration allowed analysis of banc marrow regeneration. DOS induced lymphocytopenia, granUlocytopenia and anemia with a decrease of bone marrow cellularity due to suppression of cell maturation. The effect was dose-dependent and bone marrow as well as blood changes were observed in animals treated with doses from 0.5 to 10.0 mg/kg DOS. Within 14 days after termination of the treatment, rapid recovery with normalization of all hematological parameters was observed. In the light of our data, these hematological side effects may not be a major disadvantage, if DOS is used in doses below 2.5 mg/kg, and for a course of therapy which is limited to 7 to 14 days.
Hierarchical structures among male individuals in a population are frequently reflected in differences in aggressive and reproductive behaviour and access to the females. In general social dominance requires large investments which in turn may have to be compensated for by high reproductive success. However, this hypothesis has so far only been sufficiently tested in small mating groups due to the difficulties of determining paternity by classical methods using non-molecular markers. DNA fingerprinting overcomes these problems offering the possibility to determine genetic relationships and mating patterns within larger groups. Using this approach we have recently shown (Schartl et al., 1993) that in the poeciliid fish Limia perugiae in small mating groups the dominant male has 100% mating success, while in larger groups its contribution to the offspring unexpectedly drops to zero. The reproductive failure under such social conditions is explained by the inability of the ex-male to protect all the females simultaneously against mating attempts of his numerous subordinate competitors.
No abstract available.
Fulgurites (= natural glasses formed by lightning strikes to the ground) are indicators of thunderstorms (e.g. Julien 1901). The distribution pattern of fulgurites in the study area (Grand Erg de Bilma and Erg de Tenere between 11.5°E and 16.5° and 18.5°N) shows decreasing fulgurite concentration from south to north. The fulgurite sites are concentrated in the area of fossil dune complexes, where they occur topographically above palaeolimnic deposits in mid-slope position of interdune depressions.
Wilms' tumor is a childhood nephroblastoma that is postulated to arise through the inactivation of a tumor suppressor gene by a two-hit mechanism. A candidate II p 13 Wilms' tumor gene, WTI, has been cloned and shown to encode a zinc finger protein. Patients with the WAGR syndrome (Wilms' tumor, aniridia, genitourinary abnormalities, and mental retardation) have a high risk of developing Wilms' tumor and they carry constitutional deletions of one chromosome II allele encompassing the WTI gene. Analysis of the remaining WTI allele in a Wilms' tumor from a WAGR patient revealed the deletion of a single nucleotide in exon 7. This mutation likely played a key role in tumor formation, as it prevents translation of the DNA-binding zinc finger domain that is essential for the function of the WTI polypeptide as a transcriptional regulator.
Humanfoamy virus (HFV) is a retrovirus encoding structural genes and, like human immunodeficiency virus and human T ceU leukemia virus I, several anciUary reading frames collectively termed the belgenes. We have previously shown that HFV transgenic mice develop an encephalopathy with neuronal loss in hippocampus and cerebral cortex. We have now raised and characterized rabbit antisera to various recombinant portions of gag, pot, env, and bel-I, the viraltransactivator. Immunoreactivity for gag and bel-I was observed in nuclei and processes of hippocampal and cortical neurons before the onset of morphological lesions and correlated with the appearance of HFV mRNA. Astrocyte-derived multinucleated giant ceUs containing HFV proteins were present in the brain oftransgenic mice coexpressingfuU- length HFV genes but not in mice expressing truncated gag and env, suggesting that these genes contain afusogenic domain. Expression of fuU-length structural genes decreased the life expectancy oftransgenic mice, implying an a4Juvant rolefor these proteins in HFV-induced brain damage. (Am] Pathol 1993, 142:1061-1072)
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.
Human foamy viruspol gene fragments were molecularly cloned into a procaryotic expression vector. The expression pattern of the cloned fragments and nucleotide sequence analysis of the 5' pol gene region revealed that in HFV the protease (PR) is located in the pol open reading frame. Purified recombinant proteins were used to generate antibodies in rats. ln immunoblot assay, using infected cells as antigen, a precursor protein with an apparent molecular mass (M,) of 127K was identified by antibodies directed against the reverse transcriptase (RT), RNaseH, or integrase (IN) domeins of pol. With concentrated virus as antigen, the RT and RNaseH antibodies recognized a protein of 80K, the IN antiserum recognized a protein of 40K, and the PR antiserum detected a protein of approximately 10K.
An antibody against the NDH-K subunit of the NAD(P)H-dehydrogenase from the cyanobacterium Synechocystis sp. PCC6803 was used to isolate a subcomplex ofthe enzyme from Triton X-lOO solubilized total membranes by immunoaffinity chromatography. The isolated subcomplex consisted of seven major polypeptides with molecular masses of 43, 27, 24, 21, 18, 14 and 7 kDa. The amino-terminal amino acid sequences of the polypeptides were determined. By comparing the sequences with the amino acid sequences deduced from DNA. three proteins were identified as NDH-H (43 kDa). NDH-K (27 kDa) and NDH-J (24 kDa). A fourth subunit (NDH-J, 21 kDa) was identified by Western blot analysis with an NDH-J antibody.
In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus
(1993)
The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIOS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIV\(_{mac25}\), strain as well as the infectious clone (SIV\(_239\)). Infectious viruswas produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.
Background and Purpose: We earlier reported that risk factors for stroke prepare brain stem tissue for a modified Shwartzman reaction, incIuding the development of ischemia and hemorrhage and the production of tumor necrosis factor-a, after a provocative dose of lipopolysaccharide. In the present study, we sought to determine whether blood and central nervous system cells of rats with the stroke risk factor of advanced age produce more proinflammatory and prothrombotic media tors than do those of young rats of the same strain. Methods: Levels of tumor necrosis factor-a and platelet activating factor in the cerebrospinal fluid and tumor necrosis factor-a in the serum of 2-year-old and 16-week-old Sprague-Dawley rats were monitored before and after challenge with lipopolysaccharide. Results: No consistent tumor necrosis factor-a activity was found in the cerebrospinal fluid or blood of control animals. Intravenous administration of lipopolysaccharide (1.8 mg/kg) increased serum tumor necrosis factor-a levels but had no effect on tumor necrosis factor-a in the cerebrospinal fluid. Serum tumor necrosis factor-a increased much more in aged rats than in young rats. When lipopolysaccharide was injected intracerebroventricularly, tumor necrosis factor-a activity in cerebrospinal fluid increased significantly more in old rats than in young rats. Baseline levels of platelet activating factor in cerebrospinal fluid were significantly higher in old rats than in young rats, and the levels increased to a greater degree in aged rats on stimulation. Conclusions: Rats with the stroke risk factor of advanced age respond to lipopolysaccharide with a more exuberant production of tumor necrosis factor-a and platelet activating factor than young rats of the same strain. These findings are consistent with our working hypothesis that perivascular cells are capable of exaggerated signaling of endothelium through cytokines such as tumor necrosis factor-a in animals with stroke risk factors. The effect of such signaling might be to prepare the endothelium of the local vascular segment for thrombosis or hemorrhage in accord with the local Shwartzman reaction paradigm.
The question addressed was whether Stimulation of cell proliferation could be responsible for tumor induction in the torestornach by styrene 7,8-oxide (SO). Male F344 rats were treated for 4 weeks with 0, 137,275, and 550 mglkg SO by p.o. gavage 3 times/week. Positive controls received 0, 0.5, I, and 2% butylated hydroxyanisole (BHA) in the diet for 4 weeks. Twenty-four h before termination of the experlment, the rats were implanted s.c. with an osmotic minipump deliverlog S-bromo-2'-deoxyuri· dine (BrdU). Cell proliferation in the forestomach was assessed by immunohistochemistry for BrdU incorporated into DNA. Cell number/mm section length and fraction of replicating cells (labeling Index) were determined in 3 domains of the forestomach, the saccus caecus, the midregion, and the prefundic region. With the exception of the prefundic reglon of the low-dose SO group, a significant increase of the labeling index was found in all regions both with SO and BHA. Rats treated with BHA showed, in addition, a dose-dependent increase in number and size of hyperplastic lesions. This was most pronounced in the prefundic region where carcinomas were reported to be localized. In this region, the number of dividing cells/mm section length was increased up to 17-fold. With SO, only marginal morphological changes were occasionally observed, despite the fact that the respective long-term treatment bad been reported to result in a higher carcinoma incidence than treatment with BHA. It ls concluded that the rate of replicating cells alone, numerically expressed by the labeling Index, is an lnsufficient tool for interpretlog the role of cell division in carcinogenesis. It is postulated that SO and BHA induce forestomach tumors via different mechanisms. While hyperplasia in the prefundic region most likely dominates the carcinogenicity of BHA, a mechanism combining marginal genotoxicity with strong promotion by increased cell proliferation appears to be involved in the tumorigenic action of SO.