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Which home for coelacanth?
(1993)
It is shown that the rate of convergence in the von Mises conditions of extreme value theory determines the distance of the underlying distribution function F from a generalized Pareto distribution. The distance is measured in terms of the pertaining densities with the limit being ultimately attained if and only if F is ultimately a generalized Pareto distribution. Consequently, the rate of convergence of the extremes in an lid sample, whether in terms of the distribution of the largest order statistics or of corresponding empirical truncated point processes, is determined by the rate of convergence in the von Mises condition. We prove that the converse is also true.
Interleukin 4 (IL-4) exerts a decisive role in the coord.ination of proteelive immune responses against parasites, particularly helminths. A disregulation of ll.r4 function is possibly involved in the genesis of allergic disease states. The search for important amino acid residues in human ll.r4 by mutational analysis of charged invariant amino acid positions identified two distinct functional sites in the 4-helix-bundle protein. Site 1 was marked by amino acid substitutions of the glutamic acid at position 9 in helix A and arginine at position 88 in helix C. Exchanges at both positions led to IL-4 variants deficient in binding to the extracellular domain of the ll.r4 receptor (IL-4ReJ. In parallel, up to 1000-fold increased concentrations of this type of variant were required to induce T -cell proliferation and B-eeil CD23 expression. Site 2 was marked by amino acid exchanges in helix D at positions 121, 124 and 125 (arginine, tyrosine and serine respectively in the wild-type).ß.A variants affected at site 2 exhibited partial agonist activity during T -cell proliferation; however, they still bound with high affinity to IL-4Rex. [The generation of an IL-4 antagonist by replacing tyrosine 124 with aspartic acid has been described before by Kruse et al. (1992) (EMBO }., 11, 3237-3244)]. These findings indicate that IL-4 functions by bind.ing IL-4Rex via site 1 which is constituted by residues on helices A and C. They further suggest that the association of a second, still undetined receptor protein with site 2 in helix D activates the receptor system and generates a transmembrane signal.
Melanoma formation in the teleost Xiphophorus is caused by a dominant genetic locus, Tu. This locus includes the Xmrk oncogene, which encodes a receptor tyrosine kinase. Tumor induction is. suppressed in wild-type fish by a tumor suppressor locus, R. Molecular genetic analyses revealed that the Tu locus emerged by nonhomologaus recombination of the Xmrk proto-oncogene with a previously uncharacterized sequence, D. This event generated an additional copy of Xmrk with a new promoter. Suppression of the new Xmrk promoter by R in parental fish and its deregulation in hybrids explain the genetics of melanoma formation in Xiphophorus.
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.
The sfa determinant codes for S fimbrial adhesins which constitute adherence factors of pathogenic Escherichia coli strains. Wehave recently shown that the sfa determinant is transcribed from three prömoters, pA, pB, and pC. In comparison with the promoters pB and pC, promoter pA, which is located in front of the structural gene sfaA, showed very weak activity. Herewe have determined the exact positions ofthe mRNA start points by primer extension studies. We have also shown that mRNAs of 500, 700 and 1400 bases can be detected using oligonucleotide probes specific for the genes sfaB, sfaC and sfaA. SfaB and SfaC arepositive regulators infiuencing fimbriation and the production of the S-specific adhesin which is encoded by the gene sfaS Iocated in the distal half of the determinant. In addition, it is demonstrated that SfaB and SfaC interfere with the regulatory effect of the histone-like protein H-NS, encoded by a locus termed drdX or osmZ. In a drdx+ strain the regulators are necessary for transcription of the sfa determinant. In contrast, sfa expression is activator-independent in a drdx- strain. In this latter genetic background, a substantial fraction of the sfa transcripts is initiated from promoter pA. On the basis of these data we discuss a model for the regulation of this adhesin-specific determinant.
1 We studied the effect of temperature on the binding to rat heart \(M_2\) muscarinic receptors of antagonists related to the carbon/silicon pairs pridinol/sila-pridinol and diphenidol/sila-diphenidol (including three germanium compounds) and six structurally related pairs of enantiomers [(R)- and (S)-procyclidine, (R)- and (S)-trihexyphenidyl, (R)- and (S)-tricyclamol, (R)- and (S)-trihexyphenidyl methiodide, (R)- and (S)-hexahydro-diphenidol and (R)- and (S)-hexbutinol]. Binding affinities were determined in competition experiments using \([^3H]\)-N-methyl-scopolamine chloride as radioligand. The reference drugs were scopolamine and N-methyl-scopolamine bromide.
2 The affinity of the antagonists either increased or decreased with temperature, van 't Hoff plots were linear in the 278–310°K temperature range. Binding of all antagonists was entropy driven. Enthalpy changes varied from large negative values (down to \(−29 kJ mol^{−1}\)) to large positive values (up to \(+ 30 kJ mol^{−1}\)).
3 (R)-configurated drugs had a 10 to 100 fold greater affinity for \(M_2\) receptors than the corresponding (S)-enantiomers. Enthalpy and entropy changes of the respective enantiomers were different but no consistent pattern was observed.
4 When silanols \((R_3SiOH)\) were compared to carbinols \((R_3COH)\), the affinity increase caused by C/Si exchange varied between 3 and 10 fold for achiral drugs but was negligible in the case of chiral drugs. Silanols induced more favourable enthalpy and less favourable entropy changes than the corresponding carbinols when binding. Organogermanium compounds \((R_4Ge)\) when compared to their silicon counterparts (R4Si) showed no significant difference in affinity as well as in enthalpy and entropy changes.
5 Exchange of a cyclohexyl by a phenyl moiety was associated with an increase or a decrease in drug affinity (depending on the absolute configuration in the case of chiral drugs) and generally also with a more favourable enthalpy change and a less favourable entropy change of drug binding.
6 Replacement of a pyrrolidino by a piperidino group and increasing the length of the alkylene chain bridging the amino group and the central carbon or silicon atom were associated with either an increase or a decrease of entropy and enthalpy changes of drug binding. However, there was no clear correlation between these structural variations and the thermodynamic effects.
7 Taken together, these results suggest that hydrogen bond-forming OH groups and, to a lesser extent, polarizable phenyl groups contribute significantly to the thermodynamics of interactions between these classes of muscarinic antagonists and \(M_2\) muscarinic receptors.
The thymus in SIV infection
(1993)
no abstract available
Known mutagens and carcinogens in the dict were compiled and the risk of cancer was estimated on the basis of average exposure Ievels in Switzerland and carcinogenic potencies from rodent bioassays. The analysis showed that, except for a1cohol, the sum of all known dietary carcinogens could only explain a few percent of the cancer deaths attributed by epidemiologists to dietary factors. The discrepancy was explained by a "carcinogenicity" of excess macronutrients. This hypothesis was based on an evaluation of dietary restriction experiments in rats and mice, where a dramatic reducing effect on spontaneaus tumour formation was seen. From these experiments, a "carcinogenic potency" was deduced for food in excess (TD50 approximately 16 g/kg per day). Ovemutrition in Switzerland was converted into excess food intake and the cancer risk estimated on the basis ofthe TD50 value. The resulting risk of60,000 cases per one million lives wou1d aJlow to explain by overnutrition almost all "diet-related" cancer deaths in humans.
This paper reports on a longitudinal study dealing with the development of literacy in young children. A total of 163 children were first tested during their last year in kindergarten using a variety of tasks that tapped phonological processing, memory capacity, early literacy, and intelligence. Children's ward decoding, reading comprehension, and spelling skills were assessed in elementary school several years later. As a main result, all of the predictor domains had a significant impact on the acquisition of literacy in elementary school, although the contribution of each domain differed as a function of the criterion measure. An attempt to identify children-at-risk using a kindergarten screening test provided encouraging results. Nonetheless, it was shown that whereas group predictions of reading and spelling performance can be quite accurate, the individual prognosis of school problems is far from perfect.
Molecular beam epitaxially grown short period (001) Hg\(_{1_x}\)Cd\(_x\)Te-HgTe superlattices have been systematically investigated. Several narrow well widths were chosen, e.g., 30, 35 and 40 Å, and the barrier widths were varied between 24 and 90 Å for a particular well width. Both the well width and the total period were determined directly by means of x-ray diffraction. The well width was determined by exploiting the high reflectivity from HgTe and the low reflectivity from CdTe for the (002) Bragg reflection. Knowing the well and barrier widths we have been able to set an upper limit on the average Cd concentration of the barriers, \(\overline x_b\), by annealing several superlattices and then measuring the composition of the resulting alloy. \(\overline x_b\) was shown to decrease exponentially with decreasing barrier width. The structure of a very short period superlattice, i.e., 31.4 Å, was also investigated by transmission electron microscopy, corroborating the x-ray diffraction results.
Starting from chlorodimethyl(phenyl)silane (3), acetyldimethyl(phenyl)silane (l) was prepared by a two-step synthesis in a total yield of 90% [PhMe\(_2\)SiCl (3)-> PhMe\(_2\)SiCCOMe)=CH\(_2\) (4)-> PhMe\(_2\)SiC(O)Me (1)]. The prochiral acetylsilane 1 was transfonned enantioselectively into (R)-(1-hydroxyethyl)dimethyl(phenyl)silane [(R)-2] using plant cell Suspension cultures of Symphytum officinale L. or Ruta graveolens L. Under preparative conditions (300-mg scale, not optimized), (R)-2 was isolated in 15% (Symphytum) and 9% yield (Ruta), respectively. The enantiomeric purities of the products were 81% ee (Syrnphytum) and 60% ee (Ruta), respectively.
A route to 2S,5S-and 2R,5S-hydroxypipecolic acid is presented, starting with the enantiopure 5S-5-hydroxy-piperidone 7. The key step of this reaction sequence is the chemoselsctive methylenation of the amide carbonyl group of 8 with dimethyltitanocene 9 to 10. The transformation of the exocyclic enecarbamate double bond to the carboxylic acid group is best accomplished via hydroboration/oxidation to the alcohol 11a,b. Separation and oxidation of the dlastereomers 11a,b, to 148. and 14b, and hydrolysis furnishes the diastereomeric pipecolic acids 15a and 15b in enantiopure form.
The surface sublimation of Cd and Te atoms from the zinc blende (111)A CdTe surface has been investigated in detail by reflection high energy electron diffraction and x-ray photoelectron spectroscopy. These experiments verify that Te is much easier to evaporate than Cd. The experimental value for the Te activation energy from a Te stabilized (111)A CdTe surface is 1.41 ±0.1O eV, which is apparently inconsistent with recent theoretical results.
Reliable prediction of the isotropic hyperfine coupling constant A\(_{iso}\) is still a difficult task for ab initio calculations. Strang dependence on the method employed for its ca1culation has been found. Within a CI ansatz A\(_{iso}\) is considerably affected by the excitation classes taken into account within the CI calculation. In the present work the influence of various excitation classes on A\(_{iso}\) is examined. Calculations including all single, double, triple and a large part of the quadruple excitations are performed and the individual effects of the excitation classes are studied. It is found that the surprisingly good agreement found for S-CI treatments is due to large error cancellations. The importance of higher than double excitations arises from their indirect influence on the single excitations.
The plastid genomes of higher plants contain eleven reading frames (ndhA-K) that are homologous to genes encoding subunits of the mitochondrial NADH-ubiquinone-oxidoreductase (complex I). The carboxyterminal end of the NDH-H subunit from rice (Oryza sativa L.) was expressed as a fusion protein in Escherichia coli and antibodies against the fusion protein were generated in rabbits. The antibody was used to study the expression of NDH-H, and the following results were obtained: (i) NDH-H is expressed in mono- and dicotyledonous plants, (ii) NDH-H is localized on the stroma lamellae of the thylakoid membrane and (iii) NDH-H is expressed in etioplasts. Together with the finding that two other ndh genes (ndhI and ndhK) are expressed in plastids, these results point to the existence of an NAD(P)H-plastoquinone-oxidoreductase on the thylakoid membrane. The possible function of the enzyme in plastids is discussed and it is suggested that it works in balancing the ATP/ADP and the NADPH/NADP ratios during changing external (i.e. light) or internal (i.e. ATP and NADPH demands of biosynthetic pathways of the plastid) conditions.
The expression of measles virus (MV) in six different permanent human glioma cell lines (D-54, U-251, U-138, U-105, U-373, and D-32) was analyzed. Although all celllines were permissive for productive replication of all MV strains tested, U-251, D-54, and D-32 cells spontaneously revealed restrictions of MV transcription similar to those observed for primary rat astroglial cells and brain tissue. In vitro differentiation of D-54 and U-251 cells by substances affecting tbe intracellular cyclic AMP Ievel caused a significant reduction of tbe expression of tbe viral proteins after 18, 72, and 144 b of infection. This pronounced restriction was not paralleled to a comparable Ievel by an inhibition of tbe syntbesis and biological activity in vitro of virus·specific mRNAs as sbown by quantitative Northem (RNA) blot analyses and in vitro translation. The block in viral protein syntbesis could not be attributed to tbe induction of type I interferon by any of tbe substances tested. Our findings indicate tbat down-regulation of MV gene expression in human brain cells can occur by a cell type-rlependent regulation of tbe viral mRNA transcription and a differentiation-dependent regulation of translation, botb of wbicb may be crucial for the establisbment of persistent MV infections in tbe centrat nervous system.
ln two experiments, male rats were observed in pairs under different environmental stimulations in an open field. ln Experiment 1, white noise of 85 dB(A) reduced social activities and increased defecation compared to 75 dB(A) and 65 dß(A). ln Experiment 2, the illumination of the open field was varied in addition to a variation of the noise intensity. Again, 85 dB(A) as compared to 50 dB(A) reduced social activities and increased defecation, but also led to changes in non-social behaviours such as sniffing, grooming, and rearing. ln contrast, 400 lx did not differ substantially in its effects from 40 lx in any of the observed behavioural categories. Altogether, the behaviour pattern under 85 dß(A) white noise cannot satisfactorily be explained only by increased anxiety or fear. Alternative explanations are discussed.
A novel technique for independent and simultaneous labeling of two antigens expressed on individual cells (referred to as mixed labeling) is presented. The staining procedure combined three-step (streptavidin-biotin) immunogold-silver staining with three-step immunoenzymatic labeling. To ensure both high specificity and high sensitivity, particular emphasis was placed on designing a protocol that avoids immunological crossreactivity between the antibody reagents and overlapping of the final color products. Two examples for usage of this mixed labeling technique are described: lymphocyte subpopulations were identified in inflammatory lesions of human skin and infected host cells were characterized in the skin of mice infected with the obligatory intracellular parasite Leishmania major, a cause of human cutaneous leishmaniasis.
The silver carp (Hypophthalmichthys molitrix) growth hormone (GH) genewas isolated and sequenced following amplification from genomic DNA by the polymerase chain reaction. The gene spans a region of approx. 2.5 kb nucleotides (nt) and consists of five exons. The sequence predicts a polypeptide of 210 amino acids (aa) including a putative signal peptide of 22 hydrophobic aa residues. The arrangement of exons and introns is identical to the GH genes of common carp, grass carp, and very similar to mammals and birds, but quite different from that for the GH genes of tilapia and salmonids. The silver carp GH gene shares a high homology at the nt and aa Ievels with those of grass carp (95.3% nt, 99.5% aa) and of common carp (81% nt, 95.7% aa).
In a retrospective study of 80 chronic DSM 111-R schizophrenics and 80 controls, the occurrence of obstetric complications (OCs) into the development of chronic schizophrenias was investigated using Leonhard s distinction in systematic schizophrenia (no obvious familial loading) and unsystematic schizophrenia (mainly genetically determined according to Leonhard). The Lewis & Murray and Fuchs scales were used for evaluation. In both scales, unsystematic schizophrenias did not differ from controls, but those with OCs were significantly (p < 0.01) earlier hospitalized (20.5 years) than those without OCs (25.6 years). Systematic schizophrenics had an increased frequency, severity and total score of OCs compared to controls in the Fuchs scale (p < 0.0 I). Likewise, in the Lewis & Murray scale systematic schizophrenia showed an increased presence ofOCs compared to controls (p < 0.05) and to unsystematic schizophrenia (p < 0.1 ). Systematic schizophrenias were significantly allocated to matemal infectious diseases during mid-gestation. Patients with matemal infections showed moreadditional OCs than those without (p < 0.05; Lewis & Murray scale). In systematic schizophrenia, a history of OC was not associated with an early onset of the disease. In the genetic determined schizophrenias prenatal and perinatal disturbanccs Iead to an early onset of the disease, however, in systematic schizophrenias they seem to be of causal importance for the development of the disease.
lnteractions of p-opioid receptors with the benzodiazepine system were studied by examining the modulatory effects of flumazenil (a benzodiazepine antagonist) and alprazolam (a benzodiazepine agonist) on the respiratory effects ofthe opioid peptide dermorphin. Dermorphin, 1-30 nmol administered i.c.v., to conscious, unrestrained rats decreased ventilation rate (VR) and minute volume (MV) dose-dependently. The ventilatory depression was antagonized by naloxone and by the benzodiazepine antagonist flumazenil. The benzodiazepine alprazolam potentiateri the respiratory inhibition of a small (I nmol) dose of dermorphin but antagonized that of a higher dos:~ (3 nmol). The results suggest that the benzodiazepine/GABA receptor complex modulates respiratory depression induced by centrat p-receptor Stimulation in the rat.
Hierarchical structures among male indlviduals in a population are frequently reflected ln differences in aggressive and reproductive behavior and access to the females. In general, sodal dominance requires the Investments, which in turn then may have to be compensated for by high reproductive success. However, this hypothesls has so far only been sufficiently tested in small mating groups (one or two males with one or two females) due to the difficulties of determining paternity by conventional methods. DNA fingerprinting overcomes these problems by offering the possibility to determine genetic relationships and mating patterns within larger groups [Borke, T. (1989) Trends Ecol. Evol. 4, 139-144]. We show here that in the poecUiid fish Limia perugitu, in small matlng groups the dominant male has 8 mating success of 100%, whereas ln larger groups lts contribution to the offspring unexpectedly drops to zero.
S fimbriae are able to recognize receptor molecules containing sialic acid and are produced by pathogenic E. coli strains causing urinary tract infection and menigitis. In order to characterize the corresponding genetic determinant, termed S fimbrial adhesin ( sfa) gene duster, we have cloned the S-specific genes from a urinary pathogen and from a meningitis isolate. Nine genes are involved in the production of S fimbriae, two of these, sfaB and sfaC code for regulatory proteins being necessary for the expression of S fimbriae. Two promoters, PB and Pc, are located in front of these genes. Transcription of the sfa determinant is influenced by activation of the promotersvia SfaB and SfaC, the action of the H-NS protein and an RNaseE-specific mRNA processing. In addition, a third promoter, P A• located in front of the major subunit gene sfaA, can be activated under special circumstances. Four genes of the sfa determinant code for the subunit-specific proteins, SfaA (16 kda), SfaG (17 kda), SfaS (14 kda) and SfaH (29 kda). It was demonstrated that the protein SfaA is the major subunit protein while SfaS is identical to the sialic-acid-specific adhesin of S fimbriae. The introduction of specific mutations into sfaS revealed that a region of six amino acids of the adhesin which includes two lysine and one arginine residues is involved in the receptor specific interaction of S fimbriae. Additionally, it has been shown that SfaS is necessary for the induction of fimbriation while SfaH plays a role in the stringency of binding of S fimbriae to erythrocytes.
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.
Seven monoclonal antibodies were raised against the immunoglobulin-like extracellular domain of PO (POED), the major protein of peripheral nervous system myelin. Mice were immunized with purified recombinant rat PO-ED. After fusion, 7 clones (POI-P07) recognizing either recombinant, rat, mouse, or human PO-ED were selected by ELlS A and were characterized by Western blot, immunohistochemistry, and a competition assay. Antibodies belonged to the IgG or IgM class, and P04-P07, reacted with PO in fresh-frozen and paraffin-embedded sections of human or rat peripheral nerve, but not with myelin proteins of the central nervous system of either species. Epitope specificity of the antibodies was determined by a competition enzyme-linked immunosorbent assay (ELISA) and a direct ELlS A using short synthetic peptides spanning the entire extracellular domain of PO. These assays showed that POl and P02 exhibiting the same reaction pattern in Western blot and immunohistochemistry reacted with different distant epitopes of PO. Furthermore, the monoclonal antibodies P05 and P06 recognized 2 different epitopes in close proximity within the neuritogenic extracellular sequence of PO. This panel of monoclonal antibodies, each binding to a different epitope of the extracellular domain of PO, will be useful for in vitro and in vivo studies designed to explore the role of PO during myelination and in demyelinating diseases of the peripheral nervous system.
The demonstration ofthe chromosomal mode ofsex determinationvia genetic experiments as well as the absence of heteromorphic sex chromosomes affirm poeciliid fishes as a unique group among vertebrates that are endowed with the mostprimitive form of sex chromosornes. In many different taxa the evolutionary process involved in the differentiation ofadvanced sex chromosomes is outlined through sex specifically organized repetitive sequences. In this investigation hydridization of synthetic probes specific to genomic simple repeat motifs uncovers a sex-specific hybridization pattern in certain viviparaus fishes ofthe family Poeciliidae. The hybridization pattern together with specific staining ofthe constitutive heterochromatin by C-banding reveals heterogamety in males (Poecilia reticulata) as weil as in females (P. sphenops). In P. velifera, however, C-banding alone fails to unravel the heterogametic status. The female specific W-chromosome can be detected by simple repetitive sequence probes. Therefore, the principal significance of heterochromatization as a means of generating differentiated sex chromosomes is evident.
Pericentric intrachromosomal insertion responsible for recurrence of del(11)(p13p14) in a family
(1993)
The combined use of qualitative and quantitative analysis of I I p I 3 polymorphic markers tagether with chromosomal in situ suppression hybridization (CISS) with biotin labeled probes mapping to I I p allowed us to characterize a complex rearrangement segregating in a family. We detected a pericentric intrachromosomal insertion responsible (or recurrence of del( I I )(p 13p 14) in the family: an insertion of band I I p 13-p 14 carrying the genes for predisposition to Wilms' tumor, WT I, and for aniridia, AN2, into the long arm of chromosome I I in II q 13-q 1<4. Asymptomatic balanced carriers were observed over three generations. Classical cytogenetics had failed to detect this anomaly in the balanced carriers, who were first considered to be somatic mosaics for del( II )(p 13). Two of these women gave birth to children carrying a deleted chromosome II. most likely resulting from the loss of the I I p 13 band inserted in I I q. Although in both cases the deletion encompassed exactly the same maternally inherited markers, there was a wide Variation in clinical expression. One child, with the karyotype 46,XY,del(ll)(pllpl4), presented the full-blown WAGR syndrome with anlridia, mental retardation, Wilms' tumor, and pseudohermaphroditism, but also had proteinuria and glomerular sclerosis reminiscent of Drash syndrome. In contrast, the other one, a girl with the karyotype 46,XX,del( I I )(p I 3), only had aniridia. Although a specific set of mutational sites has been observed in Drash patients, these findings suggest that the loss of one copy of the WTI gene can result in similar genital and kidney abnormalities.
Murine epidermal Langerhans cells (LC) have been demonstrated to stimulate a vigorous T cell response to Leishmania major, a cause of human cutaneous leishmaniasis. It was therefore of interest to analyze whether LC can take up viable parasites. Epidermal cells were obtained from mouse ear skin for incubation with L. major and subsequent detection of intracellular parasites by cytochemistry. Freshly isolated LC, but not cultured LC, phagocytosed L. major and the uptake was inhibited by antibodies to the complement receptor type 3. Electron microscopic studies revealed the presence of viable amastigotes within Le. Moreover, with double-Iabeling techniques, L. major-containing LC could also be detected in infected skin. The results demonstrate that LC can internalize L. major. Since the number of organisms per infected LC remained consistently low, the prime task of LC may not be the promotion of parasite spreading but the presentation of L. major antigen to T cells and, thus, the regulation of the cellular immunity during cutaneous leishmaniasis.
We have investigated oxygen on CdTe substrates by means of x-ray photoelectron spectroscopy (XPS) and reflection high-energy electron diffraction (RHEED). A Te oxide layer that was at least 15 A thick was found on the surface of as-delivered CdTe substrates that were mechanically polished. This oxide is not easily evaporated at temperatures lower than 350°C. Furthermore, heating in air, which further oxidizes the CdTe layer, should be avoided. Etching with HCI acid (15% HCl) for at least 20 s and then rinsing with de-ionized water reduces the Te oxide layer on the surface down to 4% of a monoatomic layer. However, according to XPS measurements of the 0 Is peak, 20%-30% of a monoatomic layer of oxygen remains on the surface, which can be eliminated by heating at temperatures ranging between 300 and 340 cC. The RHEED patterns for a molecular beam epitaxially (MBE)-grown CdTe film on a (lOO) CdTe substrate with approximately one monoatomic layer of oxidized Te on the surface lose the characteristics of the normal RHEED pattems for a MBE-grown CdTe film on an oxygen-free CdTe substrate.
Autolyzed, antigen-extracted, allogeneic (AAA) bone was prepared from human cortical bone and its morphologic, biomechanical, and osteoinductive properlies were compared with untreated (frozen) as well as lyophilized human bone. Scanning electron microscopy revealed removal of inprganic calcium phosphates and persistence of shrunken collagen fibrils on the surface of AAA bone matrix. Biomechanical testing of differently prepared bone samples showed that lyophilization increased both the modulus of elasticity (P < .00001) and the compressive strength (P < .00001 ). Depending on the depth of decalcification in the preparation of AAA bone, both measured values decreased in rehydrated AAA bone compared with untreated bone {P < .00001 ). Completely demineralized and rehydrated AAA bone was soft, flexible, and showed very little compressive strength. Differences in biomechanical behavior between samples drilled longitudinally or perpendicularly to the diaphyseal bone axis were observed. Xenogeneic human bone samples were implanted in muscle pouches of Sprague-Dawley rats for 6 weeks. AAA bone implants showed chondrogenesis and osteogenesis in 50% of the cases, while untreated or lyophilized bone implants induced no new cartilage or bone formation. As decalcification exposed xenogeneic organic matrix components, AAA bone implants provoked the highest inflammatory reaction. When AAA bone samples were implanted in immunosuppressed rats, the inflammatory reaction was suppressed and 94o/o of the implants showed endochondral bone formation. The chondroinductivity of the bone samples also was tested in vitro using neonatal rat muscle tissue to avoid interference with inflammatory cells and secreted cytokines. In this assay, 68°/o of AAA bone samples induced chondroneogenesis, while untreated as weil as lyophilized bone samples failed to induce any cartilage formation. The results clearly dernonstrafe that AAA bone has osteoinductive properties. Biomechanical stability of AAA bone implants depends on the degree of demineralization. Thus, they can be prepared in an appropriate manner for different indications in oral and maxillofacial surgery.
In Xiphophorus melanoma formation has been attributed by classical genetic findings to the overexpression of a cellular oncogene (Tu) due to elimination of the corresponding regulatory gene locus in hybrids. We have attempted to elucidate this phenomenon on the molecular biological level. Studies on the structure and expression of known proto-oncogenes revealed that several of these genes, especially the c-src gene of Xiphophorus, may act as effectors in establishing the neoplastic phenotype of the melanoma cells . However, these genes appear more to participate in secondary steps of tumorigenesis. Another gene, being termed Xmrk, which represents obviously a so far unknown proto-oncogene but with a cons iderably high similarity to the epidermal growth-factorreceptor gene, was mapped to the Tu-containing region of the chromosome. This gene shows features with respect to its structure and expression that seem to justify it to be regarded as a candidate for a gene involved in the primary processes leading to neoplastic transformation of pigment cells in Xiphophorus.
We have investigated theoretically the importance of the O(\(^3\)P)+CH(a\(^4\sum^-\)) and the O(\(^3\)P)+CH(X\(^2\Pi\)) channels in the collinear chemi-ionization reaction O+CH->HCO\(^+\) +e\(^-\). We have found that both channels may lead to chemi-ionization via favorable Franck-Condon overlaps with the states ofthe ionic species.
In 55 chronic DSM I11 -R schi zophre nics the occurrence of obstetr ic complica ti ons (OCs) was investigated us ing the famili al/sporael ic strategy and Leonhard's unsystemati c/systematic distin ction. The overa ll frequency and severity of OCs elid not differ be tween patie nts anel controls. A sub-sample of patients, whose genetic ri sk was supposed to be high in both class ification systems (d iagnos is 01' unsystematic anel fa mili al sc hizophre ni a), had s igni ficantly fewer OCs than controls on the Lewis anel Murray scale (P < 0.05). With reference to previous reports of inc reased morta lity rates in the offspring of schizop hre nics, high genetic risk and addition al perinatal stressors may in crease perin atal mortality. In contrast, pat ie nts whose genetic ri sk was sllpposed to be low in both systems (di agnos is of systematic and sporadic sc hizophrenia) showed a trend to an increased freqllency of OCs in the Fuchs scale. In the context of the recently reported highl y signi ficantly increased rate of matern al infections dllring midgestation in these pati e nts, it was supposed th at perin atal complications may be of so me ae tio logical importance in sc hizophrenics with low genetic ri sk.
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.