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[Risk assessment of sex offenders in a German-speaking sample. Applicability of PCL-SV, HCR-20+3, and SVR-20].

Regarding the relatively high relapse rates of sex offenders, an increasing need for forensic prognosis reports, doubts about their validity, and a continued lack of qualified forensic experts makes the supposedly simple application of instruments such as the Psychopathy Check List Screening Version (PCL-SV), HCR-20+3, or the Sexual Violence Risk 20 (SVR-20) very tempting. Those tools supply numeric values for quantifying assumed risk and have begun appearing more frequently in forensic reports. Their use for specific collectives without prior examination of accuracy, admissibility, and accountability may lead to serious mistakes and risks. This study by the Forensic Department of the Psychiatric University Hospital in Basel, Switzerland, is part of a larger cohort study on forensic risk assessment. It investigates among others the differential indication for PCL-SV, HCR-20+3, and SVR-20. In the present study, 64 sex offenders were retrospectively rated with these three instruments based on their respective reports for prior risk assessment, including criminal reports. Those ratings were then compared with prior results from the Structured Risk Assessment of Basel, as performed by the experts. Results of this study confirm the utility of PCL-SV, HCR-20+3 and SVR-20 in a German-speaking sample of sex offenders primarily as a scientific instrument. Beyond that, these instruments may also be used literally as a checklist. Their use for risk quantification should be limited primarily to the subgroup of antisocial and physically aggressive sex offenders.

Adult↗

Uptake, cytotoxicity and metabolism of m-azidopyrimethamine and related lipophilic antifolates in SV-K14 human keratinocytes in vivo.

The growth-inhibitory properties of a series of lipophilic diaminopyrimidine antifolates were evaluated in comparison with methotrexate (MTX) against SV-K14 human keratinocytes in vitro under folate-dependent and folate-independent conditions. Under folate-dependent conditions metoprine (DDMP) proved more cytotoxic than MTX, despite the greater inhibitory activity of the latter compound against mammalian dihydrofolate reductase (DHFR), possibly reflecting differences in cellular accumulation. The significantly lower activity of both compounds under folate-independent conditions indicated DHFR as the primary target. Pyrimethamine (PYM), m-azidopyrimethamine (MZP) and m-aminopyrimethamine (MAP), a metabolite of MZP, were approximately equiactive but less cytotoxic than MTX or DDMP. The unexpected activity of MAP, an inferior DHFR inhibitor, suggests differences in the mechanism of action or cellular transport of the drug, although the reduction of cytotoxicity observed under folate-independent conditions indicate folate metabolism as the cytotoxic locus. In contrast, the cytotoxicity of PYM or MZP was not reduced under folate-independent conditions implying an alternative mechanism of action. The uptake of 2-[14C]pyrimethamine by SV-K14 keratinocytes was rapid with steady-state intracellular concentrations being observed after approximately 100 min, partition of drug into the plasma membrane preceding redistribution and extensive accumulation within the particulate cell components. The previously reported NADPH-dependent metabolism of MZP to MAP by murine liver microsome preparations was not observed with SV-K14 keratinocytes nor with murine skin homogenates in the present study.

Animals↗

Protective effect of SV-IV on platelet-activating factor-induced hypotension, bronchoconstriction and gastric mucosal injury.

The inhibitory effect of one of the major proteins secreted by the rat seminal vesicles (SV-IV) on platelet-activating factor (PAF)-induced biological activities was investigated in vivo. SV-IV was found to prevent dose dependently both hypotension and acute bronchospasm caused by PAF administration in guinea-pigs. In addition, SV-IV inhibited both PAF- and ethanol-induced gastric mucosal injury in a dose-dependent manner.

Animals↗

The interaction of rifamycin-SV with the hepatic transport and sulfation of taurolithocolic acid in rats.

Sulfated and non sulfated lithocholic acid were analyzed in serum, bile and urine of bile-fistula Sprague-Dawley female rats by gas-liquid chromatography and thin-layer chromatography. In rats (group A) bile was collected during a 3 h saline infusion followed by a 3 h intravenous infusion of taurolithocholate; animals of group B and C were infused with both taurolithocholate and rifamycin-SV, but in the animals of group C the renal pedicles were ligated. Serum bile acids showed a significant increase only in animals of group C, during the infusion of rifamycin-SV. In bile of animals of group A sulfated lithocholic acid represented 18% of total, but was not found in bile of animals of group B and C, while a significant increase of sulfated lithocholic acid was evident in urine of animals of group B. The results indicate that rifamycin-SV probably interferes with the hepatic secretion of sulfated lithocholic acid in the rat.

Animals↗

Inhibition of macrophage phagocytic activity by SV-IV, a major protein secreted from the rat seminal vesicle epithelium.

The protein SV-IV, one of the major secretory proteins produced by the rat seminal vesicle epithelium, has been found to possess a marked ability to inhibit in vitro the phagocytic properties of activated peritoneal rat macrophages, by a mechanism that apparently involves phagocytes and target cells. Although SV-IV is a substrate for transglutaminase (TGase), an enzyme secreted by activated macrophages, TGase does not seem to play any significant role either in the binding of the protein to the cells participating in the phagocytic process or in the inhibition of macrophage phagocytosis by SV-IV. The significance of the findings in relation to the reproductive process and their possible clinical implications are discussed.

Animals↗

In vivo inhibition of cell-mediated and humoral immune responses to cellular antigens by SV-IV, a major protein secreted from the rat seminal vesicle epithelium.

Microgram amounts of protein SV-IV, a major secretory protein produced by adult rat seminal vesicle epithelium, markedly decrease the mouse humoral immune response to cellular xenogeneic or allogeneic antigens (sheep red blood cells (SRBC) or mouse epididymal spermatozoa). The significant reduction in the total number of splenocytes and their main cell subsets in SRBC-immunized mice, the dramatic decrease in the number of Ia+ splenic T cells and the marked inhibition of splenocyte ability to respond in vitro to polyclonal mitogen stimuli suggest that the macrophage accessory cells are the primary target of the SV-IV immunosuppressive activity in vivo. Moreover, the infection of SV-IV-treated mice with Salmonella typhimurium produced an increased mortality of the experimental animals associated with a marked decrease of the phagocytic and intracellular killing activities of their peritoneal macrophages.

Animals↗

Comparative effect of the naphthalenic ansamycins rifamycin SV, rifampin and cyclopentylrifampicin on murine neutrophil function.

The purpose of this study was to evaluate the in vitro effect of the naphthalenic ansamycins rifamycin SV, rifampin and cyclopentylrifampicin on neutrophil degranulation and cytokinesis using murine peritoneal exudate cells. It was found that the FMLP-stimulated secretion of myeloperoxidase was significantly inhibited by 80 micrograms rifamycin SV (P less than 0.05) and cyclopentylrifampicin (P less than 0.01) per ml. Nondirected and FMLP-directed migration was significantly (P less than 0.01) inhibited by rifamycin SV and rifampin at assay concentrations above 0.31 and 5.0 micrograms/ml respectively thus confirming the low dose rifamycin effect observed by others using human neutrophils. Finally, cyclopentylrifampicin was shown to have no significant effect on nondirected or FMLP-directed neutrophil migration at assay concentrations of 1.25 to 80 micrograms per ml.

Animals↗

Effects of endothelin on phospholipases and generation of second messengers in cat iris sphincter and SV-CISM-2 cells.

In both immortalized cat iris sphincter smooth muscle cells (SV-CISM-2 cells) and cat iris sphincter, endothelin-1 (ET-1) markedly increased the activities of phospholipase A2 (PLA2), as measured by the release of arachidonic acid (AA), phospholipase C (PLC), as measured by the production of inositol trisphosphate (IP3), and phospholipase D (PLD), as measured by the formation of phosphatidylethanol (PEt). In SV-CISM-2 cells, ET-1 induced AA release, IP3 production and PEt formation in a dose- and time-dependent manner. The dose-response studies showed that the peptide is more potent in activating PLD (EC50 = 1.2 nM) than in activating PLC (EC50 = 1.5 nM) or PLA2 (EC50 = 1.7 nM). The time course studies revealed that ET-1 activated the phospholipases in a temporal sequence in which PLA2 was stimulated first (t1/2 = 12 s), followed by PLC (t1/2 = 48 s) and lastly PLD (t1/2 = 106 s). In SV-CISM-2 cells, in contrast to the intact iris sphincter, sarafotoxin-c, an ETB receptor agonist, had no effect on the phospholipases, and indomethacin, a cyclooxygenase inhibitor, had no effect on the stimulatory effect of ET-1 on the phospholipases. These results suggest that in this smooth muscle cell line, ET-1 interacts with the ETA receptor subtype to activate, via G proteins, phospholipases A2, C and D in a temporal sequence.

Animals↗

Aristolochic acid-induced cell cycle G1 arrest in human urothelium SV-HUC-1 cells.

Aristolochic acid (AA) has been implicated in urothelial carcinoma in humans. To evaluate the impact of AA on the human urinary tract epithelium cells, a study of SV-HUC-1 cells cultured with mixture of AA (AAM; 41% AA I, 56% AA II) was conducted. Cell viability was assayed in cultures exposed to 0.0125-0.2mM AAM for 1, 3, and 5 days, a concentration-dependent inhibition on the growth of SV-HUC-1 cells was demonstrated. Cell cycle distribution determined by flow cytometry revealed an accumulation of cells in the G0/G1 phase (from 37.6% to 49.2%). Regarding the cell cycle control proteins, the levels of p53, p21 and p27 increased in a concentration-dependent manner. Immunoprecipitation demonstrated a decrease in the formation of cyclin E/cdk2 complex, but not cyclin D1/cdk4 complex, which leads to an increase in the free form of cdk2. Additionally, a decrease in the phospho-Rb correlates with an increase in Rb/E2F-1 complex which prevents the release of E2F transcription factor, thus preventing the transcription of the genes required for cell proliferation. Our results provide evidence that AAM induce cell cycle arrest in SV-HUC-1 cells. Whether this cell cycle block is associated with AA-related human urothelial carcinoma requires further study to clarify.

Aristolochic Acids↗

Redox-dependent modulation of the carrot SV channel by cytosolic pH.

Currents mediated by a slow vacuolar (SV) channel were recorded and characterized in vacuoles from cultured carrot cells. The carrot channel shows the typical functional characteristics reported for channels of the SV category previously identified in other plants, i.e., slow voltage-dependent activation kinetics, current activation favoured by cytosolic calcium and permeability to different monovalent cations. The carrot channel is strongly activated by cytosolic reducing agents (such as dithiothreitol, DTT, and glutathione, GSH) and has a peculiar dependence on cytosolic pH, which, in turn, is affected by the concentration of cytosolic reducing agents. Specifically, in 1 mM DTT or GSH the channel displayed a maximum conductance at neutral pH. The normalized conductance did not depend significantly on DTT concentration at acidic pH, while at alkaline pH the attenuation of the normalized conductance declines with increasing DTT concentration. Our results suggest two pH-titratable groups within the carrot SV channel, one of these depending on cysteine residues exposed to the cytosolic side of the vacuole.

Calcium Channels↗

Activation of particulate guanylyl cyclase by endothelins in cultured SV-40 transformed cat iris sphincter smooth muscle cells.

We investigated the effects of endothelins (ETs) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ET-3 increased cGMP formation in a concentration-dependent manner (EC50 = 98nM), which was 2.5 times higher than that of ET-1. The ET(B)receptor agonists sarafotoxin-S6c and IRL 1620 also increased cGMP production, mimicking the effects of the ETs. The ET(B) receptor antagonist BQ 788, but not the ET(A) receptor antagonist BQ610, dose-dependently blocked ET-3-stimulated cGMP formation (IC50=10nM). The phorbol ester, Phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylyl cyclase in smooth muscle, dose-dependently inhibited ET-3-stimulated cGMP accumulation (IC50=66nM). LY83583 and ODQ, inhibitors of soluble guanylyl cyclases, as well as inhibitors of the nitric oxide cascade and of intracellular Ca2+ elevation had no appreciable effect on ET-3-induced cGMP production. ET-3 markedly inhibited carbachol-induced intracellular Ca2+ mobilization. We conclude that ET-3 increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ET(B) receptor subtype and subsequent stimulation of the membrane-bound guanylyl cyclase. Elevation of cGMP by ET and the subsequent inhibition of muscarinic stimulation of intracellular Ca2+ mobilization by the cyclic nucleotide could serve to modulate the contractile effects of Ca2+-mobilizing agonists in the iris sphincter smooth muscle.

Animals↗

Sequentially folded SV-11 RNA: metastability is relevant to biological function.

By simulating a Markov process comprising kinetically controlled elementary chain-growth steps and upstream refolding events, we compute the sequential folding of SV-11 RNA; a species capable of acting as a template instructing its own replication when folded into a metastable conformation. The predicted structure is endowed with available primers for replication and is identical within the regions of homology to the experimentally probed active structure of MNV-11 RNA, a species from which SV-11 RNA has evolved. The uneven rate of chain growth during SV-11 RNA replication and the pause sites along the replica sequence are determined. Such predictions are testable in pulse-chase kinetic experiments.

Base Sequence↗

3-(Carboxyalkylthio) rifamycin S and SV derivatives inhibit human neutrophil functions.

In order to further investigate the potential of rifamycins as antiinflammatory drugs, twenty-five semisynthetic rifamycins were tested at concentrations ranging from 10(-9) to 10(-5) M on in vitro human neutrophil functions such as locomotion, superoxide anion production, and degranulation, under different stimulatory conditions. They were also tested as antiproliferative agents on peripheral blood lymphocytes. The present semisynthetic derivatives are in general characterized by their carrying a hydrophilic substituent; they are rifamycin S or rifamycin SV derivatives carrying at C(3) either a carboxyalkyl side-chain or a glycosyl side-chain. Derivatives of the former group displayed inhibitory activities covering the whole range of activities tested, suggesting that the sum of these different effects could support their antiinflammatory activity in vivo. These derivatives, carrying a free carboxyl, are more water soluble than rifamycin SV at physiological pH, and may serve as antiinflammatory drugs for local administration, alternative to rifamycin SV, possibly giving higher efficacy and reduced side effects of pain and tissue swelling.

Anti-Bacterial Agents↗

Role of unsaturated derivatives of spermidine as substrates for spermine synthase and in supporting growth of SV-3T3 cells.

Synthetic unsaturated analogues of the natural polyamine were examined as possible substrates for spermine synthase and as replacements for spermidine in supporting the growth of SV-3T3 cells. It was found that N-(3-aminopropyl)-1,4-diamino-cis-but-2-ene [the cis isomer of the alkene analogue of spermidine] was a good substrate for spermine synthase, but that the trans isomer [N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and the alkene analogue [N-(3-aminopropyl)-1,4-diaminobut-2-yne] were not substrates. These results provide the first demonstration of stereospecificity in the spermine synthase reaction. All three of the unsaturated spermidine analogues described above and the cis-alkene analogue of spermine [N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene] were able to support the growth of SV-3T3 cells that were prevented from the endogenous synthesis of spermidine by treatment with alpha-difluoromethylornithine. Since N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and N-(3-aminopropyl)-1,4-diaminobut-2-yne were not converted into a spermine derivative, it is apparent that this conversion is not needed for the stimulation of growth. However, since N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene was also able to support growth and was not degraded to the spermidine derivative, it appears that either polyamine can be effective in this respect. All of the unsaturated analogues tested accumulated in the SV-3T3 cells to a much greater extent than spermidine itself. This indicates that these compounds are substrates for the polyamine transport system, but that they are less effective than the natural polyamines in the feedback regulation of this system.

Animals↗

Synthesis of novel anti-inflammatory peptides derived from the amino-acid sequence of the bioactive protein SV-IV.

SV-IV is a basic, thermostable, secretory protein of low Mr (9758) that is synthesized by rat seminal vesicle (SV) epithelium under strict androgen transcriptional control. This protein is of obvious pharmacological interest because it has potent nonspecies-specific immunomodulatory, anti-inflammatory, and pro-coagulant activities. In evaluating the clinical relevance and the possible use in medicine of SV-IV, we became interested in the study of its structure-function relationships and aimed to identify in its polypeptide chain specific peptide fragments possessing the marked anti-inflammatory properties of the protein not associated with other biological activities (pro-coagulation and immunomodulation) typical of this molecule. By using two different experimental approaches (the fragmentation of the protein into peptide derivatives by chemical methods and the organic synthesis on solid phase of selected peptide fragments), data were obtained showing that in this protein: (a) the immunomodulatory activity is related to the structural integrity of the whole molecule; (b) the anti-inflammatory activity is located in the N-terminal region of the molecule, the 8-16 peptide fragment being the most active; (c) the identified anti-inflammatory peptide derivatives do not seem to possess pro-coagulant activity, even though this particular function has been located in the 1-70 segment of the molecule.

Amino Acid Sequence↗

Effect of uracil on rifamycin SV production by Amycolatopsis mediterranei MV35R.

The effect of different organic nitrogen compounds on the production of rifamycin SV by Amycolatopsis mediterranei MV35R and their optimum concentrations have been described. Results obtained indicate that rifamycin SV production increased from 4020 mg l-1 to 4575 mg l-1 when organic nitrogen compound uracil was added at 0.2% (w/v) concentration to the fermentation medium by A. mediterranei MV35R. The rifamycin SV yield was enhanced by 505 mg l-1 using uracil (2 g l-1) when compared with barbital.

Actinomycetales↗

Contrasting effects of IG20 and its splice isoforms, MADD and DENN-SV, on tumor necrosis factor alpha-induced apoptosis and activation of caspase-8 and -3.

We identified a novel cDNA (IG20) that is homologous to cDNAs encoding a protein differentially expressed in normal and neoplastic cells (DENN-SV) and human MADD (MAPK-activating death domain-containing protein). Furthermore, we show that the above variants most likely result from alternative splicing of a single gene. Functional analyses of these variants in permanently transfected HeLa cells revealed that IG20 and DENN-SV render them more susceptible or resistant to tumor necrosis factor alpha (TNF-alpha)-induced apoptosis, respectively. All variants tested could interact with TNF receptor 1 and activate ERK and nuclear factor kappaB. However, relative to control cells, only cells expressing IG20 showed enhanced TNF-alpha-induced activation of caspase-8 and -3, whereas cells expressing DENN-SV showed either reduced or no caspase activation. Transfection of these cells with a cDNA encoding CrmA maximally inhibited apoptosis in HeLa-IG20 cells. Our results show that IG20 can promote TNF-alpha-induced apoptosis and activation of caspase-8 and -3 and suggest that it may play a novel role in the regulation of the pleiotropic effects of TNF-alpha through alternative splicing.

Alternative Splicing↗

Transfection of neonatal rat Schwann cells with SV-40 large T antigen gene under control of the metallothionein promoter.

Secondary cultures of Schwann cells were transfected with a plasmid containing the SV-40 T antigen gene expressed under the control of the mouse metallothionein-I promoter. We used the calcium phosphate method for transfection and obtained a transfection efficiency of 0.01%. The colonies were cloned by limited dilution, and these cloned cell lines were carried in medium containing zinc chloride (100 microM). One cloned cell line, which has now been carried for 180 doublings, appears to have a transformed phenotype with a doubling time of 20 h. These cells express SV-40 T antigen while maintaining established Schwann cell properties (positive staining for 217c, Ran-2, A5E3, glial fibrillary acidic protein, presence of 2',3'-cyclic nucleotide phosphohydrolase [CNPase] activity, and the ability to synthesize sulfogalactosylceramide and mRNA for the myelin protein, P0). Removal of zinc chloride from the medium resulted in reduced expression of T antigen and a change in the appearance of the cells to a more bipolar shape, although they still did not exhibit contact inhibition and maintained a doubling time of 20 h. These cells now became Ran-2-negative and showed increases in CNPase activity and in their ability to synthesize sulfogalactosylceramide. The amount of P0 mRNA remained unchanged. Transfected Schwann cells, however, stopped dividing when they contacted either basal lamina or neurites and became bipolar in appearance. The Schwann cells in contact with the neurites then extended processes to wrap around bundles of neurites. Transfection with the SV-40 T antigen gene therefore provides a method for obtaining Schwann cell lines that continue to express properties associated with untransfected cells in culture and may be used to study axon-Schwann cell interaction.

Animals↗