bluuebunny/crossref_metadata_2025 huggingface dataset:
Turnover of Hepatitis B Virus X Protein Is Regulated by Damaged DNA-Binding Complex
Authors: Bergametti Françoise , Sitterlin Delphine , Transy Catherine
Published: July 2002

Mammalian hepatitis B viruses encode an essential regulatory protein, termed X, which may also be implicated in liver cancer development associated with chronic infection. X protein, also referred to as HBx in human virus and WHx in woodchuck virus, has been reported to bind to a number of cellular proteins, including the DDB1 subunit of the damaged DNA-binding (DDB) complex. Our previous work provided genetic evidence for the importance of WHx-DDB1 interaction in both the activity of the X protein and establishment of viral infection in woodchucks. In the present study, a direct action of DDB1 on the X protein is documented. Physical interaction between the two proteins leads to an increase in X protein stability. This effect results from protection of the viral protein from proteasome-mediated degradation. Protection of WHx is overcome in the presence DDB2, the second subunit of the DDB heterodimer. In keeping with observations reported for HBx, DDB2 was found to directly bind to WHx. Nonetheless, the counteracting effect of DDB2 on X stabilization requires DDB2-DDB1 interaction. Taken together, these findings substantiate the physical and functional connection between the X protein and the DDB1-DDB2 heterodimer, leading to the regulation of the pool of the viral protein.
Comparison of
Turnip Crinkle Virus
RNA-Dependent RNA Polymerase Preparations Expressed in
Escherichia coli
or Derived from Infected Plants
Authors: Rajendran K. S. , Pogany J. , Nagy P. D
Published: July 2002

Turnip crinkle virus
(TCV) is a small, plus-sense, single-stranded RNA virus of plants. A virus-coded protein, p88, which is required for replication has been expressed and purified from
Escherichia coli.
In vitro assays revealed that the recombinant p88 has an RNA-dependent RNA polymerase (RdRp) activity and can also bind to RNA. Deletion of the N-terminal region in p88 resulted in a more active RdRp, while further deletions abolished RdRp activity. Comparison of the
E. coli-
expressed p88, the N-terminal deletion mutant of p88, and a TCV RdRp preparation obtained from infected plants revealed that these preparations show remarkable similarities in RNA template recognition and usage. Both the recombinant and the plant TCV RdRp preparations are capable of de novo initiation on both plus- and minus-strand satC and satD templates, which are small parasitic RNAs associated with TCV infections. In addition, these RdRp preparations can efficiently recognize the related
Tomato bushy stunt virus
promoter sequences, including the minus- and plus-strand initiation promoters. Heterologous viral and artificial promoters are recognized poorly by the recombinant and the plant TCV RdRps. Further comparison of the single-component recombinant TCV RdRp and the multicomponent plant TCV RdRp will help dissect the functions of various components of the TCV replicase.
The VP1 Unique Region of Parvovirus B19 and Its Constituent Phospholipase A2-Like Activity
Authors: Dorsch Simone , Liebisch Gerhard , Kaufmann Bärbel , von Landenberg Philipp , Hoffmann Jörg H. , Drobnik Wolfgang , Modrow Susanne
Published: July 2002

Parvovirus B19 is the causative agent of erythema infectiosum. In addition, parvovirus B19 infection may be associated with other disease manifestations, namely, thrombocytopenia or granulocytopenia, spontaneous abortion or hydrops fetalis in pregnant women, acute and chronic arthritis, and systemic lupus erythematosus. Based on sequence homology data, a phospholipase A2 motif has been identified in the VP1 unique region of parvovirus B19. (Y. Li et al., J. Gen. Virol. 82:2821-2825, 2001; Z. Zadori et al., Dev. Cell 1:291-302, 2001). We have established a new in vitro assay based on electrospray ionization tandem mass spectroscopy to show that phospholipase A2 activity is present in the VP1 unique region produced in
Escherichia coli
and in virus-like particles consisting of combinations of VP1 and VP2 proteins expressed by recombinant baculovirus. The enzyme activity of the VP1 unique region showed typical Ca
2+
dependency and could be inhibited by manoalide and 4-bromophenacylbromide, which bind covalently to lysine and histidine residues, respectively, as part of the active center of the enzyme. By using subfragments, we demonstrated an association between the phospholipase A2-like activity and the carboxy-terminal domain of the VP1 unique region.
Genetic Control of a Mouse Serum Lipoprotein Factor That Inactivates Murine Leukemia Viruses: Evaluation of Apolipoprotein F as a Candidate
Authors: Wu Tiyun , Lee Chun G. , Buckler-White Alicia , Kozak Christine A.
Published: July 2002

Mice contain a serum factor capable of inactivating some subgroups of murine leukemia viruses. This leukemia virus-inactivating factor (LVIF) is distinct from immunoglobulin and complement; it has been associated with lipoprotein serum fractions and may be an apolipoprotein. The present study demonstrates that some Swiss-derived inbred strains are LVIF negative. Genetic crosses show this factor to be under control of a single gene that maps to distal chromosome 10 at or near the gene encoding a minor serum apolipoprotein, apolipoprotein F (ApoF). To evaluate this gene as a potential candidate for LVIF, the mouse ApoF gene was cloned and sequenced and its expression was assessed in LVIF-positive and -negative mice; no obvious differences were detected, suggesting that LVIF is under the control of a distinct linked gene.
Overexpression of the Rabies Virus Glycoprotein Results in Enhancement of Apoptosis and Antiviral Immune Response
Authors: Faber Milosz , Pulmanausahakul Rojjanaporn , Hodawadekar Suchita S. , Spitsin Sergei , McGettigan James P. , Schnell Matthias J. , Dietzschold Bernhard
Published: July 2002

A recombinant rabies virus (RV) carrying two identical glycoprotein (G) genes (SPBNGA-GA) was constructed and used to determine the effect of RV G overexpression on cell viability and immunity. Immunoprecipitation analysis and flow cytometry showed that tissue culture cells infected with SPBNGA-GA produced, on average, twice as much RV G as cells infected with RV carrying only a single RV G gene (SPBNGA). The overexpression of RV G in SPBNGA-GA-infected NA cells was paralleled by a significant increase in caspase 3 activity followed by a marked decrease in mitochondrial respiration, neither of which was observed in SPBNGA-infected cells. Furthermore, fluorescence staining and confocal microscopy revealed an increased extent of apoptosis and markedly reduced neurofilament and F actin in SPBNGA-GA-infected primary neuron cultures compared with neuronal cells infected with SPBNGA, supporting the concept that RV G or motifs of the RV G gene trigger the apoptosis cascade. Mice immunized with SPBNGA-GA showed substantially higher antibody titers against the RV G and against the nucleoprotein than SPBNGA-immunized mice, suggesting that the speed or extent of apoptosis directly determines the magnitude of the antibody response.
Patterns of Gene Expression and a Transactivation Function Exhibited by the vGCR (ORF74) Chemokine Receptor Protein of Kaposi's Sarcoma-Associated Herpesvirus
Authors: Chiou Chuang-Jiun , Poole Lynn J. , Kim Peter S. , Ciufo Dolores M. , Cannon Jennifer S. , ap Rhys Colette M. , Alcendor Donald J. , Zong Jian-Chao , Ambinder Richard F. , Hayward Gary S.
Published: July 2002

The ORF74 or vGCR gene encoded by Kaposi's sarcoma-associated herpesvirus (KSHV; also called human herpesvirus 8) has properties of a ligand-independent membrane receptor signaling protein with angiogenic properties that is predicted to play a key role in the biology of the virus. We have examined the expression of vGCR mRNA and protein in primary effusion lymphoma (PEL) cell lines, PEL and multicentric Castleman's disease (MCD) tumors, Kaposi's sarcoma lesions and infected endothelial cell cultures. The vGCR gene proved to be expressed in PEL cell lines as a large spliced bicistronic mRNA of 3.2 kb that also encompasses the upstream vOX2 (K14) gene. This mRNA species was induced strongly by phorbol ester (TPA) and sodium butyrate treatment in the BCBL-1 cell line, but only weakly in the HBL6 cell line, and was classified as a relatively late and low-abundance delayed early class lytic cycle gene product. A complex bipartite upstream lytic cycle promoter for this mRNA was nestled within the intron of the 5′-overlapping but oppositely oriented latent-state transcription unit for LANA1/vCYC-D/vFLIP and responded strongly to both TPA induction and cotransfection with the KSHV RNA transactivator protein (RTA or ORF50) in transient reporter gene assays. A vGCR protein product of 45 kDa that readily dimerized was detected by Western blotting and in vitro translation and was localized in a cytoplasmic and membrane pattern in DNA-transfected Vero and 293T cells or adenovirus vGCR-transduced dermal microvascular endothelial cells (DMVEC) as detected by indirect immunofluorescence assay (IFA) and immunohistochemistry with a specific rabbit anti-vGCR antibody. Similarly, a subfraction of KSHV-positive cultured PEL cells and of KSHV (JSC-1) persistently infected DMVEC cells displayed cytoplasmic vGCR protein expression, but only after TPA or spontaneous lytic cycle induction, respectively. The vGCR protein was also detectable by immunohistochemical staining in a small fraction (0.5 to 3%) of the cells in PEL and MCD tumor and nodular Kaposi's sarcoma lesion specimens that were apparently undergoing lytic cycle expression. These properties are difficult to reconcile with the vGCR protein's playing a direct role in spindle cell proliferation, transformation, or latency, but could be compatible with proposed contributions to angiogenesis via downstream paracrine effects. The ability of vGCR to transactivate expression of both several KSHV promoter-driven luciferase (LUC) reporter genes and an NFκB motif containing the chloramphenicol acetyltransferase (CAT) reporter gene may also suggest an unexpected regulatory role in viral gene expression.
A Protein Encoded by the Herpes Simplex Virus (HSV) Type 1 2-Kilobase Latency-Associated Transcript Is Phosphorylated, Localized to the Nucleus, and Overcomes the Repression of Expression from Exogenous Promoters When Inserted into the Quiescent HSV Genome
Authors: Thomas S. K. , Lilley C. E. , Latchman D. S. , Coffin R. S.
Published: July 2002

Herpes simplex virus (HSV) is characterized by its ability to establish a latent infection in sensory neurons, from which it can periodically reactivate. The mechanisms of latency, however, remain unclear. The HSV genome is quiescent during latency except for the expression of the latency-associated transcripts (LATs). Although the exact function of the LATs remains obscure, current evidence suggests they are multifunctional and are involved in both establishment of latency and reactivation from latency. The LATs contain several open reading frames (ORFs). One or more of the functions of the LATs could therefore be protein mediated. We have previously reported that deregulated expression of the largest of the HSV type 1 (HSV-1) LAT ORFs (∼274 amino acids) greatly enhances virus growth in cell types that are normally relatively nonpermissive for HSV replication and also that it complements mutations to the immediate-early (IE) gene ICP0 (S. K. Thomas, G. Gough, D. S. Latchman, and R. S. Coffin, J. Virol. 73:6618-6625, 1999). Here we show that LAT ORF expression overcomes the repression of expression from exogenous promoters introduced into the HSV-1 genome which normally occurs in the absence of IE gene expression. To further explore LAT ORF function, we have generated an epitope-tagged LAT ORF, LAT
myc
His, which forms punctate structures in the infected-cell nucleus reminiscent of the structures formed by ICP0. These are associated with the appearance of a phosphorylated form of the protein and are formed adjacent to, or around the edges of, viral replication compartments. These results provide further evidence that the HSV-1 LAT ORF protein is biologically functional and that the tightly regulated expression of this protein may be important in the wild-type latency phenotype in vivo.
Hepatitis C Virus-Like Particle Morphogenesis
Authors: Blanchard Emmanuelle , Brand Denys , Trassard Sylvie , Goudeau Alain , Roingeard Philippe
Published: July 2002

Although much is known about the hepatitis C virus (HCV) genome, first cloned in 1989, little is known about HCV structure and assembly due to the lack of an efficient in vitro culture system for HCV. Using a recombinant Semliki forest virus replicon expressing genes encoding HCV structural proteins, we observed for the first time the assembly of these proteins into HCV-like particles in mammalian cells. This system opens up new possibilities for the investigation of viral morphogenesis and virus-host cell interactions.
Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazoles and Their Precursors
Authors: Jedlovská Eva , Gavláková Edita
Published: July 2002

The characteristic feature of many commercial agrochemicals and drugs is the 5-nitro-2-furyl or 2,5-dimethyl-3-furyl building block. Within the scope of our research aimed at utilization of dipolar cycloaddition reactions to prepare new compounds with potential biological and phytoeffectorial activity, we report on the synthesis of some substituted hydrazones I and their intramolecular cycloaddition to 2,5-disubstituted 1,3,4-oxadiazoles II. The basic IR, 1H NMR as well as mass spectral data of final products are presented.
Chemical and 13C NMR Studies of a Rhamnoarabinogalactan from the Leaves of Plantago lanceolata L. var. libor
Authors: Kardošová Alžbeta , Capek Peter
Published: July 2002

A rhamnoarabinogalactan isolated from the leaves of Plantago lanceolata L. var. libor has been investigated by methylation analysis, partial hydrolysis, and 13C NMR spectroscopy. The structural conclusions obtained by 13C NMR measurements were consistent with the data from methylation analysis. The polysaccharide has a β-(1→6)-D-galactan core branched on O-3 by side chains of (1→5)-linked α-L-arabinofuranosyl units, some of which bear in position O-5 terminal β-D-galactopyranosyl residues. L-Rhamnose occurs as nonreducing ends.
The Synthesis of the Molecular Sieve Cloverite in the Presence of Heteroatoms
Authors: Zubowa Heide-Lore , Schreier Ellen , Jancke Karin , Steinike Ursula , Fricke Rolf
Published: July 2002

Various cloverite samples containing a series of heteroatoms have been synthesized at optimized HF : Ga2O3 ratios and characterized by XRD, adsorption measurements, infrared and ESR spectroscopy. The results show that the pure cloverite structure is only formed in the presence of Ti, Si, Zn, and Mg ions. However, no real evidence can be given for an isomorphous substitution of phosphorus or gallium by the heteroatoms. Conditions for the storage of detemplated cloverite samples are given, which avoid amorphization under the influence of moisture.
Thieno[3,2-b]benzofuran - Synthesis and Reactions
Authors: Váchal Petr , Pihera Pavel , Svoboda Jiří
Published: July 2002

Thieno[3,2-b]benzofuran was synthesized starting from benzo[b]furan-3(2H)-one or benzo[b]furan-2-carbaldehyde. Electrophilic substitution reactions such as bromination, formylation, acetylation or nitration, take place in position 2. An electron donating group in position 2 directs further electrophilic substitution into positions 3 and 6, whereas compounds with an electron acceptor in position 2 are substituted exclusively in position 6. Metallation with butyllithium took place in position 2. The 1H and 13C NMR signals of the title compound were fully assigned.
Purine Nucleoside Analogues. 11. An Alternative Synthesis of N- and O-Alkyl Derivatives of 9- and 7-[(2-Acetoxyethoxy)methyl]-N2-acetylguanine
Authors: Madre Marina , Panchenko Natella , Golbraikh Alexander , Zhuk Regina , Pandit Upendra K. , Geenevasen Jan , Koomen Gerrit-Jan
Published: July 2002

Alkylations of 9- and 7-[(2-acetoxyethoxy)methyl]-N2-acetylguanine with alkyl halogenides in the presence of base have been investigated affording a new route to the preparation of 1,N2-dimethyl- as well as O6-benzyl-9(7)-alkoxyalkylguanines. 1H NMR spectra revealed that the 1,N2-dimethyl derivatives exist as mixtures of two conformers at room temperature due to the restricted rotation about the C2-N2 bond. These findings agreed with conformational calculations.
QSPR and QSAR Models Derived Using Large Molecular Descriptor Spaces. A Review of CODESSA Applications
Authors: Karelson Mati , Maran Uko , Wang Yilin , Katritzky Alan R.
Published: July 2002

An overview on the development of QSPR/QSAR equations using various descriptor-mining techniques and multilinear regression analysis in the framework of the CODESSA (Comprehensive Descriptors for Structural and Statistical Analysis) program is given. The description of the methodologies applied in CODESSA is followed by the presentation of the QSAR and QSPR models derived for eighteen molecular activities and properties. The properties cover single molecular species, interactions between different molecular species, properties of surfactants, complex properties and properties of polymers. A review with 54 references.
Kinetics and Mechanism of the Formation and Decomposition of Imidazolin-4-ones from 2-(N-Benzoylamino)alkanamides in Aqueous Medium
Authors: Sedlák Miloš , Hanusek Jiří , Bína Radim , Kaválek Jaromír , Macháček Vladimír
Published: July 2002

The cyclization reactions of substituted 2-(N-benzoyl-N-methyl)aminoalkanamides 1a-1g have been studied in aqueous medium. The Hammett reaction constant is ρ = 1.4 for the cyclization reactions of compounds 1a-1e in sodium hydroxide solutions. 2-[N-Methyl- N-(4-nitrobenzoyl)amino]-2-(4-nitrophenyl)propanamide (1g) is cyclized to imidazolinone 2g in aqueous amine buffers of pH 9-11.5; the reaction is subject to specific base catalysis in these media, and the rate-limiting step is the formation of a tetrahedral intermediate. In sodium hydroxide solution, the primary cyclization product is hydrolyzed to give an intermediate M which is subsequently decomposed to sodium 4-nitrobenzoate and 2-methylamino- 2-(4-nitrophenyl)propanamide. At low sodium hydroxide concentration, the rate-limiting step of the opening of imidazoline ring of compound 2g is non-catalyzed decomposition of the intermediate. At higher sodium hydroxide concentrations, the other reaction path begins to make itself felt: hydroxide-ion-catalyzed decomposition of the intermediate. The dependence of observed rate constant of cyclization of compound 1f on sodium hydroxide concentration was used to determine kinetically the value of pKa = 13.5 ± 0.1. The kinetic deuterium isotope effect of cyclization of compounds 1f giving 2f (kCH/kCD = 1.7) was determined in solutions of NaOD in D2O.
Synthesis of Some Steroidal Oxazolines
Authors: Wölfling János , Mernyák Erzsébet , Sebők Melinda , Schneider Gyula
Published: July 2002

Steroidal oxazolines 4a-4d and 5a-5f were synthesized. The acid-catalyzed reactions of 21-azido-20-hydroxy- and 21-hydroxy-20-azidosteroids with substituted aromatic aldehydes led to the formation of androst-5-en-3β-ols substituted in position 17β with oxazoline residues.
Effects of physical training in asthma: a systematic review
Authors: Ram Felix S F , Robinson Stewart M , Black Peter N
Published: July 2002

Objectives—To assess the evidence for the effects of physical training on pulmonary function, symptoms, cardiopulmonary fitness, and quality of life in subjects with asthma.

Methods—A search was conducted for randomised controlled trials of subjects with asthma undertaking physical training using the Cochrane Airways Group register of controlled clinical trials, Medline, Embase, Sportdiscus, Science citation index, and Current contents index. Studies were included in the review if the subjects had asthma, were 8 years of age or older, and had undertaken physical training for at least 20 minutes per session, twice a week, for a minimum of four weeks. The eligibility of trials for inclusion in the review and the quality of the trials were independently assessed by two reviewers.

Results—Eight studies with a total of 226 subjects met the inclusion criteria for this review. Physical training had no effect on resting lung function but led to an improvement in cardiopulmonary fitness as measured by an increase in maximum oxygen uptake of 5.6 ml/kg/min (95% confidence interval 3.9 to 7.2). None of the studies measured quality of life.

Conclusions—Physical training improves cardiopulmonary fitness without changing lung function. It is not clear if the improvement in fitness translates into a reduction in symptoms or an improvement in the quality of life. There is a need for further randomised controlled trials of the effects of physical training in the management of asthma.
Effects of Helicobacter pyloriinfection on gastric acid secretion and serum gastrin levels in Mongolian gerbils
Authors: Takashima M , Furuta T , Hanai H , Sugimura H , Kaneko E
Published: July 2002

BACKGROUND AND AIMS

Body gastritis caused by Helicobacter pylori infection appears to inhibit gastric acid secretion. The aim of this study was to determine the effects ofH pylori infection on gastric acid secretion and clarify its mechanisms with reference to interleukin 1β (IL-1β).

METHODS

(1) Mongolian gerbils were inoculated orally with H pylori. Before, six, and 12 weeks after inoculation, serum gastrin levels, gastric acid output, and IL-1β mRNA levels in the gastric mucosa were determined. Pathological changes were also determined according to the updated Sydney system. (2) Effects of recombinant human IL-1 receptor antagonist (rhIL-1ra) on gastric acid output and serum gastrin levels were also determined.

RESULTS

(1) Scores for activity and inflammation of gastritis and serum gastrin levels were significantly increased, and gastric acid output was significantly decreased six and 12 weeks after inoculation withH pylori. IL-1β mRNA levels in the gastric mucosa were also elevated six and 12 weeks after inoculation withH pylori. (2) Acid output and serum gastrin levels in the infected groups returned to control levels after rhIL-1ra injection.

CONCLUSIONS

Gastric acid secretion is decreased and serum gastrin levels are increased in Mongolian gerbils infected with H pylori. This change in gastric acid secretion appears to be mediated by IL-1β induced by H pylori infection.
Sequences in the NS5A protein of hepatitis C virus and the serum alanine aminotransferase response to interferon therapy in Japanese patients
Authors: Nagayama K , Enomoto N , Izumi N , Kurosaki M , Miyasaka Y , Watanabe H , Itakura J , Chen C-H , Tazawa J , Hoshino Y , Ikeda T , Marumo F , Sato C
Published: July 2002

BACKGROUND AND AIMS

Chronic hepatitis C is a slowly progressive disease and eventually causes hepatocellular carcinoma in many patients. Although interferon (IFN) therapy has been used for viral eradication, its success rate is only about 30%. In patients in whom it has failed (non-responders), there are several patterns of serum alanine aminotransferase (ALT) values, and detection of serum HCV-RNA during and after IFN therapy and improved long term prognosis were reported in patients whose serum ALT values were normalised by IFN therapy even if HCV viraemia persisted. The present study sought to clarify the virological characteristics contributing to these differences.

METHODS

Complete or partial length dominant sequences of hepatitis C virus genotype 1b (HCV-1b) were determined by direct sequencing. Firstly, the complete sequences of HCV-1b genomes were determined in six non-responders; three showed normalisation of serum ALT values during IFN-α therapy and the other three did not. Subsequently, the amino acid residues that were different in the two groups were further analysed retrospectively in another 82 patients.

RESULTS

Comparison of the sequences suggested an association between amino acids 2154–2172 of HCV-1b and serum ALT normalisation. A retrospective analysis of 82 patients revealed that the number of amino acid substitutions in this region was the only statistically significant variable associated with ALT normalisation (odds ratio 31.0; 95% confidence interval 5.0–286) in multivariate analyses.

CONCLUSIONS

A HCV genomic region that correlates with the ALT response to IFN therapy appears to be present in virologically IFN ineffective patients.
Ethics consultation on demand: concepts, practical experiences and a case study
Authors: Reiter-Theil Stella
Published: July 2002

Despite the increasing interest in clinical ethics, ethics consultation as a professional service is still rare in Europe. In this paper I refer to examples in the United States. In Germany, university hospitals and medical faculties are still hesitant about establishing yet another “committee”. One of the reasons for this hesitation lies in the ignorance that exists here about how to provide medical ethics services; another reason is that medical ethics itself is not yet institutionalised at many German universities. The most important obstacle, however, may be that medical ethics has not yet demonstrated its relevance to the needs of those caring for patients.

The Centre for Ethics and Law, Freiburg, has therefore taken a different approach from that offered elsewhere: clinical ethics consultation is offered on demand, the consultation being available to clinician(s) in different forms.

This paper describes our experiences with this approach; practical issues are illustrated by a case study.
The paediatrician and the rabbi
Authors: Shuper Avinoam , Zeharia Avraham , Balter-Seri Judy , Steier David , Mimouni Marc
Published: July 2002

Objectives—During recent decades, rabbis in Israel have been playing an increasing role in the consultation of patients or their families on medical issues. The study was performed to determine the attitude of physicians to rabbinical consultation by parents of sick children for purposes of basic medical decision making.

Design and setting–A questionnaire was prepared which contained questions regarding physicians' reactions to specific medical situations as well as their demographic data. The study participants included all the available physicians who were employed in the study period at one tertiary medical centre in Israel, which is not associated with any religious organisation. The questionnaire was presented personally to all of the physicians who were available for the study.

Results–Between 63% and 77% of the respondents were accepting of rabbinical consultation in regard to medical decisions. Nevertheless, in cases of divergence from accepted medical practice and in emergencies, almost all stated they would take measures to resist the rabbi's advice. This attitude did not correlate with the physician's age, religious status or experience in medicine.

Conclusions–Israeli physicians respect rabbis' suggestions in the area of medical decision making, though they would not let a rabbi's advice interfere with their decisions if they believed the rabbi's opinion went against medical need. In order to prevent an untoward effect of the rabbinical involvement in medicine, rules should be set to establish norms for rabbi-physician collaboration.
It's only love? Some pitfalls in emotionally related organ donation
Authors: Biller-Andorno Nikola , Schauenburg Henning
Published: July 2002

Transplanting organs from emotionally related donors has become a fairly routine procedure in many countries. However, donors have to be chosen carefully in order to avoid not just medically, but also morally, questionable outcomes. This paper draws attention to vulnerabilities that may affect the voluntariness of the donor's decision. Suggestions are made as to how to approach the evaluation and selection of potential donors.
The ethics of surgery in the elderly demented patient with bowel obstruction: Table 1
Authors: Gallagher P , Clark K
Published: July 2002

Objective: Little has been written in the medical literature concerning the ethics of treatment of the elderly demented patient with bowel obstruction. It is one example of the issues with which we are becoming increasingly involved. We conducted a survey of our colleagues' opinions to determine current practice.

Design: A postal questionnaire study (62% response rate). Questions were posed that related to a case scenario of an elderly demented patient presenting with a presumed sigmoid volvulus.

Setting: The northern region of England.

Participants: Thirty seven surgical members of the Association of Coloproctology of Great Britain and Ireland, Northern Chapter.

Results: Sixty five per cent of respondents felt that surgery would be inappropriate, and 26% that any intervention at all upon the subject in the case scenario would be inappropriate. More would operate, however, at the request of relatives. An advance directive not to treat would be respected by 70% despite a relative's wishes.

Conclusions: Overall there was a wide variation in the approach of the surgeons to a demented patient with bowel obstruction. In an era of clinical governance, and an increased awareness of the ethics of consent, this study presents one example of the difficult decisions with which we are increasingly faced. The greater use of advance directives may provide one possible solution.
Depression and competence to refuse psychiatric treatment
Authors: Rudnick A
Published: July 2002

Individuals with major depression may benefit from psychiatric treatment, yet they may refuse such treatment, sometimes because of their depression. Hence the question is raised whether such individuals are competent to refuse psychiatric treatment. The standard notion of competence to consent to treatment, which refers to expression of choice, understanding of medical information, appreciation of the personal relevance of this information, and logical reasoning, may be insufficient to address this question. This is so because major depression may not impair these four abilities while it may disrupt coherence of personal preferences by changing them. Such change may be evaluated by comparing the treatment preferences of the individual during the depression to his or her treatment preferences during normal periods. If these preferences are consistent, they should be respected. If they are not consistent, or past treatment preferences that were arrived at competently cannot be established, treatment refusal may have to be overridden or ignored so as to alleviate the depression and then determine the competent treatment decision of the individual. Further study of the relation between depression and competence to refuse or consent to psychiatric treatment is required.
Incidence of cancer among workers exposed to vinyl chloride in polyvinyl chloride manufacture
Authors: Langård S , Rosenberg J , Andersen A , Heldaas S S
Published: July 2002

Based on results from two previous studies where an excess of melanomas was found in a cohort of workers exposed to vinyl chloride (VCM), a follow up of the incidence of cancer in the same cohort of 428 workers was carried out to scrutinise whether or not the excess could be confirmed by new cases. The total number of deaths in the study group from 1953 to the end of 1993 was 132v141 expected, and the total number of incident cancer cases was 56v57 expected. There were 11 cases of lung cancerveight expected, seven cases of melanomasv2.07 expected, and two cases of thyroid cancerv0.34 expected. Five of the seven melanoma cases had occurred in the group that had been most heavily exposed to VCMv0.7 expected. In the present follow up we also found five cases of the spinocellular cancer of the skinv1.7 expected. Out of these five cases four were diagnosed after 1984. Two of the five casesv0.7 expected had occurred in the most heavily exposed group. The total number of skin cancers (melanomas and spinocellular cancers) were 12v3.7 expected. There was one new case of melanoma between 1985 and 1993v0.7 expected. Hence, the strength of the relation between the observed and expected number of cases was reduced compared with the last follow up, and does not strengthen the previously indicated causal relation between exposure to VCM and development of malignant melanoma. There was no excess of testicular cancers in this study. The present results may indicate that occurrence of spinocellular skin cancer could bear some relation to work in the manufacture of polyvinyl chloride (PVC). Confirmation is needed from studies on other cohorts exposed to VCM.
Occupational accidents aboard merchant ships
Authors: Hansen H L , Nielsen D , Frydenberg M
Published: July 2002

Objectives: To investigate the frequency, circumstances, and causes of occupational accidents aboard merchant ships in international trade, and to identify risk factors for the occurrence of occupational accidents as well as dangerous working situations where possible preventive measures may be initiated.

Methods: The study is a historical follow up on occupational accidents among crew aboard Danish merchant ships in the period 1993–7. Data were extracted from the Danish Maritime Authority and insurance data. Exact data on time at risk were available.

Results: A total of 1993 accidents were identified during a total of 31 140 years at sea. Among these, 209 accidents resulted in permanent disability of 5% or more, and 27 were fatal. The mean risk of having an occupational accident was 6.4/100 years at sea and the risk of an accident causing a permanent disability of 5% or more was 0.67/100 years aboard. Relative risks for notified accidents and accidents causing permanent disability of 5% or more were calculated in a multivariate analysis including ship type, occupation, age, time on board, change of ship since last employment period, and nationality. Foreigners had a considerably lower recorded rate of accidents than Danish citizens. Age was a major risk factor for accidents causing permanent disability. Change of ship and the first period aboard a particular ship were identified as risk factors. Walking from one place to another aboard the ship caused serious accidents. The most serious accidents happened on deck.

Conclusions: It was possible to clearly identify work situations and specific risk factors for accidents aboard merchant ships. Most accidents happened while performing daily routine duties. Preventive measures should focus on workplace instructions for all important functions aboard and also on the prevention of accidents caused by walking around aboard the ship.
Acute myoedema: an unusual presenting manifestation of hypothyroid myopathy
Authors: Bhansali A , Chandran V , Ramesh J , Kashyap A , Dash R J
Published: July 2002

We describe a patient with primary hypothyroidism due to autoimmune thyroiditis, presenting with acute myoedema and spontaneous rhabdomyolysis. During his hospital stay, he developed altered sensorium due to hypo-osmolal hyponatraemia and later developed bilateral foot drop that responded to appropriate treatment.
Trends in the smoking habits of young adults with diabetes
Authors: MacFarlane I , Gill G , Grove T , Wallymahmed M
Published: July 2002

OBJECTIVES

To examine changes in the prevalence of smoking in young adult diabetic patients between 1990 and 1999.

SETTING

Walton Diabetes Centre, University Hospital Aintree, Liverpool, UK.

DESIGN

Direct questioning as well as the urinary cotinine:creatinine ratio were used to assess the smoking habits of 99 young type 1 diabetic patients in 1991 (mean age 21.5 years, duration of diabetes 7.3 years), and in 112 similar patients in 1999 (mean age 23.4 years, duration of diabetes 9.6 years).

RESULTS

The admitted smoking rate was 31/99 (31%) in 1990 compared with 31/112 (28%) in 1999 (not significant). However, in 1990 there were an additional 17 “covert” smokers (patients who denied smoking, but had an unequivocally raised urinary cotinine:creatinine ratio), but only three in 1999 (p<0.05). This gave a corrected validated smoking rate of 48/99 (48%) in 1990 and 34/112 (30%) in 1999, representing a significant fall (p<0.02).

CONCLUSION

Smoking rates in young type 1 diabetic patients appear to have fallen during the last decade, and reporting of smoking behaviour is now more honest.
Japanese viral encephalitis
Authors: Tiroumourougane S V , Raghava P , Srinivasan S
Published: July 2002

One of the leading causes of acute encephalopathy in children in the tropics is Japanese encephalitis (JE). Transmitted by the culex mosquito, this neurotropic virus predominately affects the thalamus, anterior horns of the spinal cord, cerebral cortex, and cerebellum. It mainly affects children <15 years and is mostly asymptomatic. The occasional symptomatic child typically presents with a neurological syndrome characterised by altered sensorium, seizures, and features of intracranial hypertension. Aetiological diagnosis is based on virus isolation or demonstration of virus specific antigen or antibodies in the cerebrospinal fluid/blood. Though no antiviral drug is available against JE, effective supportive management can improve the outcome. Control of JE involves efficient vector control and appropriate use of vaccines.
Why does smoking so often produce dependence? A somewhat different view
Authors: Hughes John R
Published: July 2002

The usual explanation for why smoking produces dependence focuses on the effects of nicotine on dopamine and other neurobiological explanations. This review offers four somewhat different explanations: (1) nicotine can offer several psychopharmacological benefits at the age when such benefits are especially needed; (2) cigarettes provide for a rapid, frequent, reliable and easy-to-obtain reward; (3) nicotine is not intoxicating, allowing chronic intake; and (4) the long duration of the nicotine withdrawal syndrome effectively undermines cessation. This article reviews the evidence for the above views and the tobacco control activities these views suggest.
Comparison of physician based reporting of tobacco attributable deaths and computer derived estimates of smoking attributable deaths, Oregon, 1989 to 1996
Authors: Thomas Ann R , Hedberg Katrina , Fleming David W
Published: July 2002

BACKGROUND

Tobacco use prevention programmes need accurate information about smoking related mortality. Beginning in 1989, Oregon began asking physicians to report on death certificates whether tobacco use contributed to the death.

OBJECTIVE

To determine the long term comparability of this method of estimating tobacco attributable mortality to estimates of smoking attributable mortality derived from a computer model.

DESIGN

For the period 1989 to 1996, we compared mortality resulting from tobacco use reported by Oregon physicians to estimates of smoking attributable deaths (SADs) derived by “Smoking attributable mortality, morbidity and economic costs” software version 3.0 (SAMMEC 3.0), a widely used software program that estimates SADs on the basis of smoking prevalence and relative risks of specific diseases among current and former smokers.

MAIN OUTCOME MEASURES

Numbers of deaths, age, sex, and category of disease.

RESULTS

Of 212 448 Oregon deaths during 1989–1996, SAMMEC 3.0 estimated that 42 778 (20.1%) were attributable to cigarette smoking. For the same 27 diagnoses, physicians reported that tobacco contributed to 42 839 (20.2%) deaths—a cumulative difference of only 61 deaths over the eight year period. The age and sex distributions of tobacco and smoking attributable deaths reported by the two systems were also similar. By category of disease, the ratio of SAMMEC 3.0 estimates to physician reported deaths was 1.11 for neoplasms, 0.88 for heart disease, and 1.04 for respiratory disease.

CONCLUSIONS

Physician reporting provides comparable estimates of smoking attributable mortality and can be a valuable source of data for communicating the risks of tobacco use to the public.
The effects of salt, manganese, and density on life history traits in Hesperis matronalis L. from oldfield and roadside populations
Authors: Rothfels Carl J , Beaton Laura L , Dudley Susan A
Published: July 2002

Plant communities in the verges of major roadways (roadsides) are similar to those of abandoned farm fields undergoing succession (oldfields). However, roadsides are subject to distinctive stresses. Here, we look at local adaptation in Hesperis matronalis L. to salinity and manganese (Mn). Plants collected from three roadside and three oldfield populations were grown in a greenhouse under controlled, high-salinity, and high-Mn conditions, and several life history traits were measured. In addition, we imposed a density treatment after vernalization. Mortality was high in both the salt (43% survival) and Mn treatments (53% survival) compared with the control (71% survival). Distinct family, population, and site variation was found in measures of plant size. There were also family-level differences in response to soil treatments. However, none of our results were consistent with local adaptation. In general, larger plants were more likely to bolt, and oldfield plants were less likely to bolt than roadside plants in all treatments (in the low-density treatment, 56% of roadside plants had bolted compared with only 16% of oldfield plants). We found that the high-density treatments resulted in earlier bolting and longer internodes, a result consistent with the shade avoidance hypothesis.Key words: biennial, salinity, phenotypic plasticity, heavy metal, local adaptation.
Recruitment overfishing in a bivalve mollusc fishery: hard clams (Mercenaria mercenaria) in North Carolina
Authors: Peterson Charles H
Published: July 2002

Because of their high fecundity, marine invertebrate fisheries are rarely considered at risk to recruitment overfishing. This presumption can be criticized on population theoretic grounds and conflicts with growing evidence of recruitment limitation in a variety of marine invertebrate populations. Sampling in 11 years spanning a 24-year period from 1978 to 2001 reveals that hard clam (Mercenaria mercenaria (L.)) recruitment declined significantly by 6572% within the fishing grounds of central North Carolina. This 24-year period began when high demand and prices drove increased clamming effort. Accordingly, landings grew rapidly 5-fold, a yield that was not sustained and subsequently fell by over 50% from 1983 to 2000. Fishery-independent sampling repeated identically in three representative habitats demonstrates declines of 17, 79, and 95% in hard clam density and of 24, 46, and 83% in spawning stock biomass during the 18+ years of 19801997. Small-scale experiments and measurements in depleted habitats show no compensatory enhancement of hard clam recruitment with local reduction in adult density. Consequently, the hard clam in North Carolina serves as perhaps the most compelling example of unsustainable fishing mortality leading to recruitment overfishing in a bivalve mollusc stock. Spawner sanctuaries could serve to restore and protect spawning stock biomass in this and other invertebrate fisheries.
Structureactivity relationship on (±)-nantenine derivatives in antiserotonergic activities in rat aorta
Authors: Indra Bachtiar , Matsunaga Kimihiro , Hoshino Osamu , Suzuki Masaji , Ogasawara Hiromichi , Ishiguro Masaji , Ohizumi Yasushi
Published: July 2002

A series of nine (±)-nantenine derivatives were synthesized and assayed for their pharmacological activities by using tension in aorta and binding experiments in rat brain membrane. Replacing a methyl group with a hydrogen ((±)-nornantenine) and an ethyl group at a nitrogen atom ((±)-ethylnornantenine) or introducing a hydroxyl group at the α/β position of C-4 or displacement of a methoxy moiety at the C-1 position with a hydroxyl ((±)-domesticine) of (±)-nantenine decreased the affinity. Moreover, changing a methyl group of (±)-domesticine to hydrogen at a nitrogen atom ((±)-nordomesticine) caused loss of the activities. These results suggest that a methyl group at a nitrogen atom and a methoxy moiety at C-1 play important roles in the development of the antiserotonergic activity. Molecular modeling analysis of the interaction between the 5-HT2A receptor and (±)-nantenine suggested that electron lone pairs of N-6 and of the oxygen atom of the methoxy group at C-1 are important in forming a hydrogen bond to Asp155 and Asn343 of the 5-HT2A receptor, respectively.Key words: antiserotonergic activity, (±)-nantenine derivative, SAR, molecular modeling.
CLOSURE PROPERTY OF PROBABILISTIC TURING MACHINES AND ALTERNATING TURING MACHINES WITH SUBLOGARITHMIC SPACES
Authors: HARVÁTH GÉZA , INOUE KATSUSHI , ITO AKIRA , WANG YUE
Published: July 2002

This paper first shows that

(1) the class of languages recognized by o(log n) space-bounded two-way Monte Carlo Turing machines is not closed under concatenation, Kleene closure, and length-preserving homomorphism, and

(2) the class of languages recognized by o(log log n) space-bounded two-way unbounded error probabilistic Turing machines is not closed under each of the above operations.

We then show that the class of languages accepted by S(n) space-bounded two-way alternating Turing machines is not closed under each of the above operations for log log n ≤ S(n) ≤ o(log n).
GEOMETRY AND ACTION-ANGLE VARIABLES OF MULTI SOLITON SYSTEMS
Authors: FUCHSSTEINER BENNO , OEVEL GUDRUN
Published: July 2002

For all completely integrable nonlinear hamiltonian systems which have a localized hereditary recursion operator, a complete action-angle variable representation is given for the multisoliton manifolds. Here multisoliton manifolds are defined as reductions with respect to suitable linear sums of symmetry generators. The embedding of these multisoliton manifolds, into the manifold of all solutions, is described in terms of the construction of its tangent bundle. The basis vectors of the respective tangent spaces are given by local densities. This local geometrical description of the tangent bundle turns out to be independent of the special structure of the particular equation under consideration. The principal tool for finding the necessary geometrical quantities are the canonical commutation relations for the so called mastersymmetries. These relations reflect the hereditary structure. All mastersymmetries turn out to be elements of the tangent space. Although the mastersymmetries, in the case under consideration, principally cannot be hamiltonian, suitable integrating factors are found which make them hamiltonian on the reduced manifold. So, up to suitable linear combinations, the mastersymmetries are shown to correspond to the angle variables. The action-angle-structure found in this way is put into one-to-one correspondence with the spectrum of the recursion operator. The spectrum of this operator is shown to be of multiplicity two and all its eigenvectors are explicitly constructed. Again, this construction is of a canonical nature, i.e., independent of the particular equation under consideration. For vanishing boundary conditions the given action-angle-structure is compared to the asymptotic data (speeds and phases), and the gradients of these global asymptotic data are given in terms of local quantities. It turns out that for all times during the evolution the derivatives of the field function with respect to any particular asymptotic datum yields an eigenvector of the recursion operator. Thus a method is given for reconstructing the spectral resolution of the recursion operator by partial derivatives. This method yields new methods of solution for other equations (for example the singularity equation and the Harry Dym equation). The superposition formula for phase shifts is shown to hold in all generality for the systems under consideration. Several examples are given. An extensive comparison of the present results with the work of others is carried out.