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At least 1,099 records · Page 61Linked to original sources
PubMed2002

Early defect in the expression of mouse sperm DNAJ 1, a member of the DNAJ/heat shock protein 40 chaperone protein family, in the spinal cord of the wobbler mouse, a murine model of motoneuronal degeneration.

Prevention of protein misfolding is ensured by chaperone proteins, including the heat shock proteins (HSP) of the DNAJ/HSP40 family. Detection of abnormal protein aggregates in various neurodegenerative diseases has led to the proposal that altered chaperone activity contributes to neurodegeneration. Msj-1, a DNAJ/HSP40 protein located around the spermatozoa acrosome, was recently found to be down-regulated in the testis of wobbler mutant mice. Wobbler is an unidentified recessive mutation which triggers progressive motoneuron degeneration with abnormal intracellular protein accumulations, and defective spermatozoa maturation. Here, we examined Msj-1 expression in the spinal cord of the mutants and their controls. Msj-1 transcripts were amplified by reverse transcription-polymerase chain reaction from mutant and wild-type spinal cord RNA. Sequencing of Msj-1 coding region revealed no change in the mutant. In contrast, decreased Msj-1 mRNA levels were observed in five to six-week-old wobbler mice spinal cord, when motoneuron degeneration is at its apex, as compared to controls. A similar decrease was observed in two-week-old wobbler spinal cord, when the number of motoneurons is still unaltered, indicating that the decreased mRNA content is intrinsic to the mutant and not simply related to the loss of cells expressing Msj-1. Assays of Msj-1 protein levels yielded similar results. Immunofluorescent labeling revealed numerous Msj-1-ir motoneurons in five-week-old control spinal cord while no signal was observed in age-matched wobbler. Our results show, therefore, that Msj-1 expression is down-regulated in both organs affected by the wobbler mutation, the CNS and the testis, and that this defect precedes the first histological signs of motoneuron degeneration. These results provide the first example of an association between transcriptional repression of a chaperone protein and a neurodegenerative process.

Animals↗
PubMed2002

Analysis of gene expression with cDNA microarrays in rat brain after 7 and 42 days of oral lithium administration.

The gene expression profile in rat brain was examined using microarrays in rats fed lithium chloride for 7 days (subacute) or 42 days (chronic). Brain lithium concentrations were 0.39 mM and 0.79 mM (therapeutically relevant), at 7 and 42 days, respectively. Of the 4132 genes represented in the microarrays, 25 genes were downregulated by at least twofold and none was upregulated after 7 days of treatment. Expression of 50 genes was downregulated by at least two-fold at 42 days, without any being upregulated. Lithium treatment for 7 days did not affect at a measurable extent expression of 37 of the 50 genes that were downregulated at 42 days. Genes whose expression was changed at 42 days coded for a number of receptors, protein kinases, transcription and translation factors, markers of energy metabolism, and signal transduction. Thus, chronic lithium at a therapeutically relevant concentration reduced expression of a large number of genes involved in multiple signaling and other pathways, without increasing expression at a comparable extent.

Administration, Oral↗
PubMed2002

Metadata tables to enable dynamic data modeling and web interface design: the SEER example.

A wealth of information addressing health status, outcomes and resource utilization is compiled and made available by various government agencies. While exploration of the data is possible using existing tools, in general, would-be users of the resources must acquire CD-ROMs or download data from the web, and upload the data into their own database. Where web interfaces exist, they are highly structured, limiting the kinds of queries that can be executed. This work develops a web-based database interface engine whose content and structure is generated through interaction with a metadata table. The result is a dynamically generated web interface that can easily accommodate changes in the underlying data model by altering the metadata table, rather than requiring changes to the interface code. This paper discusses the background and implementation of the metadata table and web-based front end and provides examples of its use with the NCI's Surveillance, Epidemiology and End-Results (SEER) database.

Databases, Factual↗
PubMed1979

Isolation and characterization of multiple forms of ovine pancreatic deoxyribonuclease. Chromatograhpic behavior of the enzyme on concanavalin A-agarose and carboxymethylcellulose columns.

A new procedure has been devised for the purification of ovine DNase, including (NH/4)2SO4 fractionation, two steps of CM-cellulose chromatography, concanavalin A-agarose chromatography, and gel filtration on Sephadex G--100. The enzyme, like bovine DNase, exhibits multiplicity due to changes in the primary structure and the sugar structure of the carbohydrate moiety. Unlike bovine DNase, ovine DNase does not have sialic acid in any of its multiple forms. Concanavalin A-agarose is useful in the purification of not only ovine but also bovine DNase. For ovine DNase, it is a necessary and key step of purification; for bovine DNase, it can be used to purify commercial preparations of DNase free from proteases in a single step as judged by its stability in Ca2+-free media at pH 8.0. The purified enzyme has a specific activity equal to that of a highly purified DNase and presumably contains predominantly DNases A and C. Two of the four forms of ovine DNase have been purified to apparent homogeneity and subjected to chemical analysis. The present results show that bovine and ovine DNases have indistinguishable molecular weights and identical end groups, suggesting that they may have the same number of amino acid residues. The amino acid composition indicates that two enzymes may have six residues of amino acids subject to substitution which can be explained by single base changes in their genetic code words. Amino acid analyses also indicate that the most likely difference between two forms of ovine DNase is the substitution of Leu for Arg.

Amino Acids↗
PubMed1999

Cloning and characterization of the nuclear AC115 gene of Chlamydomonas reinhardtii.

The nuclear ac115 mutant of Chlamydomonas reinhardtii is specifically blocked in the synthesis of the chloroplast encoded D2 protein of the photosystem II reaction center at a point after translation initiation. Here, we report the identification of the AC115 gene through complementation rescue of the ac115 mutant strain, using an indexed cosmid library of Chlamydomonas genomic DNA. AC115 is a small, novel, intronless nuclear gene which encodes a protein of 113 amino acids. The amino terminal end of the Ac115 protein is rich in basic amino acids and has features which resemble a chloroplast transit sequence. A hydrophobic stretch of amino acids at the protein's carboxyl terminus is sufficiently large to be a membrane spanning or a protein/protein interaction domain. Various models are discussed to account for the mechanism by which Ac115p works in D2 synthesis. The ac115 mutant allele was sequenced and determined to be an A-to-T transversion at the first position of the fourth codon of the coding sequence. This mutation changes an AAG codon to a TAG nonsense codon and results in a null phenotype.

Algal Proteins↗
PubMed2000

Identification of a new HLA-DRB4 allele (DRB4*01033) by PCR-SSP and direct sequencing.

In this report, we describe the identification of a novel DRB4*01 allele, DRB4*01033, found in two Spanish Caucasian individuals. The new allele was detected during routine HLA typing by an unusual pattern of amplification obtained by polymerase chain reaction using sequence-specific primers (PCR-SSP) that did not match with any of the previously described DRB4 alleles. In order to establish the polymorphism responsible for this pattern exons 2 and 3 of the DRB4 locus were amplified and directly sequenced. The new DRB4*01 allele is identical to DRB4*0103101 except for a single nucleotide substitution in codon 78 (TAC-->TAT). This nucleotide change does not cause an amino acid change as both triplets code for a tyrosine.

Alleles↗
PubMed1998

Characterization of the geranylgeranyl transferase type I from Schizosaccharomyces pombe.

The Schizosaccharomyces pombe cwg2+ gene encodes the beta-subunit of geranylgeranyl transferase I (GGTase I), which participates in the post-translational C-terminal modification of several small GTPases, allowing their targeting to the membrane. Using the two-hybrid system, we have identified the cwp1+ gene that encodes the alpha-subunit of the GGTase I. cwp1p interaction with cwg2p was mapped to amino acids 1-244 or 137-294 but was not restricted to amino acids 137-244. The genomic cwp1+ was isolated and sequenced. It has two putative open reading frames of 677 and 218 bp, separated by a 51 bp intron. The predicted amino acid sequence shows significant similarity to GGTase I alpha-subunits from different species. However, complementation of Saccharomyces cerevisiae ram2-1 mutant by overexpressing the cwp1+ gene was not possible. Expression of both cwg2+ and cwp1+ in Escherichia coli allowed 'in vitro' reconstitution of the GGTase I activity. S. pombe cells expressing the mutant enzyme containing the cwg2-1 mutation do not grow at 37 degrees C, but the growth defect can be suppressed by the addition of sorbitol. Actin immunostaining of the cwg2-1 mutant strain grown at 37 degrees C showed an abnormal distribution of actin patches. The cwg2-1 mutation was identified as a guanine to adenine substitution at nucleotide 604 of the coding region, originating the change A202T in the cwg2p. Deletion of the cwg2 gene is lethal; delta cwg2 spores can divide two or three times before losing viability. Most cells have aberrant morphology and septation defects. Overexpression of the rho1G15VC199R double-mutant allele in S. pombe caused loss of polarity but was not lethal and did not render the (1-3)beta-D-glucan synthase activity independent of GTP. Therefore, geranylgeranylation of rho1p is required for the appropriate function of this GTPase.

Actins↗
PubMed2002

Competition between SsrA tagging and translational termination at weak stop codons in Escherichia coli.

SsrA is a tmRNA involved in tagging polypeptides on stalled ribosomes. The resulting fusion proteins are then degraded. We purified endogenous SsrA-tagged proteins by means of a genetically engineered SsrA and identified some of them. Analysis of the proteins suggested that they are tagged at their C-terminal extremities. One of them, ribokinase, is expressed from a messenger with a poorly efficient stop codon, leading to translational recoding events. A change in the ribokinase coding sequence from a weak to a strong translational stop sequence (UGAc to UAAu) annihilated SsrA tagging. Translational termination by UGA recruits the translational release factor (RF) 2. We observed that SsrA tagging of ribokinase was inversely correlated with RF2 activity, revealing a dynamic competition between translational termination and SsrA tagging.

Codon, Terminator↗
PubMed2003

A group II intron has invaded the genus Azotobacter and is inserted within the termination codon of the essential groEL gene.

A group II intron that was previously identified within Azotobacter vinelandii by polymerase chain reac-tion with consensus primers has been completely sequenced, together with its flanking exons. In contrast to other bacterial members of group II, which are associated with mobile or other presumably non-essential DNA, the A. vinelandii intron is inserted within the termination codon of the groEL coding sequence, which it changes from UAA to UAG. Both the host gene and the intron appear to be functional as (i) the ribozyme component of the intron self-splices in vitro and (ii) both intron-carrying and intronless versions of the single-copy groEL gene from A. vinelandii complement groEL mutations in Escherichia coli. Moreover, analysis of nucleotide substitutions within and around a closely related intron sequence that is present at the same site in Azotobacter chroococcum provides indirect evidence of intron transposition posterior to the divergence of the two Azotobacter taxa. Somewhat surprisingly, however, analyses of RNA extracted from cells that had or had not undergone a heat shock show that the bulk of groEL transcripts end within the first 140 nucleotides of the intron. These findings are discussed in the light of our current knowledge of the biochemistry of group II introns.

Azotobacter vinelandii↗
PubMed1997

Gene frequencies of the HPA-1 and HPA-2 platelet antigen alleles among the Amerindians.

BACKGROUND AND OBJECTIVES: Platelet-specific alloantigens are important in neonatal alloimmune thrombocytopenia, posttransfusion purpura, refractoriness to platelet transfusions, and population genetics. Data are scarce on allele frequencies in ethnic groups other than whites and Asians. MATERIALS AND METHODS: Using allele-specific restriction enzyme analysis, we studied the distribution of HPA-1 and HPA-2 alleles in six Brazilian Amazon tribes of Amerindians, belonging to five different language stocks. We compared these with the values obtained for blacks and whites. RESULTS: Only the HPA-1a allele was found among 132 Amerindian chromosomes, compared with a gene frequency of HPA-1b of 0.115 and 0.113, respectively, among blacks and whites. The frequency of HPA-2b among the Amerindians (0.042) is lower than that obtained for blacks and whites (0.148 and 0.100, respectively), and the lowest thus far observed in a population of Asian origin. CONCLUSION: Differences in DNA polymorphisms in Amerindian populations have not only anthropological and genetic interest, but also practical applications when they involve coding regions that may change the functional or immunologic features of the protein.

Alleles↗
PubMed2002

[Reasons for Hospital Treatment of Psychiatric Patients before and after the Opening of a Satellite Ward].

A satellite ward is a psychiatric ward at a general hospital settled within the catchment area that is administered by a psychiatric hospital. The objective of the satellite model is to approach community treatment on the one hand and somatic medicine on the other hand, consequently diminishing the threshold for hospital treatment. This study investigated whether the diagnostic, psychopathologic and social reasons for admissions changed from this catchment area due to the lower threshold of a satellite ward. The results were controlled with another catchment area's admissions to the 30 km distant psychiatric hospital. The opening of the satellite ward was followed by an 81 % increase of admissions. In particular, admissions of patients with neuroses and personality disorders were more frequent. There was no change of the severity code of psychopathology at admission. From the catchment area of the satellite ward less patients were admitted involuntarily whereas more admissions happened due to social reasons and after patients' own decision.

Adult↗
PubMedDate not supplied

[Psychotherapy within the prison system after the change of law].

The amendment of the law limiting the professional secrecy of physicians and psychologists toward the prison authorities has triggered a discussion on the consequences involved for treatment practice in the prison system. To reduce the lack of empirically based arguments in this discussion, our study deals with the question of whether and to what extent psychotherapy in conjunction with prison health care offers also contributions to preventing recidivism. A quasi-experimental control group study showed that especially for serious violent offenses delinquents of the Tegel detention center who underwent at least 20 hours of therapy at the psychotherapeutic consultation and treatment service had a markedly lower recidivism rate a mean of four years after release from prison than an untreated group. If changes in the penal code jeopardize a regular therapeutic setting with professional secrecy, they carry the risk of excluding prisoners primarily requiring psychotherapy who have thus far apparently also derived benefit especially from prevention-oriented therapy.

Adult↗
PubMed2006

Interdisciplinary pain therapy: an innovative therapeutic but pre-DRG Economical Center of Medical Excellence.

OBJECTIVE: After the implementation of the G-DRG system in Germany, doubts arose whether and how interdisciplinary pain therapy centers should be restructured to remain profitable and maintain medical excellence for patients with a long ordeal of malaise. METHODS: To reveal structural deficits, we performed a detailed economic analysis of all patients treated at an interdisciplinary pain therapy center of a German University hospital in 2004. RESULTS: 3,672 patients were treated: 2,163 outpatients, 753 at the daycare clinic, 619 as consults and 132 inpatients. The costs for personnel were euro 736,645, consumables euro 105,061, and infrastructure euro 277,762. We calculated fixed costs of euro 236, and consumables of euro 24 per patient. The costs for surgery were euro 1,595, and for a neuroradiological examination euro 245 per patient. Overall treatment costs were euro 319 per patient. We calculated an overall loss of euro 476,752 or euro 109.19 per patient. Outpatients caused a total loss of euro 456,665.83 or euro 211 per patient, consults a total loss of euro 161 683.16 or euro 261.20 per patient, daycare patients a slight profit of euro 30,370 or euro 40 per patient and inpatients a total profit of euro 111,225 or euro 135 per day. CONCLUSION: Managerial optimization can yield considerable cost reductions in the G-DRG coding system, without any change in treatment strategies, selection of profitable patients or dismissal of personnel. Inversely, additional personnel are needed to accomplish the implementation process. Board certification was unveiled to constitute the key structural implementation that ensures the economic survival of the department and continuing medical excellence for the patients.

Chronic Disease↗
PubMed1983

[Psychiatric and ethical aspects of the termination of pregnancy].

The progress in the diagnostic and the therapeutic possibilities of medicine, the amendment of articles 218 foll. StGB (= Penal Code), and a fundamental change in the attitude towards sexuality and abortion, on the background of the demand for free self-determination of the woman, have fundamentally changed the fields of medical activities and tasks, especially those of psychiatry, in ascertaining the indication for the legal termination of pregnancy and in giving advice in cases of pregnancy conflicts. By far the most terminations of pregnancy today are carried out on the basis of a social or a social predicament indication, for whose assessment the psychiatrist, as a rule, ist not competent. This functions should be stronger orientated towards giving advice and providing therapy in cases of pregnancy conflicts. Particular attention has to be payed to special aspects of contraception and negative psychic after-effects of an abortion. Psychiatric indications should only be accepted, in cases in which they can be substantiated clearly. All advisory and therapeutic measures have to serve the aim of furthering the freedom and autonomy of decision of the pregnant woman, of facilitating the solution of intrapsychic and ethical conflicts, thus making genuine responsibility realizable.

Abortion, Induced↗
PubMed1995

[Quantification of lymph node perfusion using color duplex ultrasonography].

PURPOSE: 20 parameters were defined to differentiate benign from malignant lymphadenopathy using computer assisted analysis of the lymph node perfusion demonstrated by colour Doppler flow imaging. MATERIAL AND METHODS: In 112 lymph nodes a computer assisted analysis of 10 consecutive colour Doppler flow sonograms was performed after digital data transfer to a work station. Planimetric results, the colour coded Doppler shift frequency, changes of the perfusion during the heart cycle and the perfusion in the adjacent tissue were analysed using 20 parameters. RESULTS: Discriminant analysis resulted in 7 parameters which reclassified correctly 82% of the lymph nodes (sensitivity 84%, specificity 80%). 72% of the lymph nodes could be classified in the three groups reactive lymphadenopathy, lymph node metastasis and malignant lymphoma. CONCLUSIONS: Clinically known subjective signs of malignancy (increased size, low echogenicity, alterations of the perfusion) can be analysed quantitatively to differentiate benign from malignant lymphadenopathy.

Diagnosis, Differential↗
PubMed1999

A limit in the processing of components in odour mixtures.

We investigated the hypothesis that physiological limitations restrict the ability of humans to identify components in an odour mixture. Subjects were trained to identify the test odours, and were required to detect a single highly familiar odorant in stimuli consisting of one, four, eight, twelve, and sixteen odorants by using a selective-attention procedure. The stimuli were delivered by a computer-controlled sixteen-channel air-dilution olfactometer which provided samples of each of the sixteen odorants to be of equal perceived intensity for each subject. Identification fell to chance level when sixteen odorants were present. It is proposed that the profound loss of information was primarily due to inhibition of olfactory receptor cells by the odorants through competitive mechanisms, and the subsequent loss of odour identity through changes in the spatial code that may be used to identify odorants.

Adolescent↗
PubMed2003

Large-scale comparison of intron positions in mammalian genes shows intron loss but no gain.

We compared intron-exon structures in 1,560 human-mouse orthologs and 360 mouse-rat orthologs. The origin of differences in intron positions between species was inferred by comparison with an outgroup, Fugu for human-mouse and human for mouse-rat. Among 10,020 intron positions in the human-mouse comparison, we found unequivocal evidence for five independent intron losses in the mouse lineage but no evidence for intron loss in humans or for intron gain in either lineage. Among 1,459 positions in rat-mouse comparisons, we found evidence for one loss in rat but neither loss in mouse nor gain in either lineage. In each case, the intron losses were exact, without change in the surrounding coding sequence, and involved introns that are extremely short, with an average of 200 bp, an order of magnitude shorter than the mammalian average. These results favor a model whereby introns are lost through gene conversion with intronless copies of the gene. In addition, the finding of widespread conservation of intron-exon structure, even over large evolutionary distances, suggests that comparative methods employing information about gene structures should be very successful in correctly predicting exon boundaries in genomic sequences.

Amino Acid Sequence↗
PubMed1989

Drosophila ninaA gene encodes an eye-specific cyclophilin (cyclosporine A binding protein).

Mutations in the ninaA gene of Drosophila severely reduce the amount of rhodopsin specifically in R1-6 photoreceptors. Isolation of the ninaA gene by chromosomal walking revealed that it is expressed only in the eye and encodes a 237-amino acid polypeptide that shows strong sequence similarity to cyclophilin, a putative molecular target for cyclosporine A, a potent immunosuppressant used in human organ transplantations. Unlike most cyclophilins characterized to date, the ninaA-encoded protein has a putative signal sequence and a transmembrane domain. Each of the three ehtyl methanesulfonate-induced ninaA mutant alleles analyzed shows a single nucleotide change in the mRNA coding region leading to either a nonsense or a missense mutation. We find no evidence that the ninaA-encoded protein is directly involved in phototransduction. The only detectable mutant phenotype that correlates with the severity of molecular defects in the three mutants is the amount of depletion of R1-6 rhodopsin. The above results and the recent findings that cyclophilin is a peptidylprolyl cis-trans-isomerase suggest that the ninaA-encoded protein may be required for proper folding and stability of R1-6 rhodopsin.

Amino Acid Sequence↗