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PubMed1990

Mapping light strand transcripts near the origin of replication of Xenopus laevis mitochondrial DNA.

Transcription of the light strand of Xenopus laevis mitochondrial DNA initiates at two promoters located approximately 350 to 450 nucleotides upstream from the 5' ends of major D-loop DNA strands. Small RNAs within this region have been mapped by blot hybridization, primer extension and S1 nuclease protection methods. The results reveal that the large majority of RNAs within this region have 3' termini located at a sequence element, designated CSB 2, that is conserved in sequence and position in Xenopus, mouse, rat and human mtDNA. However, the X. laevis CSB 2 appears to be a site of RNA processing only, since RNA-to-DNA transitions are not detectable at this site. RNAs containing sequences downstream of CSB 2 are extremely rare. A significant fraction of these RNAs are processed by cleavage at a site just upstream of the most predominant 5' ends of D-loop DNAs. We suggest that RNA processing at this site may play a role in priming mtDNA replication.

Animals↗
PubMed2000

Molecular characterization of an acidic region deletion mutant of Cockayne syndrome group B protein.

Cockayne syndrome (CS) is a human genetic disorder characterized by post-natal growth failure, neurological abnormalities and premature aging. CS cells exhibit high sensitivity to UV light, delayed RNA synthesis recovery after UV irradiation and defective transcription-coupled repair (TCR). Two genetic complementation groups of CS have been identified, designated CS-A and CS-B. The CSB gene encodes a helicase domain and a highly acidic region N-terminal to the helicase domain. This study describes the genetic characterization of a CSB mutant allele encoding a full deletion of the acidic region. We have tested its ability to complement the sensitivity of UV61, the hamster homolog of human CS-B cells, to UV and the genotoxic agent N-acetoxy-2-acetylaminofluorene (NA-AAF). Deleting 39 consecutive amino acids, of which approximately 60% are negatively charged, did not impact on the ability of the protein to complement the sensitive phenotype of UV61 cells to either UV or NA-AAF. Our data indicate that the highly acidic region of CSB is not essential for the TCR and general genome repair pathways of UV- and NA-AAF-induced DNA lesions.

Acetoxyacetylaminofluorene↗
PubMed2001

DNA sequence variation in the mitochondrial control region of red-backed voles (Clethrionomys).

The complete mitochondrial DNA (mtDNA) control region was sequenced for 71 individuals from five species of the rodent genus Clethrionomys both to understand patterns of variation and to explore the existence of previously described domains and other elements. Among species, the control region ranged from 942 to 971 bp in length. Our data were compatible with the proposal of three domains (extended terminal associated sequences [ETAS], central, conserved sequence blocks [CSB]) within the control region. The most conserved region in the control region was the central domain (12% of nucleotide positions variable), whereas in the ETAS and CSB domains, 22% and 40% of nucleotide positions were variable, respectively. Tandem repeats were encountered only in the ETAS domain of Clethrionomys rufocanus. This tandem repeat found in C. rufocanus was 24 bp in length and was located at the 5' end of the control region. Only two of the proposed CSB and ETAS elements appeared to be supported by our data; however, a "CSB1-like" element was also documented in the ETAS domain.

Animals↗
PubMed2003

Primary fibroblasts of Cockayne syndrome patients are defective in cellular repair of 8-hydroxyguanine and 8-hydroxyadenine resulting from oxidative stress.

Cockayne syndrome (CS) is a genetic human disease with clinical symptoms that include neurodegeneration and premature aging. The disease is caused by the disruption of CSA, CSB, or some types of xeroderma pigmentosum genes. It is known that the CSB protein coded by the CS group B gene plays a role in the repair of 8-hydroxyguanine (8-OH-Gua) in transcription-coupled and non-strand discriminating modes. Recently we reported a defect of CSB mutant cells in the repair of another oxidatively modified lesion 8-hydroxyadenine (8-OH-Ade). We show here that primary fibroblasts from CS patients lack the ability to efficiently repair these particular types of oxidatively induced DNA damages. Primary fibroblasts of 11 CS patients and 6 control individuals were exposed to 2 Gy of ionizing radiation to induce oxidative DNA damage and allowed to repair the damage. DNA from cells was analyzed using liquid chromatography/isotope dilution mass spectrometry to measure the biologically important lesions 8-OH-Gua and 8-OH-Ade. After irradiation, no significant change in background levels of 8-OH-Gua and 8-OH-Ade was observed in control human cells, indicating their complete cellular repair. In contrast, cells from CS patients accumulated significant amounts of these lesions, providing evidence for a lack of DNA repair. This was supported by the observation that incision of 8-OH-Gua- or 8-OH-Ade-containing oligodeoxynucleotides by whole cell extracts of fibroblasts from CS patients was deficient compared to control individuals. This study suggests that the cells from CS patients accumulate oxidatively induced specific DNA base lesions, especially after oxidative stress. A deficiency in cellular repair of oxidative DNA damage might contribute to developmental defects in CS patients.

Adenine↗
PubMed1992

A theory of care-seeking behavior.

Although much research has focused upon why people do and do not engage in recommended health behaviors, there is a need to develop more accurate theories to explain and predict engagement in health behaviors. Because health behaviors differ in important ways, it could be most fruitful to understand one type of health behavior, such as secondary prevention behavior. This paper proposes a theory of care-seeking behavior (CSB), based on a theory of general behavior by Triandis. Other popular theories about health behavior (i.e., Health Belief Model and Theory of Reasoned Action) also are reviewed. Empirical support for the variables identified in the theory of CSB is presented, drawing from the literature on secondary prevention for cancer. The theory of CSB is applied to the situation of seeking care for cancer symptoms. Directions for future research based upon this theory are delineated.

Health Behavior↗
PubMed1993

Transcription factor sigma B of Bacillus subtilis controls a large stationary-phase regulon.

Transcription factor sigma B of Bacillus subtilis is active during the stationary growth phase, but its physiological role remains unknown. Understanding the function and regulation of genes controlled by sigma B (csb genes) should provide important clues to sigma B function in stationary-phase cells. To this end, we used a genetic approach to identify six new csb genes. This strategy relies on two elements: (i) random transcriptional fusions between the Escherichia coli lacZ gene and genes on the B. subtilis chromosome, generated in vivo with transposon Tn917lacZ, and (ii) a plate transformation technique to introduce a null sigB mutation into the fusion-bearing recipients directly on indicator plates. This strategy allowed the comparison of fusion expression in strains that were isogenic save for the presence or absence of a functional sigma B protein. Beginning with 1,400 active fusions, we identified 11 that were wholly or partly controlled by sigma B. These fusions mapped to six different loci that exhibit substantial contrasts in their patterns of expression in the logarithmic and stationary growth phases, suggesting that they participate in diverse cellular functions. However, for all six loci, the sigma B-dependent component of their expression was manifest largely in the stationary phase. The high frequency of six independent csb loci detected in a random collection of 1,400 fusions screened, the fact that four of the six new loci were defined by a single fusion, and the absence of the previously identified ctc and csbA genes in the present collection strongly suggest that sigma B controls a large stationary-phase regulon.

Bacillus subtilis↗
PubMed1999

Transcription elongation and human disease.

Eukaryotic mRNA synthesis is catalyzed by multisubunit RNA polymerase II and proceeds through multiple stages referred to as preinitiation, initiation, elongation, and termination. Over the past 20 years, biochemical studies of eukaryotic mRNA synthesis have largely focused on the preinitiation and initiation stages of transcription. These studies led to the discovery of the class of general initiation factors (TFIIB, TFIID, TFIIE, TFIIF, and TFIIH), which function in intimate association with RNA polymerase II and are required for selective binding of polymerase to its promoters, formation of the open complex, and synthesis of the first few phosphodiester bonds of nascent transcripts. Recently, biochemical studies of the elongation stage of eukaryotic mRNA synthesis have led to the discovery of several cellular proteins that have properties expected of general elongation factors and that have been found to play unanticipated roles in human disease. Among these candidate general elongation factors are the positive transcription elongation factor b (P-TEFb), eleven-nineteen lysine-rich in leukemia (ELL), Cockayne syndrome complementation group B (CSB), and elongin proteins, which all function in vitro to expedite elongation by RNA polymerase II by suppressing transient pausing or premature arrest by polymerase through direct interactions with the elongation complex. Despite their similar activities in elongation, the P-TEFb, ELL, CSB, and elongin proteins appear to play roles in a diverse collection of human diseases, including human immunodeficiency virus-1 infection, acute myeloid leukemia, Cockayne syndrome, and the familial cancer predisposition syndrome von Hippel-Lindau disease. here we review our current understanding of the P-TEFb, ELL, CSB, and elongin proteins, their mechanisms of action, and their roles in human disease.

Acute Disease↗
PubMed1981

Arterial baroreceptor reflexes in young and old racing greyhounds.

The characteristics of the carotid sinus baroreceptor (CSB) reflex control of arterial pressure-flow relations were studied in young (18 mo) and old (10.5 yr) racing greyhounds anesthetized with chloralose. Pressure and flow were simultaneously measured in the ascending aorta, the celiac, superior mesenteric, renal, and iliac arteries under steady-state conditions of pulsatile perfusion of the isolated carotid sinuses before and after bilateral cervical vagotomy. Operating-point (OP) values of mean pressure were not significantly different between the young or old greyhounds, but OP values of cardiac output were lower and of peripheral resistance were higher in the older animals. OP values of regional resistances were higher in the older animals, but only those of the celiac and mesenteric beds were significantly different. Values of OP sensitivity of central hemodynamic variables were not decreased in the older animals. OP values of renal and iliac resistance sensitivity tended to be lower in the older animals. The overall range of control of the various hemodynamic variables by the CSB was lower in the older group only in the case of iliac resistance. The characteristics of the CSB were not uniformly depressed in the older animals but were relatively well maintained compared with those of the younger group.

Aging↗
PubMed2000

Time course of sleep-related breathing disorders in first-ever stroke or transient ischemic attack.

To investigate the prevalence and behavior of sleep-related breathing disorders (SRBDs) associated with a first-ever stroke or transient ischemic attack (TIA), we prospectively studied 161 consecutive patients admitted to our stroke unit. Complete neurological assessment was performed to determine parenchymatous and vascular localization of the neurological lesion. Stroke subtype was categorized as TIA, ischemic (IS), or hemorrhagic (HS). A portable respiratory recording (PRR) study was performed within 48-72 h after admission (acute phase), and subsequently after 3 mo (stable phase). During the acute phase, 116 patients (71.4%) had an apnea-hypopnea index (AHI) > 10 events/h and 45 (28%) had an AHI > 30. No relationships were found between sleep-related respiratory events and the topographical parenchymatous location of the neurological lesion or vascular involvement. Cheyne-Stokes breathing (CSB) was observed in 42 cases (26.1%). There were no significant differences in SRBD according to the stroke subtype except for the central apnea index (CAI). During the stable phase a second PRR was performed in 86 patients: 53 of 86 had an AHI > 10 and 17 of 86 had an AHI > 30. The AHI and CAI were significantly lower than those in the acute phase (16.9 +/- 13.8 versus 22.4 +/- 17.3 and 3.3 +/- 7.6 versus 6.2 +/- 10.2, respectively) (p < 0.05) while the obstructive apnea index (OAI) remained unchanged. CSB was observed in 6 of 86 patients. The prevalence of SRBD in patients with first-ever stroke or TIA is higher than expected from the available epidemiological data in our country. No correlation was found between neurological location and the presence or type of SRBD. Obstructive events seem to be a condition prior to the neurological disease whereas central events and CSB could be its consequence.

Aged↗
PubMed2006

Cell migration along the lateral cortical stream to the developing basal telencephalic limbic system.

During embryogenesis, the lateral cortical stream (LCS) emerges from the corticostriatal border (CSB), the boundary between the developing cerebral cortex and striatum. The LCS is comprised of a mix of pallial- and subpallial-derived neural progenitor cells that migrate to the developing structures of the basal telencephalon, most notably the piriform cortex and amygdala. Using a combination of in vitro and in vivo approaches, we analyzed the timing, composition, migratory modes, origin, and requirement of the homeodomain-containing transcription factor Gsh2 (genomic screened homeobox 2) in the development of this prominent migratory stream. We reveal that Pax6 (paired box gene 6)-positive pallial-derived and Dlx2 (distal-less homeobox 2)-positive subpallial-derived subpopulations of LCS cells are generated in distinct temporal windows during embryogenesis. Furthermore, our data indicate the CSB border not only is comprised of separate populations of pallial- and subpallial-derived progenitors that contribute to the LCS but also a subpopulation of cells coexpressing Pax6 and Dlx2. Moreover, despite migrating along a route outlined by a cascade of radial glia, the Dlx2-positive population appears to migrate primarily in an apparent chain-like manner, with LCS migratory cells being generated locally at the CSB with little contribution from other subpallial structures such as the medial, lateral, or caudal ganglionic eminences. We further demonstrate that the generation of the LCS is dependent on the homeodomain-containing gene Gsh2, revealing a novel requirement for Gsh2 in telencephalic development.

Animals↗
PubMed1999

Enhancement of XPG mRNA transcription by human interferon-beta in Cockayne syndrome cells with complementation group B.

Human interferon-beta (HuIFN-beta) confers UV-refractoriness in association with increased DNA repair capacity to human cells. We examined the modulation of XPG gene expression by HuIFN-beta in UV-sensitive cells from Cockayne syndrome complementation B (CSB), xeroderma pigmentosum complementation A (XPA) and normal control cells. Northern blot analysis revealed that XPG mRNA was more extensively transcribed in CSB cells treated with HuIFN-beta than in those without HuIFN-beta treatment. XPG mRNA from XPA cells and normal control cells was not markedly transcribed by HuIFN-beta treatment compared to that from CSB cells. The findings suggested that different mechanisms of UV-refractoriness by HuIFN-beta exist between CS and XP.

Blotting, Northern↗
PubMed1999

Sexual coercion history, calloused sexual beliefs and judgments of sexual coercion in a date rape analogue.

This study compared men with and without a history of coercive sexual behavior on their judgments of how far a man should go in using coercion in an audiotaped date rape simulation. Calloused sexual beliefs (CSB) and a "token resistance" manipulation were expected to differentially interact with coercion history. Results showed no effect for "token resistance." Calloused sexual beliefs interacted with coercion group, such that sexually coercive men high in CSB took significantly longer to stop the date rape interaction than coercive men low in CSB, who did not differ from noncoercive men. These findings support a model of sexual coercion in which a cognitive set consisting of rape-supportive beliefs may serve as a disinhibitor of behavior.

Adolescent↗
PubMed2006

Relationship between degree of polymerization and enamel bonding strength with self-etching adhesives.

PURPOSE: To investigate the relationship between the degree of conversion of double bonds of all-in-one adhesives and their shear bond strength on ground human enamel. MATERIALS AND METHODS: Six commercially available systems and one experimental adhesive were tested: Absolute (ABS; Dentsply-Sankin), Clearfil S3 Bond (CSB; Kuraray), G-Bond (GBO; GC), Hybrid Bond (HYB; Sun Medical), iBond (IBO; Heraeus Kulzer), Xeno IV (XEN; Dentsply Caulk), and experimental iBond NG (ING; Heraeus Kulzer). Conventional shear bond strengths (SBS, n=8) of adhesive-coated enamel specimens bonded to Venus composite (Heraeus Kulzer) and degrees of conversion (DC) (FTIR, n=5) were determined after 1 and 10 min, 1, 2, and 24 h of storage. Data were statistically analyzed using ANOVA and Duncan's post hoc test (0 < 0.05). RESULTS: The adhesives' SBS (MPa) and DC (%) by testing time followed logarithmic regression lines established by the least square method. Mean shear bond strengths after 1 min/24 h were: ABS 9.8/14.9; CSB 14.7/23.4; GBO 14.8/22.0; HYB 9.7/17.0; IBO 11.3/22.3; XEN 9.1/17.3; ING 9.7/25.6. The corresponding mean DC values were: ABS 51.3/66.2; CSB 83.1/90.8; GBO 75.8/87.7; HYB 49.6/67.2; IBO 72.6/93.7; XEN 61.6/74.1; ING 64.9/89.1. Linear regressions for the relationship DC vs. SBS were significant with coefficients of determination (r2) between 0.72 and 0.97. CONCLUSION: Despite similar acidity, the adhesives showed different SBSs on enamel. Based on the relationships between DC and SBS, the cohesive failure patterns observed, and the composition-property relations discussed, it is concluded that the percentage DC is the main parameter influencing an adhesive's bonding efficacy to ground enamel.

Analysis of Variance↗
PubMed1991

Identification of a possible control element, Mt5, in the major noncoding region of mitochondrial DNA by intraspecific nucleotide conservation.

Nucleotide sequences throughout the whole major noncoding region of mitochondrial DNA of 18 subjects were determined. Previously identified control elements were classified into three groups according to the degree of intraspecific nucleotide conservations: strictly conserved elements (LSP, HSP, Mt3, Mt3 on H-strand, mtTF1-element for HSP), relatively conserved elements (CSB-III, Mt4 on H-strand, and mtTF1-element for LSP), and variable elements (TAS, CSB-I, CSB-II). Moreover, alignment of nucleotide conservations disclosed a stretch of conserved sequence (5'-ATGCTTACAAGCAAG-3', nucleotide number 16, 194-16,208, designated as Mt5 element) in the middle of the hypervariable segment. Nucleotide conservation of this element was not only intraspecific but also interspecific.

Base Sequence↗
PubMed1989

Subclavian artery revascularization: a comparison between carotid-subclavian artery bypass and subclavian-carotid transposition.

Extrathoracic revascularization has become the most popular form of surgical treatment of symptomatic subclavian disease. Despite the many theoretical advantages, subclavian-carotid transposition (SCT) has not gained wide popularity. During a 15-year period, 46 patients underwent carotid-subclavian bypass (CSB) or SCT for symptoms referable to occlusion of the subclavian artery. Follow-up ranged from 2 to 148 months (mean, 46.9 months). Seven-year actuarial patency rate was 100% for SCT and 86% +/- 7% for CSB (p = NS). Mean operative time and intraoperative blood loss were significantly reduced for SCT (p less than 0.05). After CSB a continuous deterioration of the hemodynamic status of the reconstruction was noted, whereas there were no significant changes after SCT (p less than 0.05). Whenever feasible, SCT should be considered the operation of choice for patients with symptomatic severe subclavian artery disease.

Adult↗
PubMed1982

Disruption of selective attention in the rat following chronic d-amphetamine administration: relationship to schizophrenic attention disorder.

In the blocking paradigm, prior training to one conditioned stimulus (CSA) blocks the ability to attend to a second conditioned stimulus (CSB) when the two form a compound (CSAB) in subsequent training. Blocking is an associative process by which animals learn to ignore CSB because it contains no new information regarding the reinforcing event. Experiment 1 showed that d-amphetamine disrupted rats' ability to ignore the irrelevant CSB: The animals responded equally to both elements of the CSAB compound following five dialy administrations of 4 mg/kg d-amphetamine. In Experiment 2 the disruption of blocking by d-amphetamine was eliminated by concomitant administration of 0.02 mg/kg haloperidol. These results are consistent with previous research showing that d-amphetamine disrupts rats' ability to ignore repeated presentations of a single nonreinforced stimulus in the latent inhibition paradigm. The inability of amphetamine-treated animals to ignore one element of a dual-element compound bears some resemblance to selective attention deficits seen among schizophrenic patients.

Animals↗
PubMedDate not supplied

Comparative effects of aminotriazole on normal and acatalasemic mice.

Some pharmacological and toxicological effects of dietary 3-amino-1,2,4-triazole (AT), a known catalase inhibitor, antithyroid agent, and carcinogen, have been examined, using acatalasemic (Csb) and normal catalase, "wild-type" (Csa) substrains of highly inbred C3H and C57BL mice. It was found that (a) the acatalasemic substrains are more resistant to weight loss and death on the AT diet than are their normal catalase counterparts; (b) Csb and Csa substrains of C57BL mice are more resistant to weight loss and death on the AT diet than are the Csb and Csa substrains of the C3H mouse; (c) the liver catalase, as well as the whole body catalase, of the two C57BL substrains is less inhibited by the AT diet than is that of the C3H substrains; (d) mice consuming the same quantity of either normal or AT-containing diet gain much more weight on the normal diet; (e) temporary consumption of the AT diet causes a considerable increase in thyroid weight, with an extremely slow, and only partial, return toward normal weight; and (f) the C3H/Csa mouse on an AT diet develops a scaly, necrotic tail very similar in appearance to the so-called rodent ringtail; this lesion is never observed in the acatalasemic mouse on the same diet.

Amitrole↗
PubMed1995

A controlled trial of regional sympatholysis in the treatment of photo-oculodynia syndrome.

INTRODUCTION: The mechanism(s) underlying the eye pain syndrome characterized by photo-oculodynia and decreased tears (herein referred to as PODS) is unknown. Postulating a sympathetically maintained pain mechanism, cervical sympathetic ganglion blocks (CSB) were performed in an open-label trial in two patients as a pilot test of our hypothesis. Because these patients experienced clinically dramatic reductions in signs and symptoms, a double-masked controlled trial was initiated. METHODS: With Institutional Review Board approval and written informed consent, four other subjects with PODS who had experienced temporary reduction (> 50%) of symptoms with a single lidocaine CSB were enrolled. A randomized, double-masked series of three CSBs (saline, bupivacaine, lidocaine) was scheduled for each subject 2-7 days apart. RESULTS: CSB with lidocaine and bupivicaine, but not saline, reduced spontaneous pain and light sensitivity and increased production of tears. Symptom reduction lasted for hours to days, extending beyond clinical signs of local anesthetic-induced sympatholysis. It was also observed that sympatholysis extinguished associated blepharospasm in those subjects with this dystonic condition (one subject in the open-label pilot trial and two of three in the controlled trial). CONCLUSIONS: Results of these preliminary data suggest that the sympathetic nervous system is involved in mediating symptoms associated with PODS in certain individuals.

Adult↗