NT-ProBNP independently predicts long-term mortality in patients admitted for coronary angiography.

Recently, research interests are focussed on biomarkers to predict the outcome in patients with coronary artery disease (CAD). We examined whether the levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict outcome in patients who underwent elective or acute coronary angiography (CAG). A total of 337 patients with suspected CAD who underwent elective or acute CAG were followed up for a mean period of 6.7 years. Primary end points were all-cause mortality (ACM) and the combined end point of ACM, nonfatal myocardial infarction, and revascularization. In all, 53 (16%) patients died and 88 (26%) patients reached the combined end point. Preprocedural NT-proBNP above 32 pmol/L independently predicted ACM (hazard ratio [HR] 3.11; confidence interval [CI]: 1.60-6.07; P = .001) and the combined end point (HR 2.44 [CI: 1.50-3.97]; P < .001). This study indicates that high NT-proBNP is an independent predictor of ACM on long-term follow-up. N-terminal-proBNP is a reliable predictive marker of mortality in the setting of stable or unstable angina.

Characteristics of clients to a suicide prevention centre--an epidemiological analysis of the users over a 10-year period.

BACKGROUND: Suicide prevention centres play an important role on suicide prevention in communities. A better understanding of clients to these centres is essential and informative to suicide prevention. This study aimed to document the referral pattern of clients to a suicide prevention centre over a 10-year period and to capture their characteristics. METHODS: All suicidal clients during 1996 to 2005 were included and compared with the regional population. Data were retrieved from longitudinal registers. RESULTS: There were in total 4274 contacts from 3505 individuals because of suicide attempt (38%) or suicide ideation (62%). Source of referral included self-initiation or family (25.4%), psychiatric hospitals (23.5%), general practitioners (21.7%), and somatic hospitals (15.1%). The clients were more likely females and persons at young ages. Compared with regional sex-age-matched counterparts, suicidal clients significantly more often had a history of psychiatric contact, were born by young parents, had no recorded link to a mother or father, had lost a parent, and had a parental psychiatric history. Also, they were often frequent movers and residents with a foreign citizenship. CONCLUSIONS: This study provided insights about the referral pattern of suicidal clients as well as client characteristics on selected variables at the birth and during upbringing, which may be informative to suicide intervention targeting at this group of population.

High prevalence of risk factors in coronary artery disease in EUROPA gives HOPE for ACE inhibitors after PEACE.

BACKGROUND: Routine use of ACE inhibitors (ACE-I) as secondary preventive therapy for all patients with coronary artery disease (CAD) is challenged by the PEACE trial. Currently it is unclear to what extent ACE-I should be used in CAD populations. PURPOSE: To analyze the prevalence of left ventricular systolic dysfunction, diabetes, myocardial infarction and hypertension in an unselected and consecutive population of patients with documented CAD and evaluate the potential need for ACE-I treatment in a real-life scenario. METHODS: We searched a database containing all invasive cardiac investigations in three hospitals in Copenhagen from July 1, 2000 to June 30, 2003. Patients with no angiographic sign of CAD were excluded. RESULTS: Among 7,345 patients, 4,180 had stable CAD and 3,165 had acute coronary syndrome (ACS). Among the stable CAD patients 78% had at least one of the following indications for treatment with an ACE-I: left ventricular ejection fraction <0.45 (20%), hypertension (39%), diabetes (19%), systolic blood pressure >159 mm Hg (21%), and/or myocardial infarction (42%). Among ACS patients, 90% had an indication for ACE-I treatment. CONCLUSION: Depending on the definitions, at least 78% of the patients with stable CAD and 90% with ACS have an accepted indication for treatment with an ACE-I.

Serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter region are related to peripheral measures of bone mass and fracture odds ratios.

The purpose of this study is to investigate the association of serum osteoprotegerin (OPG) and the A163G polymorphism in the OPG promoter with peripheral measures of bone mass and with odds ratios for wrist and hip fracture in a case-control study of postmenopausal Danish women. The study included 66 women with lower forearm fracture, 41 women with hip fracture, and 206 age-matched controls. All had broadband ultrasound attenuation (BUA) and speed of sound (SOS) measured at the heel as well as bone mineral density (BMD) measured by DXA at the distal forearm. S-OPG was measured by ELISA. The A163G genotypes were determined by PCR-RFLP analysis. S-OPG levels correlated positively with age ( r = 0.45; P << 0.0001) and negatively with distal forearm BMD ( r = -0.31; P << 0.0001), heel BUA ( r = -0.23; P << 0.0001), and heel SOS ( r = -0.22; P << 0.0001). Comparing the highest quartile of S-OPG to the lowest, the odds ratio for osteoporotic fracture was 2.5 (95% CI, 1.3-4.7; P = 0.006). The G allele of the A163G was associated with significantly lower t-scores of both lower forearm BMD, heel BUA, and heel SOS as well as being significantly more frequent in the fracture patients compared to the controls. Patients with a combination of the highest quartile of S-OPG and presence of the G allele ( n = 23) had a significantly elevated fracture odds ratio, 4.0 (95% CI, 1.7-9.9). A significant negative association between S-OPG with peripheral measures of bone mass and with increased fracture odds ratios was found. Furthermore, the A163G mutation in the OPG promoter had a significant influence on bone mass and fracture status independently of S-OPG level.

PLU-1, a transcriptional repressor and putative testis-cancer antigen, has a specific expression and localisation pattern during meiosis.

PLU-1, a large multi-domain nuclear protein with strong transcriptional repression activity, is a member of the ARID family of DNA binding proteins. In previous studies, high levels of expression of Plu-1 mRNA and PLU-1 protein were detected in breast cancers, while expression in normal adult tissues was detected only in the testis, ovary and transiently in the mammary gland of the pregnant female. Due to its high levels of expression in the testis and to its specific relationship to cancer, PLU-1 has been proposed to belong to the family of testis-cancer antigens. In this study we attempted to determine putative functions for PLU-1 during spermatogenesis. To address this, we analysed the pattern of expression and localisation of this protein in mouse testicular cells during postnatal development and adulthood. Using in situ hybridisation and immunostaining of testis sections we show that Plu-1 mRNA and PLU-1 protein are both highly expressed in the mitotic spermatogonia. Expression is reduced dramatically in the early prophase I stages (zygotene, leptotene), but reappears at pachytene and is still detectable in diplotene cells. We also found that PLU-1 localises diffusely over the nucleus, which indicates a potential chromatin binding ability of this protein. Consistent with this notion, we found that PLU-1 is present in the chromatin fraction in biochemical cell fractionation experiments using both somatic and meiotic cells. Our data point to a role for PLU-1 in meiotic transcription, which may be restricted to certain meiotic stages and may be mediated by the ability of this protein to associate with the chromatin.

Human PLU-1 Has transcriptional repression properties and interacts with the developmental transcription factors BF-1 and PAX9.

PLU-1 is a large (1544 amino acids) nuclear protein that is highly expressed in breast cancers and is proposed to function as a regulator of gene expression. A yeast two-hybrid screen using PLU-1 as bait has identified two unrelated PLU-1 interacting proteins, namely brain factor-1 (BF-1) and paired box 9 (PAX9), both of which are developmental transcription factors. BF-1 and PAX9 interact with PLU-1 via a novel conserved sequence motif (Ala-X-Ala-Ala-X-Val-Pro-X4-Val-Pro-X8-Pro, termed the VP motif), because deletion or site-directed mutagenesis of this motif in either protein abolishes PLU-1 interaction in vivo. In a reporter assay system, PLU-1 has potent transcriptional repression activity. BF-1 and PAX9 also represses transcription in the same assay, but co-expression of PLU-1 with BF-1 or PAX9 significantly enhances this repression. Mutation of the PLU-1 binding motifs in BF-1 and PAX9 abolishes the observed PLU-1 co-repression activity. These data support a role for PLU-1 acting as a transcriptional co-repressor of two unrelated developmental transcription factors. Because both BF-1 and PAX proteins interact with members of the groucho co-repressor family, it is plausible that PLU-1 has a role in groucho-mediated transcriptional repression.

Multiple telomeric aberrations in a telomerase-positive leukemia patient.

Bone marrow samples from a pancytopenia/leukemia patient were routinely analyzed at first and second admission. At the first presentation, the karyotype was normal, whereas 17 months later several chromosome aberrations were recognized including presumed additions to the short arms of chromosomes 1 and 16 in all cells, and numerous other aberrations in subpopulations of cells. From the predominance of aberrations at chromosome ends, we suspected insufficient telomere maintenance as an underlying mechanism behind the karyotype changes, in particular as an interstitial deletion in the region harboring the gene for the RNA component (hTERC) of the telomerase enzyme was also noticed; however, while molecular cytogenetic investigation confirmed the terminal aberrations, we found the malignant cells positive for telomerase activity and the presence of an hTERC gene on both chromosomes 3. A presumed chromosome 1 addition turned out to reflect an amplification of a tandemly repeated sequence element. Labeling of multiple tandem repeat sequences in situ by a novel multicolor primed in situ hybridization showed no evidence of instability of other repeated DNA elements.

PLU-1 nuclear protein, which is upregulated in breast cancer, shows restricted expression in normal human adult tissues: a new cancer/testis antigen?

The PLU-1 gene is expressed at the level of message in breast cancers and breast cancer cell lines and shows restricted expression in normal adult tissues with the exception of testis. The predicted protein sequence contains several domains, including the PLU domain, which is shared by other proteins involved in transcription and/or development. We have developed a polyclonal antiserum to a C-terminal fragment of the PLU-1 protein, which shows little homology to other family members. Immunohistochemical analysis with the antiserum alpha-PLU-1C confirmed the nuclear localisation of PLU-1. alpha-PLU-1C also reacted with the mouse homologue of PLU-1 (mPlu-1) but not with the closest family member, RBP2. Using Western blot analysis, PLU-1 was shown to be well expressed in breast cancers and breast cancer cell lines, while it was not detected in a range of normal adult tissues. Our results suggest that the PLU-1 protein may belong to the class of testis/cancer antigens.

[Yield of a coronary arteriography database. A study of 5.536 registrations at the cardiologic laboratory, Rigshospitalet]. / Udbyttet af en database over koronararteriografier. En opgørelse af 5.536 registreringer på kardiologisk laboratorium, Rigshospitalet.

INTRODUCTION: Coronary arteriography (CAG) is an expensive investigation that provides potentially valuable information, but also carries a risk of severe complications. It is therefore natural to examine the usefulness of an existing database on CAG. METHODS: The analysis covers all registrations of CAG entered into the database at the Heart Centre at Rigshospitalet, Copenhagen, from April 1999 to September 2000. RESULTS: Altogether, 5536 CAGs were registered. The indication was stable coronary artery disease in 52.0% and acute ischaemic heart disease in 25.5%. As an example of the medical information available from the data base, it is notable that left main coronary stenosis or three-vessel disease, conditions in which coronary bypass surgery increases long-term survival, was found in 42.4% of patients with angina pectoris in Canadian Cardiovascular Society (CCS) class 4, but also in 24.4% of patients in CCS class 1. DISCUSSION: Clinical databases, such as the one presented, can ensure that all relevant information is stored, and in this case even results in enhanced effectiveness, because data may be directly transformed into other formats, such as charts. The database furthermore provides clinical information, for instance that the severity of angina pectoris cannot identify the most ill patients in whom a CABG is potentially life-prolonging. In addition, the database provides administrative data that is used in the training of doctors, evaluation of referral patterns, surveillance of complications, and in the daily administration and planning.

Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer.

PLU-1 is a novel breast cancer associated nuclear protein containing highly conserved domains including the PLU domain, putative DNA/chromatin binding motifs, and PHD/LAP domains. Here we report the cloning of the mouse homologue (Plu-1), and document its expression in adult tissues, mammary tumours and the embryo. The overall homology with human PLU-1 is 94% at the protein level, with almost 100% identity in the conserved domains, suggesting functional conservation. As with human PLU-1 the expression of Plu-1 in adult tissues is restricted, with high expression being seen only in testis, while expression in mammary tumours from c-neu transgenic mice is high. Plu-1 is also differentially expressed in the adult mammary gland. In the developing embryo Plu-1 is expressed in a temporally restricted fashion with tissue specific expression being limited to parts of the developing brain, whisker follicle, mammary bud, thymus, limbs, intervertebral disc, olfactory epithelium, teeth, eye, and stomach. The temporal and spatial expression patterns of the transcription factors Bf-1 and Pax9, recently found to bind to PLU-1 through the PLU domain overlap with Plu-1 expression during development. Thus Plu-1 appears to play an important role in mouse embryonic development which may involve interaction with Pax9 and Bf-1.

Characterisation and developmental expression of mouse Plu-1, a homologue of a human nuclear protein (PLU-1) which is specifically up-regulated in breast cancer.

PLU-1 is a novel breast cancer associated nuclear protein containing highly conserved domains including the PLU domain, putative DNA/chromatin binding motifs, and PHD/LAP domains. Here we report the cloning of the mouse homologue (Plu-1), and document its expression in adult tissues, mammary tumours and the embryo. The overall homology with human PLU-1 is 94% at the protein level, with almost 100% identity in the conserved domains, suggesting functional conservation. As with human PLU-1 the expression of Plu-1 in adult tissues is restricted, with high expression being seen only in testis, while expression in mammary tumours from c-neu transgenic mice is high. Plu-1 is also differentially expressed in the adult mammary gland. In the developing embryo Plu-1 is expressed in a temporally restricted fashion with tissue specific expression being limited to parts of the developing brain, whisker follicle, mammary bud, thymus, limbs, intervertebral disc, olfactory epithelium, teeth, eye, and stomach. The temporal and spatial expression patterns of the transcription factors Bf-1 and Pax9, recently found to bind to PLU-1 through the PLU domain overlap with Plu-1 expression during development. Thus Plu-1 appears to play an important role in mouse embryonic development which may involve interaction with Pax9 and Bf-1.