Use of novel serum markers in clinical follow-up of Sertoli-Leydig cell turnours

Background: Sertoli-Leyclig cell tumours of the ovary account for only 0.2% of malignant ovarian tumours. Two-thirds of all patients become apparent due to the tumour's hormone production. Methods: A 41-year-old patient (gravida 4, para 4) presented with dyspnoea, enlarged abdominal girth and melaena. Diagnostic imaging was suspicious for an ovarian cancer. The standard tumour marker for ovarian cancer (CA 125) was elevated to 984 U/mL. Results: Surgical exploration of the abdomen revealed a mouldering tumour of both adnexes extending to the level of the navel. Frozen sections showed an undifferentiated carcinoma of unknown origin. Radical surgery was performed. The final histological report described a malignant sex-cord stroma tumour, a Sertoli-Leydig cell tumour, emanating from both ovaries. Analysis of preoperative blood serum showed elevated levels of CYFRA 21-1 (10.4 ng/mL), neuron-specific enolase (36.2 ng/mL), oestradiol (485 pg/mL) and CA-125 (984 U/mL). Adjuvant chemotherapy and regional hyperthermia were performed due to the malignant potential and incomplete resection of the tumour. Conclusions: Undifferentiated Sertoli-Leyclig cell tumours show a poor clinical course. As only two-thirds of patients with this rare disease present with elevated hormone levels, new markers deserve further investigation to offer more specific, individualised tumour monitoring

Recognizing Members of the Tournament Equilibrium Set is NP-hard

A recurring theme in the mathematical social sciences is how to select the "most desirable" elements given a binary dominance relation on a set of alternatives. Schwartz's tournament equilibrium set (TEQ) ranks among the most intriguing, but also among the most enigmatic, tournament solutions that have been proposed so far in this context. Due to its unwieldy recursive definition, little is known about TEQ. In particular, its monotonicity remains an open problem up to date. Yet, if TEQ were to satisfy monotonicity, it would be a very attractive tournament solution concept refining both the Banks set and Dutta's minimal covering set. We show that the problem of deciding whether a given alternative is contained in TEQ is NP-hard.Comment: 9 pages, 3 figure

Analysis of the dihydrofolate reductase-thymidylate synthase gene sequences in Plasmodium vivax field isolates that failed chloroquine treatment

<p>Abstract</p> <p>Background</p> <p>To use pyrimethamine as an alternative anti-malarial drug for chloroquine-resistant malaria parasites, it was necessary to determine the enzyme's genetic variation in dihydrofolate reductase-thymidylate syntase (DHFR-TS) among Korean strains.</p> <p>Methods</p> <p>Genetic variation of <it>dhfr-ts </it>genes of <it>Plasmodium vivax </it>clinical isolates from patients who did not respond to drug treatment (<it>n </it>= 11) in Korea were analysed. The genes were amplified using the polymerase chain reaction (PCR) with genomic DNA as a template.</p> <p>Results</p> <p>Sequence analysis showed that the open reading frame (ORF) of 1,857 nucleotides encoded a deduced protein of 618 amino acids (aa). Alignment with the DHFR-TS genes of other malaria parasites showed that a 231-residue DHFR domain and a 286-residue TS domain were seperated by a 101-aa linker region. This ORF shows 98.7% homology with the <it>P. vivax </it>Sal I strain (XM001615032) in the DHFR domain, 100% in the linker region and 99% in the TS domain. Comparison of the DHFR sequences from pyrimethamine-sensitive and pyrimethamine-resistant <it>P. vivax </it>isolates revealed that nine isolates belonged to the sensitive strain, whereas two isolates met the criteria for resistance. In these two isolates, the amino acid at position 117 is changed from serine to asparagine (S117N). Additionally, all Korean isolates showed a deletion mutant of THGGDN in short tandem repetitive sequences between 88 and 106 amino acid.</p> <p>Conclusions</p> <p>These results suggest that sequence variations in the DHFR-TS represent the prevalence of antifolate-resistant <it>P. vivax </it>in Korea. Two of 11 isolates have the Ser to Asn mutation in codon 117, which is the major determinant of pyrimethamine resistance in <it>P. vivax</it>. Therefore, the introduction of pyrimethamine for the treatment of chloroquine-resistant vivax malaria as alternative drug in Korea should be seriously considered.</p

Telomere disruption results in non-random formation of de novo dicentric chromosomes involving acrocentric human chromosomes

Copyright: © 2010 Stimpson et al.Genome rearrangement often produces chromosomes with two centromeres (dicentrics) that are inherently unstable because of bridge formation and breakage during cell division. However, mammalian dicentrics, and particularly those in humans, can be quite stable, usually because one centromere is functionally silenced. Molecular mechanisms of centromere inactivation are poorly understood since there are few systems to experimentally create dicentric human chromosomes. Here, we describe a human cell culture model that enriches for de novo dicentrics. We demonstrate that transient disruption of human telomere structure non-randomly produces dicentric fusions involving acrocentric chromosomes. The induced dicentrics vary in structure near fusion breakpoints and like naturally-occurring dicentrics, exhibit various inter-centromeric distances. Many functional dicentrics persist for months after formation. Even those with distantly spaced centromeres remain functionally dicentric for 20 cell generations. Other dicentrics within the population reflect centromere inactivation. In some cases, centromere inactivation occurs by an apparently epigenetic mechanism. In other dicentrics, the size of the alpha-satellite DNA array associated with CENP-A is reduced compared to the same array before dicentric formation. Extrachromosomal fragments that contained CENP-A often appear in the same cells as dicentrics. Some of these fragments are derived from the same alpha-satellite DNA array as inactivated centromeres. Our results indicate that dicentric human chromosomes undergo alternative fates after formation. Many retain two active centromeres and are stable through multiple cell divisions. Others undergo centromere inactivation. This event occurs within a broad temporal window and can involve deletion of chromatin that marks the locus as a site for CENP-A maintenance/replenishment.This work was supported by the Tumorzentrum Heidelberg/Mannheim grant (D.10026941)and by March of Dimes Research Foundation grant #1-FY06-377 and NIH R01 GM069514

Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]&#x3c;1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]&#x3e;&#x3e;1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

Preferential risk of HPV16 for squamous cell carcinoma and of HPV18 for adenocarcinoma of the cervix compared to women with normal cytology in The Netherlands

We present the type-distribution of high-risk human papillomavirus (HPV) types in women with normal cytology (n=1467), adenocarcinoma in situ (ACIS) (n=61), adenocarcinoma (n=70), and squamous cell carcinoma (SCC) (n=83). Cervical adenocarcinoma and ACIS were significantly more frequently associated with HPV18 (ORMH 15.0; 95% CI 8.6–26.1 and 21.8; 95% CI 11.9–39.8, respectively) than normal cytology. Human papillomavirus16 was only associated with adenocarcinoma and ACIS after exclusion of HPV18-positive cases (ORMH 6.6; 95% CI 2.8–16.0 and 9.4; 95% CI 2.8–31.2, respectively). For SCC, HPV16 prevalence was elevated (ORMH 7.0; 95% CI 3.9–12.4) compared to cases with normal cytology, and HPV18 prevalence was only increased after exclusion of HPV16-positive cases (ORMH 4.3; 95% CI 1.6–11.6). These results suggest that HPV18 is mainly a risk factor for the development of adenocarcinoma whereas HPV16 is associated with both SCC and adenocarcinoma

International practice patterns and factors associated with non-conventional hemodialysis utilization

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to determine characteristics that influence the utilization of non-conventional hemodialysis (NCHD) therapies and its subtypes (nocturnal (NHD), short daily (SDHD), long conventional (LCHD) and conventional hemodialysis (CHD) as well as provider attitudes regarding the evidence for NCHD use.</p> <p>Methods</p> <p>An international cohort of subscribers of a nephrology education website <url>http://www.nephrologynow.com</url> was invited to participate in an online survey. Non-conventional hemodialysis was defined as any forms of hemodialysis delivered > 3 treatments per week and/or > 4 hours per session. NHD and SDHD included both home and in-centre. Respondents were categorized as CHD if their centre only offered conventional thrice weekly hemodialysis. Variables associated with NCHD and its subtypes were determined using multivariate logistic regression analysis. The survey assessed multiple domains regarding NCHD including reasons for initiating and discontinuing, for not offering and attitudes regarding evidence.</p> <p>Results</p> <p>544 surveys were completed leading to a 15.6% response rate. The final cohort was limited to 311 physicians. Dialysis modalities utilized among the respondents were as follows: NCHD194 (62.4%), NHD 83 (26.7%), SDHD 107 (34.4%), LCHD 81 (26%) and CHD 117 (37.6%). The geographic regions of participants were as follows: 11.9% Canada, 26.7% USA, 21.5% Europe, 6.1% Australia/New Zealand, 10% Africa/Middle East, 10.9% Asia and 12.9% South America. Variables associated with NCHD utilization included NCHD training (OR 2.47 CI 1.25-4.16), government physician reimbursement (OR 2.66, CI 1.11-6.40), practicing at an academic centre (OR 2.28 CI 1.25-4.16), higher national health care expenditure and number of ESRD patients per centre. Hemodialysis providers with patients on NCHD were significantly more likely to agree with the statements that NCHD improves quality of life, improves nutritional status, reduces EPO requirements and is cost effective. The most common reasons to initiate NCHD were driven by patient preference and the desire to improve volume control and global health outcomes.</p> <p>Conclusion</p> <p>Physician attitudes toward the evidence for NCHD differ significantly between NCHD providers and conventional HD providers. Interventions and health policy targeting these areas along with increased physician education and training in NCHD modalities may be effective in increasing its utilization.</p