Age dependent association of endometrial polyps with increased risk of cancer involvement

BACKGROUND: Endometrial polyps (EMPs) are commonly encountered in routine surgical pathology practice, but opinions differ on whether they are intrinsically a marker for concurrent or subsequent malignancy. The objectives of the present study are 1) to investigate the age-group in which EMP are most commonly encountered 2) to document the age-group in which EMP are most commonly associated with malignancies 3) To investigate whether the age of diagnosis of the various carcinoma subtypes in EMPs is congruent with published data on similar malignancies arising in non-polypoid endometrium and 4) To investigate whether the histologic subtype distribution of malignancies associated with EMPs are similar or different from the distribution of malignancies arising from non-polypoid endometrium based on published data. PATIENTS AND METHODS: All cases of EMPs were retrieved from the files of Yale-New Haven Hospital for the period 1986-1995. The patients were divided into 5 age groups: Each group was further subclassified based on an association (or lack thereof) of EMPs with endometrial carcinoma. Chi-square test was used to compare the proportion of malignancy associated EMPs between the age groups. RESULTS: We identified 513 EMPs, of which 209 (41%) were from biopsy specimens and 304 (59%) from hysterectomy specimens. Sixty six (13%) of all EMPs were malignant. The 66 malignant EMPs included 58 endometrioid, 6 serous, 1 carcinosarcoma, and 1 clear cell carcinoma. In age group >35, only 1(2.5%) of 40 EMPs was associated with endometrial malignancy. In contrast, 37(32%) of 115 EMPs were associated with malignancy in the age group > 65. The frequency of malignant EMPs increased with age and reached statistical significance in the age group >65 (p < 0.001). The most common histologic type of malignancy was endometrioid adenocarcinoma. CONCLUSIONS: EMPs show statistically significant age dependent association with malignant tumor involvement. Careful search for malignancy, particularly in women with multiple risk factors is advised in daily practice. Additional studies are needed to address the histological features and immunohistochemical profiles in the context of association between endometrioid and high-grade endometrial carcinoma and endometrial polyps.     

Chromosomal G-dark Bands Determine the Spatial Organization of Centromeric Heterochromatin in the Nucleus

Gene expression can be silenced by proximity to heterochromatin blocks containing centromeric alpha-satellite DNA. This has been shown experimentally through cis-acting chromosome rearrangements resulting in linear genomic proximity, or through trans-acting changes resulting in intranuclear spatial proximity. Although it has long been been established that centromeres are nonrandomly distributed during interphase, little is known of what determines the three-dimensional organization of these silencing domains in the nucleus. Here, we propose a model that predicts the intranuclear positioning of centromeric heterochromatin for each individual chromosome. With the use of fluorescence in situ hybridization and confocal microscopy, we show that the distribution of centromeric alpha-satellite DNA in human lymphoid cells synchronized at G(0)/G(1) is unique for most individual chromosomes. Regression analysis reveals a tight correlation between nuclear distribution of centromeric alpha-satellite DNA and the presence of G-dark bands in the corresponding chromosome. Centromeres surrounded by G-dark bands are preferentially located at the nuclear periphery, whereas centromeres of chromosomes with a lower content of G-dark bands tend to be localized at the nucleolus. Consistent with the model, a t(11; 14) translocation that removes G-dark bands from chromosome 11 causes a repositioning of the centromere, which becomes less frequently localized at the nuclear periphery and more frequently associated with the nucleolus. The data suggest that "chromosomal environment" plays a key role in the intranuclear organization of centromeric heterochromatin. Our model further predicts that facultative heterochromatinization of distinct genomic regions may contribute to cell-type specific patterns of centromere localization.     

Liver biotransforming enzymes in woodrats Neotoma stephensi (Muridae)

Mammalian herbivores are exposed to extremely high levels of plant secondary compounds naturally present in their diet. It has been speculated that specialist herbivores should express a unique pattern of biotransforming enzymes to permit the consumption of a single species of toxic plant. Specifically, specialists should rely on pathways that effectively biotransform the toxins they routinely encounter in their diet. We examined the hepatic mRNA expression and activity or content of biotransforming enzymes in the specialist herbivorous woodrat, Neotoma stephensi, and compared results to those of laboratory rats (Sprague-Dawley strain Rattus norvegicus). In addition, we investigated the role of alpha-pinene, a specific plant toxin present in the diet of N. stephensi on the mRNA expression pattern and activity or content of biotransforming enzymes in Sprague-Dawley rats. Overall, the levels of functionalization enzyme activity and mRNA were found to be higher in specialists, while glucuronidation enzyme activity and mRNA were lower. These results support predictions that specialist herbivores rely more on functionalization biotransformation pathways rather than glucuronidation pathways.     

Picky: oligo microarray design for large genomes

MOTIVATION: Many large genomes are getting sequenced nowadays. Biologists are eager to start microarray analysis taking advantage of all known genes of a species, but existing microarray design tools were very inefficient for large genomes. Also, many existing tools operate in a batch mode that does not assure best designs. RESULTS: Picky is an efficient oligo microarray design tool for large genomes. Picky integrates novel computer science techniques and the best known nearest-neighbor parameters to quickly identify sequence similarities and estimate their hybridization properties. Oligos designed by Picky are computationally optimized to guarantee the best specificity, sensitivity and uniformity under the given design constrains. Picky can be used to design arrays for whole genomes, or for only a subset of genes. The latter can still be screened against a whole genome to attain the same quality as a whole genome array, thereby permitting low budget, pathway-specific experiments to be conducted with large genomes. Picky is the fastest oligo array design tool currently available to the public, requiring only a few hours to process large gene sets from rice, maize or human.     

Synchronously diagnosed pre-sacral neurofibroma and cutaneous spitzoid melanoma: a fortuitous association?

Background  

At a U.S prevalence of 1 in 3000, Neurofibromatosis type-1 (NF-1) is a relatively common disorder. Amongst a variety of others, occurrence of 2 or more neurofibromas in the same patient represents one of the major diagnostic criteria for this disorder. Rarely, ocular, cutaneous or anorectal malignant melanomas may be identified in patients with NF-1, This rare association has caused controversy as to whether patients with NF-1 have an inherently higher risk for melanomas or whether the associations can be explained by chance alone.     

Perivascular epithelioid cell tumor (PEComa) of the uterine cervix associated with intraabdominal "PEComatosis": A clinicopathological study with comparative genomic hybridization analysis

Background  

The World Health Organization recently recognized a family of neoplasms showing at least partial morphological or immunohistochemical evidence of a putative perivascular epithelioid cell (PEC) differentiation. These tumors include angiomyolipoma (AML), clear cell "sugar" tumors of the lung (CCST), lymphangioleiomyomatosis (LAM), clear cell myomelanocytic tumors of the falciform ligament and distinctive clear cell tumors at various other anatomic sites.     

Trypanothione reductase activity is prominent in metacyclic promastigotes and axenic amastigotes of Leishmania amazonesis. Evaluation of its potential as a therapeutic target

The activity of trypanothione reductase in Leishmania amazonensis was evaluated and it was demonstrated that TR is expressed in the soluble fractions of infective promastigotes and amastigotes, while non-infective promastigotes expressed the enzyme at basal levels. This data allows an association of enzyme activity and the infective capacity of the parasite. We have also previously demonstrated that amidine compounds (N, N'-diphenyl-4-methoxy-benzamidine and pentamidine) were active against this parasite. Here, experiments concerning the effect of these compounds on TR activity, showed that both compounds significantly inhibited the enzyme. However, against glutathione reductase, only pentamidine showed a significant inhibitory action, suggesting an association with the toxic effects of this drug used in the clinic for the treatment of leishmaniasis.