Gastric leiomyoma and hyperplastic polyposis coli in a patient with multiple cutaneous and uterine leiomyomatosis

BACKGROUND: Cutaneous leiomyomatosis has been associated with multiple uterine myomas and, more recently, with germline heterozygous mutations of the FH gene and certain types of renal cancer. Despite the growing amount of knowledge concerning this genodermatosis, its clinical spectrum remains incompletely characterized. OBJECTIVE: We report the observation of a patient with multiple cutaneous and uterine leiomyomatosis (MCUL) with unusual gastrointestinal manifestations. METHODS AND RESULTS: A gastric leiomyoma was diagnosed on a 38-year-old female MCUL patient on endoscopy performed because of mild dyspepsia. Furthermore, routine colonoscopy disclosed hyperplastic polyposis. Genetic testing revealed a previously not reported mutation of the FH gene. CONCLUSION: Gastrointestinal lesions such as the present ones are frequently asymptomatic and probably underdiagnosed. As the phenotypical spectrum associated with mutations of the FH gene keeps expanding, clinicians should keep in mind that, besides renal cancer, other unexpected tumors could also arise in this setting

Close linkage with the RET protooncogene and boundaries of deletion mutations in autosomal dominant Hirschsprung disease

Tight linkage with the RET proto-oncogene (Zmax = 3.41 at θ = 0.00), analysis of recombinants and detection of a familial microdeletion in a large pedigree restrict the mapping of the Hirschsprung (HSCR) gene previously localized on proximal 10q. The molecular characterization of the familial microdeletion and of 3 additional cytogenetically visible de novo deletions, isolated in somatic cell hybrids, identify a smallest region of overlap of 250 Kb. This contains the RET proto-oncogene where missense mutations causing multiple endocrine neoplasia type 2A (MEN 2A) phenotype were recently found. The pentagastrin test (which detects preclinical forms of MEN 2A or B) is negative in adult HSCR patients with deletions of the RET gene. This represents a good candidate for the search of mutations causing HSC

Potentiality of protein fractions from the house cricket (Acheta domesticus) and yellow mealworm (Tenebrio molitor) for pasta formulation

House cricket (Acheta domesticus; AD) and yellow mealworm (Tenebrio molitor; TM) are two promising insect species for possible novel food applications. In this research the insect protein fractions were extracted, characterised, and used in the manufacturing of pasta by replacing semolina with 14% of powdered proteins. Pasta samples were then analysed to evaluate technological quality aspects. Results showed that insect protein inclusion resulted in a darker (L* value: 76.7, 53.4, 59.9 for control, AD and TM, respectively) and firmer (12.4, 13.7, 13.8 N: control, AD and TM, respectively) AD and TM pasta, and a higher water absorption index for AD (148, 178, 150%: control, AD and TM, respectively). In conclusion, both extracts offer interesting opportunity for pasta formulations, possibly leading to an improved protein content and quality. From an industrial perspective, the present study demonstrated that the tested edible insects can provide protein extracts for the possible fortification of pasta with high-quality protein and technological traits, thus representing an ingredient with interesting potential for several food applications

Effect of Moringa oleifera L. Leaf Powder Addition on the Phenolic Bioaccessibility and on In Vitro Starch Digestibility of Durum Wheat Fresh Pasta

Fresh pasta was formulated by replacing wheat semolina with 0, 5, 10, and 15 g/100 g (w/w) of Moringa oleifera L. leaf powder (MOLP). The samples (i.e., M0, M5, M10, and M15 as a function of the substitution level) were cooked by boiling. The changes in the phenolic bioaccessibility and the in vitro starch digestibility were considered. On the cooked-to-optimum samples, by means of ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry, 152 polyphenols were putatively annotated with the greatest content recorded for M15 pasta, being 2.19 mg/g dry matter (p < 0.05). Multivariate statistics showed that stigmastanol ferulate (VIP score = 1.22) followed by isomeric forms of kaempferol (VIP scores = 1.19) and other phenolic acids (i.e., schottenol/sitosterol ferulate and 24-methylcholestanol ferulate) were the most affected compounds through the in vitro static digestion process. The inclusion of different levels of MOLP in the recipe increased the slowly digestible starch fractions and decreased the rapidly digestible starch fractions and the starch hydrolysis index of the cooked-to-optimum samples. The present results showed that MOLP could be considered a promising ingredient in fresh pasta formulation

Effect of Moringa oleifera L. Leaf Powder Addition on the Phenolic Bioaccessibility and on In Vitro Starch Digestibility of Durum Wheat Fresh Pasta

Fresh pasta was formulated by replacing wheat semolina with 0, 5, 10, and 15 g/100 g (w/w) of Moringa oleifera L. leaf powder (MOLP). The samples (i.e., M0, M5, M10, and M15 as a function of the substitution level) were cooked by boiling. The changes in the phenolic bioaccessibility and the in vitro starch digestibility were considered. On the cooked-to-optimum samples, by means of ultra-high-performance liquid chromatography-quadrupole time-of-flight (UHPLC-QTOF) mass spectrometry, 152 polyphenols were putatively annotated with the greatest content recorded for M15 pasta, being 2.19 mg/g dry matter (p < 0.05). Multivariate statistics showed that stigmastanol ferulate (VIP score = 1.22) followed by isomeric forms of kaempferol (VIP scores = 1.19) and other phenolic acids (i.e., schottenol/sitosterol ferulate and 24-methylcholestanol ferulate) were the most affected compounds through the in vitro static digestion process. The inclusion of different levels of MOLP in the recipe increased the slowly digestible starch fractions and decreased the rapidly digestible starch fractions and the starch hydrolysis index of the cooked-to-optimum samples. The present results showed that MOLP could be considered a promising ingredient in fresh pasta formulation

The expanding genetic horizon of primary aldosteronism

Aldosterone is the main mineralocorticoid hormone in humans and plays a key role in maintaining water and electrolyte homeostasis. Primary aldosteronism (PA), characterized by autonomous aldosterone overproduction by the adrenal glands, affects 6% of the general hypertensive population and can be either sporadic or familial. Aldosterone-producing adenoma (APA) and bilateral adrenal hyperplasia (BAH) are the two most frequent subtypes of sporadic PA and 4 forms of familial hyperaldosteronism (FH-I to FH-IV) have been identified. Over the last six years, the introduction of next-generation sequencing has significantly improved our understanding of the molecular mechanisms responsible for autonomous aldosterone overproduction in both sporadic and familial PA. Somatic mutations in four genes (KCNJ5, ATP1A1, ATP2B3 and CACNA1D), differently implicated in intracellular ion homeostasis, have been identified in nearly 60% of the sporadic APAs. Germline mutations in KCNJ5 and CACNA1H cause FH-III and FH-IV, respectively, while germline mutations in CACNA1D cause the rare PASNA syndrome, featuring primary aldosteronism seizures and neurological abnormalities. Further studies are warranted to identify the molecular mechanisms underlying BAH and FH-II, the most common forms of sporadic and familial PA whose molecular basis is yet to be uncovered.</jats:p

Phenotype reversion as “natural gene therapy” in Fanconi anemia by a gene conversion event

Somatic mosaicism appears as a recurrent phenomenon among patients suffering from Fanconi anemia (FA), but its direct prognostic significance mostly remains an open question. The clinical picture of FA mosaic subjects could indeed vary from just mild features to severe hematologic failure. Here, we illustrate the case of a proband whose FA familiarity, modest signs (absence of hematological anomalies and fertility issues), and chromosome fragility test transition to negative overtime were suggestive of somatic mosaicism. In line with this hypothesis, genetic testing on patient’s peripheral blood and buccal swab reported the presence of the only FANCA paternal variant (FANCA:c.2638C&gt;T, p. Arg880*) and of both parental alleles (the additional FANCA:c.3164G&gt;A, p. Arg1055Gln), respectively. Moreover, the SNP analysis performed on the same biological specimens allowed us to attribute the proband’s mosaicism status to a possible gene conversion mechanism. Our case clearly depicts the positive association between somatic mosaicism and the proband's favorable clinical course due to the occurrence of the reversion event at the hematopoietic stem cell level. Since this condition concerns only a limited subgroup of FA individuals, the accurate evaluation of the origin and extent of clonality would be key to steer clinicians toward the most appropriate therapeutic decision for their FA mosaic patients

Differences and homologies of chromosomal alterations within and between breast cancer cell lines: A clustering analysis

BACKGROUND: The MCF7 (ER+/HER2-), T47D (ER+/HER2-), BT474 (ER+/HER2+) and SKBR3 (ER-/HER2+) breast cancer cell lines are widely used in breast cancer research as paradigms of the luminal and HER2 phenotypes. Although they have been subjected to cytogenetic analysis, their chromosomal abnormalities have not been carefully characterized, and their differential cytogenetic profiles have not yet been established. In addition, techniques such as comparative genomic hybridization (CGH), microarray-based CGH and multiplex ligation-dependent probe amplification (MLPA) have described specific regions of gains, losses and amplifications of these cell lines; however, these techniques cannot detect balanced chromosomal rearrangements (e.g., translocations or inversions) or low frequency mosaicism. RESULTS: A range of 19 to 26 metaphases of the MCF7, T47D, BT474 and SKBR3 cell lines was studied using conventional (G-banding) and molecular cytogenetic techniques (multi-color fluorescence in situ hybridization, M-FISH). We detected previously unreported chromosomal changes and determined the content and frequency of chromosomal markers. MCF7 and T47D (ER+/HER2-) cells showed a less complex chromosomal make up, with more numerical than structural alterations, compared to BT474 and SKBR3 (HER2+) cells, which harbored the highest frequency of numerical and structural aberrations. Karyotype heterogeneity and clonality were determined by comparing all metaphases within and between the four cell lines by hierarchical clustering. The latter analysis identified five main clusters. One of these clusters was characterized by numerical chromosomal abnormalities common to all cell lines, and the other four clusters encompassed cell-specific chromosomal abnormalities. T47D and BT474 cells shared the most chromosomal abnormalities, some of which were shared with SKBR3 cells. MCF7 cells showed a chromosomal pattern that was markedly different from those of the other cell lines. CONCLUSIONS: Our study provides a comprehensive and specific characterization of complex chromosomal aberrations of MCF7, T47D, BT474 and SKBR3 cell lines. The chromosomal pattern of ER+/HER2- cells is less complex than that of ER+/HER2+ and ER-/HER2+ cells. These chromosomal abnormalities could influence the biologic and pharmacologic response of cells. Finally, although gene expression profiling and aCGH studies have classified these four cell lines as luminal, our results suggest that they are heterogeneous at the cytogenetic level