Genomic analyses of germline and somatic variation in high-grade serous ovarian cancer.

BACKGROUND: High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 557 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations (SCNA). RESULTS: Approximately one-third of tumors had loss-of-function (LOF) germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM, and PALB2. LOF germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP, and NF1. In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of LOF variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536, and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. CONCLUSIONS: From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 557 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

Genomic Analyses of Germline and Somatic Variation in High-Grade Serous Ovarian Cancer.

Background High-grade serous ovarian cancers (HGSCs) display a high degree of complex genetic alterations. In this study, we identified germline and somatic genetic alterations in HGSC and their association with relapse-free and overall survival. Using a targeted capture of 577 genes involved in DNA damage response and PI3K/AKT/mTOR pathways, we conducted next-generation sequencing of DNA from matched blood and tumor tissue from 71 HGSC participants. In addition, we performed the OncoScan assay on tumor DNA from 61 participants to examine somatic copy number alterations. Results Approximately one-third of tumors had loss-of-function germline (18/71, 25.4%) or somatic (7/71, 9.9%) variants in the DNA homologous recombination repair pathway genes BRCA1, BRCA2, CHEK2, MRE11A, BLM , and PALB2 . Loss-of-function germline variants also were identified in other Fanconi anemia genes and in MAPK and PI3K/AKT/mTOR pathway genes. Most tumors harbored somatic TP53 variants (65/71, 91.5%). Using the OncoScan assay on tumor DNA from 61 participants, we identified focal homozygous deletions in BRCA1, BRCA2, MAP2K4, PTEN, RB1, SLX4, STK11, CREBBP , and NF1 . In total, 38% (27/71) of HGSC patients harbored pathogenic variants in DNA homologous recombination repair genes. For patients with multiple tissues from the primary debulking or from multiple surgeries, the somatic mutations were maintained with few newly acquired point mutations suggesting that tumor evolution was not through somatic mutations. There was a significant association of loss-of-function variants in homologous recombination repair pathway genes and high-amplitude somatic copy number alterations. Using GISTIC analysis, we identified NOTCH3, ZNF536 , and PIK3R2 in these regions that were significantly associated with an increase in cancer recurrence and a reduction in overall survival. Conclusions From 71 patients with HGCS, we performed targeted germline and tumor sequencing and provided a comprehensive analysis of these 577 genes. We identified germline and somatic genetic alterations including somatic copy number alterations and analyzed their associations with relapse-free and overall survival. This single-site long-term follow-up study provides additional information on genetic alterations related to occurrence and outcome of HGSC. Our findings suggest that targeted treatments based on both variant and SCNA profile potentially could improve relapse-free and overall survival.

Impact of near-infrared fluorescence imaging with indocyanine green on structural sequelae of anastomotic leakage after laparoscopic intersphincteric resection of malignant rectal tumors.

BACKGROUND: Recent studies have indicated the potential benefit of intraoperative near-infrared fluorescence imaging (NIR-FI) with indocyanine green in reducing early anastomotic leakage in colorectal surgery. Nonetheless, whether NIR-FI is effective in reducing structural sequelae of anastomotic leakage (SSAL) remains unclear. The aim of the present study was to investigate the impact of NIR-FI on SSAL after laparoscopic intersphincteric resection (ISR) of malignant rectal tumors. METHODS: This study was a retrospective single-center cohort study. A total of 293 consecutive patients who underwent elective laparoscopic ISR from May 2010 to August 2017 were included. Patients were divided into 2 groups; those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors using NIR-F (NIR-FI group) and those who underwent elective laparoscopic ISR with lymphadenectomy for malignant rectal tumors without using NIR-FI (control group). Thirty were excluded from the analyses (13 died, 7 had pelvic recurrence, and 10 were lost to follow-up). The primary endpoint was the rate of SSAL within 2 years after the primary resection, whereas the secondary endpoint was the rate of natural defecation via the anus at 2 years after the primary resection. Using various statistical analyses, such as propensity score matching, the rate of SSAL was compared between groups. RESULTS: A total of 263 patients were analyzed [177 males and 86 females, median age 61 (27-84) years]. Prior to propensity score matching (n = 263), NIR-FI was performed in 70 patients (26.6%) The rates of SSAL were 1.4% (1/70) in the NIR-FI group and 10.4% (20/193) in the control group (p = 0.02). After propensity score matching (n = 163), the rates of SSAL were 1.5% (1/66) in the NIR-FI group and 11.7% (12/103) in the control group (p = 0.02). Propensity score analyses, as well as simple regression analyses, revealed that NIR-FI was associated with a significantly lower risk of SSAL (OR 0.10-0.13; p = 0.03-0.05). CONCLUSIONS: NIR-FI is useful in reducing the rate of SSAL after laparoscopic ISR.

Amoeba-inspired nanoarchitectonic computing implemented using electrical Brownian ratchets.

In this study, we extracted the essential spatiotemporal dynamics that allow an amoeboid organism to solve a computationally demanding problem and adapt to its environment, thereby proposing a nature-inspired nanoarchitectonic computing system, which we implemented using a network of nanowire devices called 'electrical Brownian ratchets (EBRs)'. By utilizing the fluctuations generated from thermal energy in nanowire devices, we used our system to solve the satisfiability problem, which is a highly complex combinatorial problem related to a wide variety of practical applications. We evaluated the dependency of the solution search speed on its exploration parameter, which characterizes the fluctuation intensity of EBRs, using a simulation model of our system called 'AmoebaSAT-Brownian'. We found that AmoebaSAT-Brownian enhanced the solution searching speed dramatically when we imposed some constraints on the fluctuations in its time series and it outperformed a well-known stochastic local search method. These results suggest a new computing paradigm, which may allow high-speed problem solving to be implemented by interacting nanoscale devices with low power consumption.

Coexistence effect of UVA absorbers to increase their solubility and stability of supersaturation.

OBJECTIVE: Sunscreens containing UVA absorbers in high concentrations are expected to be developed, since recent studies have suggested the possibility of involvement of UVA ray in skin cancer and early skin aging. Solubility and stability of supersaturation of UVA absorbers in UVB absorber were determined in the absence and the presence of cosmetic oil. Coexistence effect of UVA absorbers was analyzed to dissolve them in high concentrations. METHODS: Two UVA absorbers, diethylamino hydroxybenzoyl hexyl benzoate (DHHB) and butyl methoxydibenzoylmethane (BMDM), a UVB absorber, 2-ethylhexyl methoxycinnamate (EHMC), and a cosmetic oil, 2-ethylhexyl ester of oligomer of hydroxystearic acid (EH-O-HSA), were used. Their solutions were prepared at 80°C and cooled to 5°C. The solid DHHB and/or BMDM were added to it, and the time evolution of concentrations of the UVA absorbers in the solution phase was monitored. RESULTS: At the saturation in the absence of EH-O-HSA at 5°C, weight ratio of DHHB and BMDM to EHMC was 0.39/1.00 and 0.22/1.00, respectively. Addition of EH-O-HSA slightly changed the solubility of DHHB and BMDM. When the weight ratio of EH-O-HSA to EHMC was 0.20/1.00, weight ratio of DHHB and BMDM to EHMC was 0.35/1.00 and 0.25/1.00, respectively at the saturation at 5°C. In the presence of EH-O-HSA, a strong coexistence effect of DHHB and BMDM was found on their solubility. A thermodynamically stable saturated solution at 5°C having the composition that DHHB: BMDM: EHMC: EH-O-HSA = 0.47: 0.46: 1.00: 0.20 was obtained by the simultaneous addition of solid DHHB and BMDM into the initial solution. CONCLUSION: The solution type composite having the highest concentrations of DHHB and BMDM prepared in this study exhibited critical wavelength at 368 nm that was just below the border for sunscreens being qualified as 'Broad Spectrum' protection under the new rule launched by US FDA.

ANGPTL4 is a secreted tumor suppressor that inhibits angiogenesis.

Tumor suppressors with extracellular function are likely to have advantages as targets for cancer therapy, but few are known. Here, we focused on angiopoietin-like 4 (ANGPTL4), which is a secreted glycoprotein involved in lipoprotein metabolism and angiogenesis, is methylation-silenced in human cancers, but has unclear roles in cancer development and progression. We found a deletion mutation in its coiled-coil domain at its N-terminal in human gastric cancers, in addition to hypermethylation of the ANGPTL4 promoter CpG islands. Forced expression of wild-type ANGPTL4, but not ANGPTL4 with the deletion, at physiological levels markedly suppressed in vivo tumorigenicity and tumor angiogenesis, indicating that the latter caused the former. Tumor-derived ANGPTL4 suppressed in vitro vascular tube formation and proliferation of human umbilical vascular endothelial cells, partly due to suppression of ERK signaling. These showed that ANGPTL4 is a genetically and epigenetically inactivated secreted tumor suppressor that inhibits tumor angiogenesis.

Isolation of a novel Saccharophagus species (Myt-1) capable of degrading a variety of seaweeds and polysaccharides.

A bacterial strain, Myt-1, was isolated in Toyama Bay in Toyama Prefecture, Japan. Myt-1 was capable of reducing the thalli of various seaweed species to single cell detritus particles. A 16S rDNA homology search revealed that the closest relative of Myt-1 was Saccharophagus degradans 2-40 (CP000282; 100% similarity), which was first isolated in Chesapeake Bay in Virginia, USA. The Myt-1 strain was capable of degrading more than 10 polysaccharides, almost all of which were also degraded by S. degradans 2-40. Analyses of alginase gene DNA sequence homology, DNA-DNA homology, and zymogram analysis of obtained polysaccharidases suggested that Myt-1 was a new species of Saccharophagus. Thus, Myt-1 is only the second species in this genus, which has contained only one strain and species since 1988, and was tentatively designated Saccharophagus sp. Myt-1. Myt-1 has considerable potential for reducing the volume of seaweed wastes, and for producing functional materials from seaweed substrate.

Wells syndrome associated with Churg­Strauss syndrome.

Churg­Strauss syndrome (CSS) is a systemic vasculitis occurring in patients with a history of asthma. Wells' syndrome (WS) is a rare inflammatory dermatosis that clinically resembles cellulitis, and is histologically characterized by eosinophilic infiltration and flame figures. We report a case of WS associated with CSS. There have been three previous reports of WS associated with CSS; ours is the fourth. All cases had bullous lesions, and three cases were positive for antineutrophil cytoplasmic antibodies.

Long-term effects of the oral adsorbent, AST-120, in patients with chronic renal failure.

The oral adsorbent AST-120 has been widely used in Japan to delay the initiation of dialysis therapy in patients with chronic renal failure. This study evaluated the long-term effects of AST-120 in patients with chronic renal failure who had not previously undergone dialysis. One hundred out-patients were prospectively enrolled and prescribed 6 g/day oral AST-120 for >or= 1 year. The clinical effectiveness of AST-120 was evaluated by comparing changes in the slope of the reciprocal serum creatinine-time plot (1/sCr slope) before and after AST-120 administration. The 1/sCr slope improved significantly after >or= 1 year of AST-120 treatment and greatest improvement was observed in patients with the longest AST-120 administration period (> 30 months). The results suggest that long-term treatment with AST-120 may be beneficial for chronic renal failure patients in the pre-dialysis stage.

Short-term changes in temporomandibular joint function in subjects with cleft lip and palate treated with maxillary distraction osteogenesis.

OBJECTIVES: To investigate the short-term effects of maxillary distraction osteogenesis (DO) on temporomandibular joint (TMJ) function in 21 subjects with cleft lip and palate (CLP). Design - Morphological changes in the maxillofacial region were measured using lateral cephalometric radiographs taken immediately before (pre-DO) and after DO (post-DO) and 1 year after DO (1-year follow-up). A questionnaire was evaluated using a visual analog scale. A chi-square test was used to compare the prevalence of TMJ symptoms between pre-DO and 1-year follow-up. The Spearman correlation coefficient was used to determine the correlation between changes in cephalometric variables and TMJ symptoms in association with maxillary DO. Statistical significance was set at p < 0.05. Results - The ANB (anteroposterior relationship of the maxilla with the mandible) angle and the mandibular plane angle at pre-DO, post-DO, and 1-year follow-up were -4.3 degrees , +5.8 degrees , +4.3 degrees and 32.1 degrees , 33.5 degrees , 33.6 degrees , respectively. The average amounts of anterior and downward movement of the maxilla at post-DO and 1-year follow-up were 8.3, -1.3 and 0.9, 1.1 mm, respectively. The prevalence of TMJ symptoms showed no significant increase in association with maxillary DO. Moreover, there was no significant correlation between changes in cephalometric variables and TMJ symptoms. Conclusion - These results suggest that there was no short-term (i.e., up to 1 year after DO) effect of maxillary DO on TMJ function in subjects with CLP.

Dose-response to a jelly preparation of calcium polystyrene sulfonate in patients with hyperkalemia--changes in serum potassium levels with or without a RAAS inhibitor.

AIMS: In this study, dose-response of the serum potassium-lowering effect of a calcium polystyrene sulfonate (PS) preparation was investigated. Changes in the serum potassium level were also examined with or without application of a RAAS inhibitor, which is said to increase the serum potassium level. SUBJECTS AND METHODS: 23 patients diagnosed to have hyperkalemia associated with chronic renal failure were enrolled in this study. The study drug, a PS-Ca jelly preparation (Argamate jelly), was started at a daily dose of 1 preparation (5 g as PS-Ca), and the dose was increased by 1 preparation every month to finally reach 3 preparations per day. Blood samples were collected once a month and serum levels of creatinine and electrolytes were measured. RESULTS: PS-Ca jelly decreased serum potassium levels in a dose-dependent manner. Decreases were 0.67 mEq/l at 5 g of PS-Ca/day, 1.06 mEq/l at 10 g/d, and 1.33 mEq/l at 15 g/d. Irrespective of the use of the RAAS inhibitor, serum potassium levels decreased significantly in a dose-dependent manner. Furthermore, no major change in serum creatinine levels occurred in subjects in which the RAAS inhibitor was used, although in subjects in which the RAAS inhibitor was not used, serum creatinine level tended to gradually increase. CONCLUSION: Serum potassium levels were reduced in a dose-dependent manner by administration of 5-15 g/d of PS-Ca, and it appeared that together with control of serum potassium levels, renal function should be maintained by continuous administration of RAAS inhibitor.

CLOCK is involved in obesity-induced disordered fibrinolysis in ob/ob mice by regulating PAI-1 gene expression.

BACKGROUND: An increased level of obesity-induced plasma plasminogen activator inhibitor-1 (PAI-1) is considered a risk factor for cardiovascular disease. AIM: The present study investigates whether the circadian clock component CLOCK is involved in obesity-induced PAI-1 elevation. METHODS: We examined plasma PAI-1 and mRNA expression levels in tissues from leptin-deficient obese and diabetic ob/ob mice lacking functional CLOCK protein. RESULTS: Our results demonstrated that plasma PAI-1 levels were augmented in a circadian manner in accordance with the mRNA expression levels in ob/ob mice. Surprisingly, a Clock mutation normalized the plasma PAI-1 concentrations in accordance with the mRNA levels in the heart, lung and liver of ob/ob mice, but significantly increased PAI-1 mRNA levels in adipose tissue by inducing adipocyte hypertrophy in ob/ob mice. The Clock mutation also normalized tissue PAI-1 antigen levels in the liver but not in the adipose tissue of ob/ob mice. CONCLUSION: These observations suggest that CLOCK is involved in obesity-induced disordered fibrinolysis by regulating PAI-1 gene expression in a tissue-dependent manner. Furthermore, it appears that obesity-induced PAI-1 production in adipose tissue is not closely related to systemic PAI-1 increases in vivo.

Expression of endothelial cell-associated molecules in AML cells.

Recently, it has been clarified that interaction between hematopoietic cells and endothelial cells is important in normal hematopoiesis and leukemogenesis. In this study, we examined the relationship between AML cells and endothelial cells by analyzing the expression profile of angiogenic factors, angiopoietin-1 (Ang-1), Ang-2, Tie-2 (a receptor for angiopoietins) and vascular endothelial growth factor (VEGF). Our results demonstrated that CD7(+)AML expressed Ang-2 mRNA frequently and integrin-family adhesion molecules (CD11c and CD18) intensively, suggesting the close correlation with endothelial cells. On the other hand, in t(8;21) AML cells, expression of Ang-2 was infrequent and expression of integrin-family adhesion molecules (CD11b, CD11c and CD18) was weak, suggesting the sparse association with endothelial cells. As for CD7(+)AML cells, despite the frequent and intense expression of endothelial cell-associated molecules (such as Ang-2, CD11c and CD18), intensity of Tie-2 expression was quite low (P < 0.05). Ang-2 expressed in CD7(+)AML cells is not considered to act in an autocrine fashion, but to work on endothelial cells to "feed" leukemic cells. Although Ang-2 is recognized as a natural antagonist for Tie-2, our data presented here suggested the alternative role of Ang-2 in the relationship between endothelial cells and leukemia cells, at least in a subset of leukemia such as CD7(+)AML. These results were supported by the study using AML cell lines, KG-1 (CD7 negative) and its subline KG-1a (CD7 positive); KG-1 had mRNA expression profile of Ang-1(+)Ang-2(-)Tie-2(+), while KG-1a showed Ang-1(+)Ang-2(+)Tie-2(-). These difference in the expression profile of angiogenic factors between CD7(+)AML and t(8;21)AML may explain the characteristic morphological features of these leukemias (CD7(+)AML as blastic type and t(8;21)AML as differentiative type).

Adenomatoid hyperplasia of the palate mimicking clinically as a salivary gland tumor.

This report describes an illustrative case of adenomatoid hyperplasia (AH) of the minor salivary glands on the palate of a 31-year-old man. The clinical features of the present lesion corresponded with those of pleomorphic adenoma, but histologically large lobules of normal-appearing mucous acini were found. The cell proliferative activity demonstrated in histological sections, by an immunohistochemical staining of proliferating cell nuclear antigen and Ki-67, showed no statistically significant differences among AH and a matched control group of normal palatal salivary glands. This case suggests that AH apparently exhibits an idiopathic, focal hypertrophic lesion of intraoral mucous glands with limited growth potential.

Magnification views of mammography decrease biopsy rates.

Mammography is a valuable tool for screening and has increased early detection of breast cancer. Magnification views are commonly used to further elucidate suspicious changes seen on routine mammograms. The effect of magnification views and their utility have not been studied regarding the influence on treatment strategies. All patients who had magnification views performed along with their mammogram at Tulane University Medical Center over a one-year period were included. Patient charts were reviewed for mammogram readings, recommendations, and any biopsy results. The original mammograms without the magnification views were given to a physician who was blinded to the final results of the magnification views for a recommendation of whether or not to biopsy the lesion. These recommendations were compared with the results with actual recommendations. Magnification views were performed on 127 patients. After the additional magnification views were taken 27 per cent (34 of 127) of patients had biopsies performed. Biopsy results revealed benign findings in 71 per cent and nonbenign findings (lobular carcinoma in situ, ductal carcinoma in situ, or carcinoma) in 29 per cent. On the basis of the recommendations without magnification views 64 per cent of patients would have had biopsies performed. Magnification views decreased the biopsy rates by 58 per cent (P < 0.001; chi2 tests). Magnification views can help decrease the number of biopsies performed for suspicious small areas on mammograms. Their judicious use can help decrease unnecessary procedures, patient anxiety, and cost. Magnification views are useful to help surgeons and radiologists best screen for breast cancer.

Phylogenetic relationships and evolution in Chrysosplenium (Saxifragaceae) based on matK sequence data.

Chrysosplenium (Saxifragaceae) consists of 57 species widely distributed in temperate and arctic regions of the Northern Hemisphere, with two species restricted to the southern part of South America. Species relationships within the genus are highly problematic. The genus has traditionally been divided into two groups, sometimes recognized as sections (Oppositifolia and Alternifolia), based on leaf arrangement, or, alternatively, into 17 series. Based on morphological features, Hara suggested that the genus originated in South America and then subsequently migrated to the Northern Hemisphere. We conducted phylogenetic analyses of DNA sequences of the chloroplast gene matK for species of Chrysosplenium to elucidate relationships, test Hara's biogeographic hypothesis for the genus, and examine chromosomal and gynoecial diversification. These analyses revealed that both sections Oppositifolia and Alternifolia are monophyletic and form two large sister clades. Hence, leaf arrangement is a good indicator of relationships within this genus. Hara's series Pilosa and Macrostemon are each also monophyletic; however, series Oppositifolia, Alternifolia, and Nepalensia are clearly not monophyletic. MacClade reconstructions suggest that the genus arose in Eastern Asia, rather than in South America, with several independent migration events from Asia to the New World. In one well-defined subclade, species from eastern and western North America form a discrete clade, with Old World species as their sister group, suggesting that the eastern and western North American taxa diverged following migration to that continent. The South American species forms a clade with species from eastern Asia; this disjunction may be the result of ancient long-distance dispersal. Character mapping demonstrated that gynoecial diversification is dynamic, with reversals from inferior to half-inferior ovaries, as well as to ovaries that appear superior. Chromosomal evolution also appears to be labile with several independent origins of n = 12 (from an original number of n = 11) and multiple episodes of aneuploidy.

Induction of intestinal cytochrome P450 (CYP3A) by rifampicin in beagle dogs.

Both male and female beagle dogs (four dogs/sex) were orally treated with rifampicin (Rif) at the dose of 10 mg/kg/day for 7 days and an additional eight dogs (four dogs/sex) were used as a control. The inducible effect of Rif on intestinal cytochrome P450, especially CYP3A enzyme, was investigated by measuring microsomal testosterone 6beta-hydroxylation (6beta-OHT) activity, immunoblot and ELISA analysis. In male dogs, microsomal 6beta-OHT activity in the duodenum, upper, middle and lower part of the jejunum and the ileum of the control was 229, 204, 194, 129 and 57 pmol/min/mg protein, while the activity of the Rif-treated dogs significantly increased to 456, 486, 430, 192 and 138 pmol/min/mg protein, respectively. The activity of intestinal 6beta-OHT in the control and Rif-treated female dogs showed almost similar levels to those observed in the corresponding male dogs. The activity of intestinal 6beta-OHT in both control and Rif-treated dogs was specifically inhibited by anti-CYP3A12 antiserum. The apparent K(m) value for 6beta-OHT activity in all sections of the small intestine was comparable with that in the liver, and no significant changes were observed in between control and Rif-treated dogs. In both control and Rif-treated dogs, immunoblotting of intestinal microsomes with anti-CYP3A12 antiserum produced a band indistinguishable from that of purified CYP3A12 or of immunoreactive CYP3A12 in liver microsomes. A significant increase in intestinal CYP3A content by Rif treatment was quantitatively verified by the ELISA analysis and the magnitude of its increase correlated well with that of 6beta-OHT activity elevation. Furthermore, the results of immunohistochemistry using the anti-CYP3A12 antiserum indicated that CYP3A protein was specifically distributed in epithelial cells throughout the small intestine and appeared to be predominant at the apical side of villus cells. These results demonstrate that Rif induces not only hepatic CYP3A12 but also intestinal CYP3A in dogs.

Mammary duct ectasia in children presenting bloody nipple discharge: a case in a pubertal girl.

Mammary duct ectasia occurs rarely in childhood. The authors report on the case of a pubertal girl who was operated on for duct ectasia with bloody nipple discharge. Duct ectasia is regarded as a primary lesion; it is considered to be a cause of bloody secretion, and it has a mechanism similar to that of mammary duct papilloma.