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C Muller

Publications and source records attributed to C Muller.

At least 55 records · Page 3Linked to original sources

Human normal peripheral blood B-lymphocytes are deficient in DNA-dependent protein kinase activity due to the expression of a variant form of the Ku86 protein.

The heterodimeric Ku protein, which comprises a 86 kDa (Ku86) amd a 70 kDa (Ku70) subunits, is an abundant nuclear DNA-binding protein which binds in vitro to DNA termini without sequence specificity. Ku is the DNA-targeting component of the large catalytic sub-unit of the DNA-dependent protein kinase complex (DNA-PK[CS]), that plays a critical role in mammalian double-strand break repair and lymphoid V(D)J recombination. By using electrophoretic mobility shift assays, we demonstrated that in addition to the major Ku x DNA complex usually detected in cell line extracts, a second complex with faster electrophoretic mobility was observed in normal peripheral blood lymphocytes (PBL) extracts. The presence of this faster migrating complex was restricted to B cells among the circulating lymphocyte population. Western blot analysis revealed that B cells express a variant form of the Ku86 protein with an apparent molecular weight of 69 kDa, and not the 86 kDa- full-length protein. Although the heterodimer Ku70/variant-Ku86 binds to DNA-ends, this altered form of the Ku heterodimer has a decreased ability to recruit the catalytic component of the complex, DNA-PK(CS), which contributes to an absence of detectable DNA-PK activity in B cells. These data provide a molecular basis for the increased sensitivity of B cells to ionizing radiation and identify a new mechanism of regulation of DNA-PK activity that operates in vivo.

Antigens, Nuclear↗

UV sensitivity and impaired nucleotide excision repair in DNA-dependent protein kinase mutant cells.

DNA-dependent protein kinase (DNA-PK), a member of the phosphatidyl-inositol (PI)3-kinase family, is involved in the repair of DNA double-strand breaks. Its regulatory subunit, Ku, binds to DNA and recruits the kinase catalytic subunit (DNA-PKcs). We show here a new role of DNA-PK in the modulation of the process of nucleotide excision repair (NER) in vivo since, as compared with their respective parental cell lines, DNA-PK mutants (scid , V-3 and xrs 6 cells) exhibit sensitivity to UV-C irradiation (2.0- to 2.5-fold) and cisplatin ( approximately 3- to 4-fold) associated with a decreased activity (40-55%) of unscheduled DNA synthesis after UV-C irradiation. Moreover, we observed that wortmannin sensitized parental cells in vivo when combined with either cisplatin or UV-C light, but had no effect on the DNA-PKcs deficient scid cells. Despite a lower repair synthesis activity (approximately 2-fold) measured in vitro with nuclear cell extracts from DNA-PK mutants, a direct involvement of DNA-PK in the NER reaction in vitro has not been observed. This study establishes a regulatory function of DNA-PK in the NER process in vivo but rules out a physical role of the complex in the repair machinery at the site of the DNA lesion.

Androstadienes↗

Antimicrobial activity of exocrine glandular secretions, hemolymph, and larval regurgitate of the mustard leaf beetle phaedon cochleariae

Larvae and adults of the mustard leaf beetle Phaedon cochleariae (Coleoptera: Chrysomelidae) possess exocrine glands with secretions which are used in defense against predators. This study addressed the question whether these defensive secretions also display antimicrobial activity. Additionally, the effects of larval and adult hemolymph and larval regurgitate toward microorganisms were examined. The larval glandular secretion showed growth-inhibitory activity against the gram-negative bacterium Escherichia coli, but no lytic effect against cell walls of the gram-positive bacterium Micrococcus luteus. Growth of the yeast Saccharomyces cerevisiae and of the entomopathogenic fungus Beauveria bassiana was also inhibited by the larval secretion. The antibacterial and antifungal activity of the larval secretion was found to be due to its main component, the iridoid monoterpene, (epi)chrysomelidial. The mechanism of its antifungal activity was examined by different bioassays and compared to the commercially available fungicide nystatin. The antifungal activity of the larval secretion is not due to a loss of intracellular potassium in treated fungal cells, while high potassium efflux from treated cells is the mode of action of common fungicides. The larval secretion exhibited direct cytotoxicity against both fungal cells and plasmatocytes isolated from the greater wax moth Galleria mellonella. In contrast to the larval secretion, the adult glandular secretion of P. cochleariae showed lytic activity against the cell walls of the gram-positive bacterium M. luteus, but no activity against the gram-negative bacterium E. coli and eukaryotic cells. Hemolymph and larval regurgitate of P. cochleariae displayed the same activity as the tested glandular secretion of adults. Copyright 1998 Academic Press.

Journal Article↗

AT2 antagonist-sensitive potentiation of angiotensin II-induced constriction by NO blockade and its dependence on endothelium and P450 eicosanoids in rat renal vasculature.

1. We showed earlier that NO inhibition caused a left-shift and augmented Emax of the concentration-response curve of AT1-mediated (angiotensin II)-induced vasoconstrictions (AII-VC) in the rat kidney. The 0.01-0.1 nM AII-VC unmasked by the potentiating effect of NO inhibition, were sensitive not only to AT1 (L158809), but also to AT2 receptor (PD123319) antagonists. We now demonstrate the role of endothelium and eicosanoids in the NO-masked AT1/AT2-mediated component of the AII-VC in isolated indomethacin-perfused kidneys of the rat. 2. L-NAME increased 0.1 nM AII-VC 7.2 fold. Pretreatment of the kidneys with factor VIII antibody/complement or with the detergent CHAPS to damage endothelium, decreased carbachol-induced vasodilatation and blunted by 60 and 30% respectively, the enhancement of AII-VC during NO inhibition. 3. L-NAME also increased 3 microM noradrenaline (NA)-induced vasoconstriction (NA-VC) 8.1 fold. In contrast to AII-VC, endothelium damage was without effect on the enhancement of NA-VC by L-NAME, suggesting a dominant role of endothelium-derived NO in the enhancement of NA-VC. 4. During NO inhibition, ETYA (2 microM; an inhibitor of all arachidonic acid derived pathways) and alpha-naphtoflavone (10 microM; an inhibitor of the cytochrome P450 isozymes), decreased by 85% the 0.1 nM AII-VC. 5. In conclusion, during NO inhibition, the AT1-mediated constriction to low concentrations of AII, which is sensitive to AT2 antagonists, depends on intact endothelium, and can be blocked by inhibition of eicosanoid synthesis. The results suggest that the AII-mediated vasoconstriction through AT1 receptors is potentiated in the absence of NO, by the release of eicosanoids from the endothelium through AT2 receptors.

5,8,11,14-Eicosatetraynoic Acid↗

Acute myeloid leukemia cells with low P-glycoprotein expression and high rhodamine 123 efflux capacity display high clonogenicity.

This study was designed to correlate the clonogenic capacity of acute myeloid leukemia (AML) cells with P-glycoprotein (P-gp) expression level and P-gp-mediated efflux capacity. Fifty AML cell samples were tested for P-gp expression using MRK16 monoclonal antibody and flow cytometry. Among them, 12 samples were selected for sorting experiments according to the following two criteria: their clonogenic capacity in methylcellulose in the presence of 5637 conditioned medium, and the heterogeneity of P-gp distribution in leukemic cells. For each of these 12 samples, leukemic cells which displayed the highest P-gp expression level (P-gp++) and P-gp- leukemic cells were sorted after MRK16 staining and seeded into methylcellulose for primary clonogenic assay. In each case, the number of CFU-L in the P-gp fraction was significantly higher than that of the P-gp++ fraction (P < 0.01); the median number of CFU-L for 10(5) seeded cells being 147 (range 3-1855) and 495 (range 60-4100) for P-gp++ and P-gp- populations, respectively. Furthermore, in order to correlate clonogenic capacity and P-gp function, AML cells were stained with rhodamine 123 (Rh 123), washed and then sorted after 4 h incubation at 37 degrees C in Rh 123-free media on the basis of their residual fluorescence intensity before plating. For each of six samples, we found that the number of CFU-L in the AML cell fraction which displayed the most efficient Rh 123 efflux capacity (Rh 123dull) was significantly higher compared to that of the AML cell fraction which displayed high residual fluorescence signal (Rh 123bright) (P = 0.05); the median number of CFU-L for 10(5) seeded cells being 1025 (range 250-2240) and 296 (range 11-838) for Rh 123dull and Rh 123bright populations, respectively. Altogether this study suggests that, for an individual AML cell population, the clonogenic fraction is preferentially recruited in AML cells which display low P-gp expression and high P-gp-mediated efflux capacity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Role of eicosanoids in renal angiotensin II vasoconstriction during nitric oxide blockade.

Nitric oxide (NO) buffers the effect of vasoconstrictors currently active in the renovascular system. Enhancement of the angiotensin II (Ang II)-induced vasoconstriction during NO blockade comprises both AT2-sensitive potentiation, decreasing the half maximal vasoconstriction (EC50) value to the subnanomolar concentration range, and augmentation, increasing the maximal effect (Emax) value in the isolated perfused rat kidney. In this study, we examine whether constrictory prostanoids are involved in Ang II subtype receptor (AT2)-sensitive potentiation of the Ang II effect during NO blockade. Thus, Ang II-induced vasoconstriction (0.1 or 10 nM Ang II) was measured in six series of constant-flow perfused isolated rat kidneys in the presence of indomethacin under control conditions, during NO inhibition, and during combined inhibition of NO and all arachidonic pathways by eicosatetraynoic acid (ETYA), an analog of arachidonic acid. The vasoconstriction elicited by 10 nM Ang II, which is the maximal response, increased about threefold during NO inhibition compared with control. This augmentation was not affected by ETYA. In contrast, the vasoconstriction elicited by 0.1 nM Ang II increased about 20-fold during NO inhibition, reflecting mainly potentiation of the Ang II effect. This increase was abrogated by ETYA. We conclude that vasoconstrictor eicosanoids, which are suppressed by endogenous NO, mediate AT2-sensitive potentiation of the Ang II-induced vasoconstriction in the rat kidney.

5,8,11,14-Eicosatetraynoic Acid↗

Functional outcome and specific complications of gastrocystoplasty for failed bladder exstrophy closure.

PURPOSE: The encouraging initial results of gastrocystoplasty led us to perform it for failed bladder exstrophy closure. We assess the functional outcome of the augmented bladder and evaluate complications related directly to use of the stomach in this specific group of children. MATERIALS AND METHODS: We performed gastrocystoplasty in 22 children an average of 9.5 years old with a small, poorly compliant bladder after staged reconstruction of bladder exstrophy failed. Followup ranged from 6 months to 6 years (mean 3 years). RESULTS: Complete urinary continence was achieved in 14 children (64%). Voiding via the urethra was possible in 13 patients (60%) but post-voiding residual urine was significant in 12. Bladder capacity increased from a mean of 77 to 270 ml. Bladder capacity decreased during followup in 3 children, requiring repeat augmentation. Six children had isolated dysuria and 2 had dysuria with hematuria. Perforation of the gastric patch and a bleeding gastric ulcer occurred in 1 patient each. CONCLUSIONS: The disadvantages of gastrocystoplasty outnumber its advantages after failed bladder exstrophy closure. Urethral sensation makes dysuria a major discomfort. Safety is not optimal, since perforation may occur. Voiding is not efficient because gastrocystoplasty provides continence only when it is associated with intermittent catheterization. Bladder capacity is insufficiently augmented and inconsistent during followup. We believe that the use of gastrocystoplasty in cases of failed bladder exstrophy closure should be reconsidered.

Adolescent↗

Expression of PAX2 gene during human development.

The expression of human paired-box-containing PAX2 gene was examined in 7 human conceptuses 6 to 9 weeks old by in situ hybridization. The embryos were collected after legal abortions, embedded in paraffin, serially cut in transversal direction and treated with S35 labeled probe for PAX2. In the neural tube of 6-week embryos, PAX2 was expressed in the outer part of the ventricular zone on both sides of the sulcus limitans. At later stages, it was expressed in the intermediate zone of the spinal cord, both in alar and basal plates except in the region of motor neuroblasts. In the brain, expression of PAX2 extended from mesencephalic-rhombencephalic border along the entire rhombencephalon in a manner similar to that described for the spinal cord. Expression of PAX2 gene in the eye was seen in the optic cup and stalk, and later in the optic disc and nerve. In the ear, expression was restricted to the part of the otic vesicle flanking the neural tube and later to the utricle and cochlea. Expression of PAX2 was observed in developing kidneys as well. During human development PAX2 has a spatially restricted expression along the compartmental boundaries of the neural tube, and within developing eye, ear and kidneys. Differentiation of those organs seems to be mediated by PAX2 gene at the defined stages of human development.

DNA-Binding Proteins↗

Regulation of DNA-dependent protein kinase activity in leukemic cells.

The DNA-dependent protein kinase (DNA-PK) complex is composed of a catalytic (DNA-PKcs), and a regulatory subunit (Ku70/Ku86 heterodimer). The expression and function of DNA-PK subunits was investigated in purified blood lymphocytes obtained from patients with chronic lymphocytic leukemia (CLL) either refractory to chemotherapy or untreated. Variations in DNA-PK activity were found amongst CLL samples by comparison to human cell lines. It was noticeable that the low DNA-PK activity was associated with samples from untreated patients that exhibited a sensitivity phenotype, determined in vitro, to the radiomimetic agent neocarcinostatin by comparison to samples from refractory patients. The regulation in DNA-PK activity was associated with Ku heterodimer expression while DNA-PKcs was unaffected. Moreover, the presence of an altered form of the Ku86 subunit was identified in samples with low DNA-PK activity. These results suggest a regulation process of the DNA-PK activity in fresh human cells.

Aged↗

The processing routes determined by negatively charged residues in DR1-restricted T cell determinants.

The presentation pathways followed by DR1-restricted determinants from the fusion protein of measles virus were studied. By assessing the capacity of various APC preparations to stimulate fusion protein-specific T cells, it was shown that the determinant contained within the fusion protein sequence 254-268 (F254) relies on newly synthesized DR1 protein for its presentation. By contrast, the determinant contained within the fusion protein sequence 314-328 (F314) is captured by DR1 protein recycled from the plasma membrane. In vitro binding analyses showed that the F254 and F314 peptides optimally bind to DR1 at pH 4 and pH 5, respectively. In addition, it was found that binding of the F254 peptide to DR1 is much poorer at pH 7 than at pH 4, while binding of the F314 peptide was decreased only moderately at pH 7 as compared with pH 5. Substitution of the glutamic acid 261 for an alanine in the F254 peptide resulted in an analogue with an improved capacity of binding to DR1 at neutral pH. By contrast, replacement of the valine 319 by a glutamic acid in the F314 peptide generated an analogue with a decreased binding capacity at pH 7. These findings indicated that determinants that do not bear acidic residues are captured efficiently by DR1 molecules over a broader range of pH than determinants containing acidic residues. Binding analyses between DR1 and four additional peptides further supported this conclusion. Altogether, these results suggested that acidic residues, by tuning the optimal pH for the assembly of peptide-DR1 complexes, determine the processing pathway followed by the determinants.

Amino Acid Sequence↗

Deletions of chromosome 3p are frequent and early events in the pathogenesis of uterine cervical carcinoma.

To study the molecular abnormalities involved in the multistage development of cervical carcinoma (CC), we investigated the presence of oncogenic human papillomavirus (HPV) sequences, loss of heterozygosity (LOH), and microsatellite alterations at several genes/loci at 3p (3p14.2 at the FHIT gene, 3p14.3-21.1, 3p21, and 3p22-24.2), 9p21, RB and P53, and P53 gene point mutations in precisely microdissected archival tissues from 20 CCs and their accompanying precursor lesions (cervical intraepithelial neoplasia, CIN; n = 40) and normal epithelia (n = 20). In all HPV-positive cases (90% of CCs), HPV sequences were detected as the earliest appearing molecular change or simultaneously with other changes. LOH at any 3p region was found in 70% of CCs, and 3p14.2 (FHIT gene/FRA3B fragile site) (56%) and 3p21 (57%) were the most frequent 3p sites of loss. LOH at some 3p region was in the CIN I stage, and the 3p deletions in precursor CIN lesions were smaller than the 3p losses found in the associated invasive CC. LOH at the other regions studied and P53 gene mutations were less frequent and later events. Microsatellite alterations were detected in 35% of CCs, and identical abnormalities were detected in the associated precursor lesions. Although infection with oncogenic HPV strains is the earliest and most frequent molecular event, progressive deletions at one or more 3p regions (particularly at 3p14.2, and 3p21) are also frequent events occurring early in the pathogenesis of CC.

Acid Anhydride Hydrolases↗

AT2-antagonist sensitive potentiation of angiotensin II-induced vasoconstrictions by blockade of nitric oxide synthesis in rat renal vasculature.

1. Although the actions of angiotensin II (Ang II) on renal haemodynamics appear to be mediated by activation of the AT1 receptor subtype, AT2 binding sites have also been evidenced in the adult kidney vasculature. As NO is known to mask part of the renal effects of vasoconstrictor drugs, we queried whether the Ang II-induced vasoconstrictions could occur via multiple receptor subtypes during inhibition of NO synthesis. We explored the effect of AT1 and AT2 receptor (AT-R) antagonists on Ang II-induced pressure increases during NO synthase or soluble guanylyl cyclase inhibition in rat isolated kidneys perfused in the presence of indomethacin at constant flow in a single-pass circuit. 2. In the absence of NO blockade, the AT1-R antagonist L-158809 (500 nM) antagonized the Ang II-induced vasoconstrictions, while the AT2-R antagonist PD-123319 (500 nM) had no effect. 3. Perfusing kidneys in the presence of either NO synthase inhibitors, L-NAME (100 microM) or L-NOARG (1 mM), or soluble guanylyl cyclase inhibitor, LY-83583 (10 microM), significantly increased both molar pD2 (from 9.40+/-0.25 to 10.36+/-0.11) and Emax values (from 24.9+/-3.1 to 79.9+/-4.9 mmHg) of the concentration-response curve for Ang II-induced vasoconstriction. 4. In the presence of L-NAME, 500 nM L158809 abolished the Ang II-induced vasoconstrictions whatever the concentration tested. On the other hand, 500 nM PD-123319 reversed the left shift of the concentration-response curve for Ang II (molar pD2 value 9.72+/-0.13) leaving Emax value unaffected (91.3+/-7.6 mmHg). 5. In the presence of L-NAME, the potentiated vasoconstriction induced by 0.1 nM and the augmented vasoconstriction induced by 10 nM Ang II were fully inhibited in a concentration-dependent manner by L-158809 (0.05-500 nM). By contrast, PD-123319 (0.5-500 nM) did not affect the 10 nM Ang II-induced vasoconstriction and concentration-dependently decreased the 0.1 nM Ang II-induced vasoconstriction plateauing at 65% inhibition above 5 nM antagonist. 6. Similar to PD-123319, during NO blockade the AT2-R antagonist CGP-42112A at 5 nM decreased by 50% the 0.1 nM Ang II-induced vasoconstriction and at 500 nM had no effect on 10 nM Ang II-induced vasoconstriction. 7. In conclusion, the renal Ang II-induced vasoconstriction, which is antagonized only by AT1-R antagonist in the presence of endogenous NO, becomes sensitive to both AT1- and AT2-R antagonists during NO synthesis inhibition. While AT1-R antagonist inhibited both L-NAME-potentiated and -augmented components of Ang II-induced vasoconstriction, AT2-R antagonists inhibited only the L-NAME-potentiated component.

Angiotensin II↗

Serum N-terminal pro-atrial natriuretic factor 1-98 before and during thyroxine replacement therapy in severe hypothyroidism.

Decreased plasma concentrations of atrial natriuretic factor (ANF) and of its N-terminal prohormones have been demonstrated in severely hypothyroid patients compared with control subjects, and shown to normalize with thyroxine (T4) replacement therapy. Whether this depends on thyroid hormone deficiency exclusively or is secondary to hemodynamic changes that result from it remains a matter of debate. In a recent investigation dose-related increases in both ANF and N-terminal prohormones of ANF by T4 replacement therapy in incremental doses increased at 4-week intervals were demonstrated. It was suggested that thyroid hormones may enhance synthesis rather than release of atrial peptide hormones. The aim of the present study was to confirm this assumption in hypothyroid patients with normal cardiac performance. Serum N-terminal amino acids 1-98 (ie, pro-ANF 1-98) of pro-ANF was determined in 11 severely hypothyroid patients without pericardial effusion and with normal cardiac left ventricular function. Mean pro-ANF 1-98 concentration before T4 replacement therapy remained unchanged after 10 days on T4 (p = .12). After 2 months of therapy, mean pro-ANF 1-98 was significantly increased compared with pretreatment values (p < .003). A significant correlation to the increase in free T4 (r = 0.48, p < .01) but not to the decrease in thyrotropin (TSH) (r = -0.32, p = .09) was found. The present results indicate that thyroid hormones directly increase pro-ANF 1-98 independently of cardiac hemodynamics in the hypothyroid state.

Adult↗

Postnatal development of vascular resistance of the rabbit isolated perfused kidney: modulation by nitric oxide and angiotensin II.

Studies were performed on isolated perfused kidneys (IPK) from postnatal developing rabbits to ask 1) whether the high renal vascular resistance (RVR) at birth involves intrinsic renal mechanisms, 2) whether nitric oxide (NO) release is involved in the modulation of renal vascular tone, and 3) whether NO modulates exogenous angiotensin II (AII)-induced vasoconstrictions. Kidneys isolated from 1-wk-old (during nephrogenesis), 3-wk-old (after nephrogenesis), and 6-wk-old rabbits were perfused in the presence of 10(-5) M indomethacin. RVR decreased with age from 12.7 +/- 0.6 at 1 wk to 10.1 +/- 0.5 mm Hg min g mL-1 at 6 wk. N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-4) M) comparably increased RVR by about 30% at 1, 3, and 6 wk. The vasoconstrictions induced by 10(-8) M AII increased basal pressure from 28% at 1 wk to 78% at 6 wk and were potentiated by L-NAME by about 100%. In contrast, the vasoconstrictions induced by 10(-10) M AII decreased from 8% at 1 wk to 0% at 6 wk and were potentiated by L-NAME by about 250% at 1 and 3 wk. We conclude that during postnatal development: 1) RVR in IPK decreases in absence of AII and extrarenal influences, suggesting that high RVR at birth involves intrinsic mechanisms, 2) L-Arg/NO modulates basal tonus in developing IPK, and, 3) renal vasoconstrictor responses to exogenous AII are buffered by NO at early postnatal stages and follow an AII concentration-dependent developmental pattern. A specific neonatal high affinity AII/NO interaction disappearing after nephrogenesis completion precedes a low affinity AII/NO interaction, which progressively increases toward adult ages. These findings are in favor of a specific involvement of AII-NO interactions in the control of developing renal hemodynamics.

Age Factors↗

[Analysis of the results of 137 subclinical breast lesions excisions. Value of ultrasonography in the early diagnosis of breast cancer].

OBJECTIVE: Ultrasonography is invaluable for evaluation of palpable masses and masses detected by mammography. Ultrasound has no proved role in breast screening. Between 1991 and 1994, we included ultrasonography routinely in our screening mammography prescription, not only for evaluation of mass detected by mammography but also in radiographically dense, non-radiolucent breast. One hundred and thirty-seven suspicious but non palpable breast lesions were detected. We analyzed the results of the surgical excision biopsies of these lesions and evaluated the contribution of ultrasonography combined with mammography to detect occult breast cancers. MATERIAL AND METHODS: From 1991 to 1994, our institution performed 8,489 individual screening mammographies. All women underwent physical examination before mammography. Women with abnormal clinical breast examination are not included in the study. Ultrasonography was routinely performed for characterization of a mass detected by mammography and also in normal breast with dense, non-radiolucent tissue. One hundred and thirty-seven suspected breast lesions were removed after immediate preoperative stereotaxic or US-guided needle localization. Screened women were aged 29-72 years (mean 51 years). 48% of all screened women were aged 50 years and older. RESULTS: The histopathologic findings were as follow: invasive ductal carcinoma (IDC) 40 cases (59%), invasive lobular carcinoma (ILC) 7 cases (10%), ductal carcinoma in situ 21 cases (31%). Infracllnic cancer was identified by mammography alone in 45% of cases, by mammography and sonography in 43.2% of cases, by sonography alone in 11.8% of cases. About 31% of infraclinic cancer occur prior to the age of 50 (age range: 29-72, mean: 54). Cancer less than 10 mm in diameter were found in 57.5% of lesions. Axillary dissection was performed in 46 cases of invasive cancer, with a incidence of axillary node metastases of 15%. CONCLUSION: The combination of mammography and ultrasonography is effective to detect a greater number of occult breast cancers and we recommend ultrasonography not only for evaluation of a mass detected by mammography but also in radiographically dense non-radiolucent breast lesions.

Adult↗