Clinicopathologic analysis of microscopically invasive breast carcinoma

Breast biopsy or mastectomy cases having diagnoses of carcinoma in situ with "microinvasion," "minimal invasion," "focal invasion," or "suggestive of invasion" were reviewed and all histologically identified foci of invasive disease from each case were measured using an ocular micrometer. Cases in which any single focus of invasion was greater than 5 mm or the added size of separate invasive foci exceeded 10 mm were excluded, resulting in a study group of 75 patients. Invasive neoplasm was present in the initial biopsy in 69 of 75 cases (92%); however, residual invasive neoplasm was found in the subsequent lumpectomy/mastectomy from 14 of these (20%). In 59% of cases, two or more histologically separate foci of invasion were identified. Invasive foci consisted of isolated cells or cell clusters, each less than 1 mm (microfocal invasion), in 33% of cases. In 12 cases, the sum of individual invasive foci was 5 to 10 mm. Axillary lymph nodes (LN) from 5 of 69 patients (7%) contained metastatic carcinoma (four cases, one LN positive; one case, two LN positive). The cumulative sizes of all invasive foci in the LN-positive group were microfocal invasion (one case), 0.6 mm (one case), 1.1 mm, 2.5 mm, and 5.8 mm. The difference in frequency of axillary node metastasis between tumors with microfocal and measurable invasion (4.3% v 8.6%) was not statistically significant. Follow-up data were available on 55 cases (mean interval, 66.1 months). One (node-negative) patient had duct carcinoma in situ recurrence in the same breast 4 years after initial treatment. Another (with unknown node status) developed an axillary lymph node metastasis 13 months after initial treatment (96% disease-free survival). We conclude that microscopic stromal invasion in breast carcinoma, at least in the setting of significant in situ component, is often initiated from multiple foci. Patients with microscopically invasive breast carcinoma have a small but significant risk of axillary metastases, although a highly favorable survival.     

Okadaic acid-induced lens epithelial cell apoptosis requires inhibition of phosphatase-1 and is associated with induction of gene expression including p53 and bax

We report the 2.2 A resolution structure of the Drosophila engrailed homeodomain bound to its optimal DNA site. The original 2.8 A resolution structure of this complex provided the first detailed three-dimensional view of how homeodomains recognize DNA, and has served as the basis for biochemical studies, structural studies and molecular modeling. Our refined structure confirms the principal conclusions of the original structure, but provides important new details about the recognition interface. Biochemical and NMR studies of other homeodomains had led to the notion that Gln50 was an especially important determinant of specificity. However, our refined structure shows that this side-chain makes no direct hydrogen bonds to the DNA. The structure does reveal an extensive network of ordered water molecules which mediate contacts to several bases and phosphates (including contacts from Gln50), and our model provides a basis for detailed comparison with the structure of an engrailed Q50K altered-specificity variant. Comparing our structure with the crystal structure of the free protein confirms that the N and C termini of the homeodomain become ordered upon DNA-binding. However, we also find that several key DNA contact residues in the recognition helix have the same conformation in the free and bound protein, and that several water molecules also are "preorganized" to contact the DNA. Our structure helps provide a more complete basis for the detailed analysis of homeodomain-DNA interactions.     

Prophylactic efficacy of tilmicosin for bovine respiratory tract disease

The prophylactic administration of injectable tilmicosin for pneumonia in weaned beef calves was investigated in 1,806 animals. Comparisons were made among calves receiving an "on-arrival" injection of tilmicosin, calves receiving a single injection of long-acting oxytetracycline, and calves receiving no prophylaxis. Morbidity and mortality attributable to pneumonia, morbidity and mortality attributable to all causes, and case fatality were significantly lower in the group of calves that received tilmicosin, compared with calves that received long-acting oxytetracycline and calves that received no prophylactic antibiotic. Mean time to initial pneumonia treatment was significantly extended in calves that received prophylaxis, compared with those that received no antibiotic on arrival at the feedlot. Calves that received tilmicosin gained significantly more weight than calves that received oxytetracycline. Calves that were not treated for pneumonia during the trial period gained significantly more weight than did those calves that were treated for pneumonia regardless of experimental group. The majority of mortalities were attributable to fibrinous pneumonia (31/34). Important bacterial isolates (Pasteurella spp, Haemophilus somnus, Actinomyces pyogenes) obtained at necropsy did not have resistance to tilmicosin in association with administration of tilmicosin as prophylaxis for pneumonia. However, bacterial resistance to trimethoprim/sulfonamide and to oxytetracycline were commonly found in these postmortem isolates.     

Subclavian venogram as a guide to lead implantation

Melatonin synthesis in retinal photoreceptors is stimulated at night by a circadian oscillator and suppressed acutely by light. To identify photoreceptor mechanisms involved in the acute suppression of melatonin synthesis, an action spectrum was measured for dark-adapted Xenopus laevis eyecups at night. Intensity-response curves at six wavelengths from 400 to 650 nm were parallel, suggesting that a single photopigment predominates in melatonin suppression. Half-saturating intensities at 400, 440, 480, and 533 nm were not significantly different from one another, at 1-2 x 10(8) quanta cm(-2) s(-1). Significantly higher intensities of 580- and 650-nm light were required for melatonin suppression. These results indicate a predominant role for the principal green-absorbing rods in acute regulation of retinal melatonin synthesis in response to light, and argue against an important role for the red-absorbing cones. Higher than expected sensitivity at short wavelengths suggests that photoreceptors sensitive to blue and/or violet light may also contribute to melatonin suppression.     

Supplemental methionine and time of supplementation effects on ruminal fermentation, digesta kinetics, and in situ dry matter and neutral detergent fiber disappearance in cattle

Two experiments were conducted to study the effects of methionine supplementation on ruminal fermentation and digesta kinetics. In Exp. 1, nine ruminally cannulated beef heifers (average initial BW = 527 kg) in a crossover design were fed low-quality grass hay and cottonseed meal with or without 11.4 g of supplemental methionine (polysaccharide-coated). Particulate and fluid kinetics, rate of DM and NDF disappearance, ruminal VFA and NH3 N concentrations, and pH were not altered (P > .10) by supplemental methionine; however, ruminal purine concentration was greater (P < .05) in methionine-supplemented heifers than in unsupplemented heifers. In Exp. 2, 12 ruminally cannulated Holstein steers (average initial BW = 622 kg) grazing a fescue pasture were allotted to one of three groups: no supplemental methionine (CON) or 11.4 g of supplemental methionine fed at 0700 (AM) or at 1200 (PM). Forage intake, particulate kinetics, ruminal fluid kinetics, pH, VFA, and NH3 N concentrations were not altered (P > .10) by supplemental methionine or supplementation time. In situ rate of DM and NDF disappearance was greater (P < .05) in supplemented steers than in CON steers; AM steers exhibited faster (P < .05) rates than PM steers. Overall, methionine supplementation of low-quality forage increased ruminal purine concentration but did not alter in situ fermentation or digesta passage, whereas supplementation at 0700, but not at 1200, of steers grazing fescue forage increased rate of NDF fermentation.     

Bending diamonds by femtosecond laser ablation

We present a new method based on femtosecond laser ablation for the fabrication of statically bent diamond crystals. Using this method, curvature radii of 1 m can easily be achieved, and the curvature obtained is very uniform. Since diamond is extremely tolerant to high radiation doses, partly due to its densely packed lattice, such bent crystals are optimal solutions for crystal-based collimation and/or extraction. Furthermore, using interlaced ablation on both sides, the technique opens for the possibility of constructing a crystalline undulator based on the best material known, to approach the enormous beam densities required for lasing operation of such a device.     

Discovery of Ubonodin,an Antimicrobial Lasso Peptide Active against Members of the Burkholderia cepacia Complex

We report the heterologous expression, structure, and antimicrobial activity of a lasso peptide, ubonodin, encoded in the genome of Burkholderia ubonensis. The topology of ubonodin is unprecedented amongst lasso peptides, with 18 of its 28 amino acids found in the mechanically bonded loop segment. Ubonodin inhibits RNA polymerase in vitro and has potent antimicrobial activity against several pathogenic members of the Burkholderia genus, most notably B. cepacia and B. multivorans, causative agents of lung infections in cystic fibrosis patients.     

Electrochemical process for the lamination of magnetic cores in thin-film magnetic components

The lamination of the core in thin film magnetic components is necessary to reduce the eddy current losses of the structure at high frequencies. The usual way to achieve lamination of the core is by physical vapor deposition (PVD) techniques. These methods are however costly and the deposition of layers is non selective. In this article, an almost entirely aqueous-based electrochemical process for the lamination of magnetic cores is presented. The process uses an electrodepositable photoresist Eagle 2100 ED codeposited with a catalyst (palladium). The Eagle layer is left as an insulator and the catalyst allows the activation of the layer for subsequent metallization. The process can be reproduced as many times as required for producing the multilayers. It is also selective: it does not require multiple photolithography steps. As a demonstration of the multilayer process, a core constituted of two layers of Ni/sub 80/Fe/sub 20/ (6 /spl mu/m each layer), separated by an Eagle insulating layer, electroplated over three-dimensional structures, was produced.     

Role of the liver and gut in systemic diphenhydramine clearance in adult nonpregnant sheep

We investigated the contribution of the liver and gut to systemic diphenhydramine (DPHM) clearance in adult nonpregnant sheep in two separate studies. In the first study, a simultaneous 50-mg bolus each of DPHM and its deuterium-labeled analog ([2H10]DPHM) was administered to five sheep via the femoral (i.v.) and the portal venous (p.v.) routes in a randomized manner. Arterial plasma concentrations of DPHM, [2H10]DPHM, and their deaminated metabolites, DPMA (diphenylmethoxyacetic acid) and [2H10]DPMA, were measured using gas chromatography-mass spectrometry. The hepatic first-pass extraction of DPHM after p.v. administration was 94.2 +/- 3.7%. However, the area under the plasma concentration versus time profile of the metabolite after i.v. dosing was only 32.5 +/- 14.0% relative to that after p.v. administration. Thus, only approximately 32.5% of the i.v. dose is metabolized in the liver and a significant extrahepatic systemic clearance component is evident. Using the calculated total hepatic blood flow values, it was found that 98.6 +/- 9.2% of the i.v. dose eventually was delivered to the "hepatoportal" system. Because the drug delivered to the hepatoportal system is almost completely eliminated in a single pass (hepatic extraction approximately 94%), this indicates a lack of any significant pulmonary drug uptake. Also, because only approximately 32.5% of the i.v. dose is metabolized in liver, the gut is most likely responsible for the clearance of the remainder. This gut contribution to systemic DPHM clearance was confirmed in a separate direct study in four sheep where the steady-state DPHM gut extraction ratio was 49.0 +/- 3.0%. Thus, gut accounts for a significant proportion (>/=50%) of DPHM systemic clearance in sheep in spite of a very high hepatic drug extraction efficiency.