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The role of frozen section analysis of margins during breast conservation surgery.

PURPOSE: The role of frozen section analysis during breast conservation surgery is undefined. Assessment of margins using permanent section evaluation is the standard method of ensuring complete tumor excision. If the margin is positive, however, surgical re-excision is necessary to reduce the likelihood of subsequent local recurrence. Therefore, biopsy of the surgical cavity with immediate pathological evaluation during lumpectomy was performed to evaluate the effect on local recurrence, the number of re-excisions, and cosmesis. PATIENTS AND METHODS: One hundred sixty patients underwent attempted lumpectomy with frozen section margin determination. One hundred forty patients were available for long-term follow-up (mean = 57 months, median = 46 months). All patients underwent attempted breast conservation surgery, which consisted of tumorectomy with excision of a greater than 1-cm rim of grossly normal tissue. Tumor margins were obtained by intraoperative biopsy with frozen section analysis of the lumpectomy cavity walls. RESULTS: In 21 patients (15%), frozen section analyses (FSA) revealed positive margins, resulting in immediate re-excision. In seven of these patients (5%), margins were persistently positive, and these patients therefore underwent mastectomy. Fourteen patients were successfully re-excised to a negative margin. The sensitivity and specificity of FSA were 91% and 100%, respectively. Five percent of patients definitively managed by lumpectomy with FSA of margins recurred locally. The mean cosmesis score after radiotherapy was 7.0 out of a possible 10, correlating with a good to excellent result. DISCUSSION: The accuracy of FSA, low recurrence rate, avoidance of reoperation, and good cosmesis indicate that intraoperative frozen section analysis should be adopted as a safe and effective method of margin analysis during breast conservation surgery.

Breast Neoplasms↗

Who's who in Conservation Biology--an authorship analysis.

As the flagship journal of the field, Conservation Biology represents a multidisciplinary, global constituency of conservation professionals--a constituency composed of more than 5200 authors representing 1500 organizations and 89 countries. Using bibliometric records of research published in Conservation Biology, I evaluated trends in authorship of research papers from 1987 to 2005. Authorship diversified and became increasingly collaborative over time. North Americans now compose one-half of primary authorship, down from 75% in the 1990s, and European primary authors contribute a quarter of the journal's contributed research. Forty-five countries were represented in volume 19 of the journal. The top three most-cited authors are Australian. The percentage of single-authored papers declined from 57% in 1987 to 18% in 2005. Collectively, academic institutions contribute the most research to Conservation Biology, although a government agency, the U.S. Department of Agriculture Forest Service, was the single most-productive organization. The maturing of conservation biology as a discipline, the complex geographic and multidisciplinary nature of conservation questions, and the increased ease of communication in a technologically connected world contribute to the increasingly diverse and collaborative Conservation Biology authorship.

Authorship↗

Kernel density analysis of variable and conserved regions of the envelope proteins of human immunodeficiency virus type 1 and associated epitopes.

A new statistical approach to the study of conservation of amino acid and nucleotide sequences based on kernel density analysis is described that enables analysis of both conserved and highly variable HIV-1 protein sequences. The amino acid sequences of HIV-1 env proteins in 63 isolates were analysed to determine, first, whether the designations of regions identified in 1987 as conserved (C1-C6) or variable (V1-V5) were still valid. Even though the data base used was nine times larger, the designations that were based on seven isolates from five patients remain correct. Second, the new approach enabled the quantifications of the degree of conservation in reported B or T cell epitopes. Using this approach, highly conserved epitopes located in both gp41 and gp120 were identified.

Amino Acid Sequence↗

Moiety-conserved cycles and metabolic control analysis: problems in sequestration and metabolic channelling.

This paper considers certain aspects of the analysis of moiety-conserved cycles in terms of metabolic control analysis. Two response coefficients are discussed: the response coefficient with respect to the total number of moles in a cycle (RVT), and the response coefficient with respect to perturbations to the internal state of a pathway (RVS). The relationship between these two different measures is derived and two examples are given to illustrate how the results may be used to simplify the analysis of particular complex pathways. One example considers how metabolite sequestration affects the flux summation theorem for which the analysis confirms the known result that sequestration can depress the value of the summation to below unity. The second example investigates the effect of metabolic channelling on the summation theorems. The analysis indicates that in contrast to metabolite sequestration, metabolic channelling can cause the flux summation theorem to exceed the value of unity. In addition, the maximum value that the summation theorem can reach under these conditions is shown to be equal to 2. Finally, this analysis indicates how one might use control analysis through the use of enzyme titration to determine whether metabolic channelling occurs in real systems or not.

Biochemical Phenomena↗

[Urolithiasis and its conservative treatment based on analysis of the calculi].

The exact analysis of urinary calculi is the condition for an aimed conservative therapy of urolithiasis. As standardized method of the analysis of urinary calculi the X-ray diffraction was introduced in the GDR. This investigation method allows a qualitative and quantitative analysis of the concrements. The possibilities of the conservative therapy of urolithiasis were explained. To this conservative treatment belong the treatment of a colic, the removal of a calculus, the litholysis and the prophylaxis of recidivations.

Colic↗

Primary hyperparathyroidism: the case for conservative surgery.

Analysis of a series of 205 surgically treated cases of primary hyperparathyroidism was carried out to assess the long-term results of the conservative approach of selectively removing the adenoma only. If primary hyperparathyroidism is due to multiple gland involvement in one-third to one-half of patients, an appreciable number of patients with recurrent disease should have been encountered during this study of the results of conservative no instances of permanent tetany, supports the conservative approach to the treatment when only a single enlarged gland is encountered. Subtotal parathyroidectomy should be reserved for those few cases in which multiple enlarged glands are found, especially in association with multiple endocrine neoplasm, familial hyperparathyroidism, and secondary hyperparathyroidism.

Adenoma↗

Stellacyanin. Studies of the metal-binding site using x-ray absorption spectroscopy.

Stellacyanin is a mucoprotein of molecular weight approximately 20,000 containing one copper atom in a blue or type I site. The metal ion can exist in both the Cu(II) and Cu(I) redox states. The metal binding site in plastocyanin, another blue copper protein, contains one cysteinyl, one methionyl, and two imidazoyl residues (Colman et al. 1978. Nature [Lond.]. 272:319-324.), but an exactly analogous site cannot exist in stellacyanin as it lacks methionine. The copper coordination in stellacyanin has been studied by x-ray edge absorption and extended x-ray absorption fine structure (EXAFS) analysis. A new, very conservative data analysis procedure has been introduced, which suggests that the there are two nitrogen atoms in the first coordination shell of the oxidized [Cu(II)] protein and one in the reduced [Cu(I)] protein; these N atoms have normal Cu--N distances: 1.95-2.05 A. In both redox states there are either one or two sulfur atoms coordinating the copper, the exact number being indeterminable from the present data. In the oxidized state the Cu--S distance is intermediate between the short bond found in plastocyanin and those found in near tetragonal copper model compounds. Above -140 degree C, radiation damage of the protein occurs. At room temperature the oxidized proteins is modified in the x-ray beam at a rate of 0.25%/s.

Binding Sites↗

Mutational analysis of the three conserved valine residues of insulin and a proposal of "isosteric residue".

To further understand the role of the three conserved Val residues in insulin, B12Val, B18Val, and A3Val, five insulin mutants-[A3Ser]insulin, [B12Thr]insulin, (desB30)[B12Ser]insulin, [B18Thr] insulin, and [B18Leu]insulin--were obtained by means of site-directed mutagenesis and their receptor-binding activities as well as in vivo biological potencies were measured. The two B18 mutants, [B18Thr]insulin and [B18Leu]insulin, both retained relatively high receptor-binding activities (70% and 30% of native porcine insulin, respectively) as well as relatively high in vivo biological potencies. The receptor-binding activities of [B12Thr]insulin and (desB30)[B12Ser]insulin were 5.1% and 0.2%, respectively. However the in vivo biological potency of [B12Thr]insulin was still about 50% of native insulin, whereas that of (desB30)[B12Ser]insulin decreased drastically. The [A3Ser]insulin retained 1.4% of the receptor-binding activity and low in vivo biological potency. These results, together with previous reports showed that when the three conserved Val residues were replaced by residues containing a beta-branched side-chain, such as Thr or Ile, the insulin mutants retained higher biological activities than those mutants replaced by other residues. Here we propose that Val, Thr, and Ile are "isosteric residues' because they all contain a beta-branched side-chain. This proposal may have perhaps general significance in protein design and protein engineering.

Animals↗

[Sequence aanlysis of intergenic region of rice stripe virus RNA4: evidence for mixed infection and genomic variation].

The intergenic region (IR) of the RNA4 of 22 isolates of Rice stripe virus (RSV) in China was cloned and sequenced. The IR sequences were compared with one another and with that from Japan. Sequence comparisons showed that these isolates could be divided into three different types, with the IR length of 634 bp, 654 bp and 732 bp, respectively. It is interesting to note three different types all occurred in Yunnan RSV natural population, whereas other province only existed 654 bp type length isolates. Mixed infections with different types of IR length coexisting in some isolates in Yunnan was observed. IR sequences were not more conserved (83% - 100%) among the populations of RSV from China than with those of RSV isolates from Japan (83% - 94%). There were two important structure characteristics in IRs sequences. Firstly, there was a-19 nt insertion in 654 bp type isolates and a-103 nt in 732 bp type isolates in comparison to 634 bp type isolates. This inserted sequences were rather highly conserved. Blast analysis indicates the 16 nt (AGAAACATGAGAGTA) in 19 nt insertation was very similar in sequence to wheat cDNA library; and the 20 nt (AGAATTGCCTTGGTGTTAT) in 103 nt insertion was identical to a stretch sequences of barley cDNA library. Recombination hot-spot sequences existed in RNA4 IR. Secondly, IRs sequence was rich in U and A residues where two distant hairpin structures could be formed with computer-assisted folding analysis. One was highly conserved and stable, but the other was rather unstable because of bases variation. It is believed that this stabilised hairpin structure, rather than a sequence motif, might serve as a transcription terminator during the synthesis of mRNAs from the ambisense segments. Negative selection constraints imposed by secondary structure might have maintained the conserved sequences. In this paper, the relationship between the lowest free energy of the unstable hairpin structures and the different pathogenesis among some isolates was also discussed in this paper.

Amino Acid Sequence↗

Mutational analysis of the highly conserved C-terminal residues of the XylS protein, a member of the AraC family of transcriptional regulators.

The XylS protein of the TOL plasmid of Pseudomonas putida belongs to the so-called AraC/XylS family of regulators, that includes more than 100 different bacterial proteins. A conserved stretch of about 100 amino acids is present at the C-terminal end. This conserved region is believed to contain seven alpha-helices, including two helix-turn-helix (HTH) DNA binding motifs (alpha(2)-T-alpha(3) and alpha(5)-Talpha-(6)), connected by a linker alpha-helix (alpha(4)), and two flanking alpha-helices (alpha(1) and alpha(7)). The second HTH motif is the region with the highest homology in the proteins of the family, with certain residues showing almost 90% identity. We have constructed XylS single mutants in the most conserved residues and have analysed their ability to stimulate transcription from its cognate promoter, Pm, fused to 'lacZ. The analysis revealed that mutations in the alpha(5)-helix conserved residues had little effect on the XylS transcriptional activity, whereas the distribution of polarity in the alpha(6)-helix was important for the activity. The strongest effect of the mutations was observed in conserved residues located outside the DNA binding domain, namely, Gly-290 in the turn between the two helices, Pro-309 located downstream of alpha(6), and Leu-313, in the small last helix alpha(7), that seems to play an important role in the activation of RNA-polymerase. Our analysis shows that conservation of amino acids in the family reflects structural requirements rather than functionality in specific DNA interactions.

Amino Acid Sequence↗

The effects of ultrafiltration on e-aminocaproic acid: an in vitro analysis.

Blood conservation strategies have become a standard of practice in cardiac surgery, with the use of antifibrinolytic agents and ultrafiltration two popular techniques. The purpose of this study was to evaluate the effects of continuous ultrafiltration on e-aminocaproic acid (EACA) utilizing functional coagulation analysis. A fibrinolytic assay was developed to detect EACA using the thromboelastograph (TEG) and urokinase (0.138 units 0.360 mL(-1)). Fresh bovine blood (23 +/- 1% hematocrit) was pumped (100 mL min(-1)) through an ultrafiltrator (HPH 400) at 37 degrees C with a transmembrane pressure of 280 mmHg. EACA (0.065 mg mL(-1)) was circulated for 10 minutes before initiating ultrafiltration. Samples (pre- and postultrafiltrator) were obtained at baseline, 5, and 10 min of ultrafiltration and analyzed via the fibrinolytic assay for EACA determination. TEG profiles significantly decreased from concentrations of 0.065 mg to 0.0325 mg of EACA mL(-1) blood (maximum amplitude MA, 75.4 +/- 4.0 versus 63.3 +/- 2.9, p < .05, TEG index 5.4 +/- 0.7 versus 4.0 +/- 0.3, p < .05). Fibrinolysis at 30 min increased as EACA concentrations declined (0.065 mg, 0% versus 0.032 mg, 16.4 +/- 2.8%, p < .05). During ultrafiltration the MA increased significantly from baseline to 10 min postultrafiltrator (68.2 +/- 3.0 versus 75.8 +/- 10.0, p < .05) and from 5 min pre- to 10 min postultrafiltrator (69.7 +/- 4.2 versus 75.8 +/- 10.0, p < .05). The TEG index showed no significant change, and no fibrinolysis was detected at 30 min from any datapoint during ultrafiltration. In conclusion, this study demonstrates that the antifibrinolytic properties of EACA are maintained during ultrafiltration with a 25% reduction in total circulating volume.

Aminocaproic Acid↗

Mammalian mitochondrial D-loop region structural analysis: identification of new conserved sequences and their functional and evolutionary implications.

This paper reports the first comprehensive analysis of Displacement loop (D-loop) region sequences from ten different mammalian orders. It represents a systematic evolutionary study at the molecular level on regulatory homologous regions in organisms belonging to a well defined class, mammalia, which radiated about 150 million years ago (Mya). We have aligned and analyzed 26 complete D-loop region sequences available in the literature and the fat dormouse sequence, recently determined in our laboratory. The novelty of our alignment consists of the extensive manual revision of the preliminary output obtained by computer program to optimize sequence similarity, particularly for the two peripheral domains displaying heterogeneity in length and the presence of repeated sequences. The multialignment is available at the WWW site: http://www.ba.cnr.it/dloop.html. Our comparative study has allowed us to identify new conserved sequence blocks present in all the species under consideration and events of insertion/deletion which have important implications in both functional and evolutionary aspects. In particular we have detected two blocks, about 60 bp long, extended termination associated sequences (ETAS1 and ETAS2) conserved in all the organisms considered. Evaluation against experimental work suggests a possible functional role of ETAS1 and ETAS2 in the regulation of replication and transcription and targeted experimental approaches. The analyses on conserved sequence blocks (CSBs) clearly indicate that CSB1 is the only very essential element, common to all mammalian mt genomes, while CSB2 and CSB3 could be involved in different though related functions, probably species specific, and thus more linked to nuclear mitochondrial coevolutionary processes. Our hypothesis on the different functional implications of the conserved elements, CSBs and TASs, reported so far as main regulatory signals, would explain the different conservation of these elements in evolution. Moreover the intra-order comparison of the D-loop regions highlights peculiar features useful to define the evolutionary dynamics of this region in closely related species.

Animals↗

[Tumor relevance analysis of a highly conserved gene by using gene microarray hybridization].

Preliminary function research of a highly conserved human gene,which was cloned from human fetal cDNA library during large-scale cDNA sequencing,is illustrated in this article. Bioinformatics analysis indicates that this gene is highly conserved in human, mouse, fruit fly, thaliana and fission yeast. Other bioinformatics analysis implies its relevance with tumors. RT-PCR analysis shows its wide-ranging expression patterns. Its expression in 16 cancer cases (including 7 liver cancer cases, 5 pancreas cancer cases, 2 larynx cancer cases and 2 lung cancer cases) is studied by using gene microarray analysis. The result shows its relevance with tumors and implies it may have different status in different classification of tumors.

English Abstract↗

Allozyme variation and structure of the Canarian endemic palm tree Phoenix canariensis (Arecaceae): implications for conservation.

Electrophoretic analysis of 18 allozyme loci was used to estimate the levels and structuring of genetic variation within and among natural populations of the protected endemic palm species from the Canary Islands (Phoenix canariensis) to evaluate its genetic relationship with the widespread congener P. dactylifera, and to assess comparatively the genetic variation in the populations where the two species coexist with morphologically intermediate plants (mixed populations). Our survey revealed that the within-population component explains roughly 75% of the genetic variation levels detected in P. canariensis (A=1.59; P=41.8; He=0.158), which rank higher than those reported for other species of the Arecaceae. A Principal Component analysis (PCA) based on allele frequencies consistently separates populations of P. canariensis and P. dactylifera, and reveals a close genetic relationship between P. canariensis and the mixed populations. Reduced levels of genetic variation in P. canariensis with respect to P. dactylifera, the fact that the genetic makeup of the Canarian endemic (with no unique alleles) is a subset of that found in P. dactylifera, and the high genetic identity between both species strongly suggest that P. canariensis is recently derived from a common ancestor closely related to P. dactylifera.

Arecaceae↗

Conservative breast cancer treatment: analysis of cosmetic results and the role of concomitant adjuvant chemotherapy.

Fifty-eight patients conservatively treated for T1 breast cancers are analyzed for cosmetic outcome; 17 had concomitant adjuvant combination chemotherapy (cyclophosphamide, adriamycin, 5 fluorouracil). The results are evaluated by clinical criteria and a quantitative measurement by use of light field projection at 33 months median follow-up. Surgery consisted of lumpectomy and axillary dissection; radiotherapy was given to the breast only except for additional internal mammary irradiation in central and medial lesions. (50 Gy whole breast, 64 Gy electron/photon boost). Questionnaires are used for inquiry on patient experience: 88% of the patients experienced a good to excellent cosmetic outcome. According to the panel only 64% show a good to excellent cosmesis. Panel-scores on asymmetry are compared with quantitative measurements. More esophagitis and probably a higher degree of fibrosis in the boost area is found in the chemotherapy group. No differences in cosmetic outcome, complication rates, and patient experiences are seen. Results are compared with published data.

Antineoplastic Combined Chemotherapy Protocols↗

Analysis of genetic diversity and conservation priorities in Iberian pigs based on microsatellite markers.

The Iberian breed is the most important pig population of the Mediterranean type. The genetic structure of two strains (Torbiscal and Guadyerbas) and three varieties (Retinto, Entrepelado and Lampiño) of this breed was studied using 173 pigs genotyped for 36 microsatellites. In addition, 40 pigs of the related Duroc breed were also analysed. In the 1960s, the Iberian breed's numbers were severely reduced by disease, due to economic change and to crossbreeding. Varieties are in danger of disappearance or blending. A new conservation strategy is required. An analysis was performed that allows us to ascertain the loss or gain of genetic diversity if one or several subpopulations are removed. The results are compared with those using the Weitzman method. The two methodologies produce conservation priorities that are completely different, the reason being that the Weitzman method does not take into account the within-population genetic diversity. We apply optimal contribution theory and a new procedure for cluster analysis, and discuss their value in the general framework of the problems of setting of priorities and tactics for the conservation of genetic resources.

Animals↗