Ex vivo Search for Sentinel Node in Postmastectomy Specimens: Should We Use a Transverse Incision for Mastectomy?

Background According to the concept of sentinel node (SN), the lymphatic pathway leading to SN should be regarded as the main and the most important lymphatic route from primary tumor to regional lymph nodes. We performed ex vivo blue-dye SN mapping in postmastectomy specimens to assess whether the main lymphatic tract leading to SN is completely removed during mastectomy. We assumed that ex vivo identification of SN may be possible only if the entire lymphatic tract leading to sentinel node is removed from within the postmastectomy specimen. Methods Blue dye (1 mL) was injected intracutaenously, periareolary into each of 28 postmastectomy specimens. In 13 cases mastectomy was performed with the use of transverse skin incision; in 15 cases oblique incision was used. Results The use of transverse skin incision during modified radical mastectomy allowed identification of the sentinel node and removal of the entire lymphatic pathway leading to sentinel node only in 4 of 15 cases (31%). Conversely, the use of oblique skin incision during modified radical mastectomy allowed identification of the sentinel node and removal of the entire lymphatic pathway leading to sentinel node in 12 of 15 cases (80%). Conclusions Our experiment revealed that the use of transverse skin incision during modified radical mastectomy may not be the best choice for breast cancer patients. In our opinion, this observation may be especially important for patients not irradiated postoperatively.     

Oral mucosa in children with Prader–Willi syndrome

J Oral Pathol Med (2011) 40 : 778–784 Prader–Willi syndrome is a genetic disorder. Abnormal saliva secretion, emotional and behaviour problems, may affect the health status of the oral mucousa. Objectives: To assess the impact of self‐destructive behaviour and abnormal saliva secretion on the oral mucosa in children with Prader–Willi syndrome (PWS). Materials and methods: Fifteen PWS’s children (mean age 9.8 ± 4.4 years) and 15 healthy children (mean age 11.5 ± 3.5 years) were assessed for self‐destructive behaviours, such as picking at the skin, physical and chemical saliva characteristics, mycology, and the clinical status of the oral mucosa. Results: Picking at the skin was only in children with PWS (n = 12). In contrast to the control group, the moistening rate of the lower lip mucosa was slower, and the mean pH of the resting saliva was reduced in the affected subjects. Sticky frothy or frothy saliva, decreased secretion rate of the stimulated saliva, and a reduced buffer capacity were more frequently in PWS’s children; Candida spp. and oral candidiasis were also more common. Injurious lesions in the oral mucosa were found in one control child, and in eight PWS’s subjects. In affected children, the lesions were concurrent with picking at the skin. A statistical correlation was noted between the presence of Candida spp. and oral candidiasis, and unfavourable saliva properties, and between injurious lesions and a slow moistening rate of the lower lip mucosa, and oral candidiasis. Conclusions: Abnormal saliva secretion and self‐destructive behaviours in children with Prader–Willi syndrome predispose them to injurious lesions in the oral mucosa, and possibly, to oral candidiosis.     

Sarcoidosis and its otolaryngological implications

Sarcoidosis and its aetiopathogenesis, epidemiology and diagnostic procedures (including the Kveim reaction) are presented in this paper. The clinical manifestations of this disease, especially in otolaryngological organs, including the larynx, salivary glands, nose and paranasal sinuses, are described. Treatment procedures, including surgical interventions and prognosis, are also discussed.     

Identification of a single peridinin sensing Chl-a excitation in reconstituted PCP by crystallography and spectroscopy

The peridinin-chlorophyll a-protein (PCP) of dinoflagellates is unique among the large variety of natural photosynthetic light-harvesting systems. In contrast to other chlorophyll protein complexes, the soluble PCP is located in the thylakoid lumen, and the carotenoid pigments outnumber the chlorophylls. The structure of the PCP complex consists of two symmetric domains, each with a central chlorophyll a (Chl-a) surrounded by four peridinin molecules. The protein provides distinctive surroundings for the pigment molecules, and in PCP, the specific environment around each peridinin results in overlapping spectral line shapes, suggestive of different functions within the protein. One particular Per, Per-614, is hypothesized to show the strongest electronic interaction with the central Chl-a. We have performed an in vitro reconstitution of pigments into recombinant PCP apo-protein (RFPCP) and into a mutated protein with an altered environment near Per-614. Steady-state and transient optical spectroscopic experiments comparing the RFPCP complex with the reconstituted mutant protein identify specific amino acid-induced spectral shifts. The spectroscopic assignments are reinforced by a determination of the structures of both RFPCP and the mutant by x-ray crystallography to a resolution better than 1.5 Å. RFPCP and mutated RFPCP are unique in representing crystal structures of in vitro reconstituted light-harvesting pigment-protein complexes.     

Redox properties of Met(35) in neurotoxic beta-amyloid peptide. A molecular modeling study

The beta-amyloid peptide (betaAP) is the principal component of plaque associated with the pathology of Alzheimer's disease. Part of its neurotoxicity appears to correlate with the ability of the peptide to reduce Cu(II) and form free radicals. Both processes are dependent on the presence and oxidizability of Met(35) in the C-terminus of the peptide but no mechanistic details on the reactions leading to Met oxidation are known. On the basis of previous studies with model peptides, we hypothesize that a one-electron oxidation of Met(35) in betaAP is facilitated through a neighboring group effect. Complexed to Cu(II) and/or in a lipid-mimicking environment, the solution structure of betaAP includes a large alpha-helical part. The solution NMR structure of betaAP1-40 in aqueous SDS micelles reveals an alpha-helix between residues 27 and 36, containing Met(35). In this helical C-terminus of betaAP, the peptide bond C=O group C-terminal of Ile(31) is located very close to the Met(35) sulfur and could stabilize a Met(35) sulfide radical cation through formation of an (S-O) three-electron bond. In the present paper, we have computationally validated this hypothesis using Langevin dynamics methods to determine the collision frequency of the Met(35) thioether sulfur and the oxygen atoms of several peptide bonds in the betaAP sequence. Nanosecond time scale computations were carried out for four distinct betaAP congeners, betaAP26-40, betaAP26-36, betaAP26-40(Ile(31)Pro), betaAP40-26, and their respective Met(35)-sulfur-centered cation radicals. Here, betaAP26-40, betaAP26-40(Ile(31)Pro) and betaAP40-26 are representative fragments of the full length betaAP1-42 or betaAP42-1 sequence, respectively, whereas betaAP26-36 represents a unique betaAP sequence for which biological data are available. Initial structures of betaAP26-40, betaAP26-40(Ile(31)Pro), and betaAP26-36 were selected to be identical to that of the betaAP26-40 or betaAP26-36 sequence in full-length betaAP1-40. As the structures of betaAP40-26 and betaAP42-1 are not known, various initial conformations such as alpha-helix and antiparallel beta-sheet were selected for betaAP40-26. Our computational results show that betaAP26-40, representative for the same sequence in full-length betaAP1-42, has the highest tendency to form (S-O) bonds between Ile(31)C=O and Met(35)S. We conclude that native betaAP1-42 has a higher tendency to support Met(35) oxidation through (S-O) bond formation, consistent with the experimental observation that betaAP1-42 is more neurotoxic compared to the other investigated sequences.