Nanosilver Targets the Bacterial Cell Envelope: The Link with Generation of Reactive Oxygen Radicals.

The work describes the interactions of nanosilver (NAg) with bacterial cell envelope components at a molecular level and how this associates with the reactive oxygen species (ROS)-mediated toxicity of the nanoparticle. Major structural changes were detected in cell envelope biomolecules as a result of damages in functional moieties, such as the saccharides, amides, and phosphodiesters. NAg exposure disintegrates the glycan backbone in the major cell wall component peptidoglycan, causes complete breakdown of lipoteichoic acid, and disrupts the phosphate-amine and fatty acid groups in phosphatidylethanolamine, a membrane phospholipid. Consistent with the oxidative attacks, we propose that the observed cell envelope damages are inflicted, at least in part, by the reactive oxygen radicals being generated by the nanoparticle during its leaching process, abiotically, without cells. The cell envelope targeting, especially those on the inner membrane phospholipid, is likely to then trigger the rapid generation of lethal levels of cellular superoxide (O2•-) and hydroxyl (OH•) radicals herein seen with a model bacterium. The present study provides a better understanding of the antibacterial mechanisms of NAg, whereby ROS generation could be both the cause and consequence of the toxicity, associated with the initial cell envelope targeting by the nanoparticle.

Pero ¿hubo alguna vez una clasificación de Clark de los melanomas? / But was there ever a Clark classification of melanomas?

Desde hace 40 años, la inmensa mayoría de los dermatólogos y los patólogos de todo el mundo ha aceptado y ha empleado la clasificación de Clark de los melanomas cutáneos. Sin embargo, tras una cuidadosa relectura de los artículos fundamentales de Clark y sus colaboradores, hemos podido comprobar que tal clasificación ha sido en realidad muy efímera. Tras distinguir en 1968 entre melanoma nodular, melanoma de extensión superficial (MES) y melanoma del lentigo maligno (MLM), la inclusión en 1979 del melanoma lentiginoso acro (MLA) como un nuevo subtipo de melanoma fue la primera avería seria de la clasificación, ya que un melanoma lentiginoso y de aparición tardía (como el MLM) se localizaba, a diferencia de éste, en las zonas menos fotoexpuestas de la piel. Posteriormente, los mismos autores comprobaron que, contrariamente a su idea inicial, el pronóstico del MLM era el mismo que el de los demás subtipos a igualdad de espesor, según Breslow. Finalmente, diversas observaciones de los mismos autores fueron poniendo de manifiesto su creciente dificultad para distinguir al microscopio entre MLM, MES y MLA, salvo que tuviesen en cuenta la localización. Es decir, que hoy por hoy las posibles diferencias morfológicas entre uno y otro caso de melanoma cutáneo no conllevan demostradas diferencias pronósticas, y las diferencias morfológicas que puedan encontrarse se deben más a la diferente localización que a la propia neoplasia (AU)

For the past 40 years, the Clark classification of cutaneous melanoma has been accepted and used by the vast majority of dermatologists and pathologists throughout the world. However, after careful rereading of the most relevant articles by Clark and his collaborators, we can affirm that the classification was only ever of passing validity. After distinguishing between nodular melanoma, superficial spreading melanoma (SSM), and lentigo maligna melanoma (LMM) in 1968, the inclusion of acral-lentiginous melanoma (ALM) in 1979 as a new subtype was the first serious setback for the classification; in contrast to ALM, late-onset lentiginous melanomas, such as LMM, were situated on areas of skin with less exposure to sunlight. Later, the same authors found that, contrary to their initial belief, the prognosis of LMM was the same as that of other subtypes with the same Breslow thickness. Finally, a number of observations by the same authors made ever clearer the increasing difficulty for distinguishing microscopically between LMM, SSM, and ALM, except by taking their localization into consideration. This means that, today, the possible morphological differences between one case of cutaneous melanoma and another are of no proven prognostic implication. In addition, the morphological differences that can be found are much more closely related to the different localization that to the tumor itself (AU)

[But...was there ever a Clark classification of melanomas?]. / Pero...hubo alguna vez una clasificación de Clark de los melanomas?

For the past 40 years, the Clark classification of cutaneous melanoma has been accepted and used by the vast majority of dermatologists and pathologists throughout the world. However,after careful rereading of the most relevant articles by Clark and his collaborators, we can affirm that the classification was only ever of passing validity. Today, the possible morphological differences between one case of cutaneous melanoma and another are of no proven prognostic implication. In addition, the morphological differences that can be found are much more closely related to the different localization that to the tumor itself.

Exclusive measurement of coherent proton-deuteron bremsstrahlung.

For the first time a high-precision proton-deuteron bremsstrahlung experiment has been performed in which all the different exit channels have been distinguished separately. High-precision cross sections and analyzing powers in one of the outgoing channels, namely, the coherent bremsstrahlung with a proton and a deuteron in the final state, are presented at 190 MeV incoming proton beam energy and are compared to calculations based on the low-energy theorem. The results of the calculations vary considerably calling for a fully microscopic calculation. However, using a recipe including the initial- and final-state interactions, the predictions come close to the data.

Suppression of soft nuclear bremsstrahlung in proton-nucleus collisions.

Photon energy spectra up to the kinematic limit have been measured in 190 MeV proton reactions with light and heavy nuclei to investigate the influence of the multiple-scattering process on the photon production. Relative to the predictions of models based on a quasifree production mechanism, a strong suppression of bremsstrahlung is observed in the low-energy region of the photon spectrum. We attribute this effect to the interference of photon amplitudes due to multiple scattering of nucleons in the nuclear medium.

Primary osteosarcoma of the uterine corpus: report of a case with immunohistochemical and ultrastructural study.

BACKGROUND: Primary uterine osteosarcoma is extremely rare, with only 15 cases reported in the literature. CASE: A 41-year-old woman presented with abnormal vaginal bleeding due to a large tumor arising from the uterine corpus. Histologically, the tumor showed the features of a malignant mesenchymal neoplasm with osteoid formation and lacked an epithelial component. Immunohistochemical and ultrastructural studies showed no evidence of epithelial differentiation. The tumor was excised and the patient received chemotherapy and radiation therapy postoperatively, but the tumor recurred locally at the 8-month follow-up. CONCLUSION: Osteosarcoma as a primary uterine tumor is exceedingly rare and should be distinguished from carcinosarcoma, which shows different macroscopic and histologic features. Prognosis of this neoplasm is very poor with an average life expectancy of 5 months.

Genetic analysis of in vivo-selected viral variants causing chronic infection: importance of mutation in the L RNA segment of lymphocytic choriomeningitis virus.

Viral variants with different biological properties are present in the central nervous systems (CNS) and lymphoid tissues of mice persistently infected with lymphocytic choriomeningitis virus (LCMV). Viral isolates from the CNS are similar to the original Armstrong LCMV strain and induce potent virus-specific T-cell responses in adult mice, and the infection is rapidly cleared. In contrast, LCMV isolates derived from spleens of carrier mice cause persistent infections in adult mice. This chronic infection is associated with low levels of antiviral T-cell responses. In this study, we genetically characterized two independently derived spleen variants by making recombinants (reassortants) between the spleen isolates and wild-type (wt) LCMV and showed that the ability to persist in adult mice and the associated suppression of T-cell responses segregates with the large (L) RNA segment. In addition, we analyzed a revertant (isolated from the CNS) derived from one of the spleen variants. By comparing the biological properties of three reassortants that contained the same S segment but had the L segment of either the original wt Armstrong LCMV, the spleen variant derived from it, or the CNS revertant derived from the spleen variant, we were able to show unequivocally that biologically relevant mutations occurred in the L segment not only during generation of the spleen variant from wt LCMV but also in reversion of the spleen variant to the wt phenotype. Thus, our results showed that (i) genetic alterations in the L genomic segment were involved in organ-specific selection of viral variants, and (ii) these mutations profoundly affected the ability of LCMV to cause chronic infections in adult mice.

Clinical, chemical, and CT evaluation of short-term and long-term antiedema therapy with dexamethasone and diuretics.

Three independent methods were used to quantify the therapeutic effect on peritumoral brain edema with respect to different forms of treatment (dexamethasone, furosemide, and their combination with different dosages and different periods of treatment). 1. The neurological deficit evaluated by frequency distribution analysis showed an improvement in nearly all cases. In a few cases the initial improvement was followed by a secondary deterioration. The various symptoms showed significant differences in regression with regard to the extent of the reduced deficit as well as the time dependence. 2. With a certain delay (compared to item 1), diminution of brain edema was detected by CT follow-up. The effect of dexamethasone and the combination with furosemide differed depending on the nature of the brain tumor. 3. Compared to the untreated patients, the water content was reduced by nearly 3% following dexamethasone treatment 4 x 4 mg for 4 to 6 days. Following dexamethasone/furosemide therapy for 4 to 6 days, it was reduced by about 4.5%. The result of long-term therapy with dexamethasone alone was similar. The sodium content changed parallel to the water content. Dexamethasone and dexamethasone/furosemide was most effective in patients with glioblastoma, where the water content decreased by nearly 6%. The data presented suggest that preoperative antiedema treatment with dexamethasone is necessary for several days or a few weeks in some cases. The period of treatment can be reduced significantly by dexamethasone/furosemide or extremely high doses of dexamethasone. On the other hand, the results of follow-up scoring of the neurological situation show that the optimal time of pretreatment must be limited with respect to the individual case. The therapeutic results presented allow inferences to be made concerning pathophysiology of the resolution of brain edema.

CT of the base of the skull.

A systematic study of the structures of the base of the skull was performed with CT. The findings in 141 pathological cases are described. The value and some limitations of this kind of investigation are described and discussed. A comparison with conventional tomography is made.

Routine neuroradiological diagnosis with the EMI 5005 body scanner.

The experience with the EMI 5005 body scanner in the neuroradiological diagnosis of about 500 cerebral and 30 spinal examinations is reported. The advantages and disadvantages of this machine are discussed.

Failure to induce tolerance to mechlorethamine hydrochloride.

In view of the contradictory results reported in the literature regarding induction of specific immunologic tolerance to mechlorethamine hydrochloride (HN2), the problem was reinvestigated using a "tolerogenic" schedule that had been reported to be effective. Mechlorethamine hydrochloride, 200 microgram, intravenously, was given weekly for five weeks before beginning topical therapy with it. In the test group, five of 13 patients (11 with mycosis fungoides and two with psoriasis) became contact sensitized to mechlorethamine. In another patient, what was probably a contact urticarial reaction developed. In the control group, five of 13 patients (12 with mycosis fungoides, one with parapsoriasis) became contact sensitized to mechlorethamine. Thus, 38% of the patients in both groups became contact sensitized to mechlorethamine. It is concluded that this tolerogenic schedule, just as others previously tried, was not effective in inducing specific tolerance to mechlorethamine.

Angiography in vascular malformations of the face.

While angiography has been established as a useful procedure in evaluating vascular malformations of the face, the role of selective catheterization has not been stressed. Five patients with either capillary-cavernous hemangiomas or arteriovenous racemose hemangiomas were selected to illustrate the angiographic features of vascular malformations of the face as well as problems in angiographic evaluation and therapeutic techniques. Angiographic studies were valuable in establishing the extent and type of hemangioma, its blood supply and drainage, and associated intraorbital or intracranial extensions. We believe that selective catheterization is essential in preoperative evaluation of facial hemoangiomas, particularly in detecting unsuspected intracranial involvement.

Angiographic findings in basal tumours of the anterior and middle cranial fossa.

Angiographic findings in tumours located near the skull base in the anterior and middle cranial fossa are described. It is possible to distinguish local and general changes, but in general these will indicate the localisation of the tumour rather than its type.