Evidence of multiple infectious agents in mycosis fungoides lesions

The etiology of mycosis fungoides (MF) remains to be determined. Several studies have proposed a viral etiology with controversial results.In this case-control study we investigated the presence of Epstein-Barr virus (EBV) and the debated presence of Human T-cell lymphotrophic virus I (HTLV-I) sequences, by polymerase chain reaction on nucleic acid extracts from formalin-fixed paraffin-embedded skin biopsies. Moreover, by a multivariate approach we analyzed in the same case-control study also the contribution of two previously examined pathogens: Hepatitis C virus (HCV) and Borrelia burgdorferi (Bb).Significant differences in the frequency of infectious agents in cases and controls were detected for Bb, HTLV-I and EBV. In MF patients we found the concurrent presence of two or three of these pathogen sequences in 21 out of 83 cases, but only in 1 out of 83 healthy controls.Our results suggest that the persistence of multiple infectious agents may cause a long-term antigenic stimulation contributing to the malignant transformation of T lymphocytes, especially when associated with HTLV-I like sequences. However, these infectious agents do not seem to have effects on disease progression.     

Pentoxifylline augments TRAIL/Apo2L mediated apoptosis in cutaneous T cell lymphoma (HuT-78 and MyLa) by modulating the expression of antiapoptotic proteins and death receptors

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) is a promising anticancer agent but cutaneous T lymphoma cells (CTCL) are less sensitive to TRAIL-induced apoptosis. Here, we report that pentoxifylline (PTX), a phosphodiesterase inhibitor, augments TRAIL-mediated apoptosis in HuT-78 and MyLa cells through modulating extrinsic death receptors and intrinsic mitochondria dependent pathways. Our results clearly show that PTX augments TRAIL-mediated activation of caspase-8 and induces cleavage of Bid, although PTX alone cannot activate caspase-8. This is followed by cytochrome c release and subsequent, activation of caspase-9 and caspase-3 and cleavage of poly (ADP ribose) polymerase (PARP). Combined treatment downregulates the expression of various antiapoptotic proteins including c-FLIP, Bcl-xl, cIAP-1, cIAP-2 and XIAP. PTX induces the expression of death receptors DR4 and DR5 on cell surface of both the cell types where c-Jun NH2-terminal kinase (JNK) pathway plays an important role. Moreover, combined silencing of DR4 and DR5 by small interfering RNA abrogates the ability of PTX to induce TRAIL-mediated apoptosis. Thus, this is the first demonstration that PTX can potentiate TRAIL-mediated apoptosis through downregulation of cell survival gene products and upregulation of death receptors.     

Multifocal ERG changes before and after macular hole surgery

To evaluate the visual function of 15 eyes suffering from macular hole the multifocal ERG was used pre and postoperatively. In all the cases a successful vitrectomy has been done with macular hole closure in all the eyes. The Multifocal ERG shows an improvement of retinal response density in regions 1 and 2, even in the 2 eyes with unchanged visual acuity postoperatively. Although a relationship exist between the postoperative retinal response density and the visual acuity, the retinal response density varies between eyes with the same visual acuity.     

皮肤软组织肉芽肿性病变的巨细胞形态学定量研究

目的探讨巨细胞形态学定量分析在皮肤软组织肉芽肿性病变中的诊断与鉴别诊断价值。方法选择偶发分支杆菌（MF）肉芽肿、异物性肉芽肿、结核性肉芽肿及骨巨细胞瘤各10例进行组织病理学观察，并应用形态计量学分析方法对组织切片中的巨细胞参数进行测定。结果MF肉芽肿的形态学及巨细胞参数与异物性肉芽肿、结核性肉芽肿及骨巨细胞瘤的巨细胞有所不同。结论结合临床病理特点及巨细胞形态计量学检测，对皮肤软组织肉芽肿性病变的诊断与鉴别诊断有一定价值。     

Response to influenza vaccine in people with non-protective HI antibody titers

The purpose of the study was to determine which factors correlate directly with response to vaccination in such a group of subjects with non-protective HI antibody titers before vaccination. Two vaccines were used, a subunit virus vaccine adjuvanted with MF59 and a split virus vaccine. The analysis indicated that immunization with vaccine adjuvanted with MF59 was an independent variable for immune response against A/H3N2 (OR: 3.51; 95% CI: 1.81–6.79) and B (OR: 2.31; 95% CI: 1.37–3.89). The results suggest that antibody response to vaccine is satisfactory in elderly people previously lacking a protective antibody titer, and that the adjuvanted vaccine reveals a better immunogenicity.     

A computer model of the cerebellar cortex of the frog.

A computer simulation of the neuronal circuits in the cerebellar cortex of frog is developed as a means of testing the functional properties of this cortex. The model is based on present day information regarding morphology and function of the different cortical neurons. In order to allow the model to resemble as closely as possible the actual cerebellum, the model was grown by the computer to simulate data obtained from anatomical studies of the different elements.The model comprises a Purkinje cell layer consisting of 8285 Purkinje cells, 1.68 million granule cells, and 16,820 mossy fibers. Their connectivity was specified on the basis of probability density functions based on the spatial organization of these different elements.Once the cerebellar model was assembled, computer results indicated that the mossy fiber/granule cell system displayed functional specificities which were not expected a priori. (1) A spatially localized mossy fiber input in the peduncle generated localized activation in the cells of the granular layer despite the stochastic nature of the connectivity. This activation of the granular layer occurred in a spindle-like manner which tended to be localized in particular depths in the granular layer. (2) Simultaneous activation of several discrete points in the peduncle, rather than producing a diffuse activity in the granular layer, generated distinct activation of sets of neurons in this layer.In conclusion the model gives evidence for functional specificity in the absence of morphological specificity. This finding suggests that only a limited amount of genetic specificity may be necessary to generate functional specificity in certain neuronal circuits.     

Improved immunologic responses to heterologous influenza strains in children with low preexisting antibody response vaccinated with MF59-adjuvanted influenza vaccine

Vaccination is the most effective approach to reduce the substantial morbidity and mortality caused by influenza infection. Vaccine efficacy is highly sensitive to antigenic changes causing differences between circulating and vaccine viruses. Adjuvants such as MF59 increase antibody-mediated cross-reactive immunity and therefore may provide broader seasonal protection. A recent clinical trial showed that an MF59-adjuvanted vaccine was more efficacious than a nonadjuvanted comparator in subjects < 2 years of age, although not in those ≥ 2 years, during influenza seasons in which the predominant circulating virus was an A/H3N2 strain that was antigenically different from the vaccine virus. This finding suggested that the increased efficacy of the adjuvanted vaccine in younger subjects may be mediated by strain cross-reactive antibodies. A subset of the trial population, representing subjects with distinct age and/or immunological history, was tested for antibody responses to the vaccine A/H3N2 strain as well as A/H3N2 drifted strains antigenically matching the viruses circulating during the trial seasons. The neutralizing tests showed that, compared with nonadjuvanted vaccine, the adjuvanted vaccine improved not only the neutralizing antibody response to the vaccine strain but also the cross-reactive antibody response to the drifted strains in subjects with lower preexisting antibody titers, regardless of their age or vaccine history. The results demonstrated an immunological benefit and suggested a potential efficacy benefit by adjuvanted vaccine in subjects with lower preexisting antibody responses.