Dexamethasone in the treatment of meningeal leukemia

To determine if dexamethasone has a role in the treatment of meningeal leukemia, 8 consecutive patients with acute lymphoblastic and signs or symptoms of CNS were included in the study. After the confirmation of leukemic blast cells on cerebrospinal fluid, they received intrathecal and IV dexamethasone; 3 days later the patients received “triple” intrathecal chemotherapy with dexamethasone, methotrexate and cytarabine, and the spinal fluid was studied again. All patients had good clinical response and 7 out of the 8 patients showed reduction on the CSF cell count after the use of dexamethasone alone. The results suggest that dexamethasone is a lympholytic agent that could play a more active role in the prevention and therapy of meningeal leukemia and should be preferred over hydrocortisone in the so called “triple” intrathecal chemotherapy for the prevention and treatment of CNS leukemia. © 1995 Wiley-Liss, Inc.     

Axon-schwann cell interaction in the squid nerve fibre

The electrical properties of Schwann cells and the effects of neuronal impulses on their membrane potential have been studied in the giant nerve fibre of the squid.1. The behaviour of the Schwann cell membrane to current injection into the cell was ohmic. No impulse-like responses were observed with displacements of 35 mV in the membrane potential. The resistance of the Schwann cell membrane was found to be approximately 10(3) Omega cm(2).2. A long-lasting hyperpolarization is observed in the Schwann cells following the conduction of impulse trains by the axon. Whereas the propagation of a single impulse had little effect, prolonged stimulation of the fibre at 250 impulses/sec was followed by a hyperpolarization of the Schwann cell that gradually declined over a period of several minutes.3. The prolonged effects of nerve impulse trains on the Schwann cell were similar to those produced by depolarizing current pulses applied to the axon by the voltage-clamp technique. Thus, a series of depolarizing pulses in the axon was followed by a long-lasting hyperpolarization of the Schwann cells. In contrast, the application of a series of hyperpolarizing 100 mV pulses at a frequency of 1/sec had no apparent effects.4. Changes in the external potassium concentration did not reproduce the long-lasting effects of nerve excitation.5. The hyperpolarizing effects of impulse trains were abolished by the incubation of the nerve fibre in a sea-water solution containing trypsin.6. These findings are discussed in relation to the possible mechanisms that might be responsible for the long-lasting hyperpolarizations of the Schwann cells.     

Significance of PBMC response of rheumatic fever patients and control individuals to immunodominant streptococcal M5 protein epitopes

β-hemolytic streptococcal infection in developing countries still causes thousands of cases of Rheumatic Fever (RF). Molecular mimicry between streptococcal M protein (strep M) and heart components has been proposed as the triggering factor leading to autoimmunity in individuals with genetic susceptibility, which is linked to different HLA-DR alleles in different populations. In our hands, RF was significantly associated to HLA-DR7/53. Previous work in our lab has shown that heart-infiltrating T cells that simultaneously recognize strep M and heart proteins. Further, such T cells predominantly recognized the 81-103 strep M5 epitope. In this work, we analysed the proliferative response of peripheral blood mononuclear cells of 99 RF patients and 40 normal controls. Eighty-nine of the RF patients were HLA-typed. As among heart-infiltrating T cells, the 81-103 strep M5 protein epitope is the most frequently recognized epitope among RF PBMC (35.4%), against a 7.5% frequency of proliferation among normal controls (p=0.0018, chi square). However, the 81-103 epitope was as frequently recognized by HLA-DR7,53 positive as by negative individuals (45.2% vs 54.8%, respectively). Taken together, the results suggest that the 81-103 strep M5 epitope may be the immunodominant epitope, “promiscuously” recognized by T cells in a genetically diverse population. The demonstration that molecular mimicry is targeted to a discrete immunodominant “promiscuous” epitope in strep M5 may allow the development of a safe anti-streptococcal synthetic vaccine devoid of such epitopes.     

Recurrence of bronchioloalveolar carcinoma in donor lung after lung transplantation: microsatellite analysis demonstrates a recipient origin

Bronchioloalveolar carcinoma is a distinctive subtype of pulmonary adenocarcinoma, without effective therapy, although there have recently been some attempts to use lung transplantation. However, a high post-transplantation local recurrence rate is described with some controversy regarding the possible involved mechanisms, the main possibilities being the lymphatic spread and aerosolization. Presented herein is a case of a bilateral lung transplantation for a bilateral and pneumonic form of non-mucinous bronchioloalveolar carcinoma in a 43-year-old woman. The histological analysis of mediastinal lymph nodes during surgery did not show neoplastic cells. Thirty-five months after transplantation several nodular opacities in donor lungs were detected. Three pulmonary wedge resections were performed showing a non-mucinous bronchioloalveolar carcinoma with the same histological characteristics as the primary. Again, the mediastinal lymph nodes were tumor free. A complete microsatellites molecular analysis was performed to compare the primary and recurrent carcinoma using capillary electrophoresis, showing that the recurrent tumor was generated in a recipient cellular clone. The absence of lymph node metastasis and the molecular evidence of the recipient origin of the neoplasm supports the contamination of the new lungs at the time of implantation as being the reason for the high incidence of recurrence after lung transplantation in this kind of disease.     

Regulation of secondary lymphoid organ development by the nuclear factor-κB signal transduction pathway

Summary: In primary lymphoid organs, such as thymus and bone marrow, B and T lymphocytes differentiate from lymphoid stem cells into mature albeit naïve effector cells. In contrast, secondary lymphoid organs, such as the spleen, lymph nodes, and Peyer's patches (PPs), provide an environment that enable lymphocytes to interact with each other, with accessory cells, and with antigens, resulting in the initiation of antigen‐specific primary immune responses. Recently, the analysis of gene‐knockout mice has shed light on the signaling pathways, cellular requirements, and molecular mechanisms involved in secondary lymphoid organ development. In particular, signals that converge on the nuclear factor‐κB (NF‐κB) pathway have been demonstrated to play an important role in both early developmental steps as well as maintenance of secondary lymphoid organ structures. Analysis of the histopathological changes in secondary lymphoid tissues of mice lacking individual Rel/NF‐κB family members, upstream kinases, and receptors strongly indicates that activation of the recently described alternative NF‐κB pathway by membrane‐bound lymphotoxin, via p52–RelB heterodimers, plays a major role during initiation steps of secondary lymphoid organ development. Induction of the classical p50–RelA NF‐κB activity, as exemplified by tumor necrosis factor receptor signaling, clearly also contributes, but seems to be involved primarily in later developmental step, such as the proper cellular and structural organization of B‐cell follicles.     

Genome of the European elk papillomavirus (EEPV)

The genome of the European elk papillomavirus (EEPV) was found to be 8,095 base pairs (bp) long and its genetic organization was similar to that of other papillomaviruses. Ten open reading frames (ORFs), designated E1-E7 and L1-L3, were identified in the genome, all located on one strand. The presence of the L3 ORF is rare among the papillomaviruses and to date has only been identified in the genomes of EEPV, the deer papillomavirus (DPV) and the Cottontail papillomavirus (CRPV). The ORF is well conserved beteeen DPV and EEPV with regard to both length and sequence. Potential promoter regions were identified at the 5-end of the E6 ORF, at the 3-end of the E1 ORF and downstream of the L1 ORF. Furthermore, two potential polyadenylation signals were found, one located in the long control region (LCR), downstream of the L1 ORF, and another preceding the L2 ORF. The EEVP genome is closely related to the genome of the DPV, the most highly conserved regions being ORFs E1 (70%), E5 (69%), and L1 (74%).     

Imaging of the varicella zoster virion in the viral highways: comparison with herpes simplex viruses 1 and 2, cytomegalovirus,pseudorabies virus,and human herpes viruses 6 and 7

Imaging by scanning electron microscopy (SEM) can provide insight into viral egress. At a low magnification level, varicella zoster virions (VZV) emerge from an infected cell surface in a distinctive pattern previously described as "viral highways." Viral highways consist of thousands of particles arranged in linear pathways across the syncytial surface. This egress pattern has not been described with other herpesviruses, but a systematic analysis has not been performed. Therefore, the characteristic arrangement of VZV egress was compared with that of six other members of the herpes virus family, including herpes simplex virus (HSV) types 1 and 2, human cytomegalovirus (CMV), pseudorabies virus (PRV), and human herpesvirus types 6 and 7 (HHV-6 and HHV-7). Only VZV-infected cells exhibited viral highways. Subsequent SEM examination of VZ virions at an ultra high-resolution revealed that more than 70% were aberrant. Further imaging of the other herpesviruses demonstrated that VZV structure was more closely related to PRV than HSV-1 or HSV-2. Finally, it is noted that the individual members of the herpesvirus family have distinguishable SEM profiles.     

Participation of serum and membrane lectins on the oxidative burst regulation in Macrobrachium rosenbergii hemocytes

Using a spectrophotometric NBT reduction assay and phagocytosis, we identified that production of superoxide anions and phagocytic activity of hemocytes from Macrobrachium rosenbergii were significantly higher in the presence of rat, rabbit, and chicken erythrocytes than with human, pig, or horse erythrocytes. Hemocytes stimulated with MrL, MrLMab, or PMA increased 4.7, 5.1, and 6.1 fold, respectively, the oxidative response as compared to non-stimulated hemocytes. MrLMab together with MrL increased 5.7 fold the oxidative capacity of hemocytes as compared to non-stimulated cells. These effects were inhibited with 100 mM GalNAc, GlcNAc, or Neu5Ac and 0.2 microM of sialylated submaxillary gland mucin and fetuin. Piroxicam inhibited (P < 0.05) the production of O(2)(-) induced by MrL, whereas iodoacetamide inhibited the effect of MrLMAb (P < 0.05) in a dose-dependent manner. Our results suggest that MrLMab might activate the oxidative burst through the metabolism of glucose as opposed to MrL which utilizes NADPH-independent mechanisms, very probably through pro-inflammatory metabolites.