Relationships between total plasma load of torquetenovirus (TTV) and TTV genogroups carried

In 239 torquetenovirus-positive people, multiple-genogroup infections were common and associated with higher viral loads than would be expected from simple additive effects. The latter observation was restricted to the infections which included both genogroups 1 and 3, pointing to the possible existence of some kind of infection facilitation between these genogroups.     

Neutralizing and binding antibodies to IFN-beta: relative frequency in relapsing-remitting multiple sclerosis patients treated with different IFN-beta preparations.

The frequencies of anti-interferon-beta (IFN-beta) antibody development reported to date in patients treated with different IFN-beta preparations are not readily comparable mainly because of differences in underlying diseases and assay methods. Thus, the frequency of neutralizing antibody (NAb) and binding antibody (BAb) development was analyzed in a sample of sera derived from a homogeneous group of relapsing-remitting multiple sclerosis (RRMS) patients treated with different IFN-beta preparations. The frequency of developing NAb and BAb to IFN-beta varied according to the IFN-beta given. Specifically, the NAb seroconversion frequency was significantly higher in patients treated with Betaferon, Schering AG, Berlin, Germany (31.3%) than in patients treated with both preparations of recombinant IFN-beta 1a (Rebif, Serono, Geneva, Switzerland [7.4%] or Avonex, Biogen, Cambridge, MA [6.3%]). Analysis of BAb seroconversion frequency in the same patients revealed that different IFN-beta preparations may also have different capability to induce BAb development and that BAb are produced during IFN-beta therapy at a significantly higher rate than NAb. Our main conclusion is that different human IFN-beta preparations may possess different immunogenicities, leading to varying frequency of development of antibody to IFN-beta in RRMS.     

Cryptosporidium parvum-specific CD4 Th1 cells from sensitized donors responding to both fractionated and recombinant antigenic proteins

T-cell-mediated immunity plays a central role in the host response to Cryptosporidium parvum. Human T-cell clones (TCC) were isolated from peripheral blood mononuclear cells of five healthy donors with prior cryptosporidiosis by use of a C. parvum crude extract, two antigen fractions obtained by ion-exchange chromatography (IEC1 and IEC2), and two recombinant peptides (SA35 and SA40) from C. parvum sporozoites. The T-cell lines derived from the one recently infected donor had a higher proportion (26 to 38%) of T cells exhibiting the gamma/delta T-cell receptor (gamma/delta-TCR) than those from donors who had recovered from cryptosporidiosis several years earlier, suggesting that the gamma/delta T-cell population is involved in the early stage of the infection. The specific TCC had the alpha/beta-TCR, had the phenotype CD45RO(+) CD4(+) CD8(-), and were characterized by either hyperproduction of gamma interferon (IFN-gamma) alone, with a Th1 profile, or IFN-gamma hyperproduction together with interleukin-4 (IL-4) or IL-5 production, with a Th0 profile. SA35, SA40, IEC1, and IEC2 may be considered good targets of the cellular response against C. parvum and may play a role in maintaining the T-cell-mediated memory response to this parasite. Furthermore, the SA35 and SA40 peptides may be regarded as immunodominant antigens involved in the maintenance of the T-cell response in healthy C. parvum-sensitized persons.     

Metastatic pleural mesothelioma presenting with solitary involvement of the tongue: report of a new case and review of the literature

We report a new case of mesothelioma that presented with an isolated lingual metastasis 14 months after initial diagnosis. The patient was a 71-year-old man with a history of pleural decortication and chemotherapy for epithelioid mesothelioma who recently complained of chronic bleeding from a nodular consolidation of tongue. There was no clinical or instrumental evidence of extrathoracic tumor spread. Microscopic examination of a lingual biopsy specimen revealed nests of atypical polygonal cells with moderate cytoplasm, immunopositive for keratins, epithelial membrane antigen, vimentin, thrombomodulin, and calretinin. This case provides additional evidence that mesothelioma could rarely, but not exceptionally, metastatize, to unusual sites such as the tongue. In that location it can mimic primary poorly differentiated squamous carcinoma or adenocarcinoma as well as a number of other metastatic malignancies. In addition to obvious medicolegal implication, metastatic mesothelioma should be correctly recognized so as to avoid useless radical treatment.     

Trisomy 8 in myelodysplasia and acute leukemia is constitutional in 15-20% of cases.

The trisomy 8 found in malignancies may derive from a constitutional trisomy 8 mosaicism (CT8M), and in these cases the trisomy itself may be regarded as the first mutation in a multistep carcinogenetic process. To assess the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8, an informative sample of 14 patients was collected. The data ascertained included chromosome analyses of fibroblast cultures and of PHA-stimulated blood cultures in patients with normal blood differential count, as well as possible CT8M clinical signs. One patient showed trisomy 8 in all cell types analyzed and undoubtedly has a CT8M; a second patient consistently showed trisomy 8 in PHA-stimulated blood cultures when no immature myeloid cells were present in blood and should be considered as having CT8M; a third patient, with Philadelphia-positive chronic myelocytic leukemia, was more difficult to interpret, but the possibility that she had CT8M is likely. A few clinical signs of CT8M were also present in these three patients. Our data indicate that the frequency of CT8M in hematological dysplastic and neoplastic disorders with trisomy 8 is approximately 15-20%.     

Cholinergic responses in cloned human TE671/RD tumour cells

The cholinergic responses of the human tumour cell line TE671/RD were examined using digital Ca²⁺ imaging fluorescence microscopy and patch-clamp measurements. In response to stimulation of the muscarinic acetylcholine (ACh) receptor (mAChR), the intracellular concentration of Ca²⁺ ([Ca²⁺]_i) rose about two-fold, in parallel with inositol 1,4,5-trisphosphate accumulation, measured by chromatographic techniques. By contrast, there was no increment of [Ca²⁺]_i upon stimulation of the nicotinic ACh receptor (nAChR), nor after caffeine application. Electrophysiological experiments showed that TE671/RD cells lack functional voltage-activated Ca²⁺ channels. The stimulation of the nAChR induced transient whole-cell currents (I _ACh). Little or no current was detected in isotonic extracellular Ca²⁺, with Cs⁺ in the patch pipette. Cell pretreatment with muscarine reduced I _ACh by about 20%, without consistent modifications of current kinetics. Muscarine applied to the extra-patch membrane under the cell-attached configuration had no obvious effect on ACh-evoked unitary events. In conclusion, in human TE671/ RD cells, muscarinic stimulation increases [Ca²⁺]_i, while nicotinic stimulation does not. In addition, the nAChR exhibits peculiar ion permeability properties and is not functionally regulated by the breakdown of phosphoinositides.     

A one-year follow-up on the effects of raloxifene on thyroid function in postmenopausal women

OBJECTIVE: Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. DESIGN: Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. RESULTS: Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. CONCLUSIONS: These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.     

A novel mutation of varicella-zoster virus associated to fatal hepatitis.

BACKGROUND: Lethal varicella in immunocompetent hosts is rare and its pathogenesis is largely unknown. The discovery of glycoprotein E (gE) mutants showing attributes consistent with increased virulence in vitro and in animal models, provided a possible molecular mechanism underlying a more aggressive virus infection. However, these mutants have never been associated with unusually severe clinical cases. OBJECTIVES: To varicella-zoster virus (VZV) mutations that correlate with increased virulence. RESULTS: We report a case of fatal hepatitis caused by a VZV bearing a novel mutation on the 3B3 monoclonal antibody epitope of gE in an immunocompetent host. CONCLUSIONS: This report describes a mutant VZV responsible for an aggressive clinical course in an immunocompetent host. Linking these severe clinical presentations of VZV infection to virus mutations might provide insights into the underlying pathogenic mechanisms.