Hypercalcemia is associated with a poor prognosis in lymphoma a retrospective monocentric matched-control study and extensive review of published reported cases

Annals of Hematology - The prognostic significance of hypercalcemia in lymphoma has only been studied on small series to date. We conducted a retrospective, monocentric, matched-control study that...     

Breast adenocarcinoma complicating Kallmann’s syndrome

Carcinoma of the breast is relatively rare among men, accounting for less than 1% of all malignancies. An increased risk has been associated with benign breast diseases, such as gynecomastia, Klinefelter’s syndrome, testicular disorders, exogenous estrogen use, radiation, or a family history of male or female breast cancer. To date, hypogonadotrophic hypogonadism has never been associated with male breast cancer. We report here the first case of breast cancer coexisting with Kallmann’s syndrome in a 66-year-old man.     

Correlation between gI,gII, gIII,and gp 50 antibodies and virus excretion in vaccinated pigs infected with pseudorabies virus

Summary Eleven groups of 8 pigs were vaccinated with different vaccinal strains of pseudorabies virus deleted or not for non-essential glycoproteins (gI, gX, gp 63), then were challenged 8–9 weeks later with a virulent strain. Antibodies against the major viral glycoproteins (gII, gIII, gp 50) were titrated at the day of challenge. Excretion of the challenge strain, growth performance of the pigs, and gI antibody responses from pigs vaccinated with a gI minus strain, were monitored after the challenge. The results demonstrated a strong association between gII and gIII antibody titres before the challenge, with the amount of the challenge strain excreted and clinical protection after the challenge. Furthermore, gI antibody titres after the challenge were negatively correlated with the level of gII and gIII antibodies at the day of challenge, the virus excretion and the clinical protection after the challenge. Implications of these results for vaccination of pigs and gI antibody screening for the infection are discussed.     

Shortening adenovirus type 5 fiber shaft decreases the efficiency of postbinding steps in CAR-expressing and nonexpressing cells

The coxsackie B virus and adenovirus receptor (CAR) functions as an attachment receptor for multiple adenovirus serotypes. It has been shown that apart from virus-cellular receptor interactions, the fiber shaft length also influences viral tropism. We therefore generated Ad5FbDelta639 virus with 8beta-repeats in the shaft, instead of the 22beta-repeats present in the wild-type. Here, we show that the extent of attachment of the virus with shortened fiber to CAR-expressing cells was three- to fivefold lower than that of the wild-type. Transduction studies, however, clearly showed that infection of CAR-expressing cells with Ad5FbDelta639 was strongly impaired by comparison with the wild-type virus. Since this impairment was not linked to a proportional reduction in binding to cells, it appeared to be linked to subsequent/later events in infection. A similar decrease in efficacy of postbinding steps was also evidenced in cells that did not express CAR.     

Bax deletion does not protect neurons from BSE-induced death

Neurodegeneration is a common neuropathological feature of prion diseases. Although evidence of apoptosis was found in natural and experimental prion diseases, the precise mechanisms by which neurons die are poorly understood. The pro-apoptotic BAX protein, a key factor of the mitochondrial pathway, plays a central role in the regulation of neuronal apoptosis. Recently, BAX was implicated in neuronal death in a transgenic model of inherited prion disease. Nevertheless, whether neurodegeneration occurs by similar mechanisms in other prion diseases remains unknown. Here, using mice knocked out for the Bax gene, we investigated BAX implication in neuronal death induced by a prion disease of infectious origin. A mouse-adapted prion strain of bovine spongiform encephalopathy (BSE) was inoculated intracerebrally into Bax-/- mice and their wild-type littermates. We found that Bax inactivation did not alter the development of the disease. Clinical illness was not prevented. PrP(res) deposition and astrogliosis occurred to the usual extent. Neuronal integrity was not maintained, and neurons in hippocampus and thalamus were not protected. These results demonstrated that BAX is not necessary for neuron death induced by the BSE strain. They suggest the existence of multiple molecular death pathways in prion diseases.     

Axotomy-induced motoneuron death is delayed in mice overexpressing PrPc

The normal function of the cellular prion protein, PrP(c), remains largely unknown. Recently, PrP(c) has been implicated in the regulation of neuronal survival and was shown to confer neuroprotection in the brain. To pursue investigation of the role of PrP(c) in the CNS, we used the facial nerve section, a well-established experimental model of motoneuronal stress. Nerve sections were performed in 2- and 7-day-old newborn mice and in 2 month-old adult mice expressing different levels of PrP(c). We observed no differences in motoneuronal death triggered by facial nerve section between Prnp-/- and wild-type mice, whether in neonatal or adult mice. By contrast, overexpression of PrP(c) in Tga20 newborn mice was correlated with a better survival of motoneurons in the few days following axotomy. The protection was, however transient since motoneuron number in lesioned facial nuclei of Tga20 mice became identical to that of wild-type mice 7 days and 14 days following the lesion when performed in 2- and 7-day-old mice respectively. In Tga20 adult mice, no protection was observed 2 months after the lesion, a time with a significant degree of motoneuron death in adult control mice. These results, while providing further evidence that PrP(c) is endowed with neuroprotective capacity in vivo, also suggest that PrP(c) does not play a physiological role in the regulation of motoneuronal survival.     

Specific antibodies modulate the interactions of adenovirus type 5 with dendritic cells

Adenovirus type 5 (Ad5) is able to induce an efficient CD8+ T lymphocyte (CTL) response against a transgene product, a property thought to be linked to its ability to transduce dendritic cells (DCs). Little, however, is known about the capacity of Ad5 to interact with DCs in the presence of specific antibodies, although most people test positive for antibodies directed against Ad5. In the present study, we found that in the presence of Ad5 antibodies, a large fraction of Ad5 binds very efficiently to DCs, and that this binding is FcgammaRII/FcgammaRIII dependent. Nevertheless, in the presence of high levels of antibodies against the whole virion, Ad5 entry was inhibited. Increased binding led to increased entry in DCs in the presence of fiber-specific antibodies or in the presence of low amounts of a whole antiserum raised against whole virions, showing that the relative concentration of antibodies directed against fiber and penton base plays a major role in entry efficacy. Nevertheless, mice previously immunized with virions or purified fiber developed a lower transgene-specific CD8+ T cell response than naive mice, although their serum appeared to increase virus entry into DCs in vitro.