Observation of a Nuclear Recoil Peak at the 100 eV Scale Induced by Neutron Capture.

Coherent elastic neutrino-nucleus scattering and low-mass dark matter detectors rely crucially on the understanding of their response to nuclear recoils. We report the first observation of a nuclear recoil peak at around 112 eV induced by neutron capture. The measurement was performed with a CaWO_{4} cryogenic detector from the NUCLEUS experiment exposed to a ^{252}Cf source placed in a compact moderator. We identify the expected peak structure from the single-γ de-excitation of ^{183}W with 3σ and its origin by neutron capture with 6σ significance. This result demonstrates a new method for precise, in situ, and nonintrusive calibration of low-threshold experiments.

Human parvovirus B19 infection in organ transplant recipients.

We report a 61-yr-old kidney transplant recipient with human Parvovirus B19 (HPV B19) infection presenting as a severe pancytopenia 1 month after transplantation. Bone marrow aspiration revealed severe erythroid hypoplasia with giant and dystrophic proerythroblasts. Bone marrow cells were positive for HPV B19 DNA detected by polymerase chain reaction (PCR). Pancytopenia resolved shortly after administration of intravenous immunoglobulins. Nineteen cases of HPV B19 infection in organ transplant recipients have been so far reported in the literature. Immunocompromised patients should be considered at risk from developing symptomatic HPV B19 infections. In such patients, specific anti-HPV B19 IgM and IgG antibodies may be absent or transient and therefore their negativity cannot rule out the diagnosis of HPV B19 infestation. Bone marrow smear morphological findings may suggest the diagnosis but testing for viral DNA by PCR is mandatory. Patients may spontaneously recover. However, since specific anti-viral therapy is not currently available, intravenous immunoglobulin administration appears to be the more efficacious treatment.

Targeted transfection of the IL-3 gene into primary human hematopoietic progenitor cells through the c-kit receptor.

We recently showed that an antibody-mediated gene transfer procedure termed antifection can be used for targeted gene delivery into lymphoid cells in vitro and in vivo. We here report that antifection also is effective for targeted gene transfer to immature hematopoietic cells. A human IL3-expressing plasmid was chemically linked to an anti-human CD117 antibody. Delivery of the IL3 plasmid into IL-3-dependent myeloid TF-1 cells (bearing the CD117 antigen) was specific and resulted in the transient proliferation of the targeted cells in the absence of exogenous IL-3. Transfection of primary human CD34+ hematopoietic stem/progenitor cells led to transient production of IL-3 and transient proliferation of the target cells. Interestingly, by using a semisolid progenitor cell assay, we found that transfected primary CD34+ cells were able to generate normal numbers of cell colonies in the absence of exogenous IL-3. Polymerase chain reaction analysis confirmed the presence and expression of the IL-3 transgene in the progenitor-derived colonies. In conclusion, our data show that CD117 is a suitable cell surface target to specifically transfer gene by antifection into primary CD34+ cells and that delivery of IL-3 gene in these cells resulted in the expression of a functional IL-3 able to support cell growth in absence of exogenous cytokine. Thus, antifection may provide new therapeutic modality relying on the transient production of appropriate growth factors acting via autocrine and/or paracrine mechanisms.

Incidence and consequences of post-transplantation lymphoproliferative disorders.

Post-transplant lymphoproliferative disorder (PTLD) is a recognized severe complication arising in allograft recipients treated with immunosuppressive drugs. Although not common, PTLD is one of the most frequent tumours among graft recipients, comprising 15-25% of neoplasms, compared with 5% in the general population. The introduction of cyclosporin A (CyA) in the early 1980's and the very potent new immunosuppressants such as anti-CD3 monoclonal OKT3 and FK506 have been associated with a significant rise in the incidence of PTLD and with their earlier presentation. The incidence of this malignancy varies with the organ transplanted (1-2% of renal transplant recipients) and with the nature and severity of the accompanying immunosuppressive regimen. While the precise etiology of PTLD is still unclear, significant advances have been made recently in the understanding of its pathogenesis. Most PTLD tumour cells present an activated B-cell phenotype and an unrestricted pattern of latent EBV gene products. It is generally accepted that Epstein-Barr virus (EBV) infection or reactivation and intensive anti-T lymphocyte regimens play a major role in the genesis of PTLD. They include a spectrum of EBV-related disorders ranging from lymphoid hyperplasia to frank malignant non-Hodgkin's lymphoma. Although different therapeutic attempts have been proposed, optimal treatment remains elusive. The mortality rate for monoclonal lymphomas was reported to be as high as 80%. Infusion of anti-B monoclonal antibodies seems to be a promising modality. Different preventive approaches have been proposed, including EBV sero-negative donor/recipient matching and careful monitoring of EBV infection. Cautious use of anti-rejection treatment in combination with prophylactic antiviral therapy is recommended.

Antifection: an antibody-mediated method to introduce genes into lymphoid cells in vitro and in vivo.

We have developed a simple, safe and versatile method, termed antifection, by which antibodies are used as delivery vehicles to introduce genes into cells expressing specific surface antigens. Antibodies directed against CD3, CD34 or surface immunoglobulins were covalently coupled to plasmids containing marker genes (neoR, beta-galactosidase). Such conjugates were used in vitro and/or in vivo to antifect (transfect using antifection) cells bearing the respective targeted epitope on either normal splenic B lymphocytes or lymphoid-related cell lines. In these conditions the expression of the protein encoded by the marker gene was readily detected. Antifection is a method of delivering genes through a physiological cellular pathway, receptor-mediated endocytosis, into specific cell types, and thus may be considered as an alternative for gene therapy strategy.