Characterization of a very Virulent Marek’s Disease Virus Mutant Expressing the pp38 Protein from the Serotype 1 Vaccine Strain CVI988/Rispens

Marek’s disease virus (MDV), a highly cell-associated oncogenic chicken herpesvirus, causes Marek’s disease in domestic chickens. A unique phosphoprotein of MDV, pp38, has previously been associated with the maintenance of transformation in MDV-induced tumor cell lines. However, recently, the biological properties of a deletion mutant virus (rMd5Δpp38) revealed that pp38 is involved in early cytolytic infection in lymphocytes but not in the induction of tumors. Thus, pp38 is important for early cytolytic infection and not for transformation. The pp38 protein of the MDV serotype 1 vaccine strain CVI988/Rispens differs by one amino acid when compared to the pathogenic strains of MDV. Monoclonal antibody, H19, recognizes all serotype 1 MDV strains except CVI988/Rispens. Previous studies have also shown that the unique pp38 epitope in CVI988/Rispens induced high antibody response. In order to study the role of this epitope in the protective properties of CVI988/Rispens, we generated a mutant rMd5 virus in which the wild type pp38 gene has been substituted with that of CVI988/Rispens (rMd5/pp38CVI). The replication properties of rMd5/pp38CVI, both in vitro and in vivo, and tumor induction were examined. We found that the biological properties of rMd5/pp38CVI were similar to the wild type rMd5 virus with regards to in vivo replication, antibody response and tumor induction. This shows that the pp38 derived from CVI988/Rispens is not involved in protective properties as was previously suggested.     

Primary malignant lymphoma of the breast

Primary malignant lymphomas of the breast (PBL) are uncommon constituting only 0.04 to 0.53% of malignant breast neoplasms. We wish to report the clinical, cytological and histologic findings of PBL diagnosed in a 52 years old female.     

Human immune response to outer membrane protein CD of Moraxella catarrhalis in adults with chronic obstructive pulmonary disease

Moraxella catarrhalis is a common cause of lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). The antibody response to outer membrane protein (OMP) CD, a highly conserved surface protein of M. catarrhalis under consideration as a vaccine antigen, was studied in adults with COPD following 40 episodes of infection or colonization. Following infection or colonization, 9 of 40 patients developed new serum immunoglobulin G (IgG) to OMP CD, as measured by enzyme-linked immunosorbent assay. Adsorption assays revealed that a proportion of the serum IgG was directed toward surface-exposed epitopes on OMP CD in six of the nine patients who developed new IgG to OMP CD. Immunoblot assays with fusion peptide constructs indicated that the new antibodies that developed after infection or colonization recognized conformational epitopes, particularly in the carboxy region of the protein. Three of 28 patients developed new mucosal IgA to OMP CD in sputum supernatants. This study establishes that OMP CD is a target of a systemic and mucosal immune response following infection and colonization in some patients with COPD.     

Fetal liver infusion in aplastic anaemia

Forty patients with severe aplastic anaemia received an intravenous infusion of 0.004 to 11.1 x 10(8) (median: 8 x 10(8) hematopoietic cells prepared from the fetal livers of 8-32 week old abortuses. Five patients, who died within 15 days of fetal liver infusion, are excluded from analysis. Twenty-two of the 35 evaluable patients (62%) responded favourably. Six of the 7 patients with good response were alive after 9 to 44 months (median: m = 20); one died 106 months after fetal liver infusion due to renal lithiasis. Four of the 7 with moderate response were alive after 9 to 31 months; 3 died within 16 months. Of 8 patients with minimal response, one was lost to follow-up and the others died in 3.4 to 10 months (m = 6). Median survival of responders was 15.7 months. Bone marrow cellularity became normal in 12 patients following fetal liver infusion. In seven patients, there was a relapse; 6 regained a normal bone marrow cellularity after a second or third fetal liver infusion. These data strongly suggest a role of fetal liver infusion in inducing bone marrow recovery. Of 13 non-responders, 4 were lost to follow-up and 9 died within 20 days-4.3 months (m = 1.6). Fetal liver infusion appears to be an effective therapy in patients with severe aplastic anaemia.     

Optimal leaf sequencing with elimination of tongue-and-groove underdosage

The individual leaves of a multileaf collimator (MLC) have a tongue-and-groove or stepped-edge design to minimize leakage radiation between adjacent leaves. This design element has a drawback in that it creates areas of underdosages in intensity-modulated photon beams unless a leaf trajectory is specifically designed such that for any two adjacent leaf pairs, the direct exposure under the tongue-and-groove is equal to the lower of the direct exposures of the leaf pairs. In this work, we present a systematic study of the optimization of a leaf sequencing algorithm for segmental multileaf collimator beam delivery that completely eliminates areas of underdosages due to tongue-and-groove or stepped-edge design of the MLC. Simultaneous elimination of tongue-and-groove effect and leaf interdigitation is also studied. This is an extension of our previous work (Kamath et al 2003a Phys. Med. Biol. 48 307) in which we described a leaf sequencing algorithm that is optimal for monitor unit (MU) efficiency under most common leaf movement constraints that include minimum leaf separation. Compared to our previously published algorithm (without constraints), the new algorithms increase the number of sub-fields by approximately 21% and 25%, respectively, but are optimal in MU efficiency for unidirectional schedules.