Pediatric lung transplantation: The years 1985 to 1992 and the clinical trial of FK 506

The application of lung transplantation to the pediatric population was a natural extension of the success realized in our adult transplantation program, which began in 1982. Twenty pediatric patients (age range 3 to 18 years) have had heart-lung (n = 11), double lung (n = 8), and single lung (n = 1) transplantation procedures. The causes of end-stage lung disease were primary pulmonary hypertension (n = 7), congenital heart disease (n = 5), cystic fibrosis (n = 4), pulmonary arteriovenous malformation (n = 2), graft- versus-host disease (n = 1), and desquamative interstitial pneumonitis (n = 1). Four (20%) patients had thoracic surgical procedures before the transplantation operation. The survival was 80% at a mean follow-up of 2 years. Immunosuppressive drugs included cyclosporine (n = 9) or FK 506 (n = 11) based therapy with azathioprine and steroids. Children were followed up by means of spirometry, transbronchial biopsy, and primed lymphocyte testing of bronchoalveolar lavage fluid. The mean number of treated episodes of rejection was 1.4 at 30 days, 0.5 at 30 to 90 days, and 1.4 at more than 90 days, and the first treated rejection episode occurred on average 28 days after the operation. Obliterative bronchiolitis developed in four (25%) of 16 patients surviving more than 100 days. Results of pulmonary function tests have remained good in almost all recipients. The greatest infectious risk was that of cytomegalovirus: one death and one case of pneumonia. Posttransplantation lymphoproliferative disease was diagnosed in two (12.5%) patients; both recovered. The most common complications were hypertension (25%) and postoperative bleeding (15%). Early results indicate that lung transplantation is a most promising therapy for children with severe vascular and parenchymal lung disease

Identification of alleles of carotenoid pathway genes important for zeaxanthin accumulation in potato tubers

We have investigated the genetics and molecular biology of orange flesh colour in potato (Solanum tuberosum L.). To this end the natural diversity in three genes of the carotenoid pathway was assessed by SNP analyses. Association analysis was performed between SNP haplotypes and flesh colour phenotypes in diploid and tetraploid potato genotypes. We observed that among eleven beta-carotene hydroxylase 2 (Chy2) alleles only one dominant allele has a major effect, changing white into yellow flesh colour. In contrast, none of the lycopene epsilon cyclase (Lcye) alleles seemed to have a large effect on flesh colour. Analysis of zeaxanthin epoxidase (Zep) alleles showed that all (diploid) genotypes with orange tuber flesh were homozygous for one specific Zep allele. This Zep allele showed a reduced level of expression. The complete genomic sequence of the recessive Zep allele, including the promoter, was determined, and compared with the sequence of other Zep alleles. The most striking difference was the presence of a non-LTR retrotransposon sequence in intron 1 of the recessive Zep allele, which was absent in all other Zep alleles investigated. We hypothesise that the presence of this large sequence in intron 1 caused the lower expression level, resulting in reduced Zep activity and accumulation of zeaxanthin. Only genotypes combining presence of the dominant Chy2 allele with homozygosity for the recessive Zep allele produced orange-fleshed tubers that accumulated large amounts of zeaxanthin

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Scaling and measurement section: A time for change

The Fall 1991 issue of Journal of Personal Selling & Sales Management announced the establishment of the special topic section “Scaling and Measurement”. The primary purpose of the section was “to provide an authoritative centralized source for dissemination of information related to measurement and scaling issues germane to personal selling and sales management research. © 1994 Taylor & Francis Group, LLC

An Empirical Investigation Of Components Of Industrial Buyer Motivation

Motivation of industrial buyers has been virtually ignored in the marketing and purchasing literatures. This empirical void is surprising given the critical role organizational purchasers play in their firms. This paper reports the results of a study that explored the impact of individual and organizational characteristics on three expectancy model components of industrial buyers’ motivation. Findings reveal that personal factors have a greater impact on buyer motivation than do organizational variables. Implications of the study are also offered. © 1995 by The Haworth Press, Inc. All rights reserved