The longest survival of a nonhuman primate with a life-supporting kidney graft to date has been 90 days, though graft survival >30 days has been unusual. A baboon received a kidney graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for two human complement- and three human coagulation- regulatory proteins (though only one was expressed in the kidney). Immunosuppressive therapy was with ATG+anti-CD20mAb (induction) and anti-CD40mAb+rapamycin+corticosteroids (maintenance). Anti-TNF-α and anti-IL-6R were administered. The baboon survived 136 days with a generally stable serum creatinine (0.6–1.6mg/dL) until terminally. No features of a consumptive coagulopathy (e.g., thrombocytopenia, decreased fibrinogen) or of a protein-losing nephropathy were observed. There was no evidence of an elicited anti-pig antibody response. Death was from septic shock (Myroides spp). Histology of a biopsy on day 103 was normal, but by day 136 the kidney showed features of glomerular enlargement, thrombi, and mesangial expansion. The combination of (i) a graft from a specific genetically-engineered pig, (ii) an effective immunosuppressive regimen, and (iii) anti-inflammatory agents prevented immune injury and a protein-losing nephropathy, and delayed coagulation dysfunction. This outcome encourages us that clinical renal xenotransplantation may become a reality.

Human lung lavage proteins were fractionated by centrifuganon and molecular sieving. An antiserum to the post-albumin fraction of the soluble proteins reacted with a 10 KD protein and this protein was isolated by conventional chromatography. The protein, which has a p1 of 4.8, consists of two 5 KD polypeptides and is rich in glutamic acid, leucine, 5crme, and aspartic acid amino acids. The protein does not bind to concanavalin A, pancreatic elastase, leukocyte elastase, or trypsin, and lacks anti-protease activity. It constitutes about 0.15% of the soluble proteins in lung lavage. Antibodies to the 10 KD protein specifically and exclusively stain Clara cells in human, dog, and rat. Staining of granules of Clara

This paper considers the requirements for investigation of sick buildings including some guidelines for assessment of exposure risks with a particular focus on dampness, proliferation of moulds, and dispersion of fungal spores in indoor environments. Building pathology, indoors air quality management and management of bio-deterioration, and health problems in buildings are complex issues requiring multi-disciplinary investigations and environmental monitoring. Lack of maintenance, chronic neglect, and building defects leading to water ingress, condensation, and dampness in the building fabric will often produce proliferation of pathogenic toxic moulds, and other microbial and biological effects that could cause allergic response in sensitive people and generally lead to ‘‘sick buildings.’’ A general guide has been provided by this paper for environmental assessment of toxic moulds in indoor environments, including a suggested guideline for assessing the threshold levels for fungal spores in indoor air.

Zygomycosis is a rare but highly invasive fungal infection that occurs in transplant recipients. We report a case of invasive gastrointestinal zygomycosis that occurred in a heavily immunosuppressed liver transplant recipient 5 days after retransplantation and that presented as gastric perforation. Despite aggressive surgical and antifungal therapy, the patient died. We review 46 cases of invasive zygomycosis in solid-organ transplant recipients. The rhinocerebral form of zygomycosis occurred in 57% of cases; the pulmonary, cutaneous, and disseminated forms each occurred in 13%; the renal form occurred in 2%; and the gastrointestinal form occurred in 2%. The infection ensued a median of 2 months after transplantation (range, 5 days to 8 years). Seventy-six percent of the patients had diabetes or had received antirejection therapy, mainly in the form of corticosteroids, before the onset of zygomycotic infection. The mortality for patients who received antifungal therapy and/or who underwent surgery was 50% for those who had rhinocerebral zygomycosis, none for those who had pulmonary and cutaneous zygomycosis, and 100% for those who had disseminated zygomycosis. Knowledge of the diverse clinical manifestations (including gastrointestinal involvement, as is illustrated by our case) and predisposing factors in transplant recipients with zygomycosis can aid in early recognition of this disease in this patient population.

Mutations of spliceosome components are common in myeloid neoplasms. One of the affected genes, PRPF8, encodes the most evolutionarily conserved spliceosomal protein. We identified either recurrent somatic PRPF8 mutations or hemizygous deletions in 15/447 and 24/450 cases, respectively. 50% of PRPF8 mutant and del(17p) cases were found in AML and conveyed poor prognosis. PRPF8 defects correlated with increased myeloblasts and ring sideroblasts in cases without SF3B1 mutations. Knockdown of PRPF8 in K562 and CD34+ primary bone marrow cells increased proliferative capacity. Whole RNA deep sequencing of primary cells from patients with PRPF8 abnormalities demonstrated consistent missplicing defects. In yeast models, homologous mutations introduced into Prp8 abrogated a block experimentally produced in the second step of the RNA splicing process suggesting that the mutants have defects in proof-reading functions. In sum, the exploration of clinical and functional consequences suggests that PRPF8 is a novel leukemogenic gene in myeloid neoplasms with a distinct phenotype likely manifested through aberrant splicing.