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.
Results of overexpression or downregulation of a microRNA (miRNA) on its target mRNA expression are often validated by reverse-transcription and quantitative PCR analysis using an appropriate housekeeping gene as an internal control. The possible direct or indirect effects of a miRNA on the expression of housekeeping genes are often overlooked. Among many housekeeping genes, expressions of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and β-actin have been used extensively for normalization of gene expression data. Here, we show that GAPDH and β-actin are direct targets of miR-644a. Our data demonstrate the unsuitability of GAPDH and β-actin as internal controls in miR-644a functional studies and emphasize the need to carefully consider the choice of a reference gene in miRNA experiments.
Background:Magnesium ion gates the N-methyl-D-aspartate (NMDA) receptor and may protect the brain from NMDA receptor-mediated asphyxial injury. The present study evaluated the neuroprotective role of magnesium in birth asphyxia.Material and Methods:Forty term neonates with severe birth asphyxia were randomized to either the study group or the control group. Neonates in the study group received magnesium sulfate in a dose of 250 mg/kg initially within half an hour of birth followed by 125 mg/kg at 24 and 48 h of birth. Cranial computed tomography (CT) scan and electroencephalography (EEG) were performed for all the babies. Denver II was used for developmental assessment at the age of 6 months.Results:Two babies in each group died of severe hypoxic ischemic encephalopathy. EEG abnormalities occurred in 43.75% of the cases in the control group compared with 31.25% in the study group. CT scan abnormalities were present in 62.5% of the control group compared with 37.5% of the cases in the study group. The Denver II assessment at 6 months revealed that there were five babies that were either abnormal or suspect in the control group compared with three in the study group.Conclusion:Magnesium is well tolerated and does appear to have beneficial effects in babies with severe asphyxia. More data is however needed and a large multicenter trial should be conducted.
The aim of this study was to determine whether the implementation of Kangaroo Mother Care (KMC) to low birth weight infants would improve physical growth, breastfeeding and its acceptability. A randomized controlled trial was performed over 16 months in which 110 neonates were randomized into a KMC group and a control group using a random number table. The KMC group was subjected to KMC for at least 6 h per day. The babies also received KMC after moving from the neonatal intensive care unit and at home. The control group received standard care (incubator or open care system). Weight, length and occipitofrontal circumference (OFC) were measured weekly for three months. The acceptability of KMC by mothers and nursing staff was assessed on day 7 after the start of KMC using a questionnaire incorporating the Likert scale. Breastfeeding rates were calculated based on history at end of three months. The mean gestational age was 35.48 ± 1.20 weeks in the KMC group and 35.04 ± 1.09 weeks in the control group (P > 0.05). KMC was initiated at a mean age of 1.72 ± 0.45 days and the duration of KMC was 9.74 ± 1.48 h/day. The mean birth weight was 1.69 ± 0.11 kg in the KMC group compared to 1.69 ± 0.12 kg in the control group (P > 0.05). The mean weight gain in gm/day in the KMC group was 21.92 ± 1.44 compared to 18.61 ± 1.28 in the control group (P < 0.05). The mean length gain in cm/week was 1.03 ± 0.5 in the KMC group compared to 0.74 ± 0.05 in the control group (P < 0.05). The mean OFC gain in cm/week was 0.59 ± 0.04 in the KMC group compared to 0.47 ± 0.03 in the control group (P < 0.05). The exclusive breast-feeding rate at end of three months was 88% in the KMC group compared to 72% in the control group (P < 0.05). KMC improved physical growth, breastfeeding rates and was well accepted by both mothers and nursing staff.
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