N-acetylcysteine overdosage after insignificant acetaminophen intake.
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Biomedical subjects
Publications and source records attributed to T Olesen.
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Sewage sludge is frequently applied as fertilizers to cultivated land. However, municipal sewage sludge often contains organic contaminants including nonylphenol (NP), an intermediate from nonionic surfactant degradation. Knowledge about NP degradation in sludge-amended soil is an important prerequisite for adequate risk assessments. In this study, mineralization of 14C-labeled NP in homogenized and nonhomogenized sludge-soil mixtures was investigated. NP was degraded within 38 days in aerobic homogenized mixtures. In nonhomogeneous mixtures containing sludge aggregates, the degradation of NP was retarded and was generally not completed within 3 months (119-126 days). No detectable amounts of NP were transported from the sludge aggregates to the surrounding soil (detection limit: <0.04 mg of NP/kg dw of soil). Oxygen penetration into sludge aggregates was monitored for 50 days with an oxygen microelectrode. An extrapolation of the oxygen data suggested that more than 1 year was required to obtain fully aerobic conditions in a 2-cm sludge aggregate. Since NP is considered persistent in the absence of oxygen, residual amounts of NP may be present in the anaerobic center of aggregates for prolonged periods. The results demonstrate that sludge aggregate size and thus oxygen availability will be a major controlling factor for NP degradation in soil amended with sewage sludge and that the mobility of NP from sludge aggregates to the surrounding soil is negligible.
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During a scheduled visit to southern Greenland in 1992, the pediatric consultant registered signs and symptoms that had led to the children being brought for examination, and simultaneously registered the actual frequency of asthma, epilepsia and cerebral palsy. A total of 211 children or 8% of the background population under the age of fifteen were examined. The point prevalence of asthma was 1.1% which was considered to be an absolute minimum value due to selection of patients. The point of epilepsy was 0.6% and cerebral palsy 0.3%, a surprisingly high prevalence compared to prior investigations and actual patient selection. The consultant was met as well by a broad spectrum of pediatric problems, many of the social pediatric type. In conclusion, the importance of yearly visits is maintained along with a need of instruction of the local local health personnel. A systematic registration of cerebral palsy cases is required in order to implement necessary prophylactic intervention. Contact between the Greenlandic and the Danish health services could be intensified by the use of electronic media.
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We have characterized regulation of type-1 plasminogen activator inhibitor (PAI-1) gene expression by phorbol 12-myristate 13-acetate (PMA) and the cAMP-inducing agent forskolin in the human breast carcinoma cell line MCF-7. PMA caused a strong induction of PAI-1, while forskolin suppressed the PMA response. Transfection experiments with fusion genes showed that sequences mediating PMA induction as well as forskolin suppression were present between base pairs -100 and -30 of the 5'-flanking region of the PAI-1 gene. The region was found to contain two Sp1 binding sites. A proximal sequence in the region, TGAGTTCA (P box), with sequence similarity to phorbol ester response elements (TRE) as well as to cAMP response elements (CRE), bound a low-abundance, as yet unidentified nuclear protein in MCF-7 cells. This sequence had a higher affinity to purified c-jun homodimer than to c-jun/c-fos heterodimer in MCF-7 nuclear extracts; it had no affinity to the proteins binding to CRE consensus sequences in these extracts. A distal TRE-like sequence, TGAGTGG (D box), had a weak affinity to c-jun/c-fos heterodimer and c-jun homodimer; binding of proteins to this sequence was facilitated by binding of proteins to the P box. Both the P box and the D box were necessary for PMA responsiveness, suggesting a cooperativity between the two binding sites. A mutation of the P box removing the CRE similarity abolished the forskolin suppression of the PMA response. We propose that the protein kinase C and the protein kinase A signal-transduction pathways, with opposite effects on PAI-1 gene expression converge by modulating differently P-box-binding proteins.
Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-beta 1-responsive element in the 5'-flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-beta 1-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-beta 1, thus showing that both elements of the unit are necessary for the TGF-beta 1 response. We discuss the possible relationship of these findings to the complexity of the TGF-beta action.
The effect of strict metabolic control for 5 years on renal function and retinal morphology was estimated in 24 insulin-dependent diabetic individuals (age 29 +/- 8 years, diabetes duration 10 +/- 6 years) with albustix negative urine and minimal or no background retinopathy before the study. They were randomized to conventional insulin treatment (CIT) or continuous subcutaneous insulin infusion (CSII) with a portable pump. During CSII treatment the metabolic status was significantly improved. HbA1c fell from 8.9 +/- 2.0 to 7.4 +/- 1.3% (p less than 0.01) whereas HbA1c was unchanged during CIT treatment. The mean value of urinary albumin excretion (UAE) was not statistically significantly changed (from 12 +/- 10 mg/24 h to 13 +/- 5 mg/24 h in CSII patients and from 14 +/- 12 to 11 +/- 6 mg/24 h in CIT patients (p greater than 0.1). On the other hand, the elevated GFR values were significantly reduced in both CSII and CIT patients, 129 +/- 17 to 120 +/- 9 and 129 +/- 18 to 119 +/- 12 ml/min.1,73m2, respectively (p less than 0.05). Both the number of microaneurysms, haemorrhages and exudates tended to increase mor in CIT patients than in CSII patients during the 5 year study period, but the differences did not reach statistically significance (p greater than 0.1). Pump treatment did not induce proliferations or "cotton wool" exudates. We conclude that no statistically significantly differences between GFR values, UAE rates, and progression of background retinopathy was observed between normoalbuminuric IDDM patients treated for 5 years with CIT and CSII, respectively. However, due to the size of the material a type II error must be taken into consideration.
We describe, for the first time, an intron that is located in the variable loop of a tRNA. It is 18 nucleotides long and occurs within a precursor tRNAGly from the extreme thermophile Thermofilum pendens. The variable loop is less critical for tRNA function than the anticodon arm where other class III introns occur. This raises the possibility that tRNAs with a large variable loop (type II) arose from those with a small variable loop (type I) by retaining a splicing-deficient intron.
The structure of the exon-intron boundary was compared for an intron within 23S ribosomal RNA of Desulfurococcus mobilis and a newly discovered intron in tRNA(Met) from the same organism. The occurrence of a putative common structural feature suggests that intron excision occurs by the same mechanism. The possible recognition of this structural feature by the cleavage enzyme was investigated for the ribosomal RNA intron using RNA substrates exhibiting various exon and intron deletions. The results support the involvement of the structural features in the cleavage process. The evolutionary implications of these results are considered.
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The present study revealed an incidence of maltreatment of 26.8 in 100,000 children under 15 years of age, higher than previously assumed. The sample comprises 41 children suspected of having been maltreated. A systematic examination included radiography and isotope scintigraphy of the skeletal system. In 9 cases the diagnosis was not confirmed, in 23 confirmed, and in 9 children it seemed likely. The most common form of maltreatment was physical violence with bruises. A total of 6 fractures were demonstrated. Three children had been exposed to sexual abuse. Intracranial haematoma, of long standing, was found in one child. Thirteen of the children (40%) were of short statute, their height and weight below the 25th percentile. Among 27 children examined by X-rays 16 (59%) had delayed skeletal maturation. Disturbances of growth, as well as behavioural abnormalities, were particularly striking in this group of patients. The findings suggest that even the slightest suspicion of maltreatment should lead to a general medical evaluation without delay.
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In seven patients with de novo acute myeloblastic leukemia, the concentration of large unstained cells (LUC) in peripheral blood and the ratio between this quantity and the concentration of lymphocytes (LUC/LYMPH) were measured at short intervals during each patient's clinical course. An automated differential analyzer (the Hemalog-D) was used. Both quantities were significantly higher 12 days after the institution of daunomycin and cytosine arabinoside chemotherapy (between first and second treatment series when all patients were pancytopenic) in three of the patients who did not achieve remission (mean LUC = 59 cells/microliter, mean LUC/LYMPH = 13.9), as compared with four of the patients who went into remission following two series of chemotherapy (mean LUC = 16 cells/microliter, mean LUC/LYMPH = 3.11).
An alarm system for the detection of abnormal leukocytes using off-line data processing of the image of the peroxidase channel oscilloscope picture of the Hemalog-D is presented. The basic idea is that areas on the oscilloscope picture where more than a negligible number of nonpathological leukocytes may be depicted are delimited from the remaining area, which is divided into three alarm zones. The corresponding alarm quantities are the large unstained cells (LUC) or the unstained alarm (UA), the intermediate alarm (IA), and the stained alarm (SA). Reference intervals for these alarms were established using blood specimens from 15 healthy subjects. The system was tested using blood specimens from four patients with acute lymphoblastic leukemia (ALL) and 11 patients with acute myeloblastic leukemia (AML). The UA was the best alarm overall, but for seven of the AML specimens the IA or the SA alarm was superior. The high peroxidase (HPX) and the remainder alarms were inferior to the other alarms. Using the reference mean plus two standard deviations as a cutoff value, the smallest blast cell number fraction detectable by the best alarm was calculated to be smaller than 2% for each of the AML specimens, while it ranged from 7 to 2.9% for the ALL specimens.