Zebrafish retinal mutants

BACKGROUND: Development of coronary artery disease in cardiac allograft recipients is the major cause of graft failure after the first year of transplantation. Unfortunately, there is no noninvasive method of identifying patients at greatest risk of developing this disease. We have asked whether serum concentrations of cardiac troponin-T predict development of coronary artery disease. METHODS: Annual coronary angiograms, serial endomyocardial biopsies, and serum cardiac troponin-T concentrations were obtained from 68 cardiac transplant patients who were followed for 68.8+/-11.9 months after surgery. Troponin-T concentrations were measured by using an enzyme-linked immunosorbent assay, and biopsies were assessed histologically for rejection grades and immunohistochemically for cellular infiltrates, arteriolar endothelial activation, fibrin deposits, and vascular fibrinolytic and anticoagulant components. RESULTS: Troponin-T values did not associate with demographic, clinical, or laboratory findings, but they significantly associated with arteriolar endothelial activation (P<0.001), fibrin deposition (P<0.001), depletion of vascular fibrinolytic (P=0.007) and anticoagulant components (P=0.02), and infiltration of macrophages (P <0.001) but not T lymphocytes (P=0.36). Troponin-T concentrations also significantly associated with future development of coronary artery disease (P<0.001). Patients with persistent troponin-T values of 0.10 ng/ml or greater were found to develop the disease within 8.7+/-2.1 months, whereas patients who had initial troponin-T values of 0.10 ng/ml or greater and subsequently fell and remained below 0.10 ng/ml did not develop coronary artery disease in 40 months. CONCLUSIONS: Troponin-T concentrations significantly associated with macrophage infiltrates, microvascular fibrin deposits, arteriolar endothelial activation, depletion of vascular fibrinolytic and anticoagulant components, and the future development of coronary artery disease. The troponin-T assay is an outpatient procedure performed on small amounts of blood at little cost, risk, or inconvenience, and it appears to be the first biochemical predictor of transplant-induced coronary artery disease.     

Evaluation of an extremely flatulent patient: case report and proposed diagnostic and therapeutic approach

We recently encountered a patient with severe flatulence who previously had been subjected to innumerable diagnostic tests and ineffective therapies based on the belief that his rectal gas was produced in the colon. Analysis of three flatus samples demonstrated that nitrogen (N2) was the predominant flatus gas whereas the three gases produced in the gut (CO2, H2 [hydrogen], and CH4 [methane]) comprised <16% of rectal gas. This result plus a series of other diagnostic tests clearly indicated that the patient's flatus was derived almost entirely from swallowed air. Based on this case, the present report summarizes available data on excessive flatulence and suggests a rational approach to the patient complaining of this problem. Particular emphasis is placed upon a sequential strategy consisting of: 1) a count of flatus passages to determine if the subject truly is abnormal (normal: <20 passages/day); 2) an analysis of flatus to determine if the flatus originates from swallowed air (predominantly nitrogen) or intraluminal production (predominantly CO2, H2, and CH4); and 3) treatment based upon the origin of the rectal gas.     

Report of the first case of invasive fungal sinusitis caused by Scopulariopsis acremonium: review of scopulariopsis infections

Scopulariopsis acremonium is a species of saprophytic fungus not previously reported to cause invasive disease in humans, although invasive infections from other species of Scopulariopsis have been reported and are reviewed. Deep infection with this fungus is associated with a high mortality rate. Invasive fungal sinusitis, in general, is a potentially fatal disease that typically affects immunocompromised patients, such as those receiving intensive chemotherapy or undergoing bone marrow transplantation. We report a case of invasive fungal sinusitis caused by Scopulariopsis acremonium in a patient with leukemia, who was successfully treated with amphotericin B, itraconazole, endoscopic sinus surgery, and granulocyte colony-stimulating factor.     

Transduction of human trophoblastic cells by replication-deficient recombinant viral vectors. Promoting cellular differentiation affects virus entry

We investigated the transfer of the lacZ reporter gene into human trophoblastic cells using herpes simplex virus and adeno-associated virus vectors. We used an established choriocarcinoma cell line (BeWo cells) that can be induced to terminally differentiate after treatment with cyclic-AMP. Our results demonstrate that transduction of trophoblastic cells by the herpes simplex virus vector, HSV.CMVlac, and the adeno-associated virus vector, AAV.CMVlac, is affected by cellular differentiation. Treatment of BeWo cells with cyclic-AMP reduced transduction by HSV.CMVlac but increased transduction by the AAV vector. In contrast, when BeWo cells were transfected with herpes simplex virus and adeno-associated virus plasmids, lacZ expression was not affected by treatment with cyclic-AMP. Southern blot analysis demonstrated 2.75 times less herpes simplex virus DNA in cyclic-AMP treated BeWo cells, but 2.0 to 7.4 times more adeno-associated virus DNA in treated cells. We conclude that inefficient transduction of differentiated trophoblastic cells with HSV.CMVlac is because of diminished viral entry, whereas cellular differentiation is associated with increased entry of AAV.CMVlac. These observations suggest that adeno-associated virus vectors may be used to modify trophoblast function and study placental physiology. Additionally, trophoblast differentiation leads to alterations in the mechanisms of virus uptake that may affect maternal-to-fetus transmission.     

Randomized trial of an oral platelet glycoprotein IIb/IIIa antagonist, sibrafiban, in patients after an acute coronary syndrome: results of the TIMI 12 trial. Thrombolysis in Myocardial Infarction

In fMRI studies, Gaussian filtering is usually applied to improve the detection of activated areas. Such lowpass filtering enhances the signal to noise ratio. However, undesirable secondary effects are a bias on the signal shape and a blurring in the spatial domain. Neighboring activated areas may be merged and the high resolution of the fMRI data compromised. In the temporal domain, activation and deactivation slopes are also blurred. We propose an alternative to Gaussian filtering by restoring the signal using a spatiotemporal Markov Random Field which preserves the shape of the transitions. We define some interaction between neighboring voxels which allows us to reduce the noise while preserving the signal characteristics. An energy function is defined as the sum of the interaction potentials and is minimized using a simulated annealing algorithm. The shape of the hemodynamic response is preserved leading to a better characterization of its properties. We demonstrate the use of this approach by applying it to simulated data and to data obtained from a typical fMRI study.     

Potential role for wild-type p53 in leukemias with MLL gene translocations

We used single-strand conformation polymorphism (SSCP) analysis of p53 exons 4-8 to screen for possible mutations in 25 pediatric de novo leukemias with translocations of the MLL gene at chromosome band 11q23. Of the 25 patients, 21 were infants. Fifteen cases were acute myeloid leukemia (AML), eight were acute lymphoblastic leukemia (ALL), and two cases were biphenotypic. Nineteen cases were studied at diagnosis and six at time of relapse. p53 mutations were absent in all 19 cases studied at the time of diagnosis. The only mutation was a TGC-->TTC transversion (cys-->phe) at codon 141 in exon 5 in a case of infant ALL at relapse that occurred by subclone evolution after MLL gene translocation. We previously showed that p53 mutations are also absent in pediatric treatment-related leukemias with MLL gene translocations. The absence of p53 mutations at initial transformation may suggest that the anti-apoptotic effect of mutant p53 is not important in leukemias with MLL gene translocations. Alternatively, exogenous DNA damage may be the common feature in treatment-related and de novo cases. Since MLL gene translocations may occur through DNA repair and wild-type p53 is central to DNA repair, the absence of p53 mutations raises the possibility that wild-type p53, not mutant p53, may be important in the genesis of leukemias with these translocations.