OTUD3: A Lys6 and Lys63 specific deubiquitinase in early vertebrate development.

Ubiquitination and deubiquitylation regulate essential cellular processes and involve hundreds of sequentially acting enzymes, many of which are barely understood. OTUD3 is an evolutionarily highly conserved deubiquitinase involved in many aspects of cellular homeostasis. However, its biochemical properties and physiological role during development are poorly understood.

Functional validation of novel compound heterozygous variants in B3GAT3 resulting in severe osteopenia and fractures: expanding the disease phenotype.

Background: A new disease class of syndromes, described as linkeropathies, which are derived from defects in the glycosaminoglycan-linker region as well as glycosaminoglycan-side chains of proteoglycans is increasingly being recognized as a cause of human disease. Proteoglycans are an essential component of the extracellular matrix. Defects in the enzymatic process of proteoglycan synthesis broadly occur due to the incorrect addition of side chains.

Ubiquitin is a versatile scaffold protein for the generation of molecules with de novo binding and advantageous drug-like properties.

In the search for effective therapeutic strategies, protein-based biologicals are under intense development. While monoclonal antibodies represent the majority of these drugs, other innovative approaches are exploring the use of scaffold proteins for the creation of binding molecules with tailor-made properties. Ubiquitin is especially suited for this strategy due to several key characteristics.

Comparing willingness to pay for improved drinking-water quality using stated preference methods in rural and urban Kenya.

Background: Access to safe drinking water has been on the global agenda for decades. The key to safe drinking water is found in household water treatment and safe storage systems.

Objective: In this study, we assessed rural and urban household demand for a new gravity-driven membrane (GDM) drinking-water filter.

Biophysical and structural characterization of a folded core domain within the proregion of growth and differentiation factor-5.

The structure and function(s) of the very large proregions of the transforming growth factor-β structure family are known in only a few cases. The proregion of growth and differentiation factor (GDF)5 comprises 354 residues. GDF5 therefore belongs to the group of those growth factors with the largest proregions.

Outcome of treatment in adult acute lymphoblastic leukemia in southern Brazil using a modified german multicenter acute lymphoblastic leukemia protocol.

Reports on treatment outcomes in adults with acute lymphoblastic leukemia (ALL) in Brazil are sparse. To evaluate the outcome of patients with ALL managed by the public healthcare system, we studied 42 adults treated from 1990 to 1997 in the Division of Hematology at Hospital de Clínicas, Porto Alegre, Brazil. Of these patients, 14/42 were females and their median age at diagnosis was 26 (17-64) years.

A polymorphism in exon b2 of the major breakpoint cluster region (M-bcr) identified in chronic myeloid leukaemia patients.

The BCR/ABL junctional region and the b3 exon from chronic myeloid leukaemia (CML) patients were sequenced. In all 21 samples analysed the junctional region, as well as the b3 exon of 8 b3a2 mRNA molecules, presented no differences to the already described sequences. However, we identified a polymorphic base in the b2 exon in two out of seven b3a2 samples, four out of 10 b2a2 samples and all four b3a2/b2a2 samples analysed.

Prospective study of strongyloidosis in patients with hematologic malignancies.

Immunocompromised individuals infected with Strongyloides stercoralis may develop severe hyperinfection or disseminated disease with high mortality. Patients with hematological malignancies are at risk because of immunodepression produced either by the disease or its treatment. A prospective study was undertaken at the Hospital de Clínicas de Porto Alegre, from July 1994 to July 1995.

Left ventricular volume calculations using a multiplanar transoesophageal echoprobe; in vitro validation and comparison with biplane angiography.

Background: Biplane angiographic and transthoracic echocardiographic volume calculations have shown to be sufficiently reliable in symmetric hearts; however, they are unreliable in the presence of aneurysmatic distortions. Multiplane transoesophageal echocardiography offers unobstructed cross-sectional views of the heart from one stable transducer position with the potential of imaging irregular cavity forms more accurately. It was the purpose of this in vitro study to compare the precision of multiplanar transoesophageal echocardiography to that of biplane angiography in determining left ventricular volumes, especially in aneurysmatic models.

Occurrence of transcranial Doppler high-intensity transient signals in patients with potential cardiac sources of embolism. A prospective study.

Background And Purpose: Cerebral emboli can be recognized by typical "high-intensity transient signals" (HITS) in the transcranial Doppler (TCD) spectral curves. Patients with potential cardiac sources of embolism are at higher risk for stroke.

Methods: We examined the frequency of HITS in the left middle cerebral artery (MCA) with TCD over periods of 30 minutes in 100 patients having potential cardiac sources of embolism, as indicated by transthoracic or transesophageal echocardiography.

[3-dimensional reconstruction of multiplanar transesophageal echocardiography images: a methodologic report with case examples].

First experience with the dynamic three-dimensional reconstruction of transesophageal echocardiographic images in more than 100 patients with various cardiac diseases are reported. Ninety different two-dimensional image planes were acquired for each reconstruction using a conventional multiplanar transducer, connected to a stepper motor and controlled by a computer-based image acquisition system with special software. Acquisition time for one data set was 2.

Incremental value of biplane and multiplane transesophageal echocardiography for the assessment of active infective endocarditis.

In 41 patients with clinical evidence of active infective endocarditis, transesophageal echocardiography was performed in a stepwise manner, starting with evaluation of the monoplane views, followed by the longitudinal plane, and finally by the intermediate planes. Number, location, length, area, density, extent, and mobility of vegetations and abscesses were assessed in the monoplane, biplane, and best intermediate planes to identify and quantify the incremental value of the longitudinal and intermediate planes. Eighty-three vegetations and 6 abscesses were found.

[Improved evaluation of prosthetic heart valve regurgitation with multiplanar transesophageal echocardiography].

Unlabelled: To study the value of the newly introduced multiplane transesophageal transducer technology for the assessment of prosthetic valve regurgitation, 63 consecutive patients with 35 mitral and 33 aortic prostheses (23 bioprostheses and 45 mechanical prostheses) were examined. Transvalvular, paravalvular, and, in mechanical valves, normal or pathological transvalvular regurgitation were identified using first 0 degrees (transverse) and 90 degrees (longitudinal) planes combined with flexion of the echoscope tip and then additionally using multiple intermediary planes by transducer rotation. In a subgroup of 20 patients interobserver variability was evaluated.

Three-dimensional reconstruction of cardiac structures from transesophageal echocardiography.

Although tomographic imaging has been very successful in cardiology,the quantitation of volumes, surfaces, and masses,as well as understanding of complex morphologies would improve by three-dimensional imaging. This review focuses on approaches to 3-D reconstruction from transesophageal echocardiography. In the past, several attempts using either stepwise parallel translation or stepwise rotation of the transducer have been made.

Does multiplane transesophageal echocardiography improve the assessment of prosthetic valve regurgitation?

Assessment of prosthetic valve regurgitation by echocardiography remains difficult. To study the value of the newly introduced multiplane transesophageal technology for this purpose, prosthetic valve regurgitation was examined in 63 consecutive patients with 35 mitral and 33 aortic prostheses (23 bioprostheses and 45 mechanical prostheses). Transvalvular, paravalvular and, in mechanical valves, normal or pathologic transvalvular regurgitation were identified first with 0 degrees (transverse) and 90 degrees (longitudinal) planes combined with flexion of the echoscope tip and then additionally with multiple intermediary planes by transducer rotation.

Comparison of transcranial contrast Doppler sonography and transesophageal contrast echocardiography for the detection of patent foramen ovale in young stroke patients.

The prevalence of a patent foramen ovale was assessed by simultaneously performing transesophageal contrast echocardiography and transcranial contrast Doppler sonography (TCD) in 137 subjects (mean age 36 years) with stroke of unclarified etiology (n = 41), clarified etiology (n = 33), and in normal subjects (n = 63; mean age 32 years). Patent foramen ovale was found significantly more often in patients with unclarified than clarified strokes or in normal subjects (66% vs 33%, or 43%). Massive paradoxical embolism through a patent foramen ovale, identified by TCD, occurred significantly (p < 0.

Hyperinsulinism in patients with coronary artery disease.

Aim: To assess the clinical impact of hyperinsulinism and major coronary risk factors in patients with angiographically documented or excluded coronary artery disease (CAD), a clinical study was carried out in 268 men admitted for left heart catheterization.

Methods: Fasting immunoreactive insulin (IRI) levels were correlated to all major cardiovascular risk factors and to the presence and degree of CAD.

Results: IRI levels were correlated significantly with the degree of CAD (one-vessel disease: mean IRI 9.

[Quality assurance in echocardiography].

Echocardiography is the most important noninvasive diagnostic tool for the cardiologist. More than 617.000 two-dimensional echo examinations and 425.

Combined subtotal pancreatectomy with selective streptozotocin infusion--a model for the induction of insulin deficiency in dogs.

Standardized models of type I diabetes-like insulin deficiency in larger laboratory animals hardly exist. It was therefore investigated whether stable long-term insulin deficiency in dogs can be induced by selective beta-cell destruction in a safe and reliable procedure without damage of other organs. In Beagle dogs, the diabetogenic response to systemic streptozotocin administration (38.