PubMed Health⌕ Search

Biomedical subjects

A Weiss

Publications and source records attributed to A Weiss.

At least 19 recordsLinked to original sources
PubMed2006

The trans-neptunian object UB313 is larger than Pluto.

The most distant known object in the Solar System, 2003 UB313 (97 au from the Sun), was recently discovered near its aphelion. Its high eccentricity and inclination to the ecliptic plane, along with its perihelion near the orbit of Neptune, identify it as a member of the 'scattered disk'. This disk of bodies probably originates in the Kuiper belt objects, which orbit near the ecliptic plane in circular orbits between 30 and 50 au, and may include Pluto as a member. The optical brightness of 2003 UB313, if adjusted to Pluto's distance, is greater than that of Pluto, which suggested that it might be larger than Pluto. The actual size, however, could not be determined from the optical measurements because the surface reflectivity (albedo) was unknown. Here we report observations of the thermal emission of 2003 UB313 at a wavelength of 1.2 mm, which in combination with the measured optical brightness leads to a diameter of 3,000 +/- 300 +/- 100 km. Here the first error reflects measurement uncertainties, while the second derives from the unknown object orientation. This makes 2003 UB313 the largest known trans-neptunian object, even larger than Pluto (2,300 km). The albedo is 0.60 +/- 0.10 +/- 0.05, which is strikingly similar to that of Pluto, suggesting that the methane seen in the optical spectrum causes a highly reflective icy surface.

Journal Article↗
PubMed2005

Hysteroscopy may be justified after two miscarriages.

BACKGROUND: Recurrent pregnancy loss is traditionally investigated after three or more consecutive pregnancy losses. Although there is a trend to start investigation after two miscarriages, data are not available to date to justify this approach. We sought to compare the frequency of uterine anomalies between women referred to hysteroscopy for repeated miscarriages after two, and three or more, miscarriages respectively. METHODS: A retrospective analysis of acquired and congenital uterine anomalies in all patients undergoing hysteroscopy for repeated pregnancy loss at an academic and referral medical centre. RESULTS: Hysteroscopy was performed on 165 women referred for recurrent pregnancy loss: 67 after two and 98 after three or more consecutive miscarriages. The rate of uterine anomalies did not differ significantly and was 32 versus 28% respectively. CONCLUSIONS: Hysteroscopy may be justified following two spontaneous pregnancy losses.

Abortion, Habitual↗
PubMed2005

Acute respiratory failure after deep cervical plexus block for carotid endarterectomy as a result of bilateral recurrent laryngeal nerve paralysis.

We report about a case of acute respiratory distress (73-year-old female), which occurred minutes after a deep cervical plexus block (40 ml ropivacaine 0.5%) for carotid endarterectomy (CEA) and required immediate endotracheal intubation of the patient's trachea and consecutive mechanical ventilation. Subsequently, CEA was performed under general anaesthesia (TIVA) with continuous monitoring by somatosensory-evoked potentials. After a period of 14 hours, the endotracheal tube could be removed, the patient being in fair respiratory, cardiocirculatory and neurological conditions. Retrospectively, acute respiratory distress was caused by a combination of ipsilateral plexus blockade-induced and pre-existing asymptomatic contralateral recurrent laryngeal nerve (RLN) paralysis confirmed by a postoperative ENT-check and related to previous thyroid surgery more than 50 years ago. RLN paralysis, often being asymptomatic, represents a typical complication of thyroid and other neck surgery with reported incidences of 0.5-3%. Therefore, a thorough preoperative airway check is advisable in all patients scheduled for a cervical plexus block. Particularly in cases with a history of respiratory disorders or previous neck surgery a vocal cord examination is recommended, and the use of a superficial cervical plexus block may lower the risk of respiratory complications. This may prevent a possibly life-threatening coincidence of ipsilateral plexus blockade-induced and pre-existing asymptomatic contralateral RLN paralysis.

Acute Disease↗
PubMed2004

The cardiolipin-binding domain of Bid affects mitochondrial respiration and enhances cytochrome c release.

Bid is cleaved by caspase 8 during apoptosis and the truncated Bid (tBid) translocates to mitochondria by targeting cardiolipin. Amino acids 103-162 of Bid were reported as the cardiolipin-binding domain (CBD). The EGFP-CBD fusion protein targets to mitochondria and induces apoptosis. Using [(3)H]cardiolipin, we proved that recombinant CBD binds cardiolipin similar to tBid and tBid(G94E), a mutant with a defective BH3 domain. CBD could induce cytochrome c release from isolated mitochondria, but much less potent than tBid. Free cardiolipin inhibited the CBD-induced cytochrome c release, suggesting that it may be mediated by interfering with mitochondrial cardiolipin, especially with the interaction between cytochrome c and cardiolipin. This is consistent with the findings that CBD induced cytochrome c release in Bax-deficient cells, and that CBD suppressed mitochondrial respiration through directly interfering with cardiolipin, a critical lipid involved in oxidative phosphorylation. These results indicate the functional importance of CBD in tBid-induced apoptosis.

Animals↗
PubMed2004

Orthostatic hypotension in the elderly: are the diagnostic criteria adequate?

Orthostatic hypotension (OH) is a common finding in the elderly. OH is defined as a fall of at least 20 mmHg in systolic blood pressure (BP) and/or 10 mmHg in diastolic BP upon assuming an upright posture. Some patients exhibit a fall in BP of less than the defined OH upon standing. The aim of this study was to estimate the prevalence of BP changes not defined as OH among elderly in-patients and to assess the relationship between these changes in the morning and the occurrence of OH during the day. Postural BP measurements were performed in 502 in-patients; in the morning, early afternoon, and in the evening. We defined intermediate postural drop (ID) in BP as a decrease of 10-19 mmHg in systolic BP and/or of 5-9 mmHg in diastolic BP. We observed that OH and ID occurred in 39.2 and 18.5% of the measurements in the morning, respectively. The prevalence of OH and ID was lower in the evening than in the morning (P<0.05) and afternoon (P<0.005). Postural BP changes in the morning correlated with those occurring later in the day. Patients who had ID in the morning had a 57% probability of having OH later during the day. In conclusions, ID is prevalent in elderly in-patients. ID in the morning predicts OH later in the day. Thus, postural BP drops below the OH range may be an important finding in the geriatric population.

Aged↗
PubMed2003

A comparison of total intravenous with balanced anaesthesia for middle ear surgery: effects on postoperative nausea and vomiting, pain, and conditions of surgery.

We compared postoperative nausea and vomiting (PONV), pain and conditions for surgery in patients scheduled for middle ear surgery. In a double-blind study, 100 patients were randomly allocated to receive either balanced anaesthesia (group A) using fentanyl, propofol and isoflurane, or total intravenous anaesthesia (group B) using propofol and remifentanil infusions. Pain scores, nausea/vomiting scores, conditions for surgery and analgesic requirements were recorded for 18 h post operatively. In the recovery ward, patients in group B suffered significantly less PONV (p = 0.026) with a reduced requirement for anti-emetic medication (p = 0.023); however, this difference was not maintained on the ward. The overall incidence of PONV was 34% and 17% in groups A and B, respectively. Initial pain scores were higher in group B in the recovery ward (p = 0.003) and patients required more morphine administration (p = 0.002); however, pain scores were similar on the ward. Conditions for surgery were found to be better in group B.

Adult↗
PubMed2003

Pseudomembranous tracheobronchial aspergillosis: a rare manifestation of invasive aspergillosis in a non-neutropenic patient with Hodgkin's disease.

Pseudomembranous tracheobronchial aspergillosis coincident with systemic pulmonary aspergillosis represents a rare manifestation of fungal infection in immunocompromized hosts. We report on a patient with recurrent Hodgkin's disease, showing this infectious pattern after treatment with corticosteroids within the antineoplastic schedule, whereas neutropenia--the main risk factor for mold infections--had not occurred. An impaired number of helper T lymphocytes was merely detected as an additional, but hypothetical risk factor, when investigating the status of immunosuppression. Treated systemically with amphotericin B, the patient recovered quickly, although reported mortality rates are disastrous. What is crucial for the clinical management is an early diagnosis by bronchoscopy and cultural proof of the pathogen followed by an adequate antifungal treatment.

Amphotericin B↗
PubMed2003

Differential activity of the gelatinases (matrix metalloproteinases 2 and 9) in the fetal membranes and decidua, associated with labour.

Degradation of the extracellular matrix in fetal membranes has been implicated in the rupture of fetal membranes, the process of parturition and placental detachment from the decidua after parturition. In this study we assessed labour-associated changes in gelatinase activity in cultured human amnion, chorion and decidua, as well as in amniotic fluid. We found that in media conditioned by decidua, following the establishment of uterine contractions, matrix metalloproteinase-2 (MMP-2) activity is increased while the protein tissue inhibitors of matrix metalloproteinase-1 (TIMP-1) level is decreased. The formation of a 130 kDa gelatinase band was also significantly increased after contractions began. In media conditioned by chorion, the initiation of uterine contractions did not change MMP activity or TIMP-1 levels. However, an increase in MMP-9 activity and a decrease in TIMP-1 protein levels were observed following the establishment of uterine contractions in media conditioned by amnion. We suggest that this differential spatial regulation provides a form for modulatory hieratical activity of the MMPs in the onset of labour allowing rupture of the membranes while avoiding premature placental separation.

Decidua↗
PubMed2002

[Echocardiographic detection of tricuspid valve endocarditis and right atrial and ventricular masses in a patient with acute myeloid leukaemia].

In a patient with acute leukaemia, tricuspid valve vegetations and both right atrial and ventricular masses formed within a few weeks were detected by echocardiography. In addition to endocarditis which is a very rare condition in patients with acute leukaemia, the diagnostic efforts including cardiac surgery resulted in the unusual finding of right-sided cardiac thrombi which had formed autochthonously. The most likely cause was thought to be a very severe systemic infection with staphylococci characterised by repeated episodes of bacteraemia during profound and prolonged neutropenia as well as a paraneoplastic coagulopathy. Surgery performed on the grounds of the echocardiography findings and differential-diagnostic considerations resulted in the relapse-free removal of the infectious focus. The maintenance therapy for leukaemia could thus be continued and led to a distinctly improved outcome. This case report confirms the great importance of sonography in the management of fever of unknown origin in immunocompromised patients.

Acute Disease↗
PubMed2001

Hematopoietic progenitor kinase 1 associates physically and functionally with the adaptor proteins B cell linker protein and SLP-76 in lymphocytes.

B cell linker protein (BLNK) is a SLP-76-related adaptor protein essential for signal transduction from the BCR. To identify components of BLNK-associated signaling pathways, we performed a phosphorylation-dependent yeast two-hybrid analysis using BLNK probes. Here we report that the serine/threonine kinase hematopoietic progenitor kinase 1 (HPK1), which is activated upon antigen-receptor stimulation and which has been implicated in the regulation of MAP kinase pathways, interacts physically and functionally with BLNK in B cells and with SLP-76 in T cells. This interaction requires Tyr(379) of HPK1 and the Src homology 2 (SH2) domain of BLNK/SLP-76. Via homology modeling, we defined a consensus binding site within ligands for SLP family SH2 domains. We further demonstrate that the SH2 domain of SLP-76 participates in the regulation of AP-1 and NFAT activation in response to T cell receptor (TCR) stimulation and that HPK1 inhibits AP-1 activation in a manner partially dependent on its interaction with SLP-76. Our data are consistent with a model in which full activation of HPK1 requires its own phosphorylation on tyrosine and subsequent interaction with adaptors of the SLP family, providing a mechanistic basis for the integration of this kinase into antigen receptor signaling cascades.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Endogenous CD28 expressed on myeloma cells up-regulates interleukin-8 production: implications for multiple myeloma progression.

CD28 is the major costimulatory molecule on T cells. CD28 activation, in conjunction with T-cell receptor engagement, up-regulates transcription of several cytokines, including interleukin-2 (IL-2), through transcriptional activation of the RE/AP composite element. Although CD28 is not normally expressed on B cells or plasma cells, more than 90% of extramedullary myelomas (a late stage B-cell neoplasm) express CD28. The functional significance of this is unknown. The results of this study demonstrate that CD28 stimulates transcriptional activation of RE/AP-based reporters in B cells and myeloma cells. However, CD28 stimulation does not up-regulate IL-2 production in myeloma cell lines, demonstrating that the IL-2 promoter may not be a relevant RE/AP-containing target of CD28 in myelomas. Instead, an RE/AP composite element has been identified within the promoter of the IL-8 gene, a chemokine that promotes angiogenesis. Furthermore, stimulation of endogenous CD28 expressed by 3 myeloma cell lines increased IL-8 production. Therefore, the study demonstrates that CD28 is functional in myelomas to up-regulate transcription of endogenous genes, including IL-8. The proposal is made that aberrant expression of CD28 may play a role in the progression of multiple myeloma.

Animals↗
PubMed2001

Interactions between adaptor protein-1 of the clathrin coat and microtubules via type 1a microtubule-associated proteins.

The classical view suggests that adaptor proteins of the clathrin coat mediate the sorting of cargo protein passengers into clathrin-coated pits and the recruitment of clathrin into budding areas in the donor membrane. In the present study, we provide biochemical and morphological evidence that the adaptor protein 1 (AP-1) adaptor of the trans-Golgi network clathrin interacts with microtubules. AP-1 in cytosolic extracts interacted with in vitro assembled microtubules, and these interactions were inhibited by ATP depletion of the extracts or in the presence of 5'-adenylylimidodiphosphate. An overexpressed gamma-subunit of the AP-1 complex associated with microtubules, suggesting that this subunit may mediate the interaction of AP-1 with the cytoskeleton. Purified AP-1 did not interact with purified microtubules, but interaction occurred when an isolated microtubule-associated protein fraction was added to the reaction mix. The gamma-adaptin subunit of AP-1 specifically co-immunoprecipitated with a microtubule-associated protein of type 1a from rat brain cytosol. This suggests that type 1a microtubule-associated protein may mediate the association of AP-1 with microtubules in the cytoplasm. The microtubule binding activity of AP-1 was markedly inhibited in cytosol of mitotic cells. By means of its interaction with microtubule-associated proteins, we propose novel roles for AP-1 adaptors in modulating the dynamics of the cytoskeleton, the stability and shape of coated organelles, and the loading of nascent AP-1-coated vesicles onto appropriate microtubular tracks.

Adaptor Protein Complex gamma Subunits↗
PubMed2001

Identification of the minimal tyrosine residues required for linker for activation of T cell function.

The linker for activation of T cells (LAT) is essential for signaling through the T cell receptor (TCR). Following TCR stimulation, LAT becomes tyrosine-phosphorylated, creating docking sites for other signaling proteins such as phospholipase C-gamma(1) (PLC-gamma(1)), Grb2, and Gads. In this study, we have attempted to identify the critical tyrosine residues in LAT that mediate TCR activation-induced mobilization of intracellular Ca(2+) and activation of the MAP kinase Erk2. By using the LAT-deficient Jurkat derivative, J.CaM2, stable cell lines were established expressing various tyrosine mutants of LAT. We show that three specific tyrosine residues (Tyr(132), Tyr(171), and Tyr(191)) are necessary and sufficient to achieve a Ca(2+) flux following TCR stimulation. These tyrosine residues function by reconstituting PLC-gamma(1) phosphorylation and recruitment to LAT. However, these same tyrosines can only partially reconstitute Erk activation. Full reconstitution of Erk requires two additional tyrosine residues (Tyr(110) and Tyr(226)), both of which have the Grb2-binding motif YXN. This reconstitution of Erk activation requires that the critical tyrosine residues be on the same molecule of LAT, suggesting that a single LAT molecule nucleates multiple protein-protein interactions required for optimal signal transduction.

Adaptor Proteins, Signal Transducing↗
PubMed2001

A CD45 polymorphism associated with multiple sclerosis disrupts an exonic splicing silencer.

Previous studies have identified a single nucleotide polymorphism that significantly increases the splicing of variable exon 4 in transcripts of the human protein-tyrosine phosphatase CD45. Strikingly, the presence of this polymorphism correlates with susceptibility to the autoimmune disease multiple sclerosis. In this study we investigated the mechanism by which the polymorphism enhances splicing of CD45 exon 4. We found that at least four distinct splicing regulatory elements exist within exon 4 and that the strongest of these elements is an exonic splicing silencer (designated ESS1), which is disrupted by the polymorphism. We show that ESS1 normally functions to repress the weak 5' splice site (ss) of CD45 exon 4. The ESS1 sequence also suppresses the splicing of a heterologous 5'ss and associates with a specific complex in nuclear extracts. We further demonstrate that ESS1 is juxtaposed to a purine-rich enhancer sequence that activates the use of the 5'ss of exon 4. Thus, proper functioning of the immune system is dependent on a complex interplay of regulatory activities that mediate the appropriate splicing of CD45 exon 4.

Alternative Splicing↗
PubMed2001

The mouse CD1d-restricted repertoire is dominated by a few autoreactive T cell receptor families.

To define the phenotype and T cell receptor (TCR) repertoire of CD1d-dependent T cells, we compared the populations of T cells that persisted in major histocompatibility complex (MHC)-deficient mice, which lack mainstream T cells, with those from MHC/CD1d doubly deficient mice, which lack both mainstream and CD1d-dependent T cells. Surprisingly, up to 80% of the CD1d-dependent T cells were stained by tetramers of CD1d/alpha-galactosylceramide, which specifically identify the previously described CD1d autoreactive Valpha14-Jalpha18/Vbeta8 natural killer (NK) T cells. Furthermore, zooming in on the CD1d-dependent non-Valpha14 T cells, we found that, like Valpha14 NK T cells, they mainly expressed recurrent, CD1d autoreactive TCR families and had a natural memory phenotype. Thus, CD1d-restricted T cells differ profoundly from MHC-peptide-specific T cells by their predominant use of autoreactive and semiinvariant, rather than naive and diverse, TCRs. They more closely resemble other lineages of innate lymphocytes such as B-1 B cells, gammadelta T cells, and NK cells, which express invariant or semiinvariant autoreactive receptors. Finally, we demonstrate that the MHC-restricted TCR repertoire is essentially non-cross-reactive to CD1d. Altogether, these findings imply that lipid recognition by CD1d-restricted T cells may have largely evolved as an innate rather than an adaptive arm of the mouse immune system.

Animals↗