Metastatic renal cell carcinoma presenting as an aural polyp

Renal cell carcinoma may metastasize to the head and neck region at different stages of its evolution. We present a case of an undiagnosed renal cell carcinoma presenting as an ear polyp, and discuss the difficulties of the diagnosis and the management of these tumours.     

Expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases in adenocarcinoma cell lines

The levels of mRNA expression of three UDP-N-acetyl-alpha-D-galactosamine:polypeptide GalNAc N-acetylgalactosaminyltransferases (GalNAc-transferases) were quantified for human adenocarcinoma cell lines from pancreas, colon, stomach, and breast. Two of the GalNAc-transferases, GalNAc-T1 and GalNAc-T2, were expressed constitutively and at low levels in most or all cell lines examined. A third GalNAc-transferase, GalNAc-T3, was differentially expressed. Well-differentiated adenocarcinoma cell lines expressed high levels and moderately differentiated cell lines expressed lower levels of GalNAc-T3. Cell lines classified as poorly differentiated failed to express GalNAc-T3 mRNA at levels that could be detected by Northern blot analysis. Differential expression of the GalNAc-T3 protein was confirmed in these cell lines by Western blotting. We propose that glycosylation in tumor cell lines may be regulated in part by differential expression of GalNAc-transferases, and we suggest that GalNAc-T3 gene expression may be a molecular indicator of differentiated adenocarcinoma.     

Ganglioside content of human platelets--differences in resting and activated platelets

Gangliosides may play functional roles in platelet physiology, therefore this study has been designed to evaluate whether changes in ganglioside composition may occur as a consequence of platelet activation. The results obtained indicate that lactosylceramide and GM3 are the major glycosphingolipids of human platelets. The lipid-bound sialic acid (LBSA) content was 1.27 +/- 0.04 micrograms/mg of protein. Resting platelets did not express GD3; GD3 was synthesized upon platelet activation (24 +/- 8 ng/mg of protein). The stimulation of platelets with adenosine diphosphate showed the appearance of GD3 even in the absence of degranulation. Finally, incorporation of pyrene-labeled GM3 into platelet membranes, followed by stimulation with adenosine diphosphate, resulted in the appearance of a fluorescent band comigrating with GD3. The present studies indicate that sialytransferase activation may occur as an early event following platelet stimulation, leading to GD3 synthesis mainly from the GM3 pool.     

Dependence on the motif YIPP for the physical association of Jak2 kinase with the intracellular carboxyl tail of the angiotensin II AT1 receptor

Angiotensin II is the effector molecule of the renin-angiotensin system. Virtually all of its biochemical actions are mediated through a single class of cell-surface receptors called AT1. These receptors contain the structural features of the seven-transmembrane, G-protein-coupled receptor superfamily. Angiotensin II, acting through the AT1 receptor, also stimulates the Jak/STAT pathway by inducing ligand-dependent Jak2 tyrosine phosphorylation and activation. Here, we show that a glutathione S-transferase fusion protein containing the carboxyl-terminal 54 amino acids of the rat AT1A receptor physically binds to Jak2 in an angiotensin II-dependent manner. Deletional analysis, using both in vitro protocols and cell transfection analysis, showed that this association is dependent on the AT1A receptor motif YIPP (amino acids 319-322). The wild-type AT1A receptor can induce Jak2 tyrosine phosphorylation. In contrast, an AT1A receptor lacking the YIPP motif is unable to induce ligand-dependent phosphorylation of Jak2. Competition experiments with synthetic peptides suggest that each of the YIPP amino acids, including tyrosine 319, is important in Jak2 binding to the AT1A receptor. The binding of the AT1A receptor to the intracellular tyrosine kinase Jak2 supports the concept that the seven-transmembrane superfamily of receptors can physically associate with enzymatically active intracellular proteins, creating a signaling complex mechanistically similar to that observed with growth factor and cytokine receptors.     

Static and Dynamic Spins in Superconducting La2−x Sr x CuO4: The Risø Years

One important area of modern condensed matter research is the investigation of the nature of the superconducting cuprates. Much progress in this field has been obtained with the technique of neutron scattering. We here present a review of neutron scattering studies of the high-temperature superconductor La_2?xSr_xCuO₄, performed at Risø National Laboratory. We review the work on the mapping of the incommensurate spin fluctuations, the investigation of the gap in the fluctuation spectrum, the magnetic properties of the vortices appearing in an applied field, and the quantum critical behaviour of the system. We discuss our findings in the light of results of neutron scattering from other groups, on other cuprate systems, and results from other experimental methods, e.g. NMR, μSR, STM, X-ray diffraction, and ARPES. We end with a discussion on the implications of the experimental results for the progress in the general understanding of high-temperature superconductivity. PACS numbers: 61.12.Ex, 74.20.Mn, 74.72.Dn, 75.25.+z, 78.70.Nx.     

Multivariate polynomials, standard tableaux, and representations of symmetric groups

This paper is concerned with structural and algorithmic aspects of certain R-bases in polynomial rings R[X_ij] over a commutative ring R with 1. These bases are related to standard tableaux. We shall examine the main tools in full detail: (symmetrized) bideterminants, Capelli operators, hyperdominance, and generalized Laplace's expansions. These tools are then applied to the representation theory of symmetric groups. In particular, we present an algorithm which efficiently computes for every skew module of a symmetric group an R-basis which is adapted to a Specht series. This result is a constructive, characteristic-free analogue of the celebrated Littlewood-Richardson rule. This paper will serve as the basis for a possible generalization of that rule to more general shapes.     

Hereditary spherocytosis: diagnostic and anaemia-associated aberrations of ghost proteins

Various disorders of the red cell skeleton and membrane have been described in hereditary spherocytosis. To elucidate which aberrations could be used for identification of HS patients in a Danish population, we examined ghosts from 17 HS patients and 20 normals by use of SDS-gel scanning, native spectrin extraction, and limited tryptic digestion. Compared to normals, HS patients had significantly lowered alpha-spectrin (p < 0.004), protein 4.2 (p < 0.025), and actin (p < 0.05), and significantly increased anion-transporter (p < 3 x 10(-6)) and glyceraldehyde-3-phosphate dehydrogenase (G3PD, p < 0.04). Sixteen out of 17 HS patients could be identified by aberrations of the anion-transporter or protein 4.2 outside a 95% confidence interval for normals. Extraction of native spectrin and limited tryptic digest showed no difference between normals and HS patients. RBC separated into young and old fractions were used to examine the occurrence of protein aberrations associated with RBC age. Young RBC contained more G3PD (35%) and less protein 4.1 (6.5%) and actin (8.7%) than old. In male HS patients an increased G3PD content showed a linear correlation (p < 0.001) with a low concentration of blood haemoglobin. We conclude that aberrations of G3PD, and possibly protein 4.1, and actin, are associated with anaemia in HS. Increased anion-transporter or lowered protein 4.2 may be useful for diagnosis of HS, and were inherited in five out of six families where two generations were available.     

Estimating eye care workforce supply and requirements

PURPOSE: To estimate the workforce supply and requirements for eye care in the United States. METHODS: Three models were constructed for analysis: supply of providers, public health need for eye care, and demand (utilization) for eye care. Ophthalmologists, other physicians, and optometrists were included in the models. Public health need was determined by applying condition-specific prevalence and incidence rates from population-based and other epidemiologic studies. Demand was determined by use of national databases, such as the National Ambulatory Care Survey, National Hospital Discharge Survey, and Medicare Part B. Time requirements for care were obtained through a stratified sample survey of the membership of the American Academy of Ophthalmology. RESULTS: Under modeling assumptions that use a work-time ratio of one between optometrists and ophthalmologists and between specialist and generalist ophthalmologists, a significant excess of eye care providers exists relative to both public health need and demand. Changes in the work-time ratio, work-hours per year per provider, care patterns for the same condition, or other factors could significantly reduce or eliminate the surplus relative to need. CONCLUSION: If optometrists are the preferred primary eye care provider, ophthalmologists would be in excess under all demand scenarios and all need scenarios where the optometrist to ophthalmologist work-time ratio is greater than 0.6. No excess of ophthalmologists would exist if ophthalmologists are the preferred primary eye care provider. Data on the appropriate work time ratio will help refine estimates of the imbalance between supply and requirements.     

Association with capsid proteins promotes nuclear targeting of simian virus 40 DNA

All animal DNA viruses except pox virus utilize the cell nucleus as the site for virus reproduction. Yet, a critical viral infection process, nuclear targeting of the viral genome, is poorly understood. The role of capsid proteins in nuclear targeting of simian virus 40 (SV40) DNA, which is assessed by the nuclear accumulation of large tumor (T) antigen, the initial sign of the infectious process, was tested by two independent approaches: antibody interception experiments and reconstitution experiments. When antibody against viral capsid protein Vp1 or Vp3 was introduced into the cytoplasm, the nuclear accumulation of T antigen was not observed in cells either infected or cytoplasmically injected with virion. Nuclearly introduced anti-Vp3 IgG also showed the inhibitory effect. In the reconstitution experiments, SV40 DNA was allowed to interact with protein components of the virus, either empty particles or histones, and the resulting complexes were tested for the capability of protein components to target the DNA to the nucleus from cytoplasm as effectively as the targeting of DNA in the mature virion. In cells injected with empty particle-DNA, but not in minichromosome-injected cells, T antigen was observed as effectively as in SV40-injected cells. These results demonstrate that SV40 capsid proteins can facilitate transport of SV40 DNA into the nucleus and indicate that Vp3, one of the capsid proteins, accompanies SV40 DNA as it enters the nucleus during virus infection.