Somatic mosaicism of CAG repeat in dentatorubral-pallidoluysian atrophy (DRPLA)

An unstable expansion of CAG repeat in the coding region ofthe DRPLA gene on chromosome 12p is the mutation specific forhereditary dentatorubralpallidoluysian atrophy (DRPLA). We studiedthe CAG expansion in brain and other tissues from six unre latedDRPLA patients. The CAG repeat lengths showed distinct difterencesbetween tissues. The sizes of the CAG expansion in various regionsof the brain except the cerebellum were generally larger byseveral repeats than in other peripheral tissues. Brain samplesshowed greater variation of the expansion compared with othertissues, but neither the size of the CAG expansion nor the degreeof CAG repeat variation parallels the detailed findings of neuropathologicalinvolvement. We conclude that somatic instabilities of the CAGrepeat cause tissue variability of the CAG repeat size in DRPLAbut other region or cell type-specific factors would be involvedto explain the selectivity of cell damage in DRPLA.     

BASAL CELL ADENOMA WITH ACINIC DIFFERENTIATION

A case of basal cell adenoma in the left parotid region of a 45 years old male was reported. The tumor measured 1.1 cm × 0.9 cm, was spherical and covered with a fibrous capsule. Histologically, it was a monomorphic adenoma, forming solid, trabecular, tubular and acinic structure. The tumor cells secreted PAS-positive substance. Electron microscopically, the tumor consisted of three kinds of cells - secretory cells containing electron-dense secretory granules, non-secretory cells, and myoepithelial cells. The acinus was formed of single-layered secretory cells, in the base of which myoepithelial cells were observed. The tubulus was formed of both secretory and non-secretory cells, and myoepithelial cells were found in the base of the tubules. The interstitium was narrow, and was composed of a small amount of collagen fibers, myoepithelial cells, and basement membrane-like substance.     

Concentration quenching of photoluminescent Ru(bpy) dispersed in a polysiloxane film containing 2,2′-bipyridine pendant groups in dependence of molecular distribution

The photoluminescent Ru(bpy) complex was dispersed in a polysiloxane film containing 2,2′-bipyridine (bpy) pendant groups. The unusually long photoluminescence lifetime of the Ru(bpy) (1,94 μs at 25°C) and the blue-shifted photoluminescent wavelength suggest a rigid polymer matrix. The fluorescence yield becomes lower with higher probe concentration, indicating concentration quenching. According to the analysis based on Stern-Volmer plots, the quenching obeys a mechanism composed of both static and dynamic processes. A statistical intermolecular distance distribution between the probes was used to interpret the results in terms of static and dynamic quenching. It is shown that in the present system the dispersed complexes diffuse slightly during the excited state.     

Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration

LIS1 is mutated in the human neuronal migration defect lissencephaly and along with NDEL1 (formerly NUDEL) participates in the regulation of cytoplasmic dynein function during neuronal development. Targeted disruption of Ndel1 suggested that NDEL1 could have other molecular targets that regulate microtubule organization for proper neuronal migration. To further understanding the molecular mechanism of LIS1 and lissencephaly, we identified the katanin p60 microtubule-severing protein as an additional molecular target of NDEL1. We demonstrate that phosphorylation of NDEL1 by Cdk5 facilitates interaction between NDEL1 and p60, suggesting that P-NDEL1 regulates the distribution of katanin p60. Abnormal accumulation of p60 in nucleus of Ndel1 null mutants supports an essential role of NDEL1 in p60 regulation. Complete loss of NDEL1 or expression of dominant negative mutants of p60 in migrating neurons results in defective migration and elongation of nuclear-centrosomal distance. Our results suggest that NDEL1 is essential for mitotic cell division and neuronal migration not only via regulation of cytoplasmic dynein function but also by modulation of katanin p60 localization and function.     

Human neutrophils express messenger RNA of vitamin D receptor and respond to 1alpha,25-dihydroxyvitamin D3

1Alpha,25-Dihydroxyvitamin D3 (1,25(OH)2D3) has been shown to modulate the production of various cytokines or the expression of certain differentiation markers in human T cells or monocytes. Its effects on neutrophils, however, are poorly understood. In this paper, we show several lines of evidence indicating that neutrophils express functional vitamin D receptors (VDR). Sort-purified neutrophils from human peripheral blood expressed VDR mRNA at a level comparable to that of monocytes. As reported to occur in monocytes, protein expression of CD14 on the cell surface of neutrophils was augmented when the cells were incubated with 1,25(OH)2D3. To investigate the physiological roles for VDR in neutrophils, we investigated possible modulating effects of 1,25(OH)2D3 on the expression of several genes in lipopolysaccharide-stimulated neutrophils by using differential display analysis. Of the genes we identified, trappin-2/elafin/SKALP, which was originally reported to be an inhibitor of elastase, was induced in neutrophils by lipopolysaccharide, but was suppressed significantly in the presence of 1,25(OH)2D3. Under the same conditions, interleukin-1beta expression was also inhibited. These findings suggest that 1,25(OH)2D3 has a potential to affect the inflammatory process by modulating the expression of neutrophil genes.     

Pyothorax-associated lymphoma: an unusual case with both T- and B-cell genotypes

Pyothorax-associated lymphoma (PAL) is a B-cell lymphoma which develops in the pleural cavity of patients with an over-20-year history of pyothorax. Aberrant expression of surface antigens is occassional in PAL, although genotype is not fully investigated. We report here a PAL with dual genotype, i.e., simultaneous immunoglobin (Ig) and T-cell receptor (TcR) gene rearrangement. An 82-year-old woman with pain on the left side of the chest was admitted. She had been suffering from pyothorax after artificial pneumothorax for treatment of tuberculosis of the pulmonary when she was 18 years old. The mass that was confined to the left pleural cavity affected by pyothorax was biopsied and histologically diagnosed as diffuse large cell lymphoma. The tumor cells were positive for CD20, CD16, and TIA-1 but negative for CD79a, CD45RO, CD43, CD3, and CD56. Surface antigen expression was further investigated in cultured cells, showing that the cultured cells did not express representative B-cell markers, except for CD20, as well as T-cell markers, but were positive for CD16, CD30, and CD103. Southern blotting revealed the monoclonally rearranged bands of both Ig heavy chain and TcR gene. The patients died of tumors 14 months after admission. Aberrant genotype and immunophenotype of PAL cells is discussed in reviewing the pertinent literature.     

Peripheral low-density area of hepatic tumors: CT-pathologic correlation

To aid in the distinction between colorectal cancer metastasis to the liver and hepatocellular carcinoma, findings on computed tomographic (CT) scans taken more than 5 minutes after contrast material administration ("late-enhanced CT scans") and pathologic findings were compared. Late-enhanced CT scans of metastatic adenocarcinoma showed a peripheral low-density area (PLDA) that corresponded to viable tumor and a central high-density area that represented fibrous connective tissue. This phenomenon was recognized in 15 of 20 (75%) patients with metastatic adenocarcinoma and in one of 50 (2%) patients with hepatocellular carcinoma. Late-enhanced CT scans may be useful in distinguishing between metastatic nonmucinous colorectal cancer and hepatocellular carcinoma.     

Histopathological explanation of the MRI target sign in extra-axial schwannomas

BackgroundTo better understand the nature of magnetic resonance imaging (MRI) findings in schwannomas, especially in the “target sign” of these findings, the histopathological investigation was performed.MethodsThe MRI findings were correlated with histopathological features in 22 samples of schwannomas, which were mostly resected from the extremities. The histopathological analyses included alcian blue staining and immunohistochemical staining for S-100 protein, proliferating cell nuclear antigen (PCNA) and epithelial membrane antigen (EMA).ResultsSeven of the 22 samples of schwannomas of the extremities exhibited target signs including a peripheral zone of homogeneously high signal intensity and a central zone of heterogeneous signal intensity in T2-weighted images. Gadolinium-enhanced T1–weighted images demonstrated a central heterogeneous enhancement and a peripheral ring of homogeneously low signal intensity. Histopathologically, S-100 and PCNA were positive only in the central heterogeneous signal area. In contrast, EMA was only stained on the degenerative epi/perineurium in the peripheral zone.ConclusionIn schwannomas of the extremities showing target sign in T2-weighted images, histopathologically, the peripheral areas were suggested to be mucinous degeneration of the epineurium or perineurium, while the central areas were composed of truly neoplastic cells.