Localized lymphomatoid papulosis.

A 50-year-old Japanese male visited our clinic in April 1999 with a 2-year history of self-healing, reddish papules on his right palm. On examination, there were grouped erythematous papules, 2-4 mm in size, which formed a relatively well-circumscribed erythematous plaque. A biopsy specimen showed a wedge-shaped, dense dermal infiltrate consisting of variously sized mononuclear lymphoid cells mixed with few large CD30-positive cells and inflammatory cells, suggesting the diagnosis of regional lymphomatoid papulosis (LyP). Analysis of the T cell receptor gene revealed a polyclonal pattern on lesional skin. Only 5 cases of LyP presenting in a regional distribution have been reported previously. Although the etiology of localized LyP remains unknown, considering that 2 of 5 reported patients developed widespread lesions regional LyP may be the initial presentation of typical LyP.

Intracellular vesicular trafficking of tyrosinase gene family protein in eu- and pheomelanosome biogenesis.

The intracellular vesicular trafficking in the melanosome biogenesis (melanogenesis) is reviewed with the incorporation of our own experimental findings. The melanosome biogenesis involves four stages of melanosome maturation, which reflect the transport of structural and enzymatic proteins from Golgi (trans-Golgi network: TGN) to the melanosomal compartment and their organization therein. The major melanosomal proteins include tyrosinase gene family protein (tyrosinase and tyrosinase-related protein; TRP), lysosome-associated membrane protein (Lamp) and gp100 (pmel 17). They are glycosylated in the endoplasmic reticulum, and transported by vesicles from the TGN to the melanosomal compartment. During the formation of transport vesicles, they assemble on the cytoplasmic face of the TGN to select cargo by interacting directly or indirectly with coat proteins. Tyrosinase and TRP-1 possess the dileucine motifs at the cytoplasmic domain, to which adapter protein-3 binds to transport them from the TGN to stage I melanosomes (related to late endosomes) and then to stage II melanosomes. A number of small guanosine triphosphate-binding proteins, including rab 7, appear to be involved in this vesicular transport. Phosphatidyl inositol 3 kinase also regulates this membrane trafficking of melanosomal glycoprotein. Eumelanogenesis is controlled by melanocyte-stimulating hormone, and all three tyrosinase gene family proteins are transported from the TGN to stage II melanosomes that are elliposoidal and contain the structural matrix of filaments/lamellae. In contrast, pheomelanogenesis is primarily regulated by agouti signal protein, and only tyrosinase is transported from stage I melanosomes to stage II melanosomes that are spherical and related to lysosomes. Because of the absence of TRP-1 and TRP-2 in pheomelanogenesis, it may be suggested that tyrosinase is involved in lysosomal degradation after forming dopaquinone, to which the cysteine present in the lysosomal granule binds to form cysteinyldopas that will then be auto-oxidized to become pheomelanin.

UVB photosensitivity due to ranitidine.

We describe a 62-year-old male with photosensitivity due to ranitidine. An oral challenge test after taking ranitidine with UVB irradiation was positive. Ranitidine-induced UVB photosensitivity was persistent even after cessation of the medication.

Astrocytic pathology in progressive supranuclear palsy: significance for neuropathological diagnosis.

Progressive supranuclear palsy (PSP) is known to have tau-positive cytoskeletal abnormalities in astrocytes and oligodendroglia as well as neurons. Astrocytic tau-positive structures (tuft-shaped astrocytes; Tu-SA) were studied to elucidate their proper significance in the neuropathological diagnosis of PSP. The distribution and incidence of Tu-SA were examined in 26 cases of PSP. The disease specificity of Tu-SA was demonstrated by comparison with diseases accompanied by neurofibrillary tangles (NFTs) and those with or without cytoskeletal abnormalities other than NFTs. In PSP, Tu-SA appeared prominently in the precentral and premotor cortex (areas 4 and 6) of the superior and middle frontal gyri, but were quite scare in the temporal lobe and limbic area. In the subcortical nuclei, they appeared preferentially in the putamen and were also scattered in other degenerating regions. In the cerebrum the Tu-SA and NFTs were distributed in quite different regions. The assessment of the incidence of Tu-SA in area 6 revealed that only 5 of 26 PSP cases lacked Tu-SA in the examined fields. In contrast, in the control diseases, Tu-SA were found only rarely in cases of corticobasal degeneration in the cerebral cortex among other frequent tau-positive structures. One case of Pick's disease showed occasional Tu-SA but only in the hippocampal region and not in the frontal lobe or putamen. In summary, although the absence of Tu-SA does not necessarily exclude the possibility of PSP, Tu-SA in the frontal lobe and putamen is highly suggestive for PSP. Thus, detection of Tu-SA and the ranking of the characteristic distribution of NFTs contribute to the neuropathological diagnosis of PSP.

Detection of cyclic GMP binding protein and ion channel activity in frog rod outer segments.

In order to identify the cGMP-sensitive ion channel protein in frog rod outer segments (ROS), we analyzed cGMP binding proteins in the ROS by means of photoaffinity labeling with [3H]cGMP. We found four cGMP binding proteins with molecular weights (Mws) of 250K, 100K, 92K, and 53K. The 250K protein was an integral-membrane protein, which we named cG-Protein, (cG stands for cGMP). The cGMP-binding to cG-Protein was slightly increased by CaCl2. cG-Protein has a carbohydrate moiety. The amount of cG-Protein per single rod outer segment was estimated to be 9.0 x 10(6) molecules. Light-dependent phosphorylation of cG-Protein with [gamma-32P]ATP was observed. The 100K and 92K proteins were peripheral-membrane proteins, corresponding to cGMP phosphodiesterase. The 53K protein was a soluble protein. Incorporation of a membrane protein fraction of frog ROS into a planar lipid bilayer resulted in the appearance of at least three kinds of ion channel activities; two of them were related to cGMP. The possibility that cG-Protein is the cGMP-sensitive ion channel in vivo is discussed.

Detection of Ca2+-dependent cyclic GMP binding protein in frog rod outer segments.

For the identification of the cGMP-sensitive ion channel protein of frog rod outer segments (ROS), we analyzed cGMP binding proteins in the ROS by photoaffinity labeling with [3H]cGMP. We found three cGMP binding polypeptides (66 kDa, 92 kDa and 100 kDa) in the membrane protein fraction of ROS. cGMP binding to the 66 kDa polypeptide required the addition of 2 mM CaCl2. We propose that this polypeptide corresponds to the cGMP-activated channel protein reported by Cook et al. [(1987) Proc. Natl. Acad. Sci. USA 84, 585-589]. The 100 kDa and 92 kDa polypeptides are subunits of the cGMP phosphodiesterase.