p21(WAF1) and transforming growth factor-alpha mediate dietary phosphate regulation of parathyroid cell growth.

BACKGROUND: The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P reduces while low P enhances serum 1,25-dihydroxyvitamin D, whose potent antiproliferative properties result from the induction of p21. In addition to reducing p21, high P-induced PT growth could result from increased PT expression of the growth promoter transforming growth factor-alpha (TGF-alpha), known to be elevated in hyperplastic and adenomatous human PT glands. METHODS: The time course for dietary P regulation of PT expression of TGF-alpha and p21 was assessed for seven days after 5/6 nephrectomy in rats and correlated with the degree of PT hyperplasia and secondary hyperparathyroidism. RESULTS: In P-restricted 5/6 nephrectomized rats, PT-p21 mRNA and protein increased by day 2, independent of changes in serum 1,25-dihydroxyvitamin D, and remained higher than in the high P counterparts for up to seven days. The PT hyperplasia of the high P group could not be attributed to a reduction of PT-p21 expression from normal control values. Instead, PT-TGF-alpha protein was higher in uremic rats compared with normal controls and increased further with high dietary P intake. PT levels of proliferating cell nuclear antigen (PCNA), an index of cell mitoses, correlated inversely with p21 and directly with TGF-alpha. Consistent with these findings, PT gland size and serum PT hormone levels, similar in both dietary groups at day 2, were higher in the high P group by day 5. Induction of p21 by low P and of TGF-alpha by high P was specific for the PT glands. Dietary P had no effect either on intestinal growth or p21 or TGF-alpha protein content. CONCLUSIONS: These findings suggest that low P induction of p21 could prevent PT hyperplasia in early uremia, whereas high P enhancement of TGF-alpha may function as an autocrine signal to stimulate growth further.

Laser Action from a 2,6,8-Position Trisubstituted 1,3,5,7-Tetramethylpyrromethene-BF(2) Complex: Part 3.

Some laser action properties of a new Pyrromethene-BF(2) complex, 1, 3, 5, 7-tetramethyl-8-ethyl-2, 6-dicyanopyrromethene-BF(2) complex are reported. This laser dye exhibits laser action in the green-yellow portion of the spectrum, and its laser action efficiency was ~350% higher compared with Coumarin 545. Exceptional photostability of the new laser dye was observed when a mixture of 1, 4-dioxane:heptane ratio of 1:4 was used as the solvent. Further, it is suggested that dye lasers can be upscaled to high average power output when surface-emitting laser diode arrays are used as pump (excitation) sources.

Spectroscopy and molecular structure of efficient laser dyes: vibronic spin-orbit interactions in heterocyclics.

Some characteristics of selected laser dyes are reviewed, and the effect of heterocyclic atom substitutions on triplet (pi, pi*) transitions is studied experimentally. Specifically, the intensities (oscillator strengths f) of the lowest-energy singlet-singlet (S-S) and triplet-triplet (T-T) transitions of anthracene and some of its heterocyclic analogs were measured. It is shown that this type of substitution of carbon atoms by heteroatoms results in a considerable reduction of intensity of T-T transitions. This observation is important to laser dye technology. The effect is explained by the existence of an efficient vibronic coupling mechanism between (n, pi*) and (pi, pi*) triplet states in heteroatom molecules. Some general guidelines for how to find efficient laser dyes are proposed.

Cell attachment activity of the carboxyl-terminal domain of human thrombospondin expressed in Escherichia coli.

Thrombospondin (TS) is a multidomain, adhesive glycoprotein that associates with cells through multiple cell attachment sites. One of these has been located in or near the globular COOH-terminal region of TS by the monoclonal antibody (mAb) C6.7, which inhibits the attachment of human melanoma cells (G361) to TS. The epitope for C6.7 lies within the last 122 residues of the COOH-terminal domain of TS. This domain is distant from two known cell attachment sites in TS, namely the NH2-terminal heparin-binding domain and the CSVTCG sequences in the type I repeats, but is close to the RGDA sequence, an integrin-dependent cell attachment site. In order to separate the adhesive activity of the TS COOH-terminal domain from that of the RGD sequence, we have expressed the COOH-terminal 212 amino acids (residues 941-1152) of TS in Escherichia coli using the expression vector pRIT2T. The resultant fusion protein is effective in supporting G361 cell attachment even though it lacks the RGD sequence. In addition, the expressed protein inhibits adhesion of G361 cells to intact TS. mAb C6.7 blocks adhesion to the expressed TS COOH-terminal domain whereas GRGDSP and VTCG peptides are not inhibitory. These results show that the TS COOH-terminal domain contains a separate cell adhesion site, defined by mAb C6.7, that is distinct from the other adhesion sites of TS.

Laser action from 2,6,8-trisubstituted-1,3,5,7-tetramethyl-pyrromethene-BF(2) complexes: part 2.

In laser activity 1,3,5,7-tetramethyl-2,6-dicarboethoxy-8- cyanopyrromethene-BF(2)complex 5 under flash-lamp excitation was approximately 1.8 times more energy efficient than Rhodamine-B; about the same efficiency of Rhodamine-575 was found for 1,3,5, 7-tetramethyl-2,6,8-triethylpyrromethene- BF(2) complex 2.

Laser action from 2,6,8-position trisubstituted 1,3,5,7-tetramethylpyrromethene-BF(2) complexes: part 1.

Of the four new pyrromethene derivatives studied, 1,3,5,7,8-pentamethyl-2,6-diethylpyrromethene-BF(2) complex lased ~3 times more efficiently than rhodamine 560 under flashlamp excitation.