Branching and/or collateral projections of spinal dorsal horn neurons

Branching and/or collateral projections of spinal dorsal horn neurons is a common phenomenon. Evidence is presented for the existence of STTm/STTl, STTc/STTi, STT/SMT, STT/SRT, SCT/DCPS, SST/DCPS, SCT/SST, STT/SHT, STeT/SHT, STeTs and other doubly or multiply projecting spinal neurons that have been anatomically and physiologically identified and named based on the locations of the cells of origin and their terminations in the brain. These newly discovered spinal projection neurons are characterized by a single cell body and branched axons and/or collaterals that project to two or more target areas in the brain. These novel populations of neurons seem to be a fuzzy set of spinal projection neurons that function as an intersection set of the corresponding single projection spinal neurons and to be at an intermediate stage phylogenetically. Identification strategies are discussed, and general concluding remarks are made in this review.     

Predictors of receiving aftercare 1, 3, and 18 months after a psychiatric emergency room visit

The resistances to sliding were studied as a function of five angulations (0 degrees, 3 degrees, 7 degrees, 11 degrees, and 13 degrees) using nine different couples made of stainless steel, single crystal sapphire, or polycrystalline alumina brackets against stainless steel, nickel titanium, or beta-titanium arch wires. After 22 mil brackets were mounted to fixtures and 21 x 25 mil arch wires were ligated with 10 mil stainless steel ligatures, the arch wires were slid through the brackets at 1 cm/minute in the dry state at 34 degrees C. The resistance to sliding was measured by one computer while five normal forces (nominally 0.2, 0.4, 0.6, 0.8, and 1.0 kg) were serially maintained by another computer. A second couple was prepared for each material combination with five normal forces that were each 0.1 kg less. Statistical fits of linear regressions were such that p <.001 for most tests. When couples were in the passive configuration at low angulations, all stainless steel wire-bracket couples once again had the least resistance to sliding. When the angulation exceeded about 3 degrees, however, the active configuration emerged and binding quickly dominated as the resistance to sliding increased over 100-fold. Under these conditions, the relative rankings among the materials transposed; couples of stainless steel had the most resistance to sliding, whereas, couples of the more compliant alloys, such as nickel titanium wire, had the least. Results suggested that the active configuration and subsequent binding emerged when no bracket clearance remained. This binding component increased in importance with angulation and was additive to the frictional component, that is, they followed the principle of superposition.     

Prostate-specific membrane antigen: a novel folate hydrolase in human prostatic carcinoma cells

A novel monoclonal antibody has been developed that reacts strongly with human prostatic cancer, especially tumors of high grade. This antibody (7E11C-5) is currently in Phase 3 trials as an imaging agent for metastatic disease. We have cloned the gene that encodes the antigen that is recognized by the 7E11C-5 monoclonal antibody and have designated this unique protein prostate-specific membrane (PSM) antigen. PSM antigen is a putative class II transmembranous glycoprotein exhibiting a molecular size of Mr 94,000. Functionally, class II membrane proteins serve as transport or binding proteins or have hydrolytic activity. Preliminary studies have demonstrated binding of pteroylmonoglutamate (folate) to membrane fractions that also cross-reacted with the PSM monoclonal antibody. We observed substantial carboxypeptidase activity as folate hydrolase associated with PSM antigen. The purpose of our study was to demonstrate that human prostatic carcinoma cells expressing PSM antigen exhibit folate hydrolase activity using methotrexate triglutamate (MTXGlu3) and pteroylpentaglutamate (PteGlu5) as substrates. Isolated membrane fractions from four human prostate cancer cell lines (LNCaP, PC-3, TSU-Prl, and Duke-145) were examined for folate hydrolase activity using capillary electrophoresis. After timed incubations at various pH ranges and in the presence and absence of thiol reagents, separation of pteroyl(glutamate)n derivatives was achieved with an electrolyte of sodium borate and SDS, while absorbance was monitored at 300 nm. The results demonstrate clearly that LNCaP cells, which highly express PSM, hydrolyze gamma-glutamyl linkages of MTXGlu3. The membrane-bound enzyme is an exopeptidase, because it progressively liberates glutamates from MTXGlu3 and PteGlu5 with accumulation of MTX and PteGlu1, respectively. The semipurified enzyme has a broad activity from pH 2.5 to 9.5 and exhibits activity maxima at pH 5 and 8. Enzymatic activity is maintained in the presence of reduced glutathione, homocysteine, and p-hydroxymercuribenzoate (0.05-0.5 mm) but was inhibited weakly by DTT (>/=0.2 mm). By contrast to LNCaP cell membranes, membranes isolated from other human prostate adenocarcinoma cells (PC-3, Duke-145, and TSU-Pr1) did not exhibit comparable hydrolase activity, nor did they react with 7E11-C5 monoclonal antibody. After transfection of PC-3 cells with a full-length 2.65-kb PSM cDNA subcloned into a pREP7 eukaryotic expression vector, non-PSM antigen-expressing PC-3 cells developed immunoreactivity to 7E11-C5 monoclonal antibody and demonstrated folate hydrolase activities and optimum pH activity profiles identical to those of LNCaP cells. The membrane-bound enzymes from both LNCaP- and PC-3-transfected cells also have a capacity to hydrolyze an alpha-linked glutamyl moiety from N-acetyl-alpha-aspartylglutamate. We have identified that PSM antigen is a pteroyl poly-gamma-glutamyl carboxypeptidase (folate hydrolase) and is expressed strongly in human prostate cancer. Cancer cells that express this enzyme are resistant to methotrexate therapy. Those developing future therapeutic strategies in the treatment of prostate cancer that utilize folate antagonists need to consider this mechanism of resistance.