kDNA and rDNA sequences reveal a phylogenetic cluster of species originally placed in different genera of trypanosomatids

Hybridization using kDNA and rDNA sequences as probes was performed to study phylogenetic relatedness of different species of trypanosomatids. Using this approach, we identified five organisms which had been classified as Phytomonas and Herpetomonas that were more closely correlated to each other phylogenetically than to any other species or isolates from either genera. These findings raise doubts about the validity of the current classification of Trypanosomatidae. Finally, we demonstrated the usefulness of kDNA sequences as an alternative to genomic sequences in obtaining phylogenetic information on trypanosomatids.     

The use of an algorithmic method for small molecule superimpositions in the design of antiviral agents

The new American Association on Mental Retardation (AAMR) definition of mental retardation (Luckasson et al., 1992) represents a radical departure from previous definitions. In the present paper we examined the extent to which the new definition provides decision rules to guide clinicians and researchers in classification efforts. We concluded that the IQ criterion of 75 will increase the proportion of the general population eligible near the cut-off score. Moreover, the 10 adaptive skill areas adopted fail to consider developmental factors and cannot be assessed reliably with current scales. Proposed differentiation by levels of needed supports is also challenged as being imprecise and not amenable to reliable measurement. Implications of this new definition for diagnostic practices and research endeavors were explored.     

TGF-beta knockout and dominant-negative receptor transgenic mice

Use of homologous recombination and transgenic technologies have provided mouse models to study the physiological roles of the three mammalian TGF-beta isoforms, and their regulation in the context of the intact animal. Mice harboring null mutations for TGF-beta isoforms demonstrate that each exerts discrete nonoverlapping functions during development. TGF-beta1 null mice reveal a crucial role for this cytokine in modulation of the immune system, with evidence for altered development, activation and function of various immune cell populations. New approaches to tissue- and cell-restricted disruption of TGF-beta signaling pathways in transgenic mice carrying dominant-negative mutant TGF-beta receptors will be discussed.     

Biomechanical study of sternal closure using rigid fixation techniques in human cadavers

BACKGROUND: We believe rigid plate fixation may be superior to wire fixation in sternal closure, as rigid fixation used in the craniofacial skeleton has shown greater stability, lower postoperative pain, and accelerated bone healing. We hypothesize that sterna fixed with titanium plates are more stable mechanically than sterna fixed with wires. METHODS: The sterna from human cadavers were used in this two-phased study. Phase I compared wires to four-hole titanium straight plates. Phase II compared wires to four-hole titanium custom H plates. The sterna were tested biomechanically using all fixation methods. RESULTS: Phase I showed no statistically significant difference in the stiffness or lateral displacement between the wired and straight plated sterna. Phase II showed a statistically significant greater stiffness (p < 0.05) and less lateral displacement (p < 0.05) in the custom plated sterna over the wired sterna. CONCLUSIONS: Our results showed that custom titanium H plates were superior to wire fixation. Furthermore, our results established the importance of plate configuration in sternal fixation. Our study may have beneficial clinical implications, as decreased motion at the sternotomy site could mean less postoperative pain, a decreased incidence of infection, and accelerated bone healing.     

Effects of ligand priming and multiple-dose injection on tissue uptake of 111In-pentetreotide in rats

In patients undergoing somatostatin receptor scintigraphy, treatment with octreotide (Sandostatin) is usually discontinued 24-48 h before and after injection with the radioligand 111In-pentetreotide ([111In-DTPA(O)]octreotide) (Octreoscan) because octreotide competes with radioligand for the same receptors. However, D?rr et al. and Soresi et al. reported improved visualization of carcinoid and small cell lung cancer lesions, respectively, during continued octreotide treatment. We found that intravenous administration of unlabeled octreotide to rats inhibited the binding of an optimal dose (0.5 microg) of 111In-pentetreotide to somatostatin receptors in pancreas and adrenals in a mass- and time-dependent way. Pretreatment with unlabeled octreotide never increased receptor binding of 111In-pentetreotide. Administration of 100 microg of octreotide decreased receptor-bound radioactivity if given simultaneously with or 10 or 20 min after injection of the radioligand, but had no effect if given 30 min after the radioligand. These findings indicate rapid processing of receptor-bound octreotide and suggest that octreotide treatment of patients undergoing 111In-pentetreotide scintigraphy may be reinitiated as soon as 1 h after radioligand administration.     

Characteristics of multicellular spheroids formed by primary cultures of human thyroid tumor cells

Features of multicellular tumor spheroids (MCTS) differed depending on their types of cells. MCTS formed by 4000 human thyroid primary culture epithelial tumor cells displayed diameters between 0.31 and 0.33 mm within 2 days regardless of the stage of malignancy of the originating tumors. Their cellular composition reflected that of the originating tumor in regard to DNA content and the expression of cytokeratin, vimentin, as well as thyroglobulin. During the following 3 weeks, their sizes increased up to diameters of 0.42 mm when their cells had been derived from carcinomas, and MCTS originating from adenomas stopped growing within the next 2 days. After 8 days of incubation, proliferating cells were only found in carcinoma MCTS. The cells were randomly distributed over the total volume of the spheroids, which displayed irregular cell arrangements but not concentric cell layers and did not form necrotic centers.