The treatment of cancer patients with human lymphoblastoid interferon

Summary Highly purified human lymphoblastoid interferon (HLBI) derived from virus-stimulated Namalwa cells was administered by 6-h IV infusion or IM injection to 40 patients with a variety of disseminated malignancies refractory to standard therapy. Each patient received doses escalating from 0.1 to 50×10⁶ U for up to 5 weeks. Extensive monitoring for clinical effect, toxicity, and pharmacokinetics has revealed higher peak serum interferon levels and somewhat more pronounced systemic toxicity for the IV than for the IM route of administration. Objective evidence of tumor regression was observed in two patients receiving HLBI IV.     

Delineation of a Particulate Thyrotropin-Releasing Hormone-Degrading Enzyme in Rat Brain by the Use of Specific Inhibitors of Prolyl Endopeptidase and Pyroglutamyl Peptide Hydrolase

The degradation of thyrotropin-releasing hormone in rat brain homogenates was studied in the presence of N-benzyloxycarbonyl-prolyl-prolinal and pyroglutamyl diazomethyl ketone, specific and potent active-site-directed inhibitors of prolyl endopeptidase and pyroglutamyl peptide hydrolase, respectively. Substantial TRH degradation was observed, suggesting the presence of another thyrotropin-releasing hormone-degrading enzyme(s). Reports of a thyrotropin-releasing hormone-degrading enzyme with narrow specificity that cleaves the pGlu-His bond of this tripeptide led us to develop a coupled assay using pGlu-His-Pro-2NA as the substrate to measure this activity. Cleavage of the pGlu-His bond of this substrate under conditions in which pyroglutamyl peptide hydrolase is not expressed occurred in the particulate fraction of a rat brain homogenate. This particulate pyroglutamyl-peptide cleaving enzyme was not inhibited by pyroglutamyl diazomethyl ketone but was inhibited by metal chelators such as EDTA and o-phenanthroline. The particulate pyroglutamyl-peptide cleaving enzyme was found predominantly in the brain. Activity in brain regions varied widely with highest levels present in cortex and hippocampus and very low levels in pituitary. The data suggest that degradation of thyrotropin-releasing hormone by the particulate fraction of a brain homogenate is catalyzed mainly by an enzyme that cleaves the pGlu-His bond of thyrotropin-releasing hormone but is distinct from pyroglutamyl peptide hydrolase.     

A multicatalytical protease complex from pituitary that forms enkephalin and enkephalin containing peptides

The pituitary contains a high molecular weight (M.W.～700,000) neutral endopeptidase complex that behaves in solution as a single protein, but on polyacrylamide gel electrophoresis under dissociating conditions shows the presence of five components with molecular weights of 24,000 to 28,000. The complex exhibits trypsinlike, chymotrypsinlike and peptidylglutamyl-peptide bond hydrolysing activities. Experiments indicate that each of these activities is associated with a separate component of the complex. The chymotrypsinlike and trypsinlike activities efficiently generate Leu-enkephalin, Leu-enkephalin-Arg⁶ and Leu-enkephalin-Arg⁶-Phe⁷ from a single synthetic precursor. Selective inhibition of the chymotrypsinlike activity enhances the trypsinlike activity and alters the relative proportion of opioid peptides formed.     

The association between testosterone, sexual arousal, and selective attention for erotic stimuli in men

Twenty-six, eugonadal men between the ages of 18 and 27 participated in this investigation of the relationship between sexual arousal, testosterone (T) levels, and the processing of sexual information. At each of the two test sessions, subjects gave a blood sample, listened to an erotic or neutral priming audiotape, and completed a dichotic listening task designed to assess selective attention for sexual stimuli. Subjective levels of sexual arousal to the audiotape and sexual attitudes and sexual experience were assessed by self-report measures. Contrary to our hypothesis, there was no relationship between levels of free T and the strength of the selective attention bias for sexual stimuli. However, men who were more distracted by the sexual material in the task reported higher levels of sexual arousal to erotic imagery than men who were less distracted by the sexual material in the task (P less than 0.01). Moreover, men who were more sexually aroused by the erotic audiotape made significantly less shadowing errors in the erotic prime condition then they did during the neutral prime condition (P less than 0.05). There was a negative association between T and shadowing errors in the erotic prime condition (P less than 0.05). These results suggest that lower thresholds for sexual arousal are associated with a greater bias to attend to sexual information and that T may have effects on cognitive-motivational aspects of sexual behavior by enhancing attention to relevant stimuli.     

Demography and genetics suggest reversal of dolphin source‐sink dynamics,with implications for conservation

The forecast for the viability of populations depends upon metapopulation dynamics: the combination of reproduction and mortality within populations, as well as dispersal between populations. This study focuses on an Indo‐Pacific bottlenose dolphin (Tursiops aduncus) population in coastal waters near Bunbury, Western Australia. Demographic modeling of this population suggested that recent reproductive output was not sufficient to offset mortality. Migrants from adjacent populations might make up this deficit, so that Bunbury would act as a “sink,” or net recipient population. We investigated historical dispersal in and out of Bunbury, using microsatellites and mitochondrial DNA of 193 dolphins across five study locations along the southwestern Australian coastline. Our results indicated limited gene flow between Bunbury and adjacent populations. The data also revealed a net‐dispersal from Bunbury to neighboring populations, with microsatellites showing that more than twice as many individuals per generation dispersed out of Bunbury than into Bunbury. Therefore, in historic times, Bunbury appears to have acted as a source population, supporting nearby populations. In combination with the prior finding that Bunbury is currently not producing surplus offspring to support adjacent populations, this potential reversal of source‐sink dynamics may have serious conservation implications for Bunbury and other populations nearby.     

Synthesis and characterization of monosaccharide lipids as novel hydrogelators

Self-assembly of small molecules is a useful strategy for forming functional supramolecular structures. Three new series of methyl alpha-D-glucopyranoside derivatives, including esters and carbamates, have been synthesized and characterized. Several of these compounds are excellent hydrogelators and formed interesting self-assembled network structures, including birefringent fibers and tubules. The gelation properties depend on the acyl chain length and the headgroup structures. Small molecule sugar-based hydrogelators have potential applications in drug delivery and enzyme immobilization.     

Origins and nature of vessels in monocotyledons: 8. Orchidaceae

Xylem of the orchids studied provided unusually favorable material to demonstrate how conductive tissue evolves in monocotyledons. In the end walls of tracheary elements of many Orchidaceae, remnants of pit membranes were observed with scanning electron microscopy and minimally destructive methods. The full range from tracheids to vessel elements, featuring many intermediate stages, was illustrated with SEM in hand sections of fixed roots, stems, and inflorescence axes of 13 species from four subfamilies. Pit membranes in end walls of tracheary elements are porose to reticulate in roots of all species, but nonporose in stems of Cypripedioideae and Vanilloideae and porose to reticulate in stems of Orchidoideae and Epidendroideae. The distribution pattern of pit membranes and pit membrane remnants in end walls of tracheary elements of orchids parallels the findings of others. The position of Cypripedioideae and Vanilloideae as outgroups to Orchidoideae and Epidendroideae, claimed by earlier authors, is supported by clades based on molecular studies and by our studies. Little hydrolysis of pit membranes in tracheary element end walls was observed in pseudobulbs or inflorescence axes of epidendroids. The pervasiveness of network-like pit membranes of various extents and patterns in end walls of tracheary elements in Orchidaceae calls into question the traditional definitions of tracheids and vessel elements, not merely in orchids, but in angiosperms at large. These two concepts, based on light microscope studies, are blurred in light of ultrastructural studies. More importantly, the intermediate expressions of pit membranes in tracheary element end walls of Orchidaceae and some other families of angiosperms are important as indicators of steps in evolution of conduction with respect to organs (more rapid flow in roots than in succulent storage structures) and habitat (less obstruction to flow correlated with a shift from terrestrial to epiphytic).