Localization and characterization of the human ADP-ribosylation factor 5 (ARF5) gene

ADP-ribosylation factor 5 (ARF5) is a member of the ARF gene family. The ARF proteins stimulate the in vitro ADP-ribosyltransferase activity of cholera toxin and appear to play a role in vesicular trafficking in vivo. We have mapped ARF5, one of the six known mammalian ARF genes, to a well-defined yeast artificial chromosome contig on human chromosome 7q31.3. In addition, we have isolated and sequenced an approximately 3.2-kb genomic segment that contains the entire ARF5 coding region, revealing the complete intron-exon structure of the gene. With six coding exons and five introns, the genomic structure of ARF5 is unique among the mammalian ARF genes and provides insight about the evolutionary history of this ancient gene family.     

Quantitative assessment of the motion of the lumbar spine in the low back pain population and the effect of different spinal pathologies of this motion

There are few objective means by which disability caused by low back pain (LBP) can be quantified. The purpose of this study was to investigate the usefulness of motion measurements in the assessment of LBP. The motion characteristics of 138 LBP subjects were investigated, and the data compared with a previously published database of normal subjects. Values of range of motion and angular velocity were obtained for all subjects in each plane of motion. Analysis of these motion characteristics demonstrated significant differences (P < 0.0001) between the two populations; however both populations demonstrated considerable intersubject variation. Multiple regression analysis revealed that some of the variance in the LBP population was attributable to the underlying diagnosis. Patients with a spondylolisthesis tended to be hypermobile whilst those with spinal stenosis, disc prolapse or degenerative disc disease tended to be hypomobile. All diagnostic groups showed impairments in their velocity characteristics.     

Evidence of a thyrotropin-releasing activity of ovine corticotropin-releasing factor in the domestic fowl (Gallus domesticus)

New tools to prevent malaria morbidity and mortality are needed to improve child survival in sub-Saharan Africa. Insecticide treated bednets (ITBN) have been shown, in one setting (The Gambia, West Africa), to reduce childhood mortality. To assess the impact of ITBN on child survival under different epidemiological and cultural conditions we conducted a community randomized, controlled trial of permethrin treated bednets (0.5 g/m2) among a rural population on the Kenyan Coast. Between 1991 and 1993 continuous community-based demographic surveillance linked to hospital-based in-patient surveillance identified all mortality and severe malaria morbidity events during a 2-year period among a population of over 11000 children under 5 years of age. In July 1993, 28 randomly selected communities were issued ITBN, instructed in their use and the nets re-impregnated every 6 months. The remaining 28 communities served as contemporaneous controls for the following 2 years, during which continuous demographic and hospital surveillance was maintained until the end of July 1995. The introduction of ITBN led to significant reductions in childhood mortality (PE 33%, CI 7-51%) and severe, life-threatening malaria among children aged 1-59 months (PE 44%, CI 19-62). These findings confirm the value of ITBN in improving child survival and provide the first evidence of their specific role in reducing severe morbidity from malaria.     

Dopaminergic regulation of postnatal development of dynorphin neurons in rat striatum

Tautomycin, a protein serine/threonine phosphatase inhibitor, was chemically degraded, and five derivatives were investigated for their biological activities. None of them exerted any inhibitory effects on the activity of protein phosphatase types 1 and 2A. However, one derivative, named TM2a, induced a significant morphological change (bleb-formation) of human myeloid leukemia K562 cells. TM2b, the trimethyl ester of TM2, did not induce bleb-formation. Thus, the maleic anhydride structure played an important role in the biological activity. The biological properties of TM2a toward K562 cells resembled those of a phorbol ester, rather than of tautomycin. The phorbol ester-induced bleb formation was abrogated by a non-specific inhibitor of protein kinases, staurosporine, and by an inhibitor of protein kinase C (PKC), H-7, but TM2a-induced bleb formation was abrogated only by staurosporine. Enhanced phosphorylation of the two proteins was observed after their exposure to TM2a. This suggest that the effect was not due to any inhibition of protein phosphatase 1 or 2A, but rather to the activation of an unidentified kinase, possibly of the PKC family, or to inhibition of a protein phosphatase other than type 1 or 2A.     

Corrosion behaviour of dental metals and alloys in different media

The corrosion tendencies of metals are related with their position in the electromotive series. These electrode potential degrees may change due to the compositions of the alloys, the surrounding media, or due to alterations in the composition because of recurrent casting. Therefore in this research, the electrode potentials and their changes over a period of time were measured in different pH media simulating the oral electrochemical conditions in vitro. The surface structure of the first and second castings of 29 different dental metals and alloys were examined under a scanning electron microscope and their composition in percentage weight was calculated by the Energy-dispersive X-ray Analysor system. Further the current-potential curves of the dental alloys were found by the potentiodynamic method in three different solutions and, in addition, the changes of corrosion potentials over time were also determined. The corrosion rates, corrosion potentials, their changes over time and their cathodic Tafel slopes were determined. All alloys tested showed ion leakage in corrosive media. Titanium exhibited the least, but alloys with tin and cobalt content displayed the greatest corrosion tendencies. Alloys with iron and copper corroded in the acid media, conversely alloys containing chromium, nichel and molybdenum proved to be resistant to corrosion. The recurrent castings were also corrosion resistant.     

Effects of time compression and time compression plus reverberation on the intelligibility of Northwestern University Auditory Test No. 6

The Tonal and Speech Materials for Auditory Perceptual Assessment, Disc 1.0 audio compact disc developed in 1992 includes several sets of degraded speech materials, two of which, time compression and reverberation, are described in this paper. The digital techniques used to compress the NU No. 6 materials (female speaker) on an 80386-based computer are described, along with a series of experiments on subjects with normal hearing that document the effects of the time compression on recognition performance. Experiment I examined at 70 dB SPL the effect on word recognition of 45, 55, 65, 70, and 75 percent compressions. Experiment II developed psychometric functions for the 45, 65, and 75 percent time-compression conditions. Experiment III defined the effects that time-compression degradation (45% and 65%) plus reverberation degradation (0.3 sec) had on the recognition performance on the NU No. 6 materials. Based on the experiments, four conditions (45% compression, 65% compression, 45% compression plus 0.3-sec reverberation, and 65% compression plus 0.3-sec reverberation) were selected and recorded on the compact disc. In the compact disc trials, normative data on the four conditions were developed from 120 listeners with normal hearing.     

The in-vitro generation of dendritic cells from blast cells in acute leukaemia

Recent clinical observations indicate that ibuprofen may alleviate the radiation-induced dysuria that almost invariably occurs during radiation therapy for prostate cancer. Because the use of ibuprofen could consequently become common during radiation therapy for prostate cancer, we have been interested in the potential interactions between ibuprofen and ionizing radiation on prostate tumor cells. The effects of gamma-irradiation and/or ibuprofen on PC3 and DU-145 human prostate carcinoma cells were evaluated in vitro using three model systems. Clonogenic survival was determined by plating cells 24 h after treatment of nearly confluent monolayers. Analysis of cell growth, cell detachment, and apoptotic cell death was carried out over a period of up to 9 days after treatment of PC3 and DU-145 monolayers. The effect of ibuprofen and/or radiation was also probed by observing the inhibition of growth of established PC3 and DU-145 colonies that were treated on the 14th day of colony growth. Ibuprofen enhanced the radiation response of prostate cancer cells in all three in vitro models. Both the cytotoxic and radiosensitizing effects of ibuprofen seem to require concentrations that are higher than those reported to inhibit prostaglandin synthesis, suggesting that other molecular mechanisms may be responsible for ibuprofen cytotoxicity.     

In vivo binding of mouse IgG via polyreactive surface IgM abrogates progressive lymphocytosis in prolymphocytic leukemia

Surface IgM expressed by malignant CD5+ B-cells from patients with B-chronic lymphocytic leukemia (B-CLL) has previously been shown to bind mouse Ig in what appears to be an example of polyreactive antigen-binding activity. This report demonstrates the in vitro and in vivo binding of mouse Ig to the surface of malignant B-cells from a patient with B-cell prolymphocytic leukemia (B-PLL). In vitro studies showed that K121, a mouse monoclonal antibody, bound to the B-PLL cells via the same low-affinity binding interaction demonstrated to occur between mouse Ig and surface IgM expressed by B-CLL cells rather than in the conventional sense against a specific antigen via its antigen-binding site. With the view to using this phenomenon to target malignant B-cells, it was important to determine whether the low-affinity interaction also occurred in vivo. Infusions of K121 totalling 286 mg were administered to a B-PLL patient over 7 days. Binding of K121 to circulating B-PLL cells was demonstrable after the administration of 36 mg of antibody and was preceded by the appearance of free antibody in the serum. Throughout the period of the infusion, the rapid rise in the peripheral blood white cell count normally observed after leukopheresis was abrogated. However, the count rose markedly after cessation of the antibody infusion in parallel with a decrease in both free and cell-bound K121. There were no observable side effects and no host immune response to either species specific or idiotypic determinants on the mouse Ig was detected. The in vivo binding of mouse Ig together with the previous in vitro data suggest the potential for a novel targeting mechanism using a region of the mouse Ig molecule to target polyreactive Ig expressed by malignant cells in B-CLL and B-PLL.     

Delayed development of amiodarone keratopathy in a corneal graft

An asymptomatic 26-year-old woman with mild macrocytic anemia (11.6 g Hb/dl) was studied. All biochemical parameters, bone marrow histology and cytogenetics were normal. The Ham's and sucrose tests were negative. A flow cytometric analysis revealed that CD55 and CD59 staining was absent in 20% and 21% of the granulocytes, but erythrocytes and CD34-positive bone marrow cells were CD55 and CD59 positive. Seven months after the initial study, the patient suffered an episode of hemoglobinuria, with mild anemia, moderate thrombocytopenia and a weak positive sucrose lysis test. A new flow cytometric analysis disclosed an increased percentage of CD55 and CD59 negative granulocytes and a 25% of erythrocytes with an intermediate pattern of fluorescence after CD59 labelling. At fourteen months, a population of CD55-deficient erythrocytes was detected and the Ham's test became positive. The present report is, to our knowledge, the first case of smoldering paroxysmal nocturnal hemoglobinuria in a patient with no previous aplastic anemia, or evident pancytopenia. The diagnosis was established by flow cytometry of peripheral blood granulocytes, with apparently phenotipically normal progenitor cells in an early stage of the disease. Flow cytometry appears to be a useful tool in our knowledge of paroxysmal nocturnal hemoglobinuria evolution.