Introns and gene evolution

In one scenario of gene evolution, exon shuffling has a fundamental role in increasing gene diversity. As DNA sequences accumulate in the databases, the picture of the intron/exon structures of genes becomes more and more clear. We discuss in this review some features of this picture that suggest that introns have been present since the early stages of evolution, and that exon shuffling was a fundamental process in the construction of ancient as well as modern genes.     

Recombinant human interferon-alpha induced cytoreduction in chronic myelogenous leukemia

Summary Fourteen patients with Ph'-chromosome positive chronic myelogenous leukemia (CML) in first chronic phase were treated with recombinant interferon-_2c. Interferon-_2c 5 to 10×10⁶ units s.c. was given for 12 weeks as an induction therapy. Maintenance treatment consisted of interferon-_2c 5 × 10⁶ units twice weekly s.c.. Two patients (14%) attained a complete clinical remission and 6 (43%) a partial remission, 3 of whom developed progressive disease during maintenance therapy. A complete disappearance of Ph'-chromosome was achieved in 1 patient. All patients had a more than 45% initial decline of the leukocyte count. Four out of ten patients with an initially enlarged spleen demonstrated reduction in spleen size. Influenza-like symptoms, anorexia, nausea, weight loss and fatigue were common side effects. Interferon-alpha is active in CML but additional clinical investigations are warranted to assess more precisely the therapeutic value of the interferons in this disease.     

High resolution nuclear magnetic resonance imaging of the spinal cord in experimental demyelinating disease

Summary Chronic recurrent experimental allergic encephalomyelitis was induced in a strain 13 guinea pig by inoculation of isologous spinal cord homogenate. The spinal cord was obtained after perfusion with 4% paraformaldehyde and examined with nuclear magnetic resonance (NMR) imaging. Proton NMR spin echo images (repetition time: 3 s; echo times: 20 and 60 ms) were obtained from intact, isolated spinal cord in a 4.7 Tesla, 50 mm bore magnet. The slice thickness of the images was 380 m and the inplane resolution was 40×40 m. The images showed superficial areas of low signal intensity in the lateroventral regions of the white matter, in some instances with a seam of higher signal intensity. Neuropathologically, these abnormalities corresponded exactly to areas of demyelination. Control images did not show these abnormalities. The present high resolution imaging allowed a correlation between demyelination and abnormal NMR signals in a small laboratory animal with an inflammatory demyelinating disease.Supported by the Belgian Foundation of Medical Scientific Research (FGWO, grant 3.0096.86 and grant 3.0019.86), by the Institute for the promotion of Scientific Research in Industry and Agriculture (IWONL) and by the Scientic Research Planning Office of the Belgian Government (DPWB), contract no. 87/92-120     

Antiplatelet activity of dipyridamole in non anticoagulated whole blood

Dipyridamole has been reported to inhibit platelet aggregation in citrate anticoagulated whole blood (WB). However, citrate may alter the response of platelets and/or the effect of antiplatelet drugs. The present study evaluates the "ex vivo" effect of dipyridamole, two hours after a single dose (3 mg/Kg) in 25 normal subjects in non-anticoagulated (native) WB and in WB anticoagulated with citrate or hirudin. We have used the BASIC anticoagulated with citrate or hirudin. We have used the BASIC wave as analytical method, which can evaluate the early steps of platelet activation with collagen in less than 1 min after venoclysis, thus allowing the study in native WB. The results show that dipyridamole significantly inhibits (p less than 0.001) platelet activation to collagen in citrated WB (66%) while the drug's effect is much lower (21%) and non-significant if evaluated in native or hirudine anticoagulated WB. These results suggest that citrate or low calcium concentration amplify the drug's platelet inhibitory action in WB and, therefore, the laboratory results may overestimate the drug's effect "in vivo".     

Isolation of neurosecretory granules containing vasopressin and MSEL-neurophysin from guinea pig neurointermediate pituitary

Neurosecretory granules have been isolated from rat and guinea pig neurointermediate pituitaries and their contents have been analyzed by reverse-phase high-pressure liquid chromatography and polyacrylamide gel electrophoresis. Granule components have been compared with synthetic neurohypophysial hormones and chemically characterized neurophysins. In rat granules, oxytocin, arginine vasopressin and MSEL- and VLDV-neurophysins have been identified. In isolated guinea pig granules, only arginine vasopressin and mature MSEL-neurophysin have been found. From these results it can be concluded that both the "dibasic" cleavage between vasopressin and MSEL-neurophysin and the "monobasic" cleavage between MSEL-neurophysin and copeptin occur within the granule compartment. Previous isolation from frozen guinea pig glands of a partially processed precursor encompassing MSEL-neurophysin and copeptin suggests a two-step processing of the three-domain vasopressin precursor, each involving a distinct enzymic system.     

Disk hypodensity and disk herniation

The authors report the case of a patient with a herniated lumbar disk and bacterial meningitis. CT scan showed central disk hypodensity at the hernia level, whilst full cytological and bacteriological study of the disk following surgery revealed no evidence of spondylodiscitis. The problem was thus that of consequences of "degenerative" events related to the herniation. Central or peripheral disk hypodensity must in no case be considered as specific of discitis when there is a concomitant disk herniation.     

Activation of inflammatory systems during cardiopulmonary bypass

"Whole body inflammation" induced by cardiopulmonary bypass may play a role in the pathogenesis of postoperative complications after open-heart surgery. The inflammatory response, in terms of complement activation and release of granular proteins from neutrophil granulocytes, was investigated in six patients undergoing aortocoronary bypass surgery. Complement activation was demonstrated as well as substantially increased plasma levels of lactoferrin and myeloperoxidase--two granulocyte factors. The activation of inflammatory systems probably takes place on the artificial surfaces of the extracorporeal device. The biocompatibility of these components therefore should be further studied.     

The effect of isoluminant and isochromatic stimuli on latency and amplitude of saccades

When two stimuli are presented in different positions successively at short time intervals saccadic eye movements are usually directed at intermediate positions. This phenomenon of "averaging" of saccadic eye movements has been studied in responses to double-step target displacements in different stimulus conditions. In these conditions isoluminant and isochromatic stimuli were used with variable contrast and at different background luminances. Although the critical duration of temporal summation differed considerably in these stimulus conditions the duration of the phenomenon of "averaging" remained the same in all conditions. This indicates that temporal properties of the sensory system are not the prime cause of "averaging". Moreover, the onset time of "averaging" relative to the second target displacement turned out to be highly correlated with the mean latency of saccades in the different conditions. The implications of the results for models of oculomotor control are discussed.     

Selection for increased pheromone response in the male pink bollworm,Pectinophora gossypiella (lepidoptera: Gelechiidae)

The genetic basis of the duration and incidence of male wing fanning to pheromone in the pink bollworm moth,Pectinophora gossypiella (Saunders), was examined by artificial selection. Using a still-air bioassay, males from a laboratory colony were selected for increased duration of wing fanning when exposed to a 6535 blend of (Z,E)- and (Z,Z)-7,11-hexadecadienyl acetates. The mean (±SE) duration of wing fanning in the selected line increased from 5.4±1.4 to 17.4±2.7 s after six generations. The increase in wing fanning duration was the result of an increase in response duration among responders and not the percentage of males that responded. Realized heritability of wing-fanning duration was 0.16±0.02. The amount and ratio of pheromone produced by females in the male-selected line did not change.This research was supported in part by NSF Grant PCM-8309398 and a University of Massachusetts Biomedical Research Grant.