Technical bases and acquisition conditions of electron-beam computed tomography

PURPOSE: In this review the technical principle and scanner characteristics of electron beam computer tomography (EBCT) are discussed. METHODS: In contrast to conventional CT, image acquisition in EBCT is achieved without mechanically moving parts. This construction allows for short acquisition times in investigating given anatomical regions (100 ms per slice) or up to 8 levels without table movement and short interscan delays (50 ms per slice). RESULTS: Depending on the nature of the investigation, the scanner can be used in the single slice, continuous volume scanning and multi slice mode. The single slice mode is used for detection and quantification of coronary calcifications and for CT angiography of the coronary vessels. Equivalent to the spiral mode in conventional CT, continuous volume scanning may be used for routine investigation of the chest and abdomen. Functional investigations of the heart and perfusion measurement of different organs can be performed in multi slice mode. Because of the geometry of the electron beam scanner, radiation exposure for certain investigations is above the exposure with conventional CT. CONCLUSION: Future developments will focus on dose efficient radiation collimation, high resolution detector systems and artefact reducing reconstruction kernels.     

A cytokinesis checkpoint requiring the yeast homologue of an APC-binding protein

Checkpoint controls ensure that events of the cell-division cycle are completed with fidelity and in the correct order. In budding yeast with a mutation in the motor protein dynein, the mitotic spindle is often misaligned and therefore slow to enter the neck between mother cell and budding daughter cell. When this occurs, cytokinesis (division of the cytoplasm into two) is delayed until the spindle is properly positioned. Here we describe mutations that abolish this delay, indicating the existence of a new checkpoint mechanism. One mutation lies in the gene encoding the yeast homologue of EB1, a human protein that binds the adenomatous polyposis coli (APC) protein, a tumour suppressor. EB1 is located on microtubules of the mitotic spindle and is important in spindle assembly. EB1 may therefore, by associating with microtubules, contribute to the sensor mechanism that activates the checkpoint. Another mutation affects Stt4, a phosphatidylinositol-4-OH kinase. Cold temperature is an environmental stimulus that causes misalignment of the mitotic spindle in yeast and appears to activate this checkpoint mechanism.     

Function of Escherichia coli MsbA, an essential ABC family transporter, in lipid A and phospholipid biosynthesis

The Escherichia coli msbA gene, first identified as a multicopy suppressor of htrB mutations, has been proposed to transport nascent core-lipid A molecules across the inner membrane (Polissi, A., and Georgopoulos, C. (1996) Mol. Microbiol. 20, 1221-1233). msbA is an essential E. coli gene with high sequence similarity to mammalian Mdr proteins and certain types of bacterial ABC transporters. htrB is required for growth above 32 degreesC and encodes the lauroyltransferase that acts after Kdo addition during lipid A biosynthesis (Clementz, T., Bednarski, J., and Raetz, C. R. H. (1996) J. Biol. Chem. 271, 12095-12102). By using a quantitative new 32Pi labeling technique, we demonstrate that hexa-acylated species of lipid A predominate in the outer membranes of wild type E. coli labeled for several generations at 42 degreesC. In contrast, in htrB mutants shifted to 42 degreesC for 3 h, tetra-acylated lipid A species and glycerophospholipids accumulate in the inner membrane. Extra copies of the cloned msbA gene restore the ability of htrB mutants to grow at 42 degreesC, but they do not increase the extent of lipid A acylation. However, a significant fraction of the tetra-acylated lipid A species that accumulate in htrB mutants are transported to the outer membrane in the presence of extra copies of msbA. E. coli strains in which msbA synthesis is selectively shut off at 42 degreesC accumulate hexa-acylated lipid A and glycerophospholipids in their inner membranes. Our results support the view that MsbA plays a role in lipid A and possibly glycerophospholipid transport. The tetra-acylated lipid A precursors that accumulate in htrB mutants may not be transported as efficiently by MsbA as are penta- or hexa-acylated lipid A species.     

Identification of troponin C antagonists from a phage-displayed random peptide library

Affinity purification of a phage-displayed library, expressing random peptide 12-mers at the N terminus of protein III, has identified 10 distinct novel sequences which bind troponin C specifically. The troponin C-selected peptides yield a consensus binding sequence of (V/L)(D/E)XLKXXLXXLA. Sequence comparison revealed as much as a 62.5% similarity between phiT5, the peptide sequence of the phage clone with the highest level of binding to troponin C, and the N-terminal region of troponin I isoforms. Biotinylated peptides corresponding to library-derived sequences and similar sequences from various isoforms of troponin I were synthesized shown to bind troponin C specifically. Alkaline phosphatase fusion proteins of two of the phage clone sequences bound troponin C specifically, and were specifically competed by both library-derived and native troponin I peptides. Measurement of equilibrium dissociation constants of the peptides by surface plasmon resonance yielded dissociation constants for troponin C as low as 0.43 microM for pT5; in contrast, dissociation constants for calmodulin were greater than 6 microM for all peptides studied. Nondenaturing polyacrylamide gel electrophoresis demonstrated that pT5 formed a stable complex with troponin C in the presence of calcium. We also found that the pT5 peptide inhibited the maximal calcium-activated tension of rabbit psoas muscle fibers.     

Self-adaptation in evolving systems

While a high rate of cell loss is tolerated and even required to model the developing nervous system, an increased rate of cell death in the adult nervous system underlies neurodegenerative disease. Evolutionarily conserved mechanisms involving proteases, Bcl-2-related proteins, p53, and mitochondrial factors participate in the modulation and execution of cell death. In addition, specific death mechanisms, based on specific neuronal characteristics such as excitability and the presence of specific channels or enzymes, have been unraveled in the brain. Particularly important for various human diseases are excessive nitric oxide (NO) production and excitotoxicity. These two pathological mechanisms are closely linked, since excitotoxic stimulation of neurons may trigger enhanced NO production and exposure of neurons to NO may trigger the release of excitotoxins. Depending on the experimental situation and cell type, excitotoxic neuronal death may either be apoptotic or necrotic.     

New variant Creutzfeldt-Jakob disease: neurological features and diagnostic tests

BACKGROUND: In April, 1996, ten cases of Creutzfeldt-Jakob disease (CJD) with an apparently new clinicopathological phenotype were published and it was suggested that these new variant cases (nvCJD) might be causally linked to bovine spongiform encephalopathy (BSE). There have now been 21 cases of nvCJD in the UK and one case in France. We report clinical features and diagnostic test results of the first 14 cases of nvCJD in the UK. METHODS: Case ascertainment of CJD was mainly by direct referral from neurologists and neuropathologists. Clinical and investigate details were obtained by interview with patients' relatives and by examination of case notes. Ten cases in this report were examined while alive. Prion protein (PrP) gene analysis was carried out with informed consent from the patient or from a relative. The diagnosis of nvCJD was established histologically. FINDINGS: Eight cases were women. Mean age at onset of symptoms was 29 (16-48) years and the median duration of illness was 14 (9-35) months. All patients had early psychiatric symptoms, most often depression, and 13 were seen by a psychiatrist early in the clinical course. Eight patients developed early sensory symptoms which were persistent and often painful. Neurological signs, including ataxia and involuntary movements, developed in all cases and towards the end of the illness, most had akinetic mutism. The electroencephalogram was abnormal in most patients but typical periodic complexes of CJD were not seen in any case. Cerebral imaging was usually normal or showed non-specific abnormalities; in two cases magnetic-resonance imaging scans showed high signal in the thalamus. INTERPRETATION: Clinical features in these cases are similar and relatively distinct from other forms of CJD, suggesting that this is a new clinical phenotype consistent with a single strain of infectious agent. There is, however, some overlap with atypical cases of sporadic CJD, and the diagnosis of nvCJD remains dependent on neuropathological confirmation.     

Differences in mortality between elderly and younger adult trauma patients: geriatric status increases risk of delayed death

BACKGROUND: Elderly patients suffer higher mortality rates after trauma than younger patients. This increased mortality is attributable to age, preexisting disease, and complications as well as injury severity. METHODS: Records from 5,139 adult patients from a Level I trauma center were retrospectively reviewed. Injury Severity Score (ISS), Revised Trauma Score (RTS), early mortality (<24 hours), and late mortality (>24 hours) were determined for elderly (> or =65 years) and younger (16-64 years) patients. Preexisting diseases and complications were identified by International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis coding. RESULTS: Mortality in elderly patients was twice that in younger patients despite equivalent injury severity (p < 0.001), and elderly patients were more likely to suffer later death than younger patients (p < 0.005). The prevalence of preexisting disease was greater in the elderly, as was the incidence of complications. Using logistic regression, ISS, RTS, preexisting cardiovascular or liver disease, the development of cardiac, renal, or infectious complications, and geriatric status were all independently predictive of late mortality (p < 0.05). CONCLUSION: Elderly trauma patients more frequently suffer late mortality than younger patients because of the combination of injury and increased preexisting disease and complications after injury. Aggressive treatment of the elderly trauma patient is warranted; however, in the face of significant preexisting disease or complications, survival is less likely. Predictive models of survival can be developed, taking into account preexisting disease and complications as well as admission parameters such as age, ISS, and RTS, and specific risk of mortality quantitated.     

Fatal hepatitis B virus infection with fibrosing cholestatic hepatitis following renal transplantation

BACKGROUND: Coronary artery spasm in the immediate postoperative period after a coronary operation is recognized infrequently. Its severity is variable and manifestations unpredictable. The diagnosis is usually made by an awareness of the possibility and thereafter by exclusion of other causes of myocardial ischemia. An opportunity for a positive diagnosis is rarely available. METHODS: The case reports of 3 patients with similar presentations of ischemic heart disease and with severe manifestations of coronary artery spasm in the postoperative period are presented. RESULTS: All 3 patients were women aged 55 to 60 years. All had single-vessel coronary artery disease involving the left anterior descending artery and underwent a left internal mammary artery bypass graft. Severe manifestations of myocardial ischemia of abrupt onset developed approximately 7 hours postoperatively in each patient. One patient died of severe hemodynamic deterioration from which resuscitation was unsuccessful. Another sustained a large anterior myocardial infarction despite graft patency. The third patient was supported by an intraaortic balloon pump and made a full recovery. CONCLUSIONS: The early diagnosis of coronary artery spasm is achieved by an awareness of the condition. The institution of early appropriate management may prevent its consequences.     

Passive avoidance learning involves alpha2-noradrenergic receptors in a day old chick

Day-old chicks were trained on one-trial passive avoidance task, using methyl-anthranilate (MeA) as an aversive substance. Bilateral pharmacological manipulation of the intermediate hyperstriatum ventrale was performed by intracerebral application of an alpha2-noradrenergic agonist, clonidine (5 microM), or an antagonist, rauwolscine (300 microM). Only rauwolscine application (pre- or post-training) induced significant memory impairment. Quantitative receptor autoradiography was used to determine the kinetic properties of the binding sites for [3H]clonidine or [3H]rauwolscine in MeA-trained or water-trained (control) chicks, in forebrain areas known to be involved in avoidance learning. Scatchard analysis revealed that MeA-training resulted in a significant bilateral upregulation in the number of [3H]rauwolscine binding sites (Bmax) in the area of hyperstriatum ventrale. These findings suggest the importance of activation of alpha2-noradrenergic receptors in aversive learning in chicks.     

Wheat bran- but not oat bran-enriched diets increase the mucosal height of the cecum and colon of newly weaned and aged rats

BACKGROUND: The quality of pain relief during the first 48 hours following ambulatory surgery has been poorly documented. This questionnaire study was performed to evaluate the nature and severity of pain after the patient leaves the hospital. METHODS: 1100 patients in the age group 5-88 years who underwent ambulatory surgery during a period of 6 months were asked to complete a questionnaire 48 h after the end of the operation. In the case of children, parents were asked to complete a similar questionnaire. The questions were related to pain experienced during the first 48 h after surgery and to the nature and severity of postoperative complications. RESULTS: A total of 1035 out of the 1100 patients returned the questionnaire, 94.1%. Overall the majority (65%) of patients had only mild pain at home; however, patients undergoing certain types of surgery had moderate-to-severe pain: inguinal hernia surgery (62% patients), orthopaedic surgery (41%), hand surgery (37%) and varicose vein surgery (36%). In these patients the severity of pain did not decrease during the 2-day study period. About 10% patients had more severe pain than they had anticipated, and 20% had difficulty in sleeping at night due to severe pain. Despite this, over 95% of patients were satisfied with management of postoperative pain. Nausea (20%), tiredness (20%) and vomiting (8%) were the commonest complications reported during the first 48 h. A significant association was found between the administration of a general anaesthetic and the incidence of nausea postoperatively. A large number of patients were alone at home after the operation (28.4%); some (3.8%) had no access to a relative or friend in case of need. CONCLUSION: Our results show that about 35% of day-surgery patients experience moderate-to-severe pain at home in spite of analgesic medication. About 20% of patients had sleep problems due to severe pain. However, only 5% of patients were dissatisfied. Better analgesic techniques are necessary for patients undergoing certain types of surgery. Patient information and follow-up routines need to be improved.