58K, a microtubule-binding Golgi protein, is a formiminotransferase cyclodeaminase

58K was previously identified as a rat liver protein that binds microtubules in vitro and is associated with the cytoplasmic surface of the Golgi apparatus in vivo (Bloom, G. S., and Brashear, T. A. (1989) J. Biol. Chem. 264, 16083-16092). We now report that 58K is a formiminotransferase cyclodeaminase (FTCD), a bifunctional enzyme that catalyzes two consecutive steps in the modification of tetrahydrofolate to 5,10-methenyl tetrahydrofolate. Comparative immunoblotting using several monoclonal antibodies made against 58K and a polyclonal antibody made against a chicken liver protein (p60) with similar properties (Hennig, D., Scales, S. J., Moreau, A., Murley, L. L., De Mey, J., and Kreis, T. E. (1998) J. Biol. Chem. 273, 19602-19611) demonstrated precise co-purification of protein recognized by all antibodies through multiple fractionation steps, including gel filtration and ion exchange chromatography, and sucrose gradient ultracentrifugation. Eight peptides derived from 58K showed high sequence identity to amino acid sequences predicted by full length cDNA for p60 and porcine liver FTCD. Furthermore, purified 58K was associated with formiminotransferase and cyclodeaminase activities. Based on these collective results, 58K was concluded to be a rat liver version of FTCD. Microtubules assembled from brain tubulin, but not from liver tubulin, were able to bind rat liver FTCD. Binding to brain microtubules is suspected to occur via polyglutamates that are added post-translationally to tubulin in brain, which was shown to contain very low levels of FTCD, but not to tubulin in liver, which was determined to be the richest tissue source, by far, of FTCD. The physiological significance of the microtubule binding activity of FTCD is thus called into question, but an association of FTCD with the Golgi apparatus has now been established.     

Psammaplysin F, a new bromotyrosine derivative from a sponge, Aplysinella sp

A new member of the psammaplysin family, psammaplysin F (6) has been isolated from an undescribed species of Aplysinella sponge, along with the four known psammaplysins A-C (1-3) and E (5). The structure of psammaplysin F was determined by spectral analysis.     

Midazolam, a water-soluble benzodiazepine, for gastroscopy

Midazolam, a water-soluble benzodiazepine, was given intravenously in doses of 0.07 mg/kg as sedation prior to oesophago-gastro-duodenoscopy in 40 patients. This was very effective as a sedative in elderly patients but less so in the young, with a large individual variation in response. Pain on injection and venous thrombosis which are common with diazepam were not seen with midazolam.     

Sirolimus, a new, potent immunosuppressive agent

Sirolimus (SRL), a potent immunosuppressant, is currently being investigated in phase III trials for prophylaxis of renal transplant rejection. The mechanism of action of SRL is a blockade of the response of T and B cells to cytokines, thereby preventing cell cycle progression in G1 and consequently cell proliferation. There seems to be a good correlation between SRL concentrations, estimated as exposure by the area under the concentration versus time curve, and trough whole blood concentration, so that therapeutic monitoring may be done by trough levels only. Because of the low frequency of allograft rejection, there has been no documented correlation between trough concentrations and efficacy. Trough SRL concentrations of 15 ng/ml or higher seem to be associated with an increased frequency of adverse effects. Drug-associated toxicities include thrombocytopenia, leukopenia, and increases in cholesterol and triglyceride levels. The drug has synergy with cyclosporine (CsA) in vitro as well as in animal and clinical studies. In phase II trials the combination of SRL-CsA therapy reduced the frequency of acute rejection episodes, permit withdrawal of concomitant corticosteroid therapy, and allowed reduction of CsA dosages in nonblack patients.     

Hoarding: a symptom, not a syndrome

BACKGROUND: Hoarding behavior in humans spans a continuum from normal collecting to pathological self-neglect and can be associated with a variety of psychiatric disorders. METHOD: The authors summarize research in the past 15 years characterizing hoarding behavior in groups of college students, in nonclinical populations of self-named "pack rats," in outpatients treated for obsessive-compulsive disorder (OCD), and in individual pathological hoarders presented in psychiatric case reports. Two new case reports of pathological hoarding are presented here. RESULTS: The literature suggests, as do the 2 case reports presented, that certain factors may be common to all groups of hoarders, as they all show poor insight, lack of resistance to the compulsion to hoard, and poor treatment motivation. CONCLUSION: Possible biological and psychosocial determinants of pathological hoarding include association with schizophrenia, OCD, and tic disorders, as well as a possible link through the neurotransmitter dopamine. Management issues range from psychopharmacologic treatment with antipsychotic medication to behavioral therapy and environmental manipulation.     

Interaction between enoxacin, a new antimicrobial, and nimesulide, a new non-steroidal anti-inflammatory agent in mice

Convulsions induced by the combination of enoxacin, a new antimicrobial, and nonsteroidal anti-inflammatory drugs including nimesulide, ketoprofen, pranoprofen and loxoprofen sodium, were investigated in mice. The oral administration of nimesulide alone induced clonic convulsions at more than 300 mg/kg. The oral administration of ketoprofen, pranoprofen or loxoprofen sodium induced no convulsion up to 1000 mg/kg, 500 mg/kg and 600 mg/kg, respectively, and that of enoxacin induced no convulsion at more than 5000 mg/kg. The combination of nimesulide at 200 mg/kg and enoxacin at 400 mg/kg induced no convulsion. In contrast, the combination of enoxacin at 100 mg/kg and either ketoprofen at 125 mg/kg or pranoprofen at 500 mg/kg induced clonic convulsions, while that of enoxacin at 400 mg/kg and loxoprofen sodium at 600 mg/kg induced no convulsion. These results suggest that the combination of nimesulide and enoxacin may possibly induce few or less convulsions in the clinical setting.     

Interrelationships between strains of Salmonella enteritidis belonging to phage types 4, 7, 7a, 8, 13, 13a, 23, 24 and 30

Cyclin A is a nuclear protein which is part of a kinase complex with either p34cdc2 or p33cdk2. Cyclin A is required in higher eukaryotic cells at the G1/S and the G2/M transitions. To examine the relationship between cyclin A and DNA replication, we simultaneously labeled exponentially growing HeLa cells for the distribution of cyclin A and proliferating cell nuclear antigen (PCNA). We have now demonstrated, by means of immunoelectron microscopy, that cyclin A is located at the sites of DNA replication visualized by both BrdU and PCNA labeling. Thus cyclin A may play a significant role in the phosphorylation of proteins at or near the sites of DNA replication.     

Oculocerebrocutaneous syndrome: a case report, a follow-up, and differential diagnostic considerations

Is postmodernism in many ways the empiricist-liberal tradition at the inevitable end of its intellectual and political tether? Or is postmodernism the 'laughter of genius' that art and argument in their traditional forms are dead? Can postmodernism be applied to social and economic issues whilst carrying a denial of the manner by which Western thought has shaped these issues? Can postmodernism provide moral pathways to help us with contemporary ethical issues? How can postmodernist thought encompass the activities of nurses, particularly in the area of psychiatric care? Can nurses afford postmodernist suppositions in the face of suffering and pain? If postmodernism exists, does it exist everywhere (as does nursing) or is it a more localized event?     

Hepatolithiasis, a clinical study

To examine the value of transient regional asynergy on dobutamine stress echocardiography as a noninvasive predictor of future cardiac events, 51 symptomatic patients (aged 54 +/- 9 years) with suspected coronary artery disease (CAD) were studied using an incremental regimen of 5, 10, 15 and 20 micrograms/kg/min. Pretest likelihood of CAD was (mean +/- standard error of the percentage) 79.7 +/- 5.6% before and 83.4 +/- 5.2% after exercise electrocardiography using probability analysis based on age, sex and symptoms. Two-dimensional images were analyzed with reference to an 11-segment model and gave good interrater agreement. During 24 +/- 4 months (range 19 to 32) of follow-up, 23 patients had events (1 myocardial infarction, 9 unstable angina, 10 coronary bypass surgery, 3 coronary angioplasty) and 28 were event free. Age, proportion with baseline asynergy and both pretest echocardiographic ejection fraction and its response to dobutamine were similar in these 2 groups (all p = not significant). Transient asynergy was seen in 17 of 23 patients (74%) with and 8 of 28 patients (29%) without events (p < 0.01); 5 of 6 patients (83%) with involvement of 3 segments had events. Myocardial infarction or unstable angina occurred in 8 of 25 (32%) with a positive and 2 of 26 (8%) with a negative stress echocardiogram (p < 0.05). Both exercise duration (389 +/- 195 vs 517 +/- 237 seconds, p < 0.05) and time to diagnostic ST-segment shift (291 +/- 192 vs 447 +/- 212 seconds, p = 0.05) were shorter in those with inducible asynergy.(ABSTRACT TRUNCATED AT 250 WORDS)     

CTX, a Xenopus thymocyte receptor, defines a molecular family conserved throughout vertebrates

CTX, a cortical thymocyte marker in Xenopus, is an immunoglobulin superfamily (Igsf) member comprising one variable and one constant C2-type Igsf domain, a transmembrane segment and a cytoplasmic tail. Although resembling that of the TCR and immunoglobulins, the variable domain is not encoded by somatic rearrangement of the gene but by splicing of two half-domain exons. The C2 domain, also encoded by two exons, has an extra pair of cysteines. The transmembrane segment is free of charged residues, and the cytoplasmic tail (70 amino acids) contains one tyrosine and many glutamic acid residues. ChT1, a chicken homologue of CTX, has the same structural and genetic features, and both molecules are expressed on the thymocyte surface. We cloned new mouse (CTM) and human (CTH) cDNA and genes which are highly homologous to CTX/ChT1 but not lymphocyte specific. Similarity with recently described human cell surface molecules, A33 antigen and CAR (coxsackie and adenovirus 5 receptor), and a number of expressed sequence tags leads us to propose that CTX defines a novel subset of the Igsf, conserved throughout vertebrates and extending beyond the immune system. Strong homologies within vertebrate sequences suggest that the V and C2 CTX domains are scions of a very ancient lineage.     

Hypodermoclysis, a neglected approach

Patients with advanced cancer frequently present with chronic nausea, emesis, bowel obstruction, confusional syndromes or dysphagia. All these conditions make it difficult for the patient to take oral medications or to maintain an adequate level of hydration by mouth. Hypodermoclysis is a safe and simple method that allows for cost-effective sucutaneous delivery of fluids and drugs. Hypodermoclysis has some clearcut advantages over the i.v. route. It can be started without need for a physician or a nurse, does not immobilize a limb, can be stopped and restarted at any moment without concern for clotting, and its use sparses nursing time. It also allows for easier and safer home discharge. Potentiel side effects of hypodermoclysis include pain at infusion site, sloughing tissues as a result of insufficient fluid absorption, infection, and puncture of vessels with bleeding. This paper gives some guidelines for the use of hypodermoclysis for fluid, electrolytes and drugs frequently used in a palliative care setting. The controversy surrounding the treatment of dehydration in the terminally ili is also briefly examined.