Characterization of chromosomal and membrane associated plasmid in Bacillus brevis ATCC 9999

A covalently closed circular (ccc) DNA, with a weight of 44.7 x 10(6) daltons, has been isolated from Bacillus brevis ATCC 999 (a gramicidin S producer) and from the gramicidin S-negative mutant EB16. The ccc DNA in the case of the parent strain, is mainly (99%) attached to the chromosome and membrane fraction. A restriction enzyme map of the plasmid DNA was constructed for the enzymes SalI, SmaI and BamHI, which cleaved the plasmid DNA into two, two and six fragments respectively. Further digestion with the endonucleases EcoRI and HindIII cleaved the plasmid into 17 and 22 fragments.     

Addition of nitrous oxide to fentanyl anesthesia does not induce myocardial ischemia in patients with ischemic heart disease

Although nitrous oxide is commonly administered to patients with ischemic heart disease, recent reports suggest that it may induce myocardial ischemia in these patients. The authors compared the effects of nitrous oxide on segmental left ventricular (LV) function and the ST segment of the electrocardiogram with the effects of an equal concentration of nitrogen (crossover design) before the start of surgery in 18 patients who required coronary-artery bypass grafting. The patients studied did not have valvular or LV dysfunction. Anesthesia was induced and maintained with intravenous fentanyl. After endotracheal intubation and 20 min of ventilation with 100% oxygen, either 60% nitrous oxide or 60% nitrogen (randomly assigned) was added to the inspired gas mixture of each patient for 10 min. This was followed by 10 min of 100% oxygen, and then 10 min of 60% nitrous oxide or 60% nitrogen, whichever had not been administered previously. Patients were monitored for myocardial ischemia using a standard 12-lead electrocardiogram and trans-esophageal two-dimensional echocardiography. Surgery did not begin until the study was concluded. No patient experienced an ST segment change greater than 1 mm during the study, and none developed a new segmental wall motion abnormality during inhalation of either nitrous oxide or nitrogen. The authors conclude that nitrous oxide does not induce myocardial ischemia when used as an adjunct to fentanyl anesthesia in patients who have severe coronary-artery disease accompanied by well-preserved valvular and LV function.     

Eosinophilia-myalgia syndrome after L-tryptophan intake

Since 1989 there has been an increasing number of reports on the association of L-tryptophan (LT) and eosinophilia-myalgia syndrome (EMS). It has now become evident that the clinical picture of EMS can vary. We report two further cases reflecting the clinical spectrum of the disease. The first patient had been taking LT for 8 years before the onset of myalgia. Subsequently, this patient developed an illness clinically and histologically resembling eosinophilic fasciitis. The second patient had been taking LT for 8 months before the onset of symptoms, which included myalgia, severe oedema of the lower extremities and induration of the skin involving arms, lower legs and abdomen. Discontinuation of LT and administration of oral steroids resulted in little improvement of the skin changes in the first patient. However, in the second patient skin involvement improved rapidly, whereas the neurological disorders have become more prominent.     

Narcotics decrease heart rate during inhalational anesthesia

We determined the heart rate (HR) response to enflurane, halothane, and isoflurane and the effects of narcotics on this response in 81 healthy patients scheduled for elective surgery. Patients were randomly assigned to one of six treatment groups: one of the three anesthetics (approximately 0.9 MAC) in 60% nitrous oxide, and either 0.15 mg/kg of intramuscular morphine 30-60 min before induction or 1 microgram/kg of IV fentanyl 10 min after skin incision. All patients received diazepam, 10 mg orally, 60-90 min before anesthesia, a rapid sequence intravenous induction, and mechanically controlled ventilation. During inhalational anesthesia and the first 10 min of surgery, no significant change in HR occurred in any group (compared to the preinduction HR), although patients given morphine premedication tended to have a decreased HR and those not given morphine premedication tended to have an increased HR. These trends partially account for significant differences that emerged between groups after induction of anesthesia. Patients given morphine premedication and halothane had lower HR (64 +/- 3 SEM) than patients given isoflurane (80 +/- 3) or enflurane (84 +/- 3) and no morphine premedication. Patients anesthetized with enflurane and morphine premedication had lower HR (71 +/- 3) than patients given enflurane without morphine premedication. Administration of fentanyl 10 min after incision (these patients had received no morphine) significantly decreased HR in the presence of any of the vapors. We conclude that inhalational anesthetics used in the clinical setting we employed do not significantly increase heart rate, and that prior administration of morphine or concurrent administration of fentanyl may significantly decrease HR.     

Intraoperative detection of myocardial ischemia in high-risk patients: electrocardiography versus two-dimensional transesophageal echocardiography

Because acute segmental wall motion abnormalities (SWMAs) of the left ventricle are highly sensitive and specific indicators of myocardial ischemia, this study compared the incidence and significance of ischemia, as detected by two-dimensional transesophageal echocardiography and surface electrocardiography, during anesthesia and surgery in patients at high risk of myocardial ischemia. During surgery, 24 of the 50 patients studied had new SWMAs, whereas only six had ST segment changes. All patients with ST segment changes also had new SWMAs: in three instances, SWMAs occurred before the ST segment change, and in three instances, they occurred simultaneously. All three patients who had intraoperative myocardial infarctions also had persistent intraoperative SWMAs, whereas only one patient had ST segment changes. Ten healthy patients requiring noncardiovascular surgery were monitored similarly; none of these had SWMAs, ST segment changes, or myocardial infarction. This study demonstrates the superiority of two-dimensional transesophageal echocardiography over electrocardiography for the intraoperative detection of myocardial ischemia. Furthermore, when new SWMAs persist to the conclusion of surgery, myocardial infarction is likely to have occurred.     

Geldanamycin activates a heat shock response and inhibits huntingtin aggregation in a cell culture model of Huntington's disease.

Huntington's disease (HD) is a progressive neurodegenerative disorder with no effective treatment. Geldanamycin is a benzoquinone ansamycin that binds to the heat shock protein Hsp90 and activates a heat shock response in mammalian cells. In this study, we show by using a filter retardation assay and immunofluorescence microscopy that treatment of mammalian cells with geldanamycin at nanomolar concentrations induces the expression of Hsp40, Hsp70 and Hsp90 and inhibits HD exon 1 protein aggregation in a dose-dependent manner. Similar results were obtained by overexpression of Hsp70 and Hsp40 in a separate cell culture model of HD. This is the first demonstration that huntingtin protein aggregation in cells can be suppressed by chemical compounds activating a specific heat shock response. These findings may provide the basis for the development of a novel pharmacotherapy for HD and related glutamine repeat disorders.     

Zur Nierenfunktionsprüfung bei Prostatahypertrophie

Zusammenfassung Die Bechersche Funktionszahl gibt bei der P. H. kein ma\gebendes Urteil über den Zustand der Nieren. Feste Zahlen für gute und schlechte Nierenfunktion k?nnen nicht aufgestellt werden. Die Spanne von h?chstem und niedrigstem spezifischen Gewicht mu\ zur Rechtfertigung der Ektomie mindestens 15 betragen. Nieren, die nicht unter 1006 verdünnen, sind schwer gesch?digt. Das Verabreichen von nur 1 l Flüssigkeit ist für die Beurteilung der Wasserausscheidung unsicher. Bei F?llen mit totaler Retention gibt der W. V. im Anschlu\ an die Entlastung keine genügenden Werte. Verminderte Konzentrationsf?higkeit (Hyposthenurie) nachKoranyi ev. verbunden mit schlechter Verdünnung (Isosthenurie nachKoranyi) sind Sympto me der P. H. Der Wasserversuch ist die wichtigste Funktionsprüfung bei der P. H. Er genügt keineswegs allein. Indigokarminausscheidung, geprüft bei der Cystoskopie oder am Gesamturin, Restharn, Cystoskopie, Blutdruck, Reststickstoff im Blut geben wichtige Werturteile. Wir haben, seitdem wir uns nach obigen Gesichtspunkten richten, nach der Prostatektomie keinen Todesfall an Niereninsuffizienz gehabt.     

Sequence-related protein export NTPases encoded by the conjugative transfer region of RP4 and by the cag pathogenicity island of Helicobacter pylori share similar hexameric ring structures

RP4 TrbB, an essential component of the conjugative transfer apparatus of the broad-host-range plasmid RP4, is a member of the PulE protein superfamily involved in multicomponent machineries transporting macromolecules across the bacterial envelope. PulE-like proteins share several well conserved motifs, most notable a nucleoside triphosphate binding motif (P-loop). Helicobacter pylori HP0525 also belongs to the PulE superfamily and is encoded by the pathogenicity island cag, involved in the inflammatory response of infected gastric epithelial cells in mammals. The native molecular masses of TrbB and HP0525 as determined by gel filtration and glycerol gradient centrifugation suggested a homohexameric structure in the presence of ATP and Mg(2+). In the absence of nucleotides and bivalent cations, TrbB behaved as a tetramer whereas the hexameric state of HP0525 remained unaffected. Electron microscopy and image processing demonstrated that TrbB and HP0525 form ring-shaped complexes (diameter: 12 nm) with a central region (diameter: 3 nm) of low electron density when incubated in the presence of ATP and Mg(2+). However, the TrbB average image appeared to be more elliptical with strong twofold rotational symmetry whereas HP0525 complexes are regular hexagons. Six well defined triangle-shaped areas of high electron density were distinguishable in both cases. Covalent crosslinking of TrbB suggests that the hexameric ring is composed from a trimer of dimers, because only dimeric, tetrameric, and hexameric species were detectable. The toroidal structure of TrbB and HP0525 suggests that both proteins catalyze a repetitive process, most probably translocating a cognate substrate across the inner membrane.     

Biventricular Physiology of Iatrogenic Atrial Septal Defects Following Transcatheter Mitral Valve Edge-to-Edge Repair

ObjectivesThe study sought to assess the acute hemodynamic effects of iatrogenic atrial septal defect (iASD) closure following transcatheter mitral valve edge-to-edge repair (TMVR).BackgroundThe potential hemodynamic and clinical consequences of an iASD following TMVR are currently subject to controversial debates.MethodsIn 21 patients with relevant left-to-right shunt flow (50% [IQR: 38% to 60%] of systemic perfusion volume) across an iASD following TMVR, interventional closure was performed with recordings of left ventricular (LV) and right ventricular (RV) pressure-volume loops during iASD occlusion.ResultsiASD occlusion led to a volume shift from the RV (RV end-diastolic volume index: pre 102 [IQR: 80 to 120] ml/m², post 92 [IQR: 70 to 111] ml/m²; p < 0.001) to the LV (LV end-diastolic volume index: pre 91 [IQR: 74 to 124] ml/m², post 97 [IQR: 77 to 127] ml/m²; p < 0.001) with reduced RV (3.49 [IQR: 2.07 to 3.58] l/min/m² vs. 2.68 [IQR: 2.07 to 3.58] l/min/m²; p < 0.001) but increased LV cardiac index (2.25 [IQR: 1.80 to 3.28] l/min/m² vs. 2.77 [IQR: 1.90 to 3.34] l/min/m²; p = 0.039). Although RV end-diastolic pressure decreased (pre 5.0 [IQR: 4.0 to 8.5] mm Hg, post 4.5 [IQR: 3.0 to 8.3] mm Hg; p = 0.024), LV end-diastolic pressure remained unchanged (pre 11.0 [IQR: 9.5 to 14.0] mm Hg, post 13.0 [IQR: 9.0 to 15.5] mm Hg; p = 0.142). LV transmural pressure increased (7.0 [IQR: 4.0 to 11.0] mm Hg vs. 11.0 [IQR: 7.0 to 15.0] mm Hg; p = 0.001) and LV eccentricity index decreased (p < 0.001). The change in LV transmural pressure correlated significantly with the change in LV-to-RV end-diastolic volume ratio (r = 0.674; p = 0.018). Right heart failure symptoms declined at 1-month follow-up (71% vs. 35%; p = 0.003) as did New York Heart Association functional class (≥III: 48% vs. 25%; p < 0.001).ConclusionsiASD closure following TMVR leads to a volume shift from the RV to the LV with reduced pulmonary but increased systemic cardiac index and with favorable biventricular interaction at maintained LV filling pressure, resulting in a decline in heart failure symptoms at 1-month follow-up.