A computer-assisted system for reconstructing and interpreting the dynamic three-dimensional relationships of the outer surface, nucleus and pseudopods of crawling cells

Newly developed software additions to the three-dimensional dynamic image analysis system, 3D-DIAS, are described for simultaneously reconstructing and motion analyzing in three dimensions the outer surface, nucleus and pseudopods of living, crawling cells. This new system is then used to describe for the first time a nuclear behavior cycle in translocating Dictyostelium discoideum amoebae and to investigate the role of pseudopod extension in this process. The nuclear behavior cycle is tuned to the two phases of the general cell behavior cycle [Wessels et al., 1994], and includes nuclear migration both in the z- and in the x,y-axes from the proximal border of the prior anterior pseudopod to the proximal border of a newly expanding anterior pseudopod. Nuclear migration is cued by pseudopod-substratum contact, achieves velocities in excess of 50 microm/min, and is accompanied by characteristic changes in nuclear shape. The rules and characteristics of nuclear behavior are demonstrated to be intact in two mutants affecting pseudopod formation, a myosin IB null mutant (myoB-) and a myosin II heavy chain phosphorylation mutant (3XALA). The rules and characteristics of nuclear migration, however, are disrupted upon dissolution of microtubules by colcemid. Together the above results demonstrate that the newly developed 3D-DIAS system can be used to gain new insights into the dynamic changes in the intracellular 3D architecture associated with cellular translocation.     

Consulting in occupational health nursing. An overview

1. The term consultant is defined as anyone who provides professional advice or services, which may include internal and external consultants. Consulting is a challenging way to practice occupational health nursing. 2. The consulting process involves problem solving and the creation of change. This process may be illustrated by using the nursing process and the steps of assessment, analysis, planning, implementation, and evaluation. 3. Successful occupational health nursing consultants are excellent communicators, are willing to market themselves, love problem solving, and are self starters.     

Dynamic kinetic asymmetric cycloadditions of isocyanates to vinylaziridines

The first examples of the use of racemic vinylaziridines in a Pd-catalyzed dynamic kinetic asymmetric transformation have been examined. Optimization studies of the Pd-catalyzed addition of vinylaziridines to isocyanates revealed that the chiral ligand between trans-1,2-diaminocyclohexane and 2-diphenylphosphino-1-naphthoic acid is superior to that involving 2-diphenylphosphino benzoic acid. Surprisingly, high ee's required the use of an acid whose pKa was about 4.7 +/- 0.1 as a cocatalyst. Both acetic acid and hydroxybenzotriazole meet this requirement. Less electrophilic isocyanates (e.g., benzyl, p-methoxyphenyl) gave higher ee's than more electrophilic ones (phenyl or benzoyl). Both N-benzyl and N-arylaziridines react well to give good yields and ee's, whereas N-tosylaziridines gave lower ee's. A 1,1-disubstituted aziridine led to the formation of a tertiary C-N bond with ee's comparable to the formation of the secondary C-N bond. The products were easily reduced almost quantitatively to the sensitive imidazolidines which can be readily hydrolyzed to the vicinal diamines. The reactivity pattern is consistent with a Curtin-Hammett situation wherein the enantiodiscriminating event is the cyclization of a rapidly equilibrating dynamic pi-allyl palladium intermediate.     

Use of intraaortic balloon counterpulsation in patients presenting with cardiogenic shock: observations from the GUSTO-I Study. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries

OBJECTIVES: We sought to examine the use, complications and outcomes with early intraaortic balloon counterpulsation (IABP) in patients presenting with cardiogenic shock complicating acute myocardial infarction and treated with thrombolytic therapy. BACKGROUND: The use of IABP in patients with cardiogenic shock is widely accepted; however, there is a paucity of information on the use of this technique in patients with cardiogenic shock who are treated with thrombolytic therapy. METHODS: Patients who presented within 6 h of chest pain onset were randomized to one of four thrombolytic regimens. Cardiogenic shock was not an exclusion criterion, and data for these patients were prospectively collected. Patients presenting with shock were classified into early IABP (insertion within one calendar day of enrollment) or no IABP (insertion on or after day 2 or never). RESULTS: There were 68 (22%) IABP placements in 310 patients presenting with shock. Early IABP use occurred in 62 patients (20%) and none in 248 (80%). Most IABP use occurred in the United States (59 of 68 IABP placements) involving 32% of U.S. patients presenting with shock. Despite more adverse events in the early IABP group and more episodes of moderate bleeding, this cohort showed a trend toward lower 30-day and 1-year mortality rates. CONCLUSIONS: IABP appears to be underutilized in patients presenting with cardiogenic shock, both within and outside the United States. Early IABP institution is associated with an increased risk of bleeding and adverse events but a trend toward lower 30-day and 1-year all-cause mortality.     

Evidence that hepatitis C virus resistance to interferon is mediated through repression of the PKR protein kinase by the nonstructural 5A protein

This investigation was undertaken to characterize the muscarinic receptor subtypes involved in methacholine-induced vasodilation, vagal bradycardia, neurally-evoked sudomotor responses and sympathetic muscarinic ganglionic transmission in anesthetized cats. Dose-response curves were constructed using the putatively selective antagonists pirenzepine (M1), gallamine (M2) and 4-DAMP (M3: 4-diphenyl-acetoxy-N-methylpiperidine) and compared with the non-selective blocker, atropine. Methacholine hypotension and evoked sudomotor responses exhibited an M3 muscarinic receptor profile with the following potency relationships: atropine > or = 4-DAMP > pirenzepine > gallamine. Vagal bradycardia (M2) was antagonized by gallamine and exhibited a lower relative sensitivity to 4-DAMP when corrected for atropine effect. Pirenzepine was inactive in inhibition of bradycardia but was highly potent against transmission in the sympathetic ganglion (M1) with the following potency relationships: atropine > or = pirenzepine > 4-DAMP > gallamine. In comparison with atropine, 4-DAMP exhibited a significantly lower potency for M1 and M2 muscarinic receptors as compared to its effect on the M3 muscarinic receptor subtypes.     

Relationship of endometrial thickness with the menstrual timing of leuprolide acetate administration for preoperative preparation for hysteroscopic surgery

OBJECTIVES: To investigate the changes in the cholesterol:phospholipids (C/PL) ratio of erythrocyte membrane in post-menopausal women with and without hormone replacement therapy (HRT). STUDY DESIGN: A cross-sectional study including 83 patients divided into three groups according to HRT (group 1, no HRT (n = 52); group 2, combined HRT (n = 16); and group 3, estrogen-only therapy (n = 15)). RESULTS: The C/PL ratio was lower in group 2 with respect to group 1 and group 3 (P = 0.03). No difference was found in erythrocyte membrane cholesterol between the three groups; however, the phospholipid concentration was higher in group 2 with respect to the other groups (P < 0.05). In the control group, C/PL values correlated positively with plasma LDL levels (P < 0.005) and negatively with HDL levels (P < 0.005). CONCLUSIONS: From our data the addition of progestogens in HRT appears to decrease the C/PL of the erythrocyte membrane possibly resulting in a beneficial effect on rheological properties of erythrocyte membrane. The results of our study thus suggest additional benefits from supplementation of progestogens in HRT, in addition to prevention of estrogen dependent endometrial hyperplasia and adenocarcinoma.     

Ventilation inhomogeneities and mixed venous blood N2 in multibreath N2 washout

OBJECTIVE: To examine the relationship between allergy-related symptoms, food intolerance and psychological distress in primary care. METHODS: Two thousand three hundred and thirty two adults in five General Practices in the South of England completed questionnaires regarding allergy-related symptoms and psychological symptoms, but no association was demonstrated between a history of diagnosed or treated asthma, eczema or hay fever and psychological morbidity. Cases of food intolerance had lower levels of psychological distress than expected compared to hospital samples. Current, but not past wheezing and eczema, was associated with an excess of life stresses in the previous six months. CONCLUSIONS: The association between psychological distress and the label of food allergy/intolerance found in specialist care does not extend to primary care.     

Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo

Following exposure to some types of antigen (superantigens), responsive T cells expand and then decline in numbers, a phenomenon that has been called 'peripheral deletion'. This process may play a role in limiting autoimmune reactions and in the maintenance of immune homeostasis. Here we describe experiments on peripheral deletion in mice carrying the lpr/lpr defect, which has been shown to be due to defective production of the CD95/Fas molecule. Young lpr/lpr mice with no apparent immunologic abnormalities display a defect in bacterial superantigen-induced peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion. Apoptotic death of the expanded T cell population associated with such peripheral deletion in normal animals is dramatically reduced in the mutant mice. Further, the levels of Fas on responding cells in normal mice increases and decreases together with increases and decreases in cell numbers, suggesting that cells with the highest levels of Fas are preferentially deleted. These observations are consistent with the known ability of CD95 to transduce a signal leading to apoptosis, and they implicate this signal transduction pathway in peripheral deletion. In contrast, bacterial superantigen-induced deletion of thymocytes appears to be fully functional in these mice, and thus Fas/APO-1 does not appear to be required for this process. Further, antibody ligation of the TCR on activated T cells from normal or young lpr/lpr mice can induce apoptosis and therefore under some circumstances this phenomenon is not dependent upon CD95/Fas. Thus, to avoid autoreactivity and ensure immune homeostasis, several different apoptotic mechanisms exist in peripheral T lymphocytes, only some of which involve Fas.(ABSTRACT TRUNCATED AT 250 WORDS)