Tri-armed star polymers by living cationic polymerization, 3. Synthesis of tri-armed star poly(p-methoxystyrene)

Tri-armed star polymers of p-methoxystyrene (pMOS) were synthesized by living cationic polymerization with a trifunctional initiator CH₃? C[(p-)C₆H₄OCH₂CH₂OCH(CH₃)? I]₃ (6) or C₆H₃? (1,3,5-)[COOCH₂CH₂OCH(CH₃)? I]₃ (9) with zinc iodide as activator in toluene at ?15°C. The number-average molecular weight (M _n) of the polymers increased proportionally to the monomer conversion and further increased upon addition of fresh feed of pMOS to completely polymerized reaction mixtures; the polymers invariably exhibited very narrow molecular-weight distributions (MWD) (M _w/M _n < 1,1). The living polymers were terminated with 2-hydroxyethyl methacrylate to give a tri-armed macromonomer where each arm is capped with a methacrylate group, and the quantitative end-capping, in turn, showed the existence of three living ends per molecule. When the ester-type initiator residue (core) of the poly(pMOS), obtained with the 9 /ZnI₂ system, was hydrolyzed under alkaline conditions, M _n was reduced to one third of the original value, with the narrow MWD being unchanged, thus indicating that the polymer possesses three arms with uniform and controlled length.     

Nitrite‐derived nitric oxide: a possible mediator of ‘acidic–metabolic’ vasodilation

The fundamental, yet poorly understood, physiological mechanism known as ‘acidic–metabolic’ vasodilation, contributes to local blood flow regulation during hypoxia/ischaemia and increased metabolic activity. The vasodilator nitric oxide (NO) has been suggested to be involved in this event. Besides enzymatic production by NO synthases, a novel mechanism for generation of this gas in vivo was recently described. This involves non‐enzymatic reduction of inorganic nitrite to NO, a reaction that takes place predominantly during acidic/reducing conditions. We have studied the effects of physiological amounts of nitrite on NO generation and relaxation of rat aorta in vitro in a situation where environmental pH was reduced to levels seen in tissues during hypoxia/ischaemia. The relaxatory effect of nitrite was increased in an acidic buffer solution (pH 6.6) compared with neutral pH; EC50 for nitrite was reduced from 200 to 40 μM . Nitrite‐evoked relaxation was effectively prevented by coadministration of an inhibitor of soluble guanylyl cyclase. The relaxation was further potentiated by the addition of ascorbic acid. In parallel, NO was generated from nitrite in a pH dependent manner with even larger amounts seen after addition of ascorbic acid. NO generation from nitrite correlated to the the degree of relaxation of rat aorta. These results illustrate non‐enzymatic release of NO from nitrite at physiological concentrations. This may be an important auto‐regulated physiological mechanism involved in the regulation of vascular tone during hypoxia/ischaemia.     

Solid pseudopapillary tumor of the pancreas: ‘Experiences’ and ‘Lessons’ at a tertiary‐care oncology center

Solid pseudopapillary tumor of the pancreas (SPT) is a rare and fascinating entity of elusive histogenesis and unpredictable biology. It has a peculiar proclivity to afflict young females and involve the pancreatic body‐tail region. Cytology diagnosis of these rare neoplasms remains a challenge. We analyzed the cytology features of all SPT cases diagnosed on fine needle aspiration cytology (FNAC) from 2003 to 2009 along with their histopathology slides. Nineteen consecutive cases were diagnosed as SPT on FNAC. Fifteen out of nineteen cases were confirmed as true SPT on histopathology. Amongst the true SPT, all except one occurred in females. Age ranged from 14 to 50 years. Pseudopapillae bearing stout branches terminating in bulbous tips and enclosing transgressing vessels, separated from a collar of tumor cells by a clear zone of myxohyaline coat were pathognomonic of SPT. Singly dispersed monomorphic tumor cells with bland chromatin formed the second diagnostic component of SPT. Nuclear grooves and hyaline globules were in addition helpful in segregating SPT from its close differentials. In four cases diagnosed as SPT on FNAC, histopathology revealed a different final diagnosis (one case each of paraganglioma, extragastrointestinal stromal tumor, metastatic papillary renal cell carcinoma and inflammatory myofibroblastic tumor). Conversely, one case of SPT had been erroneously diagnosed as neuroendocrine tumor on FNAC. Six cases (40%) developed metastasis; commonest site being liver. In conclusion, cytology in conjunction with clinico‐radiologic findings plays a key role in making a correct diagnosis. Awareness of unique cytomorphological features is important in distinguishing this tumor from its diverse mimics. Diagn. Cytopathol. 2013. © 2012 Wiley Periodicals, Inc.     

Locating the ‘Usefully Problematic’ in a Novel and a Memoir by Ian McEwan

This article looks at aspects of a novel and a memoir, written over the same period in 2001, by author Ian McEwan. In ‘Mother tongue’, his memoir, McEwan reflects on his insular upbringing on various military bases abroad. His father, a soldier, was a periodic presence whose volatile moods interrupted the home‐life otherwise exclusively spent with his mother, to whom he was strongly attached. Meanwhile McEwan's novel, Atonement, employs the perspective of an adolescent girl, antagonistic to the link forming in her sister's mind towards someone else. I look at how in the novel this situation leads to a denial of oedipal hierarchy, and ultimately to what Chasseguet–Smirgel terms ‘pseudo‐creative’ solutions. Atonement, however, lays stress on the integrating effect of the creative process itself. In writing the novel in conjunction with the memoir, particularly where one interrupted the other, I speculate that McEwan embarked on a similar process, in which the initial disruption, delivered a gain in perspective, which came to promote further psychic and creative development. I explore this from the Kleinian viewpoint of the here and now, and contrast this with that of Chasseguet–Smirgel, and with the more recursive temporality found within the French tradition.     

Circulatory Effects Evoked by ‘Physiological’ Increases of Arterial Osmolality

The effects of moderate arterial hyperosmolality (+ 20 mOsm/kg H₂O), produced by short term intravenous hypertonic infusion, on vascular resistance in skin, skeletal muscle, intestine, and kidney were analysed in the anesthetized cat. Vascular resistance decreased in all four regions in response to the hypertonicity both before and after regional sympathectomy and the effects were not significantly altered by β-adrcno-ceptor blockade. Arterial blood pressure rose during the hypertonic infusion despite the decreased vascular resistance and an unchanged heart rate, indicating an increased stroke volume and cardiac output. Similar increases of arterial osmolality are known to occur in heavy exercise and in hemorrhage. The present results may therefore suggest that blood borne hyperosmolality is a factor which can contribute to the overall cardiovascular adjustments in these situations.     

Synthesis and characterization of the poly(sulfobetaine)s and the corresponding cationic polymers derived from N,N‐dialkylamino phenyl methacrylamide

Different types of sulfobetaines and their corresponding cationic monomers and polymers derived from N,N‐dialkylamino phenyl methacrylamide have been synthesized for this study. Comparing the chemical shifts in ¹H and ¹³C NMR of the methylene groups in the cationic monomers and betaines reveal that the respective methylene groups are clearly distinguishable from each other. Results obtained from the intrinsic viscosity for zwitterionic poly(DEMAPhAPS) are opposite to that for the corresponding cationic poly(DEMMAPhAMS).     

Identification of Bacillus species from ‘iru’, a fermented African locust bean product

Thirty-seven Bacillus isolates were obtained from fermenting locust bean (‘iru’) from three different locations in Nigeria. The isolates were characterized on the basis of biochemical and physiological tests. Thirty-two of the isolates were identified as B. subtilis, two as B. pumilus and three as B. licheniformis. The Bacillus species were sub-divided into strains. Five different strains of B. subtilis and two of B. pumilus were identified. Biochemical tests showed that the strains differ in starch hydrolysis nitrate reduction and methyl red reaction and in their ability to produce acetylmethylcarbinol. They also vary in their patterns of sugar fermentation. This study shows that various strains or dossibly subspecies of B. subtilis are the major Bacillus species involved in the fermentation of the African locust bean (Parkia biglobosa).     

Stabilization and surface modification of monoclonal antibodies by ‘bi-layer encagement’

A two step simple procedure for antibody stabilization in soluble form was developed. The antibody is first treated with low molecular weight polyaldehyde (polyglutaraldehyde). Following removal of non-bound polyaldehyde the antibody-polyaldehyde conjugate is crosslinked by polyamine (alkyl amine derivative of polyglutaraldehyde). Feasibility studies were successfully conducted employing monoclonal antibody raised against horseradish peroxidase as model system. The stabilized antibody preparation exhibited improved thermal stability, enhanced resistance to proteolytic digestion and higher ‘specific binding activity’ in ELISA test, without losing its capability to bind large antigen (enzyme) or being recognized by another antibody (goat anti-mouse IgG).     

‘Poor me’ versus ‘Bad me’ paranoia: The association between self‐beliefs and the instability of persecutory ideation

Objectives. To investigate whether different self‐attributes would be associated with different degrees of deservedness of persecution in a clinical paranoid sample. Background. Some studies have shown differences between the self‐esteem (SE) of individuals with ‘Poor Me’ (PM) and ‘Bad Me’ (BM) paranoia ( Bentall et al., 2009 ; Chadwick, Trower, Juusti‐Butler, & Maguire, 2005 ). Most studies investigating this relationship have employed a cross‐sectional design, precluding the investigation of changes over time. Methods. In the cross‐sectional part of the study, 45 clinical participants and 25 controls were assessed in terms of paranoia, deservedness of persecution, SE, self‐discrepancies, daily events, and coping strategies. In the longitudinal part of the study, the clinical group was re‐assessed over a period of another 2 days, in order to study changes in these variables. Results. At baseline, there were no differences between the SE of the two paranoia presentations, which was significantly lower than the controls’. However, the paired‐samples repeated analysis found the SE of individuals when in a PM presentation was higher than when they were BM. Only BM paranoia was found to be associated with higher self‐ideal:self‐actual self‐discrepancies than the other groups. The longitudinal analysis indicated that, having been PM and having low SE at the previous assessment day made it more likely that individuals would be in BM subsequently. No differences in causal attributions made for ecological events were found between the groups. Higher SE was found to be more likely when individuals coped with adversities by using social support. Conclusions. Both deservedness of persecution and self‐views appear to be unstable in individuals with paranoia and to change consistently over time, a finding which is in keeping with Bentall et al.'s (2001) dynamic model of paranoia.     

Characterization and Comparison of ‘Standard’ and ‘Young’ Tumour‐Infiltrating Lymphocytes for Adoptive Cell Therapy at a Danish Translational Research Institution

Adoptive cell therapy (ACT) with ex vivo expanded tumour‐infiltrating lymphocytes (TILs) in combination with IL‐2 is an effective treatment for metastatic melanoma. Modified protocols of cell expansion may allow the treatment of most enrolled patients and improve the efficacy of adoptively transferred cells. The aims of this study were to establish and validate the novel ‘Young TIL’ method at our institution and perform a head‐to‐head comparison of clinical‐grade products generated with this protocol opposed to the conventional ‘Standard TIL’, which we are currently using in a pilot ACT trial for patients with melanoma. Our results confirm that ‘Young TILs’ display an earlier differentiation state, with higher CD27 and lower CD56 expression. In addition, CD8⁺ TILs expressing CD27 had longer telomeres compared with the CD27^?. A recently described subset of NK cells, endowed with a high expression of CD56 (CD56^bright), was detected for the first time in both types of cultures but at a higher frequency on Young TILs. Young and Standard TILs’ reactivity against autologous tumours was similar, with significant expression of TNF‐α/IFN‐γ/CD107a by CD8⁺ TILs detected in all cultures analysed. However, either slow expansion with high‐dose IL‐2 only or large numerical expansion with a rapid expansion protocol, which is required for current therapeutic protocols, significantly modified TIL phenotype by reducing the frequency of less differentiated, cancer‐specific TILs. These studies further support the adoption of the Young TIL method in our current ACT trial and highlight the importance of continuous quality control of expansion protocols.     

What Do We Mean by ‘Psychodynamic’? A Contribution to the Development of a Model

I hope to make a preliminary contribution to the development of a model that more clearly reformulates the practices of psychoanalytic psychotherapy in a way that recognizes a diversity of analytic practice that I think has been misdescribed - technically and politically - as 'psychodynamic'. The paper firstly considers the question of definition and suggests four identifiable meanings of the term' psychodynamic'. The discussion then reviews a number of core and inextricably connected questions of theory and practice under the following headings: setting and regression, time and frequency, countertransference, creativity and the real relationship, interpretation and pure technique, and the problem of eclecticism. The paper concludes by briefly exploring the parameters of psychodynamic practice in relation to eclecticism in psychotherapy, and makes a plea for a model that is consistent, authentic and ecumenical.     

Secretion of 3H-acetylcholine from guinea-pig ileum myenteric plexus is enhanced by 8-Br adenosine 3‘,5’-cyclic monophosphate but not changed by 8-Br guanosine 3‘,5’-cyclic monophosphate

The acetylcholine (ACh) stores of cholinergic neurons of the myenteric plexus of guinea-pig ileum were labelled by preincubation with ³H-(methyl)-choline. The secretion of labelled transmitter evoked by electrical field stimulation at 1 Hz in the presence of eserine increased by 55% after addition of 0.5 mM 8-Br adenosine 3‘,5’-cyclic monophosphate (8-Br cAMP). Atropine further enhanced the secretory response, but not more than in the absence of 8-Br cAMP. 8-Br guanosine 3‘,5’-cyclic monophosphate (8-Br cGMP, 0.5 mM) did not change the secretory response to 0.5 or 1 Hz stimulation, either at 1.8 mM or at 0.6 mM calcium, in the absence of eserine. Nor did 1 mM 8-Br cGMP alter the effects of atropine or of oxotremorine. Activation of guanylate cyclase by 0.1 mM N-methyl-N‘-nit-ro-N-nitroso guanidine failed to alter the secretory response to 0.5 Hz stimulation in the absence of eserine, or to influence the depression of the secretion caused by oxotremorine. The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (1 mM) neither altered the secretory response in the presence of eserine, nor the enhancing effect of atropine. The results suggest that cyclic nucleotides are probably not critically involved as “second messengers” in the muscarinic “autoinhibition” of ACh secretion from cholinergic myenteric neurons of guinea-pig ileum.