Study of resonance effects in allenic and related systems

In order to investigate the possibility of resonance effects through a non-coplanar substituted acetylene, synthesis of bis-(2,5,8-trimethyl-l-naphthyl)-acetylene was attempted. Condensation of acetylene with 2,5,8-trimethyl-l-tetralone to yield an acetylenic glycol followed by dehydration and dehydrogenation was expected to yield the desired non-coplanar acetylene. Comparison of its ultraviolet spectrum with that of di-l-naphthyl-acetylene would have suggested the true nature of the acetylene pi cloud. The acetylene condensation was unsuccessful, however. Substituted allenes, which contain one sp hybridized carbon atom, were then successfully synthesized for a similar analysis of potential resonance effects. A series of para-substituted 4-phenyl-2-methylbutadienoic acids were synthesized and their pKa\u27s determined in water solution. The pKa\u27s of the para-methyl, para-chloro and para-hydrogen substituted allenic acids were identical, indicating that resonance effects are not transmitted through the allene function --Abstract, page iii

Distribution of enteric glia and GDNF during gut inflammation

<p>Abstract</p> <p>Background</p> <p>The enteric glia network may be involved in the pathogenesis of inflammatory bowel disease (IBD). Enteric glia cells (EGCs) are the major source of glial-derived neurotrophic factor (GDNF), which regulates apoptosis of enterocytes. The aim of the study was to determine the distribution of EGCs and GDNF during gut inflammation and to elucidate a possible diminished enteric glia network in IBD.</p> <p>Methods</p> <p>The expression of glial fibrillary acidic protein (GFAP) in colonic biopsies of patients with IBD, controls and patients with infectious colitis was detected by immunohistochemistry and Western blot. Tissue GDNF levels were measured by ELISA.</p> <p>Results</p> <p>The expression of GFAP and GDNF in the mucosal plexus is highly increased in the inflamed colon of patients with ulcerative colitis (UC) and infectious colitis. Although the GDNF and GFAP content are increased in Crohn's disease (CD), it is significantly less. Additionally the non-inflamed colon of CD patients showed a reduced GFAP and no GDNF expression compared to controls and the non-inflamed colon of UC patients.</p> <p>Conclusions</p> <p>GFAP and GDNF as signs of activated EGCs are increased in the inflamed mucosa of patients with UC and infectious colitis, which underline an unspecific role of EGC in the regulation of intestinal inflammation. The reduced GFAP and GDNF content in the colon of CD patients suggest a diminished EGC network in this disease. This might be a part of the pathophysiological puzzle of CD.</p

Megaloblastic anaemia, diabetes and deafness in a 2-year-old child

Megaloblastic anaemia in childhood usually occurs as a result of dietary folate deficiency or, rarely, congenital disorders of vitamin B12 metabolism. We present a 2-year-old girl with megaloblastic anaemia and insulin-dependent diabetes mellitus, both of which proved responsive to pharmacological doses of thiamine. She was also found to have sensorineural hearing loss. Also known as Rogers\' syndrome, thiamine-responsive megaloblastic anaemia is the result of inactivating mutations in a gene encoding a thiamine transporter. A clinical diagnosis is supported by characteristic bone marrow findings and can be confirmed by demonstrating apoptosis in skin fibroblasts cultured in thiamine-depleted medium. Where available, DNA sequencing is definitive. There is rapid reticulocytosis after thiamine administration. We recommend a trial of therapy for megaloblastic anaemia not responding to folate and vitamin B12, especially in a deaf and/or diabetic child.Journal of Endocrinology, Metabolism and Diabetes of South Africa Vol. 10(2) 2005: 62-6

Studies of the decays B+→ppˉh+ and observation of B+→Λˉ(1520)p

Dynamics and direct CP violation in three-body charmless decays of charged B mesons to a proton, an antiproton and a light meson (pion or kaon) are studied using data, corresponding to an integrated luminosity of 1.0  fb-1, collected by the LHCb experiment in pp collisions at a center-of-mass energy of 7 TeV. Production spectra are determined as a function of Dalitz-plot and helicity variables. The forward-backward asymmetry of the light meson in the pp- rest frame is measured. No significant CP asymmetry in B+→pp- K+ decay is found in any region of the Dalitz plane. We present the first observation of the decay B+→Λ- (1520)(→K+p- )p near the K+p- threshold and measure B(B+→Λ- (1520)p)=(3.9-0.9+1.0(stat)±0.1(syst)±0.3(BF))×10-7, where BF denotes the uncertainty on secondary branching fractions

Effect of Spatial Inhomogeneities on the Membrane Surface on Receptor Dimerization and Signal Initiation

Important signal transduction pathways originate on the plasma membrane, where microdomains may transiently entrap diffusing receptors. This results in a non-random distribution of receptors even in the resting state, which can be visualized as “clusters” by high resolution imaging methods. Here, we explore how spatial in-homogeneities in the plasma membrane might influence the dimerization and phosphorylation status of ErbB2 and ErbB3, two receptor tyrosine kinases that preferentially heterodimerize and are often co-expressed in cancer. This theoretical study is based upon spatial stochastic simulations of the two-dimensional membrane landscape, where variables include differential distributions and overlap of transient confinement zones (“domains”) for the two receptor species. The in silico model is parameterized and validated using data from single particle tracking experiments. We report key differences in signaling output based on the degree of overlap between domains and the relative retention of receptors in such domains, expressed as escape probability. Results predict that a high overlap of domains, which favors transient co-confinement of both receptor species, will enhance the rate of hetero-interactions. Where domains do not overlap, simulations confirm expectations that homo-interactions are favored. Since ErbB3 is uniquely dependent on ErbB2 interactions for activation of its catalytic activity, variations in domain overlap or escape probability markedly alter the predicted patterns and time course of ErbB3 and ErbB2 phosphorylation. Taken together, these results implicate membrane domain organization as an important modulator of signal initiation, motivating the design of novel experimental approaches to measure these important parameters across a wider range of receptor systems

Does Early Treatment Prevent Deafness in Thiamine-Responsive Megaloblastic Anaemia Syndrome?

Thiamine-responsive megaloblastic anaemia (TRMA; OMIM 249270) syndrome is an autosomal recessive disorder characterized by diabetes mellitus, megaloblastic anaemia, and sensorineural deafness. Progressive hearing loss is one of the cardinal findings of the syndrome and is known to be irreversible. Whether the deafness in TRMA syndrome can be prevented is not yet known. Here, we report a four-month-old female infant diagnosed with TRMA syndrome at an early age. There was no hearing loss at the time of diagnosis. The patient’s initial auditory evoked brainstem response measurements were normal. Although she was given thiamine supplementation regularly following the diagnosis, the patient developed moderate sensorineural hearing loss at 20 months of age, indicating that early diagnosis and treatment with oral thiamine (100 mg/day) could not prevent deafness in TRMA syndrome. It would be premature to draw general conclusions from one case, but we believe that further patient-based observations can shed light on the pathophysiology of this rare syndrome as well as prediction of its prognosis

Colorado Native Plant Society Newsletter, Vol. 5 No. 3, July-September 1981

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1883-84 Xavier University Course Catalog

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