Systematic investigations on the reactivity of oxazolinium salts

The termination reaction of the cationic polymerization of 2-phenyl- and 2-nonyl-2-oxazolines was examined by reacting the corresponding model oxazolinium salts having tosylate and trifluoromethansulfonate counterions with various nucleophiles. The reaction was monitored by ¹H NMR spectroscopy. Piperidine and KOH react with the oxazolinium salts very fast and quantitatively. In the case of piperidine, the use of a double molar amount of piperidine is necessary to achieve complete conversion. The addition of piperidine, pyridine, 4-dimethylaminopyridine and morpholine takes place in position 5 of the oxazolinium ring, whereas water and KOH add in position 2. The rate of the termination reaction depends on the electron density of the nucleophile which can be correlated with the pK_a value. With CF₃SO as counterion the addition of nucleophiles in position 5 is distinctly faster, whereas the addition of water in position 2 is much slower than with TsO^? as counterion. The ring-opening of the nonyl oxazolinium ion is slower than that of the phenyl oxazolinium ion.     

hSKCa3: no association of the polymorphic CAG repeat with bipolar affective disorder and schizophrenia

hSKCa3 is a neuronal small conductance calcium-activated potassium channel, which contains a polyglutamine tract, encoded by a polymorphic CAG repeat in the gene. Since an association between longer alleles of this CAG repeat and bipolar disorder or schizophrenia has been reported, we genotyped the polymorphic CAG repeat in 91 German family trios of patients with bipolar disorder I and used the transmission disequilibrium test (TDT) to test for association. Applying a dichotomized model (< or = 19 or > 19 CAG triplets), we found no evidence for an association of longer alleles with bipolar disorder (TDT = 0.75, P = 0.386). Regarding the whole range of alleles, there was no preference in transmitting the larger of the two observed alleles from parents to the affected offspring. In parallel we performed an independent case-control study on German patients with bipolar disorder and schizophrenia. Again we did not detect an overrepresentation of longer CAG repeats in patients. Thus, our data do not support the hypothesis that longer CAG repeats in the hSkCa3 gene contribute to the susceptibility for bipolar disorder and schizophrenia.     

The role of IL-1beta in stress-induced sensitization of proinflammatory cytokine and corticosterone responses

Proinflammatory cytokines often sensitize neuronal, hormonal, and behavioral responses to subsequent challenge. Recently, it was observed that exposure to inescapable tailshock enhances peripheral and central proinflammatory cytokine and corticosterone (CORT) responses to subsequent immune challenge up to 4 days later. Thus, we examined the role of central interleukin-1beta (IL-1beta) in stress-induced sensitization of proinflammatory cytokine and CORT responses to a subsequent immune challenge. Rats were administered IL-1 receptor antagonist (IL-1ra) or vehicle into the intra-cisterna magna 1 h prior to tailshock (100, 1.6 mA 5 s shocks) exposure. Twenty-four hours later, rats were challenged i.p. with 10 microg/kg lipopolysaccharide (LPS) and killed 1 h later. IL-1ra had no effect on basal proinflammatory cytokines, but completely blocked the stress-induced enhancement in central and pituitary IL-1beta and plasma IL-6 release following LPS challenge. IL-1ra had no effect on stress-induced enhancement in CORT responses following LPS challenge. Additional rats were administered i.c.v. hrIL-1beta or vehicle and returned to their home cage. Twenty-four hours later, rats were challenged i.p. with either saline or 10 microg/kg LPS and killed 1 h later. Central hrIL-1beta administration significantly elevated central IL-1beta levels and plasma CORT following LPS challenge compared with vehicle-injected controls. These data demonstrate that elevations in central IL-1beta, whether stress-induced or exogenously administered, are sufficient for sensitizing central IL-1beta and CORT responses to subsequent immune challenge. However, during times of stress, exogenous central IL-1ra administration only blocked sensitization of subsequent central IL-1beta responses, not CORT responses, suggesting other factors during the stress response can sensitize CORT responses.     

Phase I testing of a malaria vaccine composed of hepatitis B virus core particles expressing Plasmodium falciparum circumsporozoite epitopes

We report the first phase I trial to assess the safety and immunogenicity of a malaria vaccine candidate, ICC-1132 (Malarivax), composed of a modified hepatitis B virus core protein (HBc) containing minimal epitopes of the Plasmodium falciparum circumsporozoite (CS) protein. When expressed in Escherichia coli, the recombinant ICC-1132 protein forms virus-like particles that were found to be highly immunogenic in preclinical studies of mice and monkeys. Twenty healthy adult volunteers received a 20- or a 50-microg dose of alum-adsorbed ICC-1132 administered intramuscularly at 0, 2, and 6 months. The majority of volunteers in the group receiving the 50-microg dose developed antibodies to CS repeats as well as to HBc. Malaria-specific T cells that secreted gamma interferon were also detected after a single immunization with ICC-1132-alum. These studies support ICC-1132 as a promising malaria vaccine candidate for further clinical testing using more-potent adjuvant formulations and confirm the potential of modified HBc virus-like particles as a delivery platform for vaccines against other human pathogens.     

Contours and distribution of sites that react with antiacetylcholinesterase in chicken intrafusal fibers

Serial cross and longitudinal sections of intrafusal fibers from the intracapsular portions of chicken tibialis anterior muscle spindles were incubated with a monoclonal antibody specific for chicken acetylcholinesterase (AchE) and examined by immunofluorescence for the presence of the enzyme on presynaptic and postsynaptic membranes of neuromuscular junctions. The midequatorial sensory region which lacks organized sarcomeres was negative, but immediately distal to it faintly staining regions of AchE localization were observed on intrafusal fibers. In cross sections at the juxtaequator, the outlines of areas that were positive for AchE were either thin and crescentlike or thick and compact. The distribution of both types of localization continued into the polar region. Toward the more distal polar region, the intensity of sites on the postsynaptic membrane that reacted with the anti-AchE progressively increased. In longitudinal sections, AchE localization was largely limited to two configurations. One was elongate, while the other was more round or oval and often also smaller. Both types might occur on the same, or on different, intrafusal fibers. Examination of silver-impregnated sections revealed the presence of platelike and of traillike axon terminals. The variety of shapes observed on presynaptic and postsynaptic membranes warrants further study to determine whether chicken muscle spindles are innervated by more than one type of motor neuron.     

Fundic gland polyps (Elster's cysts) of the gastric mucosa. A marker for colorectal epithelial neoplasia?

The results of several retrospective studies allow us to conclude that the detection of fundic gland polyps (Elster's cysts) is associated with an increased incidence of colorectal tumors. In this survey, we present the results of a prospective study investigating such a possible relationship. A total of 144 patients were investigated, of whom 80 had fundic gland polyps of the gastric corpus mucosa. Sixty-four of these patients underwent a colonoscopy, whereas the other 64 patients belonged to a sex- and age-matched control group with no fundic gland polyps. In the group with known fundic gland polyps, colorectal neoplasias were found in 29 (45.3%) patients. Eight of these patients had (12.5%) adenocarcinomas, 3 (4.7%) had high-grade intraepithelial neoplasia, and 18 (28.1%) had tubular adenomas. In one patient, a synchronous carcinoma of the rectum and the colon was detected. In comparison, 6 patients of the control group (9.3%) developed tubular adenomas and 9 (14.1%) had hyperplastic polyps of the colonic and rectal mucosa. Our results suggest that it is necessary to conduct a careful diagnostic work-up of the colon in patients with gastric fundic gland polyps.     

Immunohistochemically detectable p53 and mdm-2 oncoprotein expression in colorectal carcinoma: prognostic significance

Aims—To investigate the correlation between the expression of the p53 and mdm-2 oncoproteins and to assess their prognostic value in colorectal cancer.     

Stabile polysauerstoff-radikale. I. Synthese von polymerisationsfähigen monomeren mit sterisch behinderter freier oder geschützter phenolischer hydroxylgruppe

New monomers with sterically hindered free or blocked phenolic hydroxyl groups were used as starting compounds for the preparation of stable oxygen polyradicals. In this paper the synthesis of these monomers is described: 2,6-Di-(tert-butyl)-4-vinylphenol was obtained by decarboxylation of 3-[3,5-di-(tert-butyl)-4-hydroxyphenyl]acrylic acid in yields of 80–;90%. 2,6-Di-(tert-butyl)-4-isopropenylphenol was prepared from 3,5-di-(tert-butyl)-4-hydroxyphenyl methyl ketone and methyl iodide by a GRIGNARD reaction followed by the dehydration of 2-[3,5-di-(tert-butyl)-4-hydroxyphenyl]-2-propanol. 2,6-Di-(tert-butyl)-4-isopropenylphenyl methyl ether was obtained with 64% yield from 3,5-di-(tert-butyl)-4-methoxybenzonitrile by two consecutive GRIGNARD reactions with methyl iodide via the unknown compounds 3,5-di-(tert-butyl)-4-methoxyphenyl methyl ketone and 2-[3,5-di-(tert-butyl)-4-methoxyphenyl]-2-propanol, followed by dehydration of the tertiary alcohol with 89% phosphoric acid.