Long-term maintenance of hematopoietic stem cells does not require contact with embryo-derived stromal cells in cocultures

We recently established that two midgestation-derived stromal clones--UG26-1B6, urogenital ridge-derived, and EL08-1D2, embryonic liver-derived--support the maintenance of murine adult bone marrow and human cord blood hematopoietic repopulating stem cells (HSCs). In this study, we investigate whether direct HSC-stroma contact is required for this stem cell maintenance. Adult bone marrow ckit+ Ly-6C- side population (K6-SP) cells and stromal cells were cocultured under contact or noncontact conditions. These experiments showed that HSCs were maintained for at least 4 weeks in culture and that direct contact between HSCs and stromal cells was not required. To find out which factors might be involved in HSC maintenance, we compared the gene expression profile of EL08-1D2 and UG26-1B6 with four HSC-nonsupportive clones. We found that EL08-1D2 and UG26-1B6 both expressed 21 genes at a higher level, including the putative secreted factors fibroblast growth factor-7, insulin-like growth factor-binding proteins 3 and 4, pleiotrophin, pentaxin-related, and thrombospondin 2, whereas 11 genes, including GPX-3 and HSP27, were expressed at a lower level. In summary, we show for the first time long-term maintenance of adult bone marrow HSCs in stroma noncontact cultures and identify some secreted molecules that may be involved in this support.     

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.     

Association analysis of a polymorphism in the G‐protein stimulatory α subunit in patients with major depression*

Growing evidence suggests that G‐proteins may be involved in pathogenesis and treatment of affective disorders. Several studies have reported altered levels and/or activities of stimulatory G‐proteins in depression. The aim of this study was to investigate whether a polymorphism in the stimulatory α subunit of G‐proteins (T/C point mutation in exon 5; ATT → ATC at codon 131) is associated with major depression or response to antidepressant treatment. Therefore, we performed a case‐control association study with 212 depressive patients and 137 healthy, unrelated controls. There was no evidence for an association between the investigated polymorphism in the Gα_s gene and major depression, as well as to treatment response. The results of our study are in concordance with recently published findings which do not support the hypothesis that the gene for the stimulatory α subunit of G‐proteins is a major susceptibility factor in the pathophysiology of major depression. © 2002 Wiley‐Liss, Inc.     

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.     

Current Biotechnological Approaches to the Prevention of Restenosis

No systemic pharmacological treatment has been convincingly shown to reduce the incidence of restenosis after angioplasty in patients. The lack of success of many pharmaceutical agents in reducing restenosis rates post-angioplasty and following stent implantation, as documented in dozens of clinical trials, has encouraged the development of new biotechnological approaches to the treatment of restenosis. Gene therapy and other agents, including antibodies, fusion toxins and ribozymes, have the potential to prevent some of the sequelae after arterial injury, particularly cell proliferation. Mechanical methods of preventing restenosis, for example sophisticated local drug delivery strategies and biodegradable stents using new materials, in combination with novel therapeutic agents or radiation, may also be of use.     

The relevance of categorical and dimensional classification systems for the comparability of patient samples in psychopharmacological research of depression

Operational diagnoses of endogenous depression have gained special importance for psychopharmacological research. The high reliability of operationally defined diagnoses is a prerequisite for sampling comparable patient group. The simultaneous application of competing categorical diagnostic system ("polydiagnosis") allows us to determine whether differences in research findings are due to differences in patient samplings. Furthermore, a dimensional classification of patients by means of a newly developed polydiagnostic scale (so called OPD scale) allows us to compare the diagnostic homogeneity of patient groups diagnosed as endogenous depression cases and to select extreme groups with high diagnostic homogeneity for comparing the distribution of variables under research in patients with endogenous and nonendogenous depression.