Browsing by Author "Mueller, I."

2,5-Bis(di-tert-butylfluorosilyl)furan reacts with potassium hydroxide in a 1:2 molar ratio to give 2,5-bis(di-tert-butylhydroxysilyl)furan, O(CRCH)(2) [R = SiOH(CMe3)(2) (1)], Compound I is very selective in its adduct formation and forms host-guest complexes in the presence of KF [1.1/2KF (2)], H2O [1.H2O (3)], NH3 [MeNH3 (4)] and MeNH2 [1.2MeNH(2) (5)], The host-guest complexes are stable at room temperature. Compound 4 is the first neutral ammonia cage that is stable up to 100 degreesC. The crystal structures of 2, 3, 4 and 5 have been determined.

The purpose of this randomized trial was to evaluate the efficacy of combination chemoimmunotherapy compared with chemotherapy alone. A total of 124 patients were randomized to receive intravenous cisplatin (35 mg m(-2), days 1-3), carmustine (150 mg m-2, day 1, cycles 1 and 3 only), dacarbacine (220 mg m-2, days 1-3) and oral tamoxifen (20 mg m-2, daily) in combination with (n=64) or without (n=60) sequential subcutaneous IL-2 and IFN-alpha. In those patients who received sequential immunothenapy, each cycle of chemotherapy was followed by outpatient s.c. IL-2 (10x 10(6) IU m(-2), days 3-5, week 4; 5 x 10(6) IU m(-2), days 1, 3, 5, week 5) and s.c. IFN-alpha (5 x 10(6) IU m(-2), day 1, week 4; days 1, 3, 5, week 5). The overall response rate of patients treated with the combination of chemotherapy and IL-2/IFN-a was 34.3% with seven complete responses (10.9%) and 15 partial responses (23.4%). In patients treated with chemotherapy, only, the overall response rate was 29.9% with eight complete responses (13.3%) and 10 partial responses (16.6%). There was no significant difference in median progression free survival (0 months vs 4 months) and in median overall survival (12 months vs 13 months) for combined chemoimmunotherapy and for chemotherapy, respectively. (C) 2002 The Cancer Research Campaign.

1-Fluorodimethylsilyl-2,2,4,4,6,6-hexamethylcyclotrisilazane reacts with n-BuLi to give the 1-fluorodimethylsilyl-3-lithi- um-2,2,4,4,6,6-hexamethylcyclotrisilazane (1). Starting with F2B-N(CHMe2)(2) and 1 1-diisopropylamino-fluoroboryl-3-fluorodimethylsilyl- and 1,3-bis(diisopropylamino-fluoroboryl)-5-fluorodimethylsilyl-2,2,4,4,6,6-hexamethylcyclotrisilazanes 2 und 3 are formed. 1,3-Bis- and 1,3,5-tris(diisopropylamino-fluoroboryl)2,2,4,4,6,6 -hexamethylcyclotrisilazanes 4 and 5 are the products from F2BN(CHMe2)2 and di- or trilithiated (Me2Si-NH)(3). The dilithium salt of the eight-membered ring (Me2Si-NH)4 reacts with F2B-NR,R'(6: R,R' = CHMe2,7: R = Me, R' = 2,6-C6H3 (CHMe2)(2)) with retention of the ring size to give 1,5-bis(amino-fluoroboryl)-2,2,4,4,6,6,8,8-octamethylcyclotetrasilazanes 6 and 7. Coupling of cyclosilazanes and borazines occurs in the reaction of lithiated cyclotrisilazane and (FB-NR)(3) in a molar ratio 1:1 (8, 9), 2:1 (11, 12), 3:1 (13) and 1:3 (14); Me2Si(NH-SiMe2)(2)N-B(NR-BF)(2)NR (8, 9); [Me2Si(NH-SiMe2)(2)N](2)(BNR)(2)BFNR (11, 12); [Me2Si(NH-SiMe2)(2)N](3)(BNR)(3) (13); (Me2Si-N)(3) (B(NR-BF)(2)NR)(3) (14); (R = Me: 8, 11, 13); (R = Et: 9, 12, 14); 8 reacts with n-BuLi under substitution of the fluorine by n-C4H9 (10). The isomerization of the cyclotri- to the cyclodisilazane in the reaction of the dilithiated (Si-N)(3) ring with 2 (Me3CN-BF)(3) has kinetical reasons. Me3CN(BF-NCMe3)(2)B-NHSiMe2-(N-SiMe2)(2)- B(CMe3N-BF)(2)NCMe3 (15) is formed. Mono- and dilithiated (Me2Si-NH)(4) reacts with (FB-NEt)(3) in a molar ratio 1:1 and 1:2 to give the exptected mono- and disubstituted cyclotetrasilazanes, the isomeric cyclodisilazane, [Me3CN(BF-NCMe3)(2)B-NHSiMe2-N-SiMe2](2) (18) is obtained in the reaction with (Me3CN-BF)(3) in a molar ratio 1:2. Lithium-bis(trimethylsilyl)amide substitutes successively at the (FB-NEt)(3) one or two fluorine atoms. EtN(BF-NEt)(2)B-N(SiMe3)(2) (19) and FB(NEt-B)(2)[N(SiMe3)(2)](2)NEt (20) are formed. 20 reacts with (Me3Si)(2)NH to give Me3SiF and bis(3,5-bis(bis(trimethylsilyl)amino-2,4,6-triethyl)borazinyl)amine (21); [EtN(B-N(SiMe3)(2)NEt)(2)B](2)NH. The crystal structures of 1, 3, 6, 12 - 15, 18 and 21 are reported.

In the following article similarities and differences concerning the treatment of sex offenders in the psychiatric forensic commitment (A A 63 German penal code) and of persons with a self-reported sexual interest in children, who were diagnosed and treated in the outpatient prevention of sexual abuse (PSM) in Gottingen are demonstrated. Diagnostic and therapeutic characteristics of outpatient prevention as well as the initial results of the evaluation of the Gottingen therapy manual are presented and differentiated from the normal treatment program in psychiatric forensic commitment.

Perinatal hypoxia is known to induce long-lasting changes in the central dopaminergic system. In order to understand the cellular mechanism of these changes, we studied the effects of hypoxia on the levels of dopamine (DA) and tyrosine hydroxylase (TH) mRNA in untreated and NGF treated PC12 cells. On the second day after plating (DAP), cells were exposed to a hypoxic episode (pO(2) = 10-20 mm Hg, 24 h), and the levels of DA and TH mRNA were examined on DAP 4 and DAP 8. In untreated cells, hypoxia induced a two fold increase both in DA and TH mRNA levels on DAP 4 which normalized up to DAP 8. This increase correlated with an activation of the hypoxia inducible factor (HIF-1alpha), measured with a reporter gene. In contrast, NGF treated cells responded to hypoxia with an increase of DA level on DAP 8. In these cells neither an increase of the HIF-1 alpha activity measured immediately after hypoxia nor a significant increase of the TH mRNA level on DAP 8 were found. The findings indicate that NGF shifts the hypoxia induced changes of DA levels from a short-term to a long-term mode. The long-term increase of dopamine levels is the most likely result of changes connected with cell growth and differentiation and not the result of a long-term TH mRNA level increase. (C) 2000 Elsevier Science Inc. All rights reserved.

The first enantioselective syntheses of the Ipecacuanha alkaloid emetine (1) and the Alangium alkaloid tubulosine (2) is described employing a domino Knoevenagel/hetero-Diels-Alder reaction and an enantioselective catalytic transfer hydrogenation of imines as key steps. Thus, hydrogenation of the imine 15 with the catalyst (R,R)-16 gives the tetrahydroisoquinoline 14 with 95% ee which was transformed into the aldehyde (1S)-7. The three-component domino reaction of (1S)-7 with 6 and 8 led to 19, which in a second domino process was treated with K2CO3 in methanol followed by a hydrogenation to give the benzoquinolizidine 4 together with the diastereomers 22 and 23 in a overall yield of 66%. Further transformation of 4 with the amines 3 and 5 yielded enantiopure emetine (1) and tubulosine (2), respectively. In addition, starting from 19 the novel benzoquinolizidine alkaloid 34 was synthesised; this compound resembles the vallesiachotamine alkaloid dihydroantirhin 31, which has not been isolated so far but probably must also exist in nature.

Renal elimination of drugs bound to plasma proteins is mediated mainly by tubular secretion. Furosemide, a frequently used diuretic, is tightly bound to plasma proteins and is believed to be secreted. It contains a carboxyl group and a sulfamoyl moiety and may therefore be a substrate for the sodium-dependent dicarboxylate cotransporter from human kidney (hNaDC-3). Furosemide, besides inhibiting [C-14]succinate uptake, reduced succinate-associated currents in a dose-dependent manner with an IC50 of 2.2 mM. Furosemide showed sodium-dependent inward currents as evidence for its translocation by hNaDC-3. The concentrations necessary to affect hNaDC-3, however, are far higher than the therapeutically relevant plasma concentrations of furosemide. This implies that dicarboxylate uptake necessary for drug excretion via organic anion/dicarboxylate exchange will not be altered by therapeutical doses of furosemide.

Cetoniacytone A (1) and some related minor. components (2, 6, 7) were produced by Actinomyces sp. (strain Lu 9419), which was isolated from the intestines of a rose chafer (Cetonia aureata). The structures of the novel metabolites were established by detailed spectroscopic analysis. The absolute configuration of 1 was determined by X-ray analysis and derivatisation with chiral acids. 1 exhibits a significant cytotoxicity against selected tumor cell lines. The biosynthesis of 1 was studied by feeding C-13 labelled precursors. The results suggest that the characteristic p-C7N skeleton of the aminocarba sugar is formed via the pentose phosphate pathway by cyclisation of a heptulose phosphate intermediate.

The reaction of the beta -diketoiminate lithium complex (dipp)NacNacLi . OEt2 ((dipp)NacNac = 2-((2,6-diisopropylphenyl)amino) -4- ((2,6-diisopropylphenyl)imino) -pent-2-enyl) with iPrMgCl and MgI2 yield the corresponding (dipp)NacNacMgiPr degrees OEt2 (1) and (dipp)NacNacMgI . OEt2 (2). The reaction of 2 with NaBH4 in diethylether gives (dipp)NacNacMg(mu -H)(3)BH . OEt2 (3). The core element of compounds 1-3 is a six-membered ring formed by N(1)-C(1)-C(2)-C(3)-N(2) and magnesium. The structures of 1 and 2 show the beta -diketoiminate backbone in a boat-conformation with the tetrahedrally coordinated metal center at the prow and the opposing carbon atom at the stern. The magnesium atom in 3 is octahedrally coordinated and out of the beta -diketoiminate plane.

We have focused on the synthesis of monomeric, functionalized starting materials containing manganese(II), zinc(II), and cadmium(II) by taking advantage of the sterically demanding and chelating property of the substituted vinamidine ligand 2-[(2,6-diisopropylphenyl) amino]-4-[ (2,6-diisopropylphenyl) imino]pent-2-ene (NacNacH). Metal iodine derivatives containing vinamidines as the bulky ligand can be regarded as interesting precursors for preparing complexes with low-valent metal centers by reduction as long as they are free of coordinated ether. The vinamidine complexes NacNacM(mu -I)(2)Li(OEt2)(2) [M = Mn (3), Zn (4), Cd (5)] are obtained from the corresponding vinamidine lithium complex and MI, (M = Mn, Zn, Cd) in good yields. A crystal structure analysis of 3, 4, and 5 shows them to be isostructural. All three structures have the vinamidine backbone in a boat conformation with the tetrahedrally coordinated metal center at the prow and the opposing carbon atom at the stern.

We have determined the sequence of a 4-Mb interval on rat chromosome 20p12 that encompasses the rat major histocompatibility complex (MHC). This is the first report of a finished sequence for a segment of the rat genome and constitutes one of the largest contiguous sequences thus far for rodent genomes in general. The rat MHC is, next to the human MHC, the second mammalian MHC sequenced to completion. Our analysis has resulted in the identification of at least 220 genes located within the sequenced interval. Although gene content and order are well conserved in the class II and class III gene intervals as well as the framework gene regions, profound rat-specific features were encountered within the class I gene regions, in comparison to human and mouse. Class I region-associated differences were found both at the structural level, the number, and organization of class I genes and gene families, and, in a more global context, in the way that evolution worked to shape the present-day rat MHC.

The textbook "Human heredity and Racial Hygiene" by Erwin Baur, Eugen Fischer, and Fritz Lenz went through five editions between 1921 and 1940. In contemporary journals, it received almost only positive review articles and was considered to be the standard textbook on racial hygiene in the Weimar Republic. After Hitler's takeover in 1933, it became the "scientific" basis for eugenic sterilization programs. In that year, the Nazis enacted a law allowing the involuntary sterilization of persons with diseases thought to be hereditary, mostly neurological and psychiatric disorders. Using review articles on the book, the position of neurologists and psychiatrists towards racial hygiene is analyzed. We describe how they prepared and maintained the acceptance of eugenic politics in the medical profession by praising the standard work on racial hygiene.