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Biomedical subjects

M Moll

Publications and source records attributed to M Moll.

At least 19 recordsLinked to original sources
PubMed2004

Binding H2, N2, H-, and BH3 to transition-metal sulfur sites: synthesis and properties of [RuL(PR3)(N2Me2S2)] Complexes (L=eta2-H2, H-, BH3; R=Cy, iPr).

The reactions of [Ru(N(2))(PR(3))('N(2)Me(2)S(2)')] ['N(2)Me(2)S(2)'=1,2-ethanediamine-N,N'-dimethyl-N,N'-bis(2-benzenethiolate)(2-)] [1 a (R=iPr), 1 b (R=Cy)] and [micro-N(2)[Ru(N(2))(PiPr(3))('N(2)Me(2)S(2)')](2)] (1 c) with H(2), NaBH(4), and NBu(4)BH(4), intended to reduce the N(2) ligands, led to substitution of N(2) and formation of the new complexes [Ru(H(2))(PR(3))('N(2)Me(2)S(2)')] [2 a (R=iPr), 2 b (R=Cy)], [Ru(BH(3))(PR(3))('N(2)Me(2)S(2)')] [3 a (R=iPr), 3 b (R=Cy)], and [Ru(H)(PR(3))('N(2)Me(2)S(2)')](-) [4 a (R=iPr), 4 b (R=Cy)]. The BH(3) and hydride complexes 3 a, 3 b, 4 a, and 4 b were obtained subsequently by rational synthesis from 1 a or 1 b and BH(3).THF or LiBEt(3)H. The primary step in all reactions probably is the dissociation of N(2) from the N(2) complexes to give coordinatively unsaturated [Ru(PR(3))('N(2)Me(2)S(2)')] fragments that add H(2), BH(4) (-), BH(3), or H(-). All complexes were completely characterized by elemental analysis and common spectroscopic methods. The molecular structures of [Ru(H(2))(PR(3))('N(2)Me(2)S(2)')] [2 a (R=iPr), 2 b (R=Cy)], [Ru(BH(3))(PiPr(3))('N(2)Me(2)S(2)')] (3 a), [Li(THF)(2)][Ru(H)(PiPr(3))('N(2)Me(2)S(2)')] ([Li(THF)(2)]-4 a), and NBu(4)[Ru(H)(PCy(3))('N(2)Me(2)S(2)')] (NBu(4)-4 b) were determined by X-ray crystal structure analysis. Measurements of the NMR relaxation time T(1) corroborated the eta(2) bonding mode of the H(2) ligands in 2 a (T(1)=35 ms) and 2 b (T(1)=21 ms). The H,D coupling constants of the analogous HD complexes HD-2 a ((1)J(H,D)=26.0 Hz) and HD-2 b ((1)J(H,D)=25.9 Hz) enabled calculation of the H--D distances, which agreed with the values found by X-ray crystal structure analysis (2 a: 92 pm (X-ray) versus 98 pm (calculated), 2 b: 99 versus 98 pm). The BH(3) entities in 3 a and 3 b bind to one thiolate donor of the [Ru(PR(3))('N(2)Me(2)S(2)')] fragment and through a B-H-Ru bond to the Ru center. The hydride complex anions 4 a and 4 b are extremely Brønsted basic and are instantaneously protonated to give the eta(2)-H(2) complexes 2 a and 2 b.

Journal Article↗
PubMed2004

The effect of combined thrombolysis with rtPA and tirofiban on ischemic brain lesions.

To determine the effect of systemic thrombolysis with low-dose recombinant tissue plasminogen activator (rtPA) and the body-weight adjusted platelet GPIIb/IIIa receptor antagonist tirofiban, the authors performed lesion volumetry on magnetic resonance perfusion and diffusion images recorded before thrombolysis and on T2-weighted magnetic resonance images on day 8. Treatment with rtPA and tirofiban (n = 13) resulted in a 50% lesion reduction (p < 0.03), while lesion reduction was less in rtPA treatment (n = 16) and absent in nontreated patients (n = 18).

Adult↗
PubMed2004

Binding N2, N2H2, N2H4, and NH3 to transition-metal sulfur sites: modeling potential intermediates of biological N2 fixation.

In the quest for low-molecular-weight metal sulfur complexes that bind nitrogenase-relevant small molecules and can serve as model complexes for nitrogenase, compounds with the [Ru(PiPr(3))('N(2)Me(2)S(2)')] fragment were found ('N(2)Me(2)S(2)'(2-)=1,2-ethanediamine-N,N'-dimethyl-N,N'-bis(2-benzenethiolate)(2-)). This fragment enabled the synthesis of a first series of chiral metal sulfur complexes, [Ru(L)(PiPr(3))('N(2)Me(2)S(2)')] with L=N(2), N(2)H(2), N(2)H(4), and NH(3), that meet the biological constraint of forming under mild conditions. The reaction of [Ru(NCCH(3))(PiPr(3))('N(2)Me(2)S(2)')] (1) with NH(3) gave the ammonia complex [Ru(NH(3))(PiPr(3))('N(2)Me(2)S(2)')] (4), which readily exchanged NH(3) for N(2) to yield the mononuclear dinitrogen complex [Ru(N(2))(PiPr(3))('N(2)Me(2)S(2)')] (2) in almost quantitative yield. Complex 2, obtained by this new efficient synthesis, was the starting material for the synthesis of dinuclear (R,R)- and (S,S)-[micro-N(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] ((R,R)-/(S,S)-3). (Both 2 and 3 have been reported previously.) The as-yet inexplicable behavior of complex 3 to form also the R,S isomer in solution has been revealed by DFT calculations and (2)D NMR spectroscopy studies. The reaction of 1 or 2 with anhydrous hydrazine yielded the hydrazine complex [Ru(N(2)H(4))(PiPr(3))('N(2)Me(2)S(2)')] (6), which is a highly reactive intermediate. Disproportionation of 6 resulted in the formation of mononuclear diazene complexes, the ammonia complex 4, and finally the dinuclear diazene complex [micro-N(2)H(2)[Ru(PiPr(3))('N(2)Me(2)S(2)')](2)] (5). Dinuclear complex 5 could also be obtained directly in an independent synthesis from 1 and N(2)H(2), which was generated in situ by acidolysis of K(2)N(2)(CO(2))(2). Treatment of 6 with CH(2)Cl(2), however, formed a chloromethylated diazene species [[Ru(PiPr(3))('N(2)Me(2)S(2)')]-micro-N(2)H(2)[Ru(Cl)('N(2)Me(2)S(2)CH(2)Cl')]] (9) ('N(2)Me(2)S(2)CH(2)Cl'(2-) =1,2-ethanediamine-N,N'-dimethyl-N-(2-benzenethiolate)(1-)-N'-(2-benzenechloromethylthioether)(1-)]. The molecular structures of 4, 5, and 9 were determined by X-ray crystal structure analysis, and the labile N(2)H(4) complex 6 was characterized by NMR spectroscopy.

Journal Article↗
PubMed2001

A single amino acid change in the cytoplasmic domains of measles virus glycoproteins H and F alters targeting, endocytosis, and cell fusion in polarized Madin-Darby canine kidney cells.

As we have shown previously, release of measles virus (MV) from polarized epithelial cells is not determined by the viral envelope proteins H and F. Although virus budding is restricted to the apical surfaces, both proteins were abundantly expressed on the basolateral surface of Madin-Darby canine kidney cells. In this report, we provide evidence that the basolateral expression of the viral proteins is of biological importance for the MV infection of polarized epithelial cells. We demonstrate that both MV glycoproteins possess a basolateral targeting signal that is dependent upon the unique tyrosine in the cytoplasmic tails. These tyrosines are shown to be also part of an endocytosis signal. In MV-infected cells, internalization of the glycoproteins was not observed, indicating that recognition of the endocytosis signals is disturbed by viral factors. In contrast, basolateral transport was not substantially hindered, resulting in efficient cell-to-cell fusion of polarized Madin-Darby canine kidney cells. Thus, recognition of the signals for endocytosis and polarized transport is differently regulated in infected cells. Mutation of the basolateral sorting signal in one of the MV glycoproteins prevented fusion of polarized cells. These results suggest that basolateral expression of the MV glycoproteins favors virus spread in epithelia.

Amino Acid Sequence↗
PubMed2000

Recombinant measles virus requiring an exogenous protease for activation of infectivity.

Proteolytic cleavage of the fusion protein (F) is an important control mechanism of the biological activity of paramyxoviruses. The sequence R-R-H-K-R(112) at the cleavage site of the F protein of measles virus (MV) was altered by site-directed mutagenesis to R-N-H-N-R(112), which is not recognized by the ubiquitous cellular protease furin. When transiently expressed in cell cultures standard F protein was cleaved, whereas the mutant remained in the uncleaved form. Syncytium formation by the mutant that was analysed after coexpression with haemagglutinin protein depended on the presence of trypsin. Recombinant MV containing the mutation required trypsin activation for fusion and infectivity in cell culture. Intranasal infection of transgenic mice susceptible to MV infection (Ifnar(tm)-CD46Ge) resulted in a moderately productive infection and inflammation of the lung. In contrast to parental virus, intracerebral inoculation did not induce neural disease. The possible effects of the change in cleavage activation on tissue tropism and pathogenicity are discussed.

Amino Acid Sequence↗
PubMed2000

[Ni]

How do [NiFe] hydrogenases activate H(2)? Hydrogenases are key enzymes in the biological hydrogen and energy metabolism; the mechanism of H(2) activation, however, is unclarified. In particular, the oxidation states of the metals involved are discussed controversially. The title complex demonstrates that a distorted diamagnetic Ni(II) center and thiolate donors are sufficient (see picture) to catalyze the key reaction of hydrogenases, the H(2) heterolysis.

Journal Article↗
PubMed1998

Chamber-specific alterations of norepinephrine uptake sites in cardiac hypertrophy.

The present study investigated local differences of sympathetic activation and sympathetic neuroeffector defects in nonhypertrophied right and hypertrophied left ventricles in a rat model with renin-induced pressure overload [TG(mREN2)27]. As judged from the depletion of myocardial norepinephrine stores, sympathetic activation was more pronounced in the left than in the right ventricles. In addition, norepinephrine uptake1 carrier sites were reduced in left but unchanged in right ventricles. Gene expression of the carrier was unchanged in stellate ganglia. An increase of Gialpha expression and a heterologous adenylyl cyclase desensitization occurred only in the left but not in the right ventricles, whereas a reduction of beta-adrenergic receptors was observed in both chambers. We concluded that general sympathetic activation can lead to beta-adrenoceptor downregulation but that pressure overload further increases sympathetic activation involving norepinephrine uptake mechanisms in the left ventricles, resulting in heterologous beta-adrenergic desensitization.

Adenylyl Cyclases↗
PubMed1995

Alterations of cardiac alpha- and beta-adrenoceptors and inotropic responsiveness in hypertensive transgenic rats harbouring the mouse renin gene (TGR(mREN2)27).

In the present study, we investigated the alpha- and beta-adrenoceptor-mediated effects on myocardial force of contraction (using phenylephrine in the presence of propranolol and isoprenaline) and receptor densities (binding studies using [3H]-prazosin and [125I]-iodocyanopindolol) in hypertensive transgenic rats (TGR(mREN2)27) and age-matched Sprague-Dawley rats (SP) as controls. In TGR(mREN2)27 the positive inotropic effects of isoprenaline and phenylephrine were reduced, while the effect of Ca2+ was unchanged. The EC50-values did not differ in both groups. A down-regulation of the beta-adrenoceptors was observed in the hypertrophied left ventricles of transgenic rats, which is postulated to be involved in the reduced beta-adrenoceptor-mediated positive inotropic effect. The alpha-adrenoceptor density was increased, which could represent a compensatory mechanism for the impaired effectiveness of the beta-adrenergic pathway. However, since the effect of alpha-adrenoceptor agonist is not enhanced but even reduced, an uncoupling of alpha-adrenoceptors from post receptor events could play a role in the observed effects.

Animals↗
PubMed1994

Retrograde ureteral intussusception.

A soft tissue mass causing ureteral obstruction should be considered malignant until proved otherwise. We report a case of retrograde ureteral intussusception that caused obstruction. To our knowledge, this condition has not been described in the recent literature.

Female↗
PubMed1994

CD7-negative helper T cells accumulate in inflammatory skin lesions.

Recently, we identified a particular T-cell subset in the peripheral blood of normal individuals that lack CD7 expression. In this study we determined the portion of CD7- T cells in the peripheral blood and skin of patients with various inflammatory skin diseases. We found that skin-infiltrating lymphocytes isolated from different benign and malignant skin lesions (n = 20) contain a high portion of CD7- helper T cells, whereas the number of CD7- T cells in the peripheral blood was not altered compared to healthy controls. Cell activation in vitro did not induce CD7 expression in negative T cells but increased CD7 expression in CD7-positive cells. Thus, lack of CD7 expression seems to be a stable characteristic in a major subset of skin-infiltrating lymphocytes. During long-term culture of CD7- helper T-cell clones derived from a psoriasis skin lesion, no phenotypic change in the CD7 phenotype could be monitored by sequential flow-cytometric analyses. No CD7 mRNA could be detected by Northern blot analysis, indicating transcriptional regulation of CD7 expression. The results show that CD7- T cells accumulate in certain inflammatory skin lesions without alteration of the circulating CD7- population. These cells may be identical to or derived from CD7- T cells of the peripheral blood.

Antigens, CD↗
PubMed1994

Beta-adrenergic neuroeffector mechanisms in cardiac hypertrophy of renin transgenic rats.

We studied neuroeffector defects in hypertrophied myocardium of hypertensive transgenic rats harboring the mouse Ren-2d gene. In transgenic rats, epinephrine and neuropeptide Y concentrations were reduced. A heterologous desensitization of adenylyl cyclase was observed, which was accompanied by a downregulation of beta 1-adrenergic receptors, an increase of inhibitory G protein alpha-subunits, and a mildly depressed catalyst activity of adenylyl cyclase, whereas the bioactivity of stimulatory G protein alpha-subunits and beta 2-adrenergic receptors was unchanged. Desensitization of adenylyl cyclase was accompanied by a reduced positive inotropic response to isoproterenol, whereas the effect of Ca2+ was unchanged. We conclude that sympathetic neuroeffector defects occur in transgenic rats similar to those observed in human failing myocardium. These alterations occur in the stage of hypertrophy and could contribute to contractile dysfunction in later stages.

Adenylyl Cyclases↗
PubMed1993

CD7- T cells represent a subset of normal human blood lymphocytes.

In the peripheral blood of normal adults we identified a subpopulation of mature human T cells that lacks expression of CD7. These CD3+CD7- T cells represent 9% +/- 3.4 SD of PBMC as estimated by analyses of 38 different normal donors. The majority of CD7- T cells express TCR alpha/beta, and are of CD4 helper and CD45RO+CD45RA- "memory" phenotype as determined by three-color fluorescence analysis. We established seven CD4+CD7- T cell clones in vitro from purified CD7- blood T cells and compared these cells to CD4+CD7+ clones. Nonexpression and expression, respectively, of CD7 was a stable feature of all clones during long term culture for more than 6 mo. No CD7 mRNA could be detected by dot blot and Northern blot analysis of purified CD7- T cells and of expanded T cell clones implicating a transcriptional regulation of CD7 Ag expression. Ionomycin/TPA and PHA stimulation were not capable to induce CD7 expression in CD7- cells but up-regulated CD7 expression in CD7+ cells. Whereas CD7- cells of cutaneous T cell lymphoma exhibit a cerebriform nucleus (Sézary cells), no evidence was obtained for cerebriform nuclear morphology in normal CD7- T cells from peripheral blood. We suggest that these CD7- T cells represent a physiologic subset of mature T cells and may be the circulating counterpart of those lymphocytes that are found to be enriched in normal skin and in a variety of benign and malignant skin diseases.

Antigens, CD↗
PubMed1991

Congenital earpits or auricular sinuses.

Congenital earpits or auricular sinuses are defects in the development of the outer ear from the 1st and 2nd branchial arch. They are most often located in front of the ear. Six cases are described. Early surgery is recommended because of a tendency towards infection with scarring. They can be associated with serious internal abnormalities, especially deafness and kidney malformations.

Adolescent↗