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Biomedical subjects

M Albrecht

Publications and source records attributed to M Albrecht.

At least 37 records · Page 2Linked to original sources
PubMed2001

Multiple use of soluble metallodendritic materials as catalysts and dyes.

Different sizes of core-functionalized metallodendritic wedges were prepared by anchoring sensor-active arylplatinum(II) sites at the focal point of Fréchet-type polyether dendritic wedges of various generations. The strong color of these metallodendrimers in the presence of SO2 was used to assess the permeability of nanofiltration membranes (molecular weight cut-off of 400 dalton) at ambient pressure. A primary result of these studies is that dendrimers do not have to be exceptionally large for successful retention. Hence, nanofiltration, membrane-capped. immersion vials were developed, which operate as sensor devices when loaded with metallodendrimers with good retention properties. Appropriate substitution of the dye site at the focal point of these metallodendritic wedges by a catalytically active group afforded dendritic catalysts that exhibit essentially the same physical properties (shape, retention) as the corresponding dyefunctionalized dendritic wedges. When this homogeneous catalyst is compartmentalized in membrane-capped vials, a unique and convenient method for its retrieval from product solutions is available. Moreover, such immobilized metallodendritic catalysts can be regenerated and stored for months without losing their activity; this provides access for the development of novel sustainable homogeneous catalysts.

Journal Article↗
PubMed2001

Identification and characterization of neutral endopeptidase (EC 3. 4. 24. 11) from human prostasomes--localization in prostatic tissue and cell lines.

BACKGROUND: An antibody directed against a 100 kDa protein was immunoselected from a polyvalent antiserum against human prostasomes. The antibody as well as biochemical characteristics of the respective antigen were used to study the structural relationship of the latter with prostate membrane specific antigen (PMSA), another 100 kDa membrane protein of the prostate. METHODS: The isolated purified 100 kDa protein was characterized by tryptic degradation, aminoacid-sequencing and mass spectroscopy peptide-fingerprinting as well as mono-saccharide analysis and lectin binding and identified as a prostasomal neutral endopeptidase (NEP, EC 3.4.24.11). Immunohistochemistry, immunoelectron microscopy, in situ hybridization, and RT-PCR were performed to analyze the expression and distribution of the protein in normal and malignant human prostatic tissues and cell lines. RESULTS: Prostatic NEP, which has no relationship with PMSA, is a glycosylated, integral membrane protein type II. The prevalent glycosyl residues are NeuNAc, GlcNAc, GalNAc, Gal, Man, Fuc. NEP-mRNA is expressed in human prostatic epithelial and some stromal cells. NEP-immunoreactivity is strong in normal prostatic epithelium and confined to the apical plasma membrane. During apocrine secretion, the enzyme is released from the secretory cells, contributing to the formation of prostasomes. In prostate cancer specimens, immunoreactivity of apical plasma membranes is lost, while generalized cytoplasmic immunoreactivity develops. CONCLUSIONS: Prostatic secretory cells contain a membrane-bound, highly glycosylated neutral endopeptidase which is restricted to the apical plasma membrane. The enzyme is released from the cells in an apocrine fashion and contributes to the formation of prostasomes. In prostate cancer cells a preferential cytoplasmic localization is observed, pointing to alterations in intracellular targeting.

Amino Acid Sequence↗
PubMed2001

Virologic and CD4 cell response to zidovudine or zidovudine and lamivudine following didanosine treatment of human immunodeficiency virus infection.

To optimize nucleoside reverse transcriptase inhibitor (nRTI) antiretroviral therapy, 137 subjects who had been treated with didanosine monotherapy for more than 3 years in the AIDS Clinical Trials Group (ACTG) 175 study were randomized to zidovudine and didanosine (dual therapy) or zidovudine, didanosine, and lamivudine (triple therapy). Evaluation of early (8 week) change in HIV plasma RNA demonstrated that addition of lamivudine and zidovudine provided significantly greater virologic suppression compared to the addition of zidovudine alone (mean decrease of 1.27 vs. 0.74 log(10) copies/ml, n = 108, p = 0.007). Both dual and triple therapy provided significant long-term decreases (from study entry to mean at Weeks 40 and 48) in HIV plasma RNA: 0.62 and 0.86 log(10) copies/ml, respectively (n = 110). However, the difference between treatments was not significant (p = 0.16). At 48 weeks, 26% of subjects starting study treatment had <500 copies/ml of plasma HIV RNA. The CD4 count response was greater at 4 weeks for triple versus dual therapy: a mean increase of 51 vs. 12 CD4 cells/ml(3) (n = 126, p = 0.039). The difference at Weeks 40 and 48 was not significant (a 22 cell increase vs. a 1 cell decrease, n = 129, p = 0.41). Zidovudine and didanosine treatment, with or without lamivudine, was well tolerated and only 2 of 137 (1.5%) of study participants developed an AIDS-defining event over 48 weeks.

Adult↗
PubMed2001

Effects of inhalation of perfluorocarbon aerosol on oxygenation and pulmonary function compared to PGI2 inhalation in a sheep model of oleic acid-induced lung injury.

OBJECTIVE: To evaluate the effects of PFC aerosol compared to PGI2 aerosol and NaCl aerosol on gas exchange and lung mechanics in oleic acid-induced acute lung injury. DESIGN: A prospective, controlled, randomised, in vivo animal laboratory study. SETTING: Research laboratory at an university hospital. SUBJECTS: Twenty one (n = 21) adult sheep of either gender weighing 26.8+/-6.4 kg. INTERVENTIONS: The animals were randomised to three groups: PFC aerosol (perfluorooctane), PFC group; prostacyclin aerosol (Flolan), PGI2 group; and NaCl aerosol (0.9% sodium chloride solution), control group. After induction of anaesthesia and placement of vascular catheters, lung injury was induced with 0.12 ml x kg(-1) oleic acid. Aerosols were continuously administered for 2 h using a jet nebuliser. Gas exchange, pulmonary mechanic, and haemodynamic parameters were obtained at regular intervals. MEASUREMENTS AND MAIN RESULTS: PFC aerosol increased oxygenation (PaO2) 15 min after the initiation of treatment up to 120 min (P < 0.05). Transpulmonary shunt improved in the PFC group (P < 0.05) while it did not change in the two other groups. PFC aerosol reduced maximum airway pressure (Pmax) (median) significantly from (median) 38 mbar to 32 mbar (P < 0.05). Static compliance improved significantly in the PFC group (P < 0.05). CONCLUSION: The inhalation of a PFC aerosol led to a significant improvement in pulmonary mechanics and gas exchange, which was not observed in the other two groups. These data suggest that a small dose of perfluorocarbon will have beneficial effects on gas exchange and respiratory mechanics. Therefore, the non-invasive aerosol application technique seems to be a reasonable alternative to administer perfluorocarbons in severe lung injury.

Aerosols↗
PubMed2001

Dysfunction of vasomotor reactivity in severe sepsis and septic shock.

OBJECTIVE: Perfusion abnormalities are an overall phenomenon in severe sepsis and septic shock, leading to organ dysfunction. We investigated whether carbon dioxide (CO2)-induced vasomotor reactivity (VMR) is impaired in septic patients, compared with values obtained outside sepsis. DESIGN: Prospective, clinical study. SETTING: Six-bed neurologic critical care unit of a university hospital. PATIENTS AND PARTICIPANTS: Eight consecutive patients with severe sepsis and septic shock. MEASUREMENTS AND RESULTS: CO2-reactivity was measured during and outside a period of severe sepsis or septic shock according to ACCP/SCCM criteria by means of transcranial Doppler sonography and near-infrared spectroscopy (NIRS). VMR was calculated as the percentage change of cerebral blood flow velocity (normalized CO2-reactivity, NCR) and absolute changes in concentration of oxygenated hemoglobin, deoxygenated hemoglobin, total hemoglobin (HbO2, Hb, HbT) and Hbdiff (difference between HbO2 and Hb) in micromol/l per 1% increase in end-tidal CO2 (CR-HbO2, CR-Hb, CR-HbT, CR-Hbdiff). NCR and NIRS-reactivities were significantly reduced during severe sepsis and septic shock compared with values outside sepsis (mean, SD, Wilcoxon): NCR 11.0 (7.1) versus 30.7 (13.0), p < 0.02; CR-HbO2 0.70 (0.61) versus 2.33 (1.11), p < 0.02; CR-Hb -0.17 (0.74) versus -1.42 (1.28), p < 0.04; CR-HbT 0.53 (0.48) versus 1.05 (0.40), p < 0.03; CR-Hbdiff 0.91 (1.33) versus 3.75 (2.33), p < 0.02. This indicates a severely disturbed VMR. CONCLUSIONS: In the advent of a disturbed cerebral autoregulation, critical drops in blood pressure during sepsis are transferred directly into the vascular bed, leading to cerebral hypoperfusion. This mechanism might contribute to the pathogenesis of septic encephalopathy.

Aged↗
PubMed2001

The fat redistribution syndrome in patients infected with HIV: measurements of body shape abnormalities.

OBJECTIVE: To describe the body shape changes in the syndrome of fat redistribution or lipodystrophy seen in patients infected with HIV. DESIGN: An objective description of patients with HIV with fat redistribution syndrome. Body-height, weight, shape, and composition were measured by anthropometrics and biolectrical impedance analysis by a single observer. Clinical data were collected by chart review. SUBJECTS/SETTING: Thirty-nine patients with HIV receiving primary HIV care at a university hospital-affiliated infectious disease clinic who presented with complaints of body shape changes or who were referred by their primary care providers for body shape changes. ANALYSIS: Descriptive statistics were performed. RESULTS: Four of the 39 patients (10%) had not used protease inhibitor therapy. HIV status (by clinical presentation, CD4 and VL) varied widely. Laboratory abnormalities were moderate. Percent body fat differed widely when measured by bioelectrical impedance analysis and anthropometry (23% vs 13%). The mean body mass index was 25.6 kg/m2 for men and 25.8 kg/m2 for women. The mean waist/hip ratio was above normal, at 1.02. The mean mid-arm circumference and triceps skinfolds were below national standards for both men (30.4 cm and 8.1 mm, respectively) and women (26.7 cm and 7.5 mm, respectively). Nine patients (23%) had an increased dorso-cervical pad. Seventeen patients returned for follow-up measurements at 3 months; no significant differences were found between baseline and follow-up measurements. CONCLUSIONS: The waist/hip ratio, mid-arm and mid-thigh circumference, and triceps skinfolds were useful measures to define and follow the fat redistribution syndrome in patients with HIV. These body composition changes were not transitory in this short follow-up period.

Adipose Tissue↗
PubMed2001

Assessment of fibronectin as a potential new clinical tool in andrology.

In this prospective clinical study, 892 patients with normal and impaired semen were examined in order to investigate the correlation between the concentration of fibronectin in seminal plasma and the motility of spermatozoa. The fibronectin concentration in seminal plasma, total sperm motility and linear sperm motility were measured. We report here a significant negative correlation between the fibronectin concentration in seminal plasma and total sperm motility (r=-0.3474). There was no link between varicocele and vasectomy, or between varicocele and variation in the concentration of fibronectin. It is concluded that higher concentrations of the acute-phase protein fibronectin may be a cause of severe reduction in sperm motility. The investigation of fibronectin concentrations in seminal fluid could be a new and helpful clinical tool in the assessment of male fertility.

Adolescent↗
PubMed2001

Expression of a ketolase gene mediates the synthesis of canthaxanthin in Synechococcus leading to tolerance against photoinhibition, pigment degradation and UV-B sensitivity of photosynthesis.

The potential of ketocarotenoids to protect the photosynthetic apparatus from damage caused by excess light and UV-B radiation was assessed. Therefore, the cyanobacterium Synechococcus was transformed with a foreign beta-carotene ketolase gene under a strong promoter leading to the accumulation of canthaxanthin. This diketo carotenoid is absent in the original strain. Most of the newly formed canthaxanthin was located in the thylakoid membranes. The endogenous beta-carotene hydroxylase was unable to interact with the ketolase. Therefore, only traces of astaxanthin were found. The transformant was treated with strong light (500 or 1200 mumol m-2 s-1) and with UV-B radiation. In contrast to a nontransformed strain the overall photosynthesis, measured as oxygen evolution, was protected from inhibition by light of 500 mumol m-2 s-1 and UV-B radiation of 6.8 W m-2. Furthermore, degradation in the light of chlorophyll and carotenoids at an irradiance of 1200 mumol m-2 s-1, which was substantial in the nontransformed control, was prevented. These results indicate that in situ canthaxanthin, which is formed at the expense of zeaxanthin and replaces this hydroxy carotenoid within the photosynthetic apparatus, is a better protectant against solar radiation. These findings are discussed on the basis of the in vitro properties such as inactivating peroxyl radicals, quenching of singlet oxygen and oxidation stability of these different carotenoid structures.

Bacterial Proteins↗
PubMed2000

Ferromagnetic hcp chromium in Cr/Ru(0001) superlattices.

We report the first observation of a weak ferromagnetic state of Cr in Cr/Ru(0001) superlattices, based on magnetic hysteresis and corroborated by x-ray magnetic circular dichroism at the CrL(2,3) edges. In situ reflection high-energy electron diffraction, x-ray diffraction, and Cr K-edge polarized x-ray absorption investigations have shown that the Cr layers thinner than 8 angstroms adopt a slightly distorted hcp structure, accompanied by a large atomic volume expansion of up to 14% compared to the bcc packing volume. The expanded hcp structure clearly induces the observed ferromagnetism, in agreement with theory.

Journal Article↗
PubMed2000

New peptide labels containing covalently bonded platinum(II) centers as diagnostic biomarkers and biosensors.

[reaction: see text] Water- and acid-resistant arylplatinum(II) complexes have been covalently bonded to the N-terminus of L-valine, thus providing organometallic biomolecules with excellent stability properties. Owing to the (195)Pt nucleus (I = (1)/(2)), these building blocks are potentially versatile biomarkers (e.g., MRI). Moreover, they display efficient in vitro biosensor characteristics since they detect SO(2) gas selectively and fully reversibly by an instantaneous change of the spectroscopic properties including a diagnostic (195)Pt NMR signal.

Biomarkers↗
PubMed2000

Crucial role of Cu-S bonding for structural changes accompanying the reversible CuI/CuII transition in an unrestrained Cu(N[symbol: see text]S)2 coordination arrangement. An experimental and DFT study.

The structure of reversibly oxidizable [Cu(mmb)2](BF4) with 1-methyl-2-(methylthiomethyl)-1H-benzimidazole (mmb) as bidentate N,S-donor ligand has been determined and compared with that of the copper(II) species [Cu(mmb)2(eta 1-ClO4)](ClO4). In the complex ions of the equilibrium [CuI(mmb)2](+) + ClO4- reversible e- + [CuII(mmb)2-(eta 1-ClO4)]+ the almost linear N-Cu-N backbone is invariant whereas the bonds to the thioether sulfur centers and especially the changing S-Cu-S angle (145.18(5) degrees for the CuII species, 109.33(3) degrees for the CuI form) reflect the metal oxidation state. In contrast to the perchlorate coordinating copper(II) species, [CuI(mmb)2](BF4) contains a cation with a very large vacant site at the metal center, resulting in elliptical channels within the crystal. DFT calculations on [CuI(mb)2]+, [CuII(mb)2]2+, and [CuII(mb)2(OClO3)]+ with mb = 2-methylthiomethyl-1H-benzimidazole confirm the essential role of the metal-sulfur bonds in responding to the reversible CuI/II electron transfer process, even in the absence of electronically stronger interacting thiolate sulfur centers or sophisticated oligodentate ligands.

Journal Article↗
PubMed2000

How do they know? Influencing the relative stereochemistry of the complex units of dinuclear triple-stranded helicate-type complexes

Dinuclear triple-stranded helicates or meso-helicates are formed by self-assembly of linear ligand strands with appropriate metal ions. Very often this self-assembly proceeds with high diastereoselectivity leading either to the helicate or the meso-helicate. The stereoselectivity of the self-assembly process can be influenced by different factors such as the rigidity of the ligand (-->helicate), the number of methylene units in the alkyl spacers (even number of CH2 units --> helicate; odd number --> meso-helicate), template effects, or chiral substituents.

Journal Article↗
PubMed2000

Organoplatinum crystals for gas-triggered switches

Considerable effort is being devoted to the fabrication of nanoscale devices. Molecular machines, motors and switches have been made, generally operating in solution, but for most device applications (such as electronics and opto-electronics), a maximal degree of order and regularity is required. Crystalline materials would be excellent systems for these purposes, as crystals comprise a vast number of self-assembled molecules, with a perfectly ordered three-dimensional structure. In non-porous crystals, however, the molecules are densely packed and any change in them (due, for example, to a reaction) is likely to destroy the crystal and its properties. Here we report the controlled and fully reversible crystalline-state reaction of gaseous SO2 with non-porous crystalline materials consisting of organoplatinum molecules. This process, including repetitive expansion-reduction sequences (on gas uptake and release) of the crystal lattice, modifies the structures of these molecules without affecting their crystallinity. The process is based on the incorporation of SO2 into the colourless crystals and its subsequent liberation from the orange adducts by reversible bond formation and cleavage. We therefore expect that these crystalline materials will find applications for gas storage devices and as opto-electronic switches.

Journal Article↗
PubMed2000

Virologic and CD4+ cell responses to new nucleoside regimens: switching to stavudine or adding lamivudine after prolonged zidovudine treatment of human immunodeficiency virus infection. ACTG 302 Study Team. AIDS Clinical Trials Group.

Clinical benefit of zidovudine alone in the treatment of HIV infection wanes after several years, with decreasing CD4+ cell numbers and increasing HIV RNA in plasma. To develop treatment strategies following prolonged zidovudine treatment, 92 subjects from the AIDS Clinical Trials Group (ACTG) 175 study after a median of 3.6 years of zidovudine monotherapy were randomized to treatment with stavudine or zidovudine and lamivudine. Evaluation of long-term changes, the average of 40- and 48-week HIV plasma RNA, demonstrated that lamivudine and zidovudine provided significantly greater virologic suppression compared with stavudine (mean decrease 0.70 versus 0.18 1og10 copies/ml,p = 0.003). Twenty-nine percent of zidovudine plus lamivudine recipients had HIV RNA levels below 500 copies per milliliter at 48 weeks as compared with 4% of stavudine recipients (p = 0.02). Both regimens significantly increased CD4+ cell numbers, the means of weeks 40 and 48 rose to 49 and 36 CD4+ cells per cubic millimeter among zidovudine plus lamivudine and stavudine recipients, respectively. Treatments were well tolerated and only 3 of 92 subjects died or developed AIDS within 48 weeks. In zidovudine-experienced subjects, addition of lamivudine resulted in significantly decreased plasma HIV RNA levels at 48 weeks compared with treatment with stavudine alone.

Adult↗
PubMed2000

Diagnostic organometallic and metallodendritic materials for SO2 gas detection: reversible binding of sulfur dioxide to arylplatinum(II) complexes

A series of square-planar platinum(II) complexes of the N,C,N'-terdentate-coordinating monoanionic "pincer" ligand, [PtX(4-E-2,6-[CH2NRR']2-C6H2](X=Cl, Br, I, tolyl; R, R'=Et, Me; E=H, OH, OSiMe2tBu) has been prepared. In the presence of sulfur dioxide, these complexes spontaneously adsorb this gas to form penta-coordinated adducts. Solid-state crystal-structure analyses of the SO2 adducts 8c (X=I, R=R=Me, E=OSiMe2tBu) and 11 (X=Cl, R=R'=Me, E=OH) show a square-pyramidal geometry around the metal center with SO2 in the apical position. Most interestingly. the adduct 11 forms similar Pt-Cl... H-O hydrogen-bonded alpha-type networks as the corresponding SO2-free complex 5. The conservation of the supramolecular information (hydrogen-bonded self-assembly) throughout a reaction (SO2 adsorption) is unprecedented in crystal engineering. Adduct formation in the solid state or in solution is fast and reversible and is indicated by a characteristic color change of the material from colorless to bright orange. Since facile methods have been developed to remove SO2 from the adducts and to regenerate the square-planar starting complexes, these complexes fulfill several essential prerequisites of sensor materials for repeated diagnostic SO2 detection. The platinum sensors have been found to be highly selective for sulfur dioxide and particularly sensitive for submilimolar to molar gas quantities. Their response capacity is tuneable by electronic and steric modifications of the ligand array by introduction of, for example, different substituents on the nitrogen donors. The periphery of dendrimers is shown to be an appropriate macromolecular support for anchoring the detection-active sites, thus allowing full recovery of the sensor materials for repeated use. By using this concept, metallo-dendrimers 3 and 15 have been prepared. Owing to the dendritic connectivity, these sensors are suitable for repetitive qualitative and quantitative detection of small amounts of SO2.

Journal Article↗
PubMed2000

Cell lineage characteristics of human prostatic stromal cells cultured in vitro.

BACKGROUND: An in vitro model of prostatic stromal cells suitable for experimental studies of the pathogenesis of BPH is still lacking. We therefore standardized the isolation, cultivation, and characterization of human prostatic stromal cell lineages. METHODS: Stromal cells were isolated from a surgical specimen of BPH. Using antibodies specific for either epithelial or stromal cells of the human prostate, the isolated cells were morphologically and immunohistochemically characterized. Viability and functional activity were assessed by proliferation assays and stimulation experiments. Gene expression was monitored by RT-PCR. RESULTS: In early passages (P8), cells showed a high purity (>/=98%) for stromal markers; about 60% displayed the characteristics of fibroblasts, and the remaining 40% were classified as smooth muscle cells. In late passages (P20), the proportion of muscle cells declined to 10%. Stimulation experiments including basic fibroblast growth factor (bFGF) resulted in enhanced proliferation, whereas dihydrotestosterone (DHT), estrogen, and flutamide did not influence proliferation. Gene expression studies demonstrated a positive signal for androgen receptor and keratinocyte growth factor (KGF). CONCLUSIONS: Prostatic stromal cells can be propagated several times and show karyotypic stability for up to 18 subculture experiments. The ratio of myoid and fibroblastic cells can be used for standardization of cell cultures with stable characteristics.

Cell Division↗
PubMed2000

Novel hydroxycarotenoids with improved antioxidative properties produced by gene combination in Escherichia coli.

We have used combinatorial biosynthesis to synthesize novel lipophilic carotenoids that are powerful cellular antioxidants. By co-expressing three different carotenoid desaturases in combination with a carotenoid hydratase, a cyclase, and a hydroxylase on compatible plasmids in Escherichia coli, we synthesized four novel carotenoids not previously detected in biological material or chemically synthesized. Their identification was based on their relative retention times on HPLC, spectroscopic properties, molecular weights, number of hydroxy groups, and 1H-NMR spectra. The carotenoids were designated as 1-HO-3', 4'-didehydrolycopene, 3, 1'-(HO)2-gamma-carotene, 1,1'-(HO)2-3, 4, 3', 4'-tetradehydrolycopene, and 1, 1'-(HO)2-3, 4-didehydrolycopene. These novel acyclic derivatives differ from structurally related compounds by extension of the conjugated polyene chain as well as additional hydroxy groups at position C-1'. We determined their antioxidative activity in a liposome-membrane model system, which showed that their ability to protect against photooxidation and radical-mediated peroxidation reactions was linked to the length of the conjugated double-bond system and the presence of a single hydroxy group. The protection of membrane degradation was superior to the related 1-HO and 1, 1'-(HO)2 lycopene derivatives, making them interesting pharmaceutical candidates.

Antioxidants↗