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Biomedical subjects

M Schreiber

Publications and source records attributed to M Schreiber.

At least 19 recordsLinked to original sources

Cognitive plasticity in people at risk for dementia: optimising the testing-the-limits-approach.

A topic of great interest in gerontology research is the prediction of cognitive deterioration which marks the transition from mild cognitive impairment (MCI) to dementia. In this area, the term cognitive plasticity can be of great interest. We examined the utility of the Adaptive Figure Series Learning Test (ADAFI) to evoke cognitive plasticity and to show whether reduced plasticity can be found in people with MCI. In a pre-test-intervention-post-test design, intervention with the ADAFI was compared to an unspecific brain jogging task in MCI participants and healthy controls. A total of 42 subjects were included. Independent of mental health status only using the ADAFI led to pronounced improvements in post-test performances, but MCI participants profited less from the intervention with the ADAFI than healthy controls, that is, showed lower cognitive plasticity. Thus, the overlap in performance distributions between healthy participants and MCI individuals at pre-test was reduced at the time of post-test once the ADAFI had been given as intervention. The findings of the present article indicate that plasticity oriented information can be gained when the ADAFI is given as an intervention in a pre-test-training-post-test-design. The cognitive plasticity approach seems potentially useful for purposes of early identification of dementia.

Aged↗

[The lactobacilli-protection system of pregnant women--efficient prevention of premature births by early detection of disturbances].

BACKGROUND: The most frequent cause of preventable early premature births (< 32 + 0 gestational weeks) is urogenital tract infection (UTI). Screening for UTI and Chlamydia are now standard examinations. Detection of ascending genital infections, especially bacterial vaginosis, plays an ever-increasing role. Lactobacilli, which produce, e. g., lactic acid, H2O2, biosurfactants and coaggregation molecules, are particularly important for the vaginal biosystem. Some evaluations suggest that early diagnosis and therapy within this "lactobacilli-protection system" apparently leads to better results in the prevention of prematurity. Our screening recommendations for the pregnant patient comprise vaginal pH measurements both at the regular prenatal care visits and particularly the self measurement within the framework of our Self-Care Program. MATERIALS: 140 participating women were questioned for a second time. The data were compiled by the patients themselves. RESULTS: Due to elevated pH values, 21% of the women consulted their physician earlier than foreseen. Diagnoses: In 46% there was a disturbance of the vaginal milieu, in 4% bacterial vaginosis, in 33% Candida infection and in 21% "everything was OK". In spite of self-measured normal pH values in 25% of the patients the physician diagnosed the following: 25% disturbance of the vaginal milieu, 7% bacterial vaginosis, 32% infection with other bacteria (mainly Streptococci) and 50% Candida infection. CONCLUSION: Elevated pH values (measured by the patient) seem to indicate much more often a disturbance of vaginal milieu rather than an already existing bacterial vaginosis. Further investigations are necessary. The chances to treat vaginal disturbances--before a concrete infection is diagnosed--seem to be better for participants in the Self-Care Program.

Candidiasis, Vulvovaginal↗

Structural effects of an innovative surgical technique to repair heart valve defects.

The structural and functional effects of the "edge-to-edge" technique on the human mitral valve have been investigated, paying particular attention to the diastolic phase. An advanced finite element model of the valve has been developed, using a hyperelastic material schematization, suitable geometry and constraint conditions, and an effective fluidodynamic analysis. The edge-to-edge suture has been applied on this model and the diastolic phase has been simulated. The results of this calculation show that the operation increases the transvalvular pressure and the maximum stress in the leaflets, which reaches a level similar to that of the systolic phase. The influence of suture position and extension, and the mitral annulus dimension has also been investigated. The results indicate that a lateral location of the stitch is better than a central one, both regarding valve functionality (pressure level and mobility) and internal stresses level, that a longer suture worsens the valve functionality but reduces the stresses level, finally, that the dilatation of the mitral annulus does not affect the valve functionality but increases the stresses level.

Cardiac Surgical Procedures↗

Functionally associated molecular genetic marker map construction in perennial ryegrass (Lolium perenne L.).

A molecular marker-based map of perennial ryegrass (Lolium perenne L.) has been constructed through the use of polymorphisms associated with expressed sequence tags (ESTs). A pair-cross between genotypes from a North African ecotype and the cultivar Aurora was used to generate a two-way pseudo-testcross population. A selection of 157 cDNAs assigned to eight different functional categories associated with agronomically important biological processes was used to detect polymorphic EST-RFLP loci in the F(1)(NA(6) x AU(6)) population. A comprehensive set of EST-SSR markers was developed from the analysis of 14,767 unigenes, with 310 primer pairs showing efficient amplification and detecting 113 polymorphic loci. Two parental genetic maps were produced: the NA(6) genetic map contains 88 EST-RFLP and 71 EST-SSR loci with a total map length of 963 cM, while the AU(6) genetic map contains 67 EST-RFLP and 58 EST-SSR loci with a total map length of 757 cM. Bridging loci permitted the alignment of homologous chromosomes between the parental maps, and a sub-set of genomic DNA-derived SSRs was used to relate linkage groups to the perennial ryegrass reference map. Regions of segregation distortion were identified, in some instances in common with other perennial ryegrass maps. The EST-derived marker-based map provides the basis for in silico comparative genetic mapping, as well as the evaluation of co-location between QTLs and functionally associated genetic loci.

Base Sequence↗

Theoretical investigation of excited states of C(3).

In this work, we present ab initio calculations for the potential energy surfaces of C(3) in different electronic configurations, including the singlet ground state [X (1)Sigma(g) (+),((1)A(1))], the triplet ground state [a (3)Pi(u),((3)B(1), (3)A(1))], and some higher excited states. The geometries studied include triangular shapes with two identical bond lengths, but different bond angles between them. For the singlet and triplet ground states in the linear geometry, the total energies resulting from the mixed density functional--Hartree-Fock and quadratic configuration interaction methods reproduce the experimental values, i.e., the triplet occurs 2.1 eV above the singlet. In the geometry of an equilateral triangle, we find a low-lying triplet state with an energy of only 0.8 eV above the energy of the singlet in the linear configuration, so that the triangular geometry yields the lowest excited state of C(3). For the higher excited states up to about 8 eV above the ground state, we apply time-dependent density functional theory. Even though the systematic error produced by this approach is of the order of 0.4 eV, the results give different prospective to insight into the potential energy landscape for higher excitation energies.

Journal Article↗

A microsatellite map of white clover.

The white clover ( Trifolium repens) nuclear genome (n = 2x = 16) is an important yet under-characterised genetic environment. We have developed simple sequence repeat (SSR) genetic markers for the white clover genome by mining an expressed sequence tag (EST) database and by isolation from enriched genomic libraries. A total of 2,086 EST-derived SSRs (EST-SSRs) were identified among 26,480 database accessions. Evaluation of 792 EST-SSR primer pairs resulted in 566 usable EST-SSRs. Of these, 335 polymorphic EST-SSRs, used in concert with 30 genomic SSRs, detected 493 loci in the white clover genome using 92 F1 progeny from a pair cross between two highly heterozygous genotypes--364/7 and 6525/5. Map length, as estimated using the joinmap algorithm, was 1,144 cM and spanned all 16 homologues. The R (red leaf) locus was mapped to linkage group B1 and is tightly linked to the microsatellite locus prs318c. The eight homoeologous pairs of linkage groups within the white clover genome were identified using 96 homoeologous loci. Segregation distortion was detected in four areas (groups A1, D1, D2 and H2). Marker locus density varied among and within linkage groups. This is the first time EST-SSRs have been used to build a whole-genome functional map and to describe subgenome organisation in an allopolyploid species, and T. repens is the only Trifolieae species to date to be mapped exclusively with SSRs. This gene-based microsatellite map will enable the resolution of quantitative traits into Mendelian characters, the characterisation of syntenic relationships with other genomes and acceleration of white clover improvement programmes.

Chromosome Mapping↗

Antitumour effect of cyclin-dependent kinase inhibitors (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)) on malignant glioma cells.

Cyclin-dependent kinase inhibitors (CDKIs) are considered as novel anticancer agents because of their ability to induce growth arrest or apoptosis in tumour cells. It has not yet been fully determined, however, which CDKI is the best candidate for the treatment of malignant gliomas and whether normal brain tissues are affected by CDKI expression. Using recombinant adenoviral vectors that express CDKIs (p16(INK4A), p18(INK4C), p19(INK4D), p21(WAF1/CIP1) and p27(KIP1)), we compared the antitumour effect of CDKIs on malignant glioma cell lines (A172, GB-1, T98G, U87-MG, U251-MG and U373-MG). p27(KIP1) showed higher ability to suppress the growth of all tumour cells tested than other CDKIs. Interestingly, overexpression of p27(KIP1) induced autophagic cell death, but not apoptosis in tumour cells. On the other hand, p27(KIP1) overexpression did not inhibit the viability of cultured astrocytes (RNB) nor induced autophagy. Overall, our findings suggest that gene transfer of p27(KIP1) may be a promising approach for the therapy of malignant gliomas.

Antineoplastic Agents↗

Sevoflurane versus isoflurane--anaesthesia for lower abdominal surgery. Effects on perioperative glucose metabolism.

BACKGROUND: The aim of this study was to determine the impact of sevoflurane anaesthesia on metabolic and endocrine responses to lower abdominal surgery. METHODS: A prospective randomized controlled study in 20 patients undergoing abdominal hysterectomy. Patients were randomly assigned to receive either sevoflurane (S) or isoflurane anaesthesia (I). Using a stable isotope dilution technique, endogenous glucose production (EGP) and plasma glucose clearance (GC) were determined pre- and postoperatively (6,6-2H2-glucose). Plasma concentrations of glucose, insulin, cortisol, epinephrine and norepinephrine were measured preoperatively, 5 min after induction of anaesthesia, during surgery and 2 h after the operation. RESULTS: EGP increased in both groups with no intergroup differences (preop. S 12.2 +/- 1.6, I 12.4 +/- 1.6; postop. S 16.3 +/- 1.9*, I 19.0 +/- 3.1* micromol kg(-1) min(-1), all values are means +/- SD, *P < 0.05 vs. preop.). Plasma glucose concentration increased and GC decreased in both groups. There were no differences between groups. (Glucose conc. mmol l(-1) preop.: S 4.1 +/- 0.3, I 3.9 +/- 0.5; 5 AI S 5.1 +/- 0.6*, I 5.1 +/- 1.0*, postop. S 7.0 +/- 1.0*, I 7.1 +/- 1.4*; * = P < 0.05 vs. preop.; GC ml kg(-1)min(-1) preop. S 3.0 +/- 0.4, I 3.2 +/- 0.4; postop. S 2.4 +/- 0.3*, I 2.7 +/- 0.3*; *=P < 0.05 vs. preop.) Insulin plasma concentrations were unchanged. Cortisol plasma concentrations increased intra- and postoperatively with no changes between the groups. Norepinephrine plasma concentration increased in the S group after induction of anaesthesia. I group norepinephrine was increased 2 h after operation and showed no intergroup differences. CONCLUSION: Sevoflurane, as well as isoflurane, does not prevent the metabolic endocrine responses to surgery.

Abdomen↗

Long-term results of Rehbein's procedure: a retrospective study in German-speaking countries.

AIM: In contrast to other countries, no collective study of Rehbein's procedure in German-speaking nations has been performed. Therefore, our intention was, analogously to Goto and Ikeda's (10) Japanese study in 1984, Kleinhaus's (13) study on Swenson's procedure in 1979, Bourdelat's (2) French-Canadian investigation into Duhamel's technique in 1997 and Martuciello's (11) and Teitelbaum's (16) follow-up in the year 2000, to perform a follow-up study of Rehbein's technique of deep anterior resection. METHODS: The data of 200 patients from 22 German-speaking centers in Switzerland, Austria and Germany were collected. These data were gathered by questionnaire and the children were followed up in the individual participating hospitals for at least 3.5 years after the procedure. The procedure was performed between 1993 and 1997, over a 5-year period. The questionnaire contained 74 items including anamnestic data, diagnostic postoperative treatment and reoperations. RESULTS: Concerning the incidence of anastomotic leaks and resolving anastomotic strictures there was no significant difference between the results in our series and those of the collective analyses made by Hofmann von Kap-herr (7), Holschneider (9) and Sherman (18). In 6.6 % of the 191 patients an anastomotic leak and in 9.9 % a rectal stricture, which had to be dilated, was observed. Concerning late complications, 22.8 % of the children suffered from constipation, 4.3 % from encopresis, 10.6 % from enterocolitis and only 0.5 % from enuresis. The frequency of constipation diminishes over the years. A comparison of the different large series in the literature clearly shows that the incidence of constipation is higher after Rehbein's procedure and the frequency of urinary incontinence and encopresis higher following Swenson's, Soave's and Duhamel's techniques. The incidence of enterocolitis is less after Rehbein's procedure than after Swenson's, Soave's and Duhamel's techniques. CONCLUSIONS: The different results in the literature are due to the individual experience of the author, the very different follow-up methods and the date of follow-up. Therefore, the different results are hard to compare with our study. Nevertheless, Rehbein's anterior resection still could be presented as an adequate and important method to treat Hirschsprung's disease.

Austria↗

Within-gene interaction between c.135 G/A genotypes and RET proto-oncogene germline mutations in HSCR families.

Hirschsprung disease (HSCR) is considered a model for a complex inheritance disorder. Several genes, including the major HSCR-susceptibility RET proto-oncogene, play an aetiological role in the development of HSCR. Genetic linkage analysis in familial HSCR with both long- and short-segment phenotypes has demonstrated a tight linkage to the RET locus, while the phenotype within a HSCR family is characterised by an incomplete penetrance or a variable extension of the aganglionosis. Therefore, additional genetic alterations of RET are postulated in the aetiology or modification of the HSCR phenotype. In this study, the coding region of all 21 exons of the RET proto-oncogene, including the flanking intronic sequences, were investigated by direct DNA sequencing in a HSCR population. We genotyped the c.135 G/A polymorphism and resolved haplotypes comprising the mutation locus and the c.135 G/A polymorphism. Twenty different mutations were detected in 18 of 76 HSCR patients. In ten families the mutations were inherited from the parents, while only four patients had a positive family history for the disease. Moreover, in all ten families an incomplete penetrance of the HSCR phenotype was observed. We have investigated the effect of the non-mutated wild-type allele as well as the c.135 G/A polymorphism on the phenotype within the HSCR families. Our findings support the notion that both RET alleles are involved in the pathogenesis of a subgroup of HSCR patients in a dose-dependent fashion. Additionally, we have shown a modifying effect of the c.135 G/A polymorphism on the HSCR phenotype within HSCR families.

Alleles↗

Interleukin-1 system and sex steroid receptor gene expression in human endometrial cancer.

OBJECTIVES: The interleukin-1 system is known to play a pivotal role in human physiology and reproduction. In the cycling endometrium, interleukin-1alpha activity is controlled by sex steroids and is confined to the perimenstrual phase, where it is involved in the events leading to tissue lysis and menstruation. Since local tissue degradation is also a feature of malignant tumors, our goal was to analyze the gene expression of interleukin-1alpha and other interleukin-1 family members and compare it with estrogen receptor alpha, estrogen receptor beta, and progesterone receptor mRNA expression in 27 endometrial carcinomas and 13 normal endometria. METHODS: Endometrial tumor tissues were obtained during hysterectomy for endometrial cancer, and normal endometrium was sampled in women undergoing surgical procedures for nonendometrial pathologies. Gene expression was analyzed by reverse transcription polymerase chain reaction. Protein expression was detected and localized by immunohistochemical staining. RESULTS: A strong gene expression of interleukin-1 type I receptor, estrogen recptor alpha, and progesterone receptor was detected in all tumor tissues and in the majority of benign endometrial tissues. However, in contrast to nonmalignant endometria, variable amounts of interleukin-1beta and interleukin-1 receptor antagonist mRNA were also detected in most of the tumor samples. Gene expression of interleukin-1alpha and estrogen receptor beta was considerably less frequent, with interleukin-1alpha being absent in all peri- and postmenopausal endometria and in all but one of the well-differentiated tumors. With decreasing differentiation interleukin-1alpha gene expression became more frequent. In these cases, interleukin-1alpha protein was detected predominantly in epithelial tumor cells of lower-grade tumors. CONCLUSION: We have demonstrated the presence of the interleukin-1 system in endometrial malignancies, and found a negative correlation between interleukin-1alpha and tumor differentiation. We hypothesize that the nonphysiological expression of interleukin-1alpha in less differentiated tumors might contribute to their invasiveness and malignant behavior.

Carcinoma, Endometrioid↗

Advanced proximal colon cancer.

BACKGROUND: Two recent studies have documented that sigmoidoscopy as a screening tool for colorectal cancers may miss advanced proximal colonic neoplasms. The purpose of this study was to assess the prevalence of distal synchronous lesions in patients with proximal colon cancer. We sought to determine if screening sigmoidoscopy would have missed these proximal colon cancers. METHODS: Data were collected on all patients (n = 305) diagnosed with colorectal cancer over a 6-year period. Patients were stratified by age, sex, tumor location, presenting complaint, AJCC stage, and TNM classification. The colonoscopy results of patients diagnosed with proximal colon cancer were analyzed to determine the incidence of synchronous distal colon lesions. RESULTS: Proximal colon cancer was diagnosed in 88 patients (29%). Of those studied, 45 (54%) did not have synchronous distal lesions detected by colonoscopy. The patients with proximal colon cancer were elderly (mean age 67), had advanced tumor size [59 patients (67%) T3/T4], and had advanced AJCC stages [37 patients (42%) stage III/IV]. Nearly all patients [84 (95%)] with proximal colon cancer were symptomatic. CONCLUSION: In this study, the majority of patients with proximal colon cancer did not have a synchronous lesion in the distal colon. Current screening methods for colon cancer based on sigmoidoscopy would not have identified these proximal lesions. These findings support the incorporation of screening colonoscopy in protocols designed to identify early colon cancer.

Aged↗

Highly functionalized dimeric tetraethynylethenes and expanded radialenes: strong evidence for macrocyclic cross-conjugation.

A selection of dimeric tetraethynylethenes (TEEs) and perethynylated expanded radialenes, containing different donor/acceptor substitution patterns, have been prepared and fully characterized. The first X-ray crystal structure of an expanded [6]radialene, with twelve peripheral 3,5-di(tert-butyl)phenyl substituents, is presented. This macrocycle, the all-carbon core of which is isomeric with fullerene C60, adopts a non-planar, "chair-like" conformation. Also a TEE dimer, carrying N,N-dimethylaniline donor substituents, has been subjected to an X-ray crystallographic analysis. The electronic properties were studied by UV/Vis spectroscopy and electrochemistry, providing fundamental insight into mechanisms of pi-electron delocalization in the acyclic and macrocyclic chromophores. Donor or donor-acceptor-substituted dimeric TEE derivatives show very strong absorptions extending over the entire UV/Vis region; their longest wavelength absorption bands have high charge-transfer character. Macrocyclic cross-conjugation in the expanded radialenes becomes increasingly efficient with increasing donor-acceptor polarization. A dual, strongly solvent-polarity-dependent fluorescence was observed for a tetrakis(N,N-dimethylaniline)-substituted dimeric TEE; this interesting emission behavior is explained by the twisted intramolecular charge-transfer (TICT) state model. Donor-substituted expanded radialenes display huge resonance-enhanced third-order nonlinear optical coefficients.

Journal Article↗

Embryonic lethality and fetal liver apoptosis in mice lacking the c-raf-1 gene.

The Raf kinases play a key role in relaying signals elicited by mitogens or oncogenes. Here, we report that c-raf-1(-/-) embryos are growth retarded and die at midgestation with anomalies in the placenta and in the fetal liver. Although hepatoblast proliferation does not appear to be impaired, c-raf-1(-/-) fetal livers are hypocellular and contain numerous apoptotic cells. Similarly, the poor proliferation of Raf-1(-/-) fibroblasts and hematopoietic cells cultivated in vitro is due to an increase in the apoptotic index of these cultures rather than to a cell cycle defect. Furthermore, Raf-1- deficient fibroblasts are more sensitive than wild- type cells to specific apoptotic stimuli, such as actinomycin D or Fas activation, but not to tumor necrosis factor-alpha. MEK/ERK activation is normal in Raf-1-deficient cells and embryos, and is probably mediated by B-RAF. These results indicate that the essential function of Raf-1 is to counteract apoptosis rather than to promote proliferation, and that effectors distinct from the MEK/ERK cascade must mediate the anti-apoptotic function of Raf-1.

Animals↗

Protective role of Raf-1 in Salmonella-induced macrophage apoptosis.

Invasive Salmonella induces macrophage apoptosis via the activation of caspase-1 by the bacterial protein SipB. Here we show that infection of macrophages with Salmonella causes the activation and degradation of Raf-1, an important intermediate in macrophage proliferation and activation. Raf-1 degradation is SipB- and caspase-1-dependent, and is prevented by proteasome inhibitors. To study the functional significance of Raf-1 in this process, the c-raf-1 gene was inactivated by Cre-loxP-mediated recombination in vivo. Macrophages lacking c-raf-1 are hypersensitive towards pathogen-induced apoptosis. Surprisingly, activation of the antiapoptotic mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and nuclear factor kappaB pathways is normal in Raf-1-deficient macrophages, and mitochondrial fragility is not increased. Instead, pathogen-mediated activation of caspase-1 is enhanced selectively, implying that Raf-1 antagonizes stimulus-induced caspase-1 activation and apoptosis.

Animals↗

Ab initio (CASPT2) excited state calculations, including circular dichroism, of helically twisted cyanine dyes.

Ab initio calculations at the CASSCF/CASPT2 level were performed on helically twisted mono-, tri-, and pentamethine cyanine dyes in the all-Z-configurations. Excitation energies and oscillator and rotatory strengths were calculated for the five lowest energy singlet states. Both the long wavelength methine band and the cis-band could be identified unambiguously from their configurational parentage. The calculated state energies are within 0.09 eV of the experimental value for the methine band and within 0.16 eV for the cis-band. The calculated rotatory strengths of the methine band shows sign inversion as the length of the chromophore increases: negative for the short monomethine, strongly positive for the pentamethine. The trimethine presents a borderline case: the measured rotatory strength is almost nil, the calculated one depends on the geometry. There is good agreement between rotatory strengths calculated in the velocity and in the length formalism.

Journal Article↗