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Biomedical subjects

R Winter

Publications and source records attributed to R Winter.

At least 37 records · Page 2Linked to original sources

Characterization of the temperature- and pressure-induced inverse and reentrant transition of the minimum elastin-like polypeptide GVG(VPGVG) by DSC, PPC, CD, and FT-IR spectroscopy.

We investigated the temperature- and pressure-dependent structure and phase behavior of a solvated oligopeptide, GVG(VPGVG), which serves as a minimalistic elastin-like model system, over a large region of the thermodynamic phase field, ranging from 2 to 120 degrees C and from ambient pressure up to approximately 10 kbar, applying various spectroscopic (CD, FT-IR) and thermodynamic (DSC, PPC) measurements. We find that this octapeptide behaves as a two-state system which undergoes the well-known inverse-temperature folding transition occurring at T approximately 36 degrees C, and, in addition, a slow trend reversal at higher temperatures, finally leading to a reentrant unfolding close to the boiling point of water. Furthermore, the pressure-dependence of the folding/unfolding transition was studied to yield a more complete picture of the p, T-stability diagram of the system. A molecular-level picture of these processes, in particular on the role of water for the folding and unfolding events of the peptide, presented with the help of molecular-dynamics simulations, is presented in a companion article in this issue.

Biomimetic Materials↗

Macrophage specificity of three anti-CD68 monoclonal antibodies (KP1, EBM11, and PGM1) widely used for immunohistochemistry and flow cytometry.

OBJECTIVES: To investigate the specificity of three anti-CD68 monoclonal antibodies (mAbs) for macrophages (Mphi) in immunohistochemistry (IHC) and flow cytometry (FACS). METHODS: IHC was performed on cryostat sections of rheumatoid arthritis (RA) and osteoarthritis (OA) synovial membranes using the anti-CD68 mAbs KP1, EBM11, and PGM1, and the fibroblast (FB) markers CD90 and prolyl 4-hydroxylase. Expression of CD68 was also analysed by FACS on the monocytic cell lines THP-1 and U937, as well as on synovial fibroblasts (SFB), skin FB, and gingival FB (both surface and intracellular staining). RESULTS: In IHC, there was an overlap between CD68 (mAbs KP1 and EBM11) and the FB markers CD90/prolyl 4-hydroxylase in the lining layer, diffuse infiltrates, and stroma of RA and OA synovial membranes. In FACS analysis of THP-1 and U937 cells, the percentage of cells positive for the anti-CD68 mAbs KP1 and EBM11 progressively increased from surface staining of unfixed cells, to surface staining of pre-fixed cells, to intracellular staining of the cells. Upon intracellular FACS of different FB, nearly all cells were positive for KP1 and EBM11, but only a small percentage for PGM1. In surface staining FACS, a small percentage of FB were positive for all three anti-CD68 mAbs. CONCLUSION: An overlap between CD68 (mAbs KP1 or EBM11) and the FB markers CD90 or prolyl 4-hydroxylase may prevent unequivocal identification of Mphi in synovial tissue by IHC or in monocytic cells and FB upon intracellular FACS. This may be due to sharing of common markers by completely different cell lineages.

Aged↗

Microarray based comparative genomic hybridisation (array-CGH) detects submicroscopic chromosomal deletions and duplications in patients with learning disability/mental retardation and dysmorphic features.

The underlying causes of learning disability and dysmorphic features in many patients remain unidentified despite extensive investigation. Routine karyotype analysis is not sensitive enough to detect subtle chromosome rearrangements (less than 5 Mb). The presence of subtle DNA copy number changes was investigated by array-CGH in 50 patients with learning disability and dysmorphism, employing a DNA microarray constructed from large insert clones spaced at approximately 1 Mb intervals across the genome. Twelve copy number abnormalities were identified in 12 patients (24% of the total): seven deletions (six apparently de novo and one inherited from a phenotypically normal parent) and five duplications (one de novo and four inherited from phenotypically normal parents). Altered segments ranged in size from those involving a single clone to regions as large as 14 Mb. No recurrent deletion or duplication was identified within this cohort of patients. On the basis of these results, we anticipate that array-CGH will become a routine method of genome-wide screening for imbalanced rearrangements in children with learning disability.

Adolescent↗

[Preterm labour and risk factors].

Infections, stress and haemorrhages are risk factors in the pathophysiology of preterm delivery. Genital infections can be diagnosed and treated, and thus the frequency of preterm labour is lowered. How psychosocial burdens which are also stress factors can be influenced remains uncertain.

Adult↗

[Must the postgraduate medical training for specialists of gynecology and obstetrics be reconsidered?].

Our specialty is based on a 3-pillared concept. The professional political development again requires a discussion on the separation of 'nonoperating' and 'operating' specialists. In addition, the future model of the 'gynecologist as family doctor for women' becomes an interesting topic. The guidelines for the proceedings in the case of suspect and positive cytological smears of the cervix have been revised with regard to the Bethesda nomenclature and will be published this year.

Clinical Competence↗

[Contraception and proception--competence of the gynaecologist in the planning of a woman's life].

Contra- and proception provoke different answers in our country and culture than globally speaking, particularly regarding non-industrialized nations. Contraception should be viewed as a means of preventive medicine, especially as a means of avoiding the psychosocial emergency of an unwanted pregnancy and potentially subsequent pregnancy termination. In this light, contraceptive counselling to teenagers is of particular importance. Reliable contraception does not cause a change of morals but supports and facilitates lifestyle and provides security. This aspect interacts closely with social and family politics. The integration of contraception into a woman's concept of life is decidedly dependent on these circumstances. The gynaecologist is a participant in the development of this concept, particularly for women who initially practice contraception, often in pursuit of a professional career, and later--often too late or perhaps never--bear an only child with maximal intention or potentially even after assisted reproductive medical intervention. The initially desired infertility frequently turns into the unfulfilled desire to bear children. The issues at hand are innovative social and sexual pedagogics that eliminate the separation between career and family. In the awareness of this pedagogic task, gynaecologists participate in the design of a woman's life concept as well as in the demographic change of society.

Abortion, Induced↗

[Wound rupture after Misgav-Ladach cesarean section: a case report].

INTRODUCTION: We describe a patient with wound rupture and burst abdomen after cesarean section with the Misgav-Ladach technique. CASE REPORT: A 33-year-old woman underwent primary cesarean section at 36 + 5 weeks gestation for a fetal indication. The procedure was done according to the Misgav-Ladach technique, i.e. the uterus was closed with a one-layer continuous locking stitch and the visceral and parietal peritoneal layers were left open. The rectus sheath was stitched with a continuous nonlocking stitch, the skin was closed with a continuous intracutaneous suture. On the seventh postoperative day, omentum was seen extruding from the skin incision. Reexploration showed that the suture of the rectus sheath had ruptured. The further postoperative course was uneventful. CONCLUSION: Although no general recommendations can be deduced from a single case, further reports on any complications of this technique will show whether it is as safe as believed until now.

Adult↗

Temperature-pressure configurational landscape of lipid bilayers and proteins.

High hydrostatic pressure has been used as a physical parameter for studying the stability and energetics of biomolecular systems, such as lipid bilayers and proteins, but also because high pressure is an important feature of certain natural membrane environments. By using a variety of spectroscopic and scattering techniques, the temperature and pressure dependent structure and phase behaviour of various lipid systems and proteins have been studied and are discussed. A thermodynamic approach is presented for studying the stability of proteins as a function of both temperature and pressure. Moreover, the effect of various chaotropic and kosmotropic cosolvents on the temperature- and pressure-dependent structure and stability of proteins is discussed. The results demonstrate that combined temperature-pressure-cosolvent dependent studies can help delineate the free energy landscape of proteins and hence help elucidate which features and thermodynamic parameters are essential in determining the stability of the native conformational state of proteins. We also introduce pressure as a kinetic variable. Applying the pressure-jump relaxation technique in combination with time-resolved synchrotron X-ray diffraction and spectroscopic techniques, the kinetics of un/refolding of lipid mesophases and proteins has been studied. Finally, recent advances in using pressure for studying misfolding and aggregation of proteins will be elucidated.

Amyloid↗

Characterization of the pressure-induced intermediate and unfolded state of red-shifted green fluorescent protein--a static and kinetic FTIR, UV/VIS and fluorescence spectroscopy study.

The green fluorescence proteins (GFP) are widely used as reporters in molecular and cell biology. For their use it in high-pressure microbiology and biotechnology studies, their structural properties, thermodynamic parameters and stability diagrams have to be known. We investigated the pressure stability of the red-shifted green fluorescent protein (rsGFP) using Fourier-transform infrared spectroscopy, fluorescence and UV/Vis spectroscopy. We found that rsGFP does not unfold up to approximately 9kbar at room temperature. Its unique three-dimensional structure is held responsible for the high-pressure stability. At higher temperatures, its secondary structure collapses below 9kbar (e.g. the denaturation pressure at 58 degrees C is 7.8kbar). The analysis of the IR data shows that the pressure-denatured state contains more disordered structures at the expense of a decrease of intramolecular beta-sheets. As indicated by the large volume change of DeltaV degrees (u) approximately -250(+/-50)mlmol(-1) at 58 degrees C, this highly cooperative transition can be interpreted as a collapse of the beta-can structure of rsGFP. For comparison, the temperature-induced unfolding of rsGFP has also been studied. At high temperature (T(m)=78 degrees C), the unfolding resulted in the formation of an aggregated state. Contrary to the pressure-induced unfolding, the temperature-induced unfolding and aggregation of GFP is irreversible. From the FT-IR data, a tentative p,T-stability diagram for the secondary structure collapse of GFP has been obtained. Furthermore, changes in fluorescence and absorptivity were found which are not correlated to the secondary structural changes. The fluorescence and UV/Vis data indicate smaller conformational changes in the chromophore region at much lower pressures ( approximately 4kbar) which are probably accompanied by the penetration of water into the beta-can structure. In order to investigate also the kinetics of this initial step, pressure-jump relaxation experiments were carried out. The partial activation volumes observed indicate that the conformational changes in the chromophore region when passing the transition state are indeed rather small, thus leading to a comparably small volume change of -20 ml mol(-1) only. The use of the chromophore absorption and fluorescence band of rsGFP in using GFP as reporter for gene expression and other microbiological studies under high pressure conditions is thus limited to pressures of about 4kbar, which still exceeds the pressure range relevant for studies in vivo in micro-organisms, including piezophilic bacteria from deep-sea environments.

Animals↗

Productivity effects of bovine mange and control with ivermectin.

A randomised block design study was conducted to evaluate the effects of mange on cattle. Twenty-four Simmentaler Fleckvieh bulls were formed into eight replicates of three bulls based on Day -56 body weight (288-414 kg). Within replicates bulls were randomly allocated to groups G1: uninfested control, G2: infested control or G3: infested, treated with 0.2mg ivermectin/kg (1% ivermectin injection; IVOMEC, Merial) on Day 0. The G2 and G3 bulls were infested with Sarcoptes/Chorioptes mites on Days -56 and -49. Feed consumption was recorded daily throughout the study (Days -56 to 56). Body weights were measured and serum samples collected. Mites were counted at bi-weekly intervals from Day -14 on. The carcasses of the bulls and the leather produced from their hides were evaluated. Differences between variables were declared significant if P</=0.05. All G2 and G3 bulls became infested. No Sarcoptes or Chorioptes mites were detected on the G3 bulls after Day 14 or Day 28, respectively, whereas G2 bulls maintained infestation throughout the study. From Days -42 to 0, anti-Sarcoptes antibody levels in the two infested groups increased linearly, while levels in the uninfested G1 remained near zero. From Day 14 to Day 56, antibody levels in G2 continued to increase and those in G3 decreased (P</=0.05). From Days -56 to 0, G1 had significantly greater mean weight gain (94.0 kg) than the infested G2 and G3 (76.1 and 75.9 kg). During Days 0-56, G3 gained significantly more weight (90.4 kg) than G2 (58.8 kg), while G1 gained 76.0 kg, not significantly different from either G2 or G3. During Days -56 to 0, the feed conversion efficiency (kg gain/kg feed) of the infested G2 and G3 was significantly lower than that of the uninfested G1; during the 56 days following treatment, feed conversion efficiency of G3 was significantly higher than that of G2, while the uninfested G1 was intermediate. Carcass weight of G2 was significantly lower than those of G1 and G3, which did not differ significantly. Carcass yield, rib eye area and weight of kidney fat of the uninfested G1 were significantly greater than those of G2 and G3. Weights of the adrenal glands, prescapular and precrural lymph nodes were significantly higher for the infested G2 than for the other two groups. Significantly less of leather area from the infested G2 was of usable quality than of the leathers from the uninfested G1 or the infested, treated G3, and the leathers from G2 showed significantly more severe gouging or etching than leathers from the two other groups.

Adrenal Glands↗

[Analysis of risk factors and comparison of heparin and hemodilution therapies for retinal artery occlusion].

No standards are available for the treatment of central retinal artery occlusion (CRAO). The aim of this study was to compare data about visual acuity development under heparin treatment with those from hemodilution. Data on 139 patients suffering from CRAO between 1991 and 2000 were examined retrospectively. Risk factors were listed. Therapies were compared in 38 of these patients, 23 of whom received full heparinization and 15 of whom received hemodilution. Many risk factors were shown. Neither therapy showed serious complications. Visual acuity improved significantly, by three or more lines, in five of 23 patients (21.7%) under full heparinization and six of 15 patients (40%) receiving hemodilution. Differences were not significant. For ethical reasons, the normal cause of disease in these patients cannot be studied and is still unknown. Because of many vascular risk factors, we recommend adapted therapies. Treatments should be examined in controlled studies.

Adolescent↗

Telomeres: a diagnosis at the end of the chromosomes.

In recent years, subtelomeric rearrangements have been identified as a major cause of mental retardation and/or malformation syndromes. So far, over 2500 subjects with mental retardation have been tested and reported of whom approximately 5% appeared to have a subtelomeric rearrangement. In this review, the clinical aspects of each known (submicroscopic) subtelomeric deletion will be presented and the various methods available for detecting subtelomeric abnormalities will be discussed. Not only will the patients and their families benefit from a good collection and report of the various telomeric abnormalities and their clinical phenotype, but it will also give more insight into the aetiology of mental retardation and malformation syndromes.

Chromosome Deletion↗

[Science and law in assisted reproductive medicine -- two sides of the same token].

The topic of assisted reproductive medicine (ART) illustrates the two-sidedness of all medical advances. It encompasses not only a responsibility for research, but also a responsibility to research. Current discussion revolves around the central question whether an all too strict interpretation of the German 'Embryonenschutzgesetz' (law to protect the embryo) with the resulting medical guidelines hinders the establishment of an ART practice corresponding to international standards. Current discussion, particularly in view of a new ART legislature in process, leaves the following topics open to debate: heterologous oocyte and sperm donations and a possible 'split' parenthood, the marital status of prospective couples and the serious clinical problem of multiple-gestation pregnancies. The technically feasible frequently surpasses what can or should ethically and legally be made possible.

Adult↗

[Anti-aging or better aging: a contribution to the prevention of aging?].

Anti-aging wants to influence the quality of the second half of life so that chronic damage to health can also be prevented at a higher age with a good quality of life. Thus, molecular biological tests should become the basis for an individualized, preventive hormone therapy. In this context, the question arises whether for each woman in the menopause a risk profile of disturbances of hormone metabolism can already be recognized in her pattern of polymorphisms, although scientific evidence has been lacking until now. Even the topic of the adrenopause, which--among other features--is characterized by an age-specific, partial adrenal insufficiency, must not be neglected in the context of the problem of anti-aging.

Aging↗