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Biomedical subjects

F Sommer

Publications and source records attributed to F Sommer.

At least 37 records · Page 2Linked to original sources

Measurement of vaginal and minor labial oxygen tension for the evaluation of female sexual function.

PURPOSE: Female sexual dysfunction is a new, rapidly expanding area of sexual medicine. Female sexual arousal disorder may, in part, be due to decreased pelvic blood flow. Therefore, we developed a simple noninvasive reproducible technique to measure vaginal and minor labial blood flow. MATERIALS AND METHODS: The study included 12 healthy young women able to have orgasm through self-stimulation. Observations at orgasm were recorded in the 12 subjects after self-stimulation. Measurements were obtained intravaginally and on the minor labia using a modified Clark oxygen electrode to obtain partial oxygen pressure (pO(2)). RESULTS: Mean basal vaginal value was 3.8 +/- 0.9 mm Hg and mean basal pO(2) on the minor labia was 18.3 +/- 3.7 mm. Hg. As soon as self-stimulation was initiated an increase in oxygen tension occurred and continued during sexual stimulation. Just before orgasm a further increase was noted with peak values measured immediately after the orgasm began (pO(2) 28.6 +/- 3.1 mm Hg intravaginally and 47.3 +/- 4.1 labial). Labial pO(2) measurement decreased relatively rapidly soon after orgasm. The time to return to basal vaginal values after orgasm varied from 20 to 30 minutes. CONCLUSIONS: Previously, changes in female sexual arousal responses have been difficult to evaluate and quantify clinically. We developed a simple noninvasive reproducible technique to measure vaginal and minor labial blood flow. Age based and cycle dependent normograms now can be produced for vaginal and labial blood flow using this method.

Adult↗

Risk adjustment for evaluating the outcome of urological operative procedures.

PURPOSE: Considerable public and media attention has been directed in recent years toward comparing performance at individual hospitals. So-called death league tables have been published in the media, ranking hospitals according to crude mortality rates. Crude rates of mortality and morbidity are clearly misleading. Therefore, scoring systems comparing treatment outcomes among physicians or hospitals on an objective basis are urgently required. MATERIALS AND METHODS: During a 12-month period we prospectively evaluated 651 patients at 2 urological units using a simple and well validated surgical scoring system. Patients had been admitted to the units for routine urological operations. The scoring system consists of a simple preoperative physiological score, a postoperative severity score and defined types of complications. RESULTS: The morbidity and mortality rates for unit 1 were 7.4% and 1.3%, respectively. For unit 2 the morbidity and mortality rates were 14% and 8.8%, respectively. Despite the marked differences in these crude rates risk adjusted analysis revealed no significant difference (p <0.05). Receiver operating characteristics curve analysis likewise demonstrated no significant difference in mortality and morbidity for the 2 units. CONCLUSIONS: Raw rates of mortality and morbidity are often inappropriately used to compare the performance of various surgical procedures, especially vascular and cardiothoracic surgery. In Great Britain at some institutions urological units are ranked according to mortality and morbidity outcome. As a consequence, important variables, such as patient physiological state at surgery and the type of procedure, are not considered. Our study shows that the scoring system applied is suitable for urological audit and may be a valuable tool for comparing performance at various units.

Female↗

Helicobacter pylori gastritis: a Th1 mediated disease?

Helicobacter pylori is now considered to be the main cause for most stomach diseases including ulcer, MALT lymphoma, adenocarcinoma and gastritis. The infection with this bacterium is chronic despite a local and systemic immune response towards it. Among the cellular infiltrate that arises during H. pylori-mediated gastritis, there is a considerable frequency of CD4+ Th1 cells producing IFNgamma, but not of Th2 cells producing IL-4. Since IFNgamma may induce binding of H. pylori to gastric epithelial cells followed by apoptosis of these cells, one may speculate that H. pylori-mediated diseases are in part autoimmune diseases initiated by H. pylori-specific Th1 cells infiltrating the gastric mucosa. Recent support for this hypothesis comes from an animal model in which mice are infected with H. pylori and display strongly reduced gastritis in the absence of IFNgamma.

Animals↗

Artificial tear adsorption on soft contact lenses: methods to test surfactant efficacy.

Spoilage is a primary factor in the biocompatibility of soft contact lenses (SCL) within the lacrimal fluid. Tears are a complex mixture of proteins, lipids, natural surfactants and salts. The spoilation process is due to a contribution of all these components and of the nature of SCL materials themselves. The aim of this study was to set up methods to observe and quantify lacrimal deposits and to select efficient surfactants for preventing protein deposits. The present study was performed on PMMA-NVP SCL. The behaviour of SCL in presence of tears was studied by means of an in vitro artificial tear model consisting of the main tears components and quantified by a colorimetric technique (BCA) performed directly on the lenses. The nature of the deposit was observed directly by atomic force microscopy (AFM) in a liquid medium showing the same adsorption trend noticed in the quantitative results and identifying specific adsorption sites. The assessment of surfactant adsorption was performed using Maron's method, as a mean to evaluate the affinity of surfactant to the surface, while the action of selected surfactants on pre-treated SCL was assessed using the BCA method. Promising results were obtained with these two different methods which can be used easily for the pre-selection of surfactants for further cleaning solution formulation studies.

Adsorption↗

Protein encapsulation within poly(ethylene glycol)-coated nanospheres. II. Controlled release properties.

The development of injectable nanoparticulate "stealth" carriers for protein delivery is a major challenge. The aim of this work was to investigate the possibility of achieving the controlled release of a model protein, human serum albumin (HSA), from poly(ethylene glycol) (PEG)-coated biodegradable nanospheres (mean diameter of about 200 nm) prepared from amphiphilic diblock PEG-poly(lactic acid) (PLA) copolymers. HSA was efficiently incorporated into the nanospheres, reaching loadings as high as 9% (w/w). Results of the in vitro release studies showed that it is possible to control the HSA release by choosing the appropriate nanosphere size, loading, and composition. These results also revealed that, following their release, HSA molecules readsorbed onto the nanospheres surfaces when they were not protected by a PEG coating. We were surprised to observe that in spite of the water uptake of the PLA-PEG nanospheres [11-29% (w/w)], the copolymer did not significantly degrade after a 15-day incubation period. Therefore, we concluded that during this time HSA release from PLA-PEG nanospheres followed a diffusion mechanism where bulk erosion and surface desorption were negligible.

Biodegradation, Environmental↗

Protein encapsulation in biodegradable amphiphilic microspheres.

MPOE-PLA microspheres containing bovine serum albumin (BSA) were prepared by the double emulsion method with high encapsulation efficiency ( approximately 93%). Confocal scanning microscopic analysis using MPOE-PLA labelled with 1-pyrenemethanol showed the MPOE coating of the microsphere surface. This coating improves the performance of the release system compared with PLA microspheres; the hydrophilic chains reduce the BSA adsorption onto the microspheres and increase the amount of BSA released in the supernatant. Microsphere analysis using atomic force microscopy showed that the presence of the MPOE chains also leads to surface roughness. Studies of the diffusion of 1% rhodamine aqueous solution into the microspheres by means of confocal microscopy showed a fast diffusion of water through the matrices containing high molecular weight MPOE chains (?10 000 g mol-1) and could explain the fast release of BSA from these microspheres.

Adsorption↗

Lidocaine-loaded biodegradable nanospheres. I. Optimization Of the drug incorporation into the polymer matrix.

Spherical nanoparticulate drug carriers made of poly(d,l-lactic acid) with controlled size were designed. A local anesthetic, lidocaine, a small hydrophobic molecule, was incorporated in the core with loadings varying from about 7 to 32% (w/w) and increasing with the particle size. Particles with sizes from about 250 to 820 nm and low polydispersity were prepared with good reproducibility; the polymer concentration (at constant surfactant concentration) governed the particle size. The large particles with a high loading ( approximately 30%) showed under in vitro conditions a slow release over 24-30 h, the medium sized carriers (loading of approximately 13%) released the drug over about 15 h, whereas the small particles with small loading ( approximately 7%) exhibited a rapid release over a couple of hours. It seems that the drug release rate is related to the state (crystallized or dispersed) of the drug incorporated in the polymer matrix.

Anesthetics, Local↗

A multidrug-resistance protein (MRP)-like transmembrane pump is highly expressed by resting murine T helper (Th) 2, but not Th1 cells, and is induced to equal expression levels in Th1 and Th2 cells after antigenic stimulation in vivo.

A transmembrane pump for organic anions was identified in resting murine T helper (Th) 2, but not Th1 lymphocyte cell clones, as revealed by extrusion of a fluorescent dye. Dye extrusion inhibition studies suggested that the pump may be the multidrug-resistance protein (MRP). The different expression of the pump in resting Th1 and Th2 cell clones correlated with their respective levels of MRP mRNA. The pump was inducible in Th1 cells by antigenic stimulation in vitro leading to equal expression in activated Th1 and Th2 cell clones. This suggested that dye extrusion might allow the detection of Th2 (resting or activated) or of activated Th1 cells ex vivo based on a functional parameter. To test this, mice were infected with Leishmania major parasites to activate L. major-specific T cells of either Th1 (C57BL/6 mice) or Th2 (BALB/c mice) phenotype: 2-3% of CD4+ lymph node T cells of both strains of mice extruded the dye, defining a cell subset that did not coincide with subsets defined by other activation markers. Fluorescence-activated cell-sorting revealed that the lymphokine response (Th1 or Th2, respectively) to L. major antigens was restricted to this dye-extruding subset.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Protein encapsulation within polyethylene glycol-coated nanospheres. I. Physicochemical characterization.

The development of injectable nanoparticulate "stealth" carriers for protein delivery is a major challenge. We have shown the possibility of entrapping human serum albumin (HSA) in polyethylene glycol (PEG)-coated monodisperse biodegradable nanospheres with a mean diameter of about 200 nm, prepared from amphiphilic diblock PEG-polylactic acid (PLA) copolymers, with loadings up to 9% (w/w). Microscopic techniques and surface analysis studies enabled us to prove that the protein was well entrapped and not adsorbed onto the particle surface. Zeta potential and water uptake studies corroborated that part of the PEG chains are located in the nanosphere matrix. Water uptake in the nanospheres was related to their chemical composition, i.e., the respective wt% of PEG and PLA in the matrix, and not on their fabrication procedure. The hydrophilic PEG blocks absorbed up to 130% (w/w) water, whereas PLA absorbed only about 10% (w/w). However, the rate of swelling at the beginning of the process was related to the structure of the matrix, more particularly to the manner in which PEG was disposed at the surface. Furthermore, it was shown that the PEG "brush" at the nanosphere surface drastically reduces HSA adsorption on the PEG-PLA nanospheres compared to the PLA ones.

Adsorption↗

Systemic antibiotic therapy on multiple intracerebral abscesses of unknown origin.

A 68-year old patient presented with increasing right-sided weakness, dysarthria, pyrexia and a deteriorating general condition. CT and MRI showed about 20 round hyperdense lesions with peripheral enhancement of contrast material up to 1.5 cm in diameter. Antibiotic triple-therapy using ceftriaxone, gentamycin and metronidazole for 39 days and followed by antibiotic double-therapy using ceftriaxone and metronidazole for a further 22 days resulted in a radiologically proven reduction of the abscesses to very small remnants which disappeared completely during the follow-up period of two years. Simultaneously the general condition of the patient improved significantly. Repeated attempts at isolation of bacteria, fungi, protozoa and parasites from a subdural empyema failed. The histological examination of an abscess, which was entirely removed on occipital craniotomy, showed a structure resembling actinomycosis.

Actinomycosis↗

Analysis of cytokine patterns produced by individual CD4+ lymph node cells during experimental murine leishmaniasis in resistant and susceptible mice.

The concept of subdividing CD4+ T cells into Th0, Th1 and Th2 cells is based on the cytokine pattern produced by long-term in vitro cultured T cell lines. However, there exists uncertainty whether this classification can also be applied to CD4+ T cells in vivo. Herein it was investigated whether and at which frequency Th0, Th1 and Th2 cells are induced in vivo during an infection of mice with Leishmania major. Cytokine co-production in single IFN-gamma+ or IL-4+ CD4+ T cells as well as the frequency of such cells were assessed in the lymph nodes (LN) of infected mice. For this purpose, T cells derived from the draining LN were activated by phorbol myristate acetate (PMA)/ionomycin, and the intracellular cytokines IL-2, IL-4, IL-5, IL-10 and IFN-gamma were analyzed by immunofluorescence. One week after infection, a strong, but comparable increase of IFN-gamma+ CD4+ and IL-4+ CD4+ cells (up to 7% of all CD4+ cells) in the LN was observed in resistant C57BL/6 mice and susceptible BALB/c mice. IFN-gamma and IL-4 were not co-produced by single cells ('Th0 cells'). At later stages of the infection, the number of IL-4+ CD4+ cells decreased in C57BL/6, but not in BALB/c mice. All IL-4+ CD4+ cells showed an unexpected phenotype, because at least half of these cells co-produced IL-2, and the majority of the IL-4+ CD4+ did not co-produce the Th2 cytokines IL-5 and IL-10. Similar cytokine profiles were obtained when the CD4+ T cells were stimulated by Leishmania major-antigen instead of PMA/ionomycin. This study demonstrates that 'classical' Th1 cells (IFN-gamma+IL-2+), but no 'classical' Th2 cells (IL-4+IL-5+IL-10+) and no Th0 cells (IFN-gamma+IL-4+) are generated during L. major infection of mice in vivo.

Animals↗

Antrum- and corpus mucosa-infiltrating CD4(+) lymphocytes in Helicobacter pylori gastritis display a Th1 phenotype.

In this study, cytokine patterns produced by CD4(+) T cells isolated from antrum or corpus gastral biopsy specimens of 10 patients with Helicobacter pylori-positive gastritis were compared. To this end, expression of intracellular cytokines (interleukin-4 [IL-4] and gamma interferon) and of CD4 was assessed by flow cytometry. Ten to 60% of the isolated CD4(+) T cells produced gamma interferon upon stimulation. With the exception of one patient, IL-4-positive CD4(+) cells were not detected. Therefore, CD4(+) cells infiltrating antrum and corpus stomach mucosa during H. pylori infection show a Th1 phenotype. This polarized Th1-type response may contribute to the inability of the immune system to eradicate H. pylori infection.

Adult↗

Characterization of lacrymal component accumulation on worn soft contact lens surfaces by atomic force microscopy.

The purpose of this study was to investigate lacrymal component accumulation on a soft contact lens (SCL) surface after various periods of continuous wear, using the recently developed atomic force microscopy (AFM). AFM allowed high resolution images of unworn and worn SCL, and presented two main advantages. 1. The SCL are analysed under nearly physiological conditions without being dried or destroyed. So the same SCL was analysed at various times during a long wearing period. To identify the deposited tear proteins, a qualitative analysis of solubilized deposit by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) on 4-15% gradient minigels was performed as well. We present typical images which emphasize the importance of the coating by lacrymal components. AFM analysis of worn SCL showed the deposition on the surface of a uniform lacrymal component coating (named deposit type I) with a progressive accumulation of numerous discrete granules (named deposit type II). SDS-PAGE of extracted deposits revealed the main tear proteins as: IgA, lactoferrin, tear lipocalin and lysozyme and the unknown protein of molecular weight 30,000. There is no clear difference in the protein patterns of the two types of deposits. Furthermore, a particular mode of use of AFM is described to illustrate the potential of this technique as a local tool for measuring protein coating thickness. Thus, for analysis of protein deposits on SCL surfaces, SDS-PAGE on minigels and AFM were easy and rapid to perform. When associated, these two techniques could find use in a wide range of worn SCL evaluation and most generally in biocompatibility evaluation studies.

Adult↗

CD44 plays a co-stimulatory role in murine T cell activation: ligation of CD44 selectively co-stimulates IL-2 production, but not proliferation in TCR-stimulated murine Th1 cells.

The murine CD44 receptor family is thought to be involved in a variety of lymphocyte functions, including lymphopoesis, lymphocyte homing and cell migration. Herein, we show that murine CD44 also plays a role as a co-stimulatory molecule for the activation of CD4+ T cells. Ligation of CD44 by mAb enhanced IL-2 production of long-term cultured, anti-CD3-stimulated Th1 cell lines. Moreover, anti-CD44 mAb synergized with anti-CD28 mAb in exerting this effect. A synergism of anti-CD28 and anti-CD44 mAb to co-stimulate IL-2 production was also observed in anti-CD3-triggered, freshly isolated splenic CD4+ T cells. Blocking experiments with cyclosporin A indicated that the intracellular pathways used by the CD28 and CD44 molecules appear to be different. In contrast to the effects on the IL-2 production of Th1 cells, neither anti-CD44 mAb alone nor the combination of anti-CD44 with anti-CD28 were able to induce proliferation of anti-CD3-triggered Th1 cells. In accordance, triggering of CD44 and/or CD28 by mAb was not sufficient to reverse the previously described 'proliferative block'. This term describes the unresponsiveness of Th1 cells against IL-2, which occurs when Th1 cells are triggered by anti-CD3 in the absence of co-signals. These data lead us to propose a model of Th1 cell activation which includes two functionally different types of co-signals: one for IL-2 production and a separate one for proliferation.

Animals↗

Anthony Blunt and Guy Burgess, gay spies.

Anthony Blunt and Guy Burgess were prominent figures in the Cambridge spy ring operating on behalf of the USSR from the 1930s into the 1960s. The essay describes the complex personalities of Blunt and Burgess, whose homosexuality and communism were related aspects of a rebellious, antibourgeois culture in 1930s leftist Britain. The focus is on male homosexuality, and the question is put whether, and in what sense, Blunt and Burgess served the left, and whether they can be role models for gays at the end of this century.

Communism↗

Normal protein and glycoprotein profiles of reflex tears and trace element composition of basal tears from heavy and slight deposits on soft contact lenses.

We investigated the hypothesis that lacrimal component accumulation on soft contact lenses (SCL) may be induced by an abnormal protein, glycoprotein, or trace element composition of the tear fluid. Individual tear samples were collected from healthy non-SCL wearers (normal patients) and SCL wearers grouped as either "slight-depositor" or "heavy-depositor" following SCL spoilage rate and frequency. The reflex tear proteins were analyzed by three electrophoretic procedures: sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) on minigels, isoelectric focusing (IEF) on immobilized pH gradients (IPG 4-7), and two-dimensional separation combining IEF in the first dimension to orthogonal SDS-PAGE. After separation, the proteins were detected by silver staining and identified by immunologic probes. The reflex tear glycoproteins were analyzed by lectin affinity associated electrotransfer of SDS-PAGE with a panel of five biotinylated lectin probes: Canavalia ensiformis (Con A), Artocarpus integrifolia (Jacalin), glycine max (SBA), Ulex europaeus (UEA 1), and Triticum vulgaris (WGA) agglutinins. The basal tear trace elements were analyzed by Synchrotron Radiation X-ray Fluorescence. Despite the highly sensitive techniques used in the study, the profiles of reflex tear proteins, glycoproteins, and trace elements appeared to vary slightly among individuals. No evident qualitative difference in reflex tear fluid related to SCL wear or deposit formation susceptibility was found. The presence or absence of a particular protein, glycoprotein, or trace element could not be correlated with a different reactivity to SCL. However, potassium and carbohydrate residues having affinity with Jacalin and WGA presented little but not significant variations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Demonstration of organic anion transport in T lymphocytes. L-lactate and fluo-3 are target molecules.

In this paper, we describe for the first time the existence of organic anion transport in T lymphocytes, exemplified by the transmembrane transport of the anions L-lactate and the Ca2+ indicator fluo-3. The transport of either anion was found to be inhibitable by probenecid, a common blocker of organic anion transport. Transport of L-lactate was observed in long-term cultured T cell lines, as well as in freshly ex vivo isolated T cells, and occurred via a saturable, pH-dependent, and stereospecific process. L-Lactate uptake was dependent on the activation state of the T cells, because activation of T cells by Con A strongly enhanced accumulation of L-lactate from the medium. Because L-lactate may be transported bidirectionally through the T cell membrane in vivo, different physiologic roles of L-lactate transport are discussed. L-Lactate uptake may serve as an alternative source of energy in an inflamed, glucose-deficient tissue or may represent a prerequisite for the earlier-published immunoregulatory function of this molecule on T cells. On the other hand, release of L-lactate emerging from glycolysis could be necessary to avoid acidification of the cell. The fact that the Ca2+ indicator fluo-3 is also transported through the cellular membranes of long-term cultured T cells via organic anion transport has important implications for the determination of Ca2+ influx into T cells. Even though the transport of both molecules, L-lactate and fluo-3, represents organic anion transport, evidence is presented that confirms that the respective transport systems are different.

Aniline Compounds↗