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Biomedical subjects

S Lang

Publications and source records attributed to S Lang.

At least 343 records · Page 19Linked to original sources

Determination of bone and tissue concentrations of teicoplanin mixed with hydroxyapatite cement to repair cortical defects.

A highly specific and sensitive isocratic reversed-phase high performance liquid chromatography (HPLC) method for the determination of the major component of teicoplanin in tissue is reported. Comparing fluorescamine and o-phthalaldehyde (OPA) as derivatizing agents, the derivative formed with the latter exhibits superior fluorescence intensity allowing detection of femtomole quantities. Pretreatment for tissue samples is by solid-phase extraction which uses Bakerbond PolarP C(18) cartridges and gives effective clean up from endogenous by-products. Linearity was given from 0.6 to 100 ng per injection. The coefficient of variation did not exceed 5.8% for both interday and intraday assays. It was found that when bone defects are repaired with a hydroxyapatite-teicoplanin mixture, the antibiotic does not degrade, even when it is in the cement for several months. The stability of teicoplanin in bone cement was determined fluorodensitometrically.

Animals↗

Surface-active lipids in rhodococci.

Like other hydrocarbon-oxidising bacteria, rhodococci respond to the presence of alkanes by producing biosurfactant molecules to improve their ability to utilise these hydrophobic compounds as growth substrates. In the rhodococci these surfactants are predominantly glycolipids, the majority of which remain cell-bound during unrestricted growth. Most work has been done on the trehalose mycolates formed by Rhodococcus erythropolis, but nitrogen-limited conditions lead to the production of anionic trehalose tetraesters also. As surfactants, these compounds, whether purified or in crude form, are able to reduce the surface tension of water from 72 mN m-1 to a low of 26, thus making them among the most potent biosurfactants known. They are also able to reduce the interfacial tension between water and a hydrophobic phase (e.g. n-hexadecane) from 43 mN m-1 to values less than one (Table 1). Biosurfactants have about a ten- to 40-fold lower critical micelle concentration than synthetic surfactants. Such properties suggest a range of industrial applications, where a variety of surface-active characteristics are appropriate. Interest in biosurfactants as industrial chemicals results from the toxicity of many petrochemical-derived surfactants. Currently world-wide surfactant production is on a very large scale, and the demand for them is increasing. However, the drive towards less environmentally damaging chemicals makes biosurfactants attractive as they have lower toxicity. The reason they have not achieved a significant market share is the cost of production, which is considerably higher than for synthetic surfactants. This problem is being addressed using several strategies. An approach where there is great scope for improvement with the rhodococci is an understanding of the genetic basis of glycolipid production, which is largely unknown. They may find applications in the near future in the environmental remediation industries, where the requirement for purified molecules is of less importance. This review summarises knowledge of the chemistry, biochemistry and production of Rhodococcus surface-active lipids. Where they have been used, or there is potential for use, in industrial applications is discussed.

Biodegradation, Environmental↗

[Osteosarcoma and Ewing's sarcoma--The most frequent malignant bone tumors in children--therapy and outcome].

BACKGROUND: Osteosarcoma and Ewing's sarcoma are the most frequent malignant bone tumors in children and young adults with relatively poor overall survival rates. METHODS: Between January 1980 and December 1994, 175 children with osteosarcoma and 64 children with Ewing's sarcoma were treated at the author's institution. 22 children had synchronous metastases, 19 patients had a pathologic fracture. Both groups were treated systemically with chemotherapy regimens (COSS and CESS). Local therapy was amputation or tumor resection and endoprosthetic replacement or biological reconstruction with wide or radical resection margins. In case of Ewing's sarcoma in 35 patients postoperative radiation therapy was done. RESULTS: Five-year overall survival rate for osteosarcoma and Ewing's sarcoma patients is about 63 %, ten-year survival rate for osteosarcoma patients is 60.2 %, for Ewing's sarcoma patients 54.5 %. Prognostic factors significantly influencing overall survival rates are tumor response to chemotherapy (p values = 0.0056 and 0.013, respectively), surgical treatment with adequate resection margins (p value = 0.0001 for osteosarcoma patients) and development of postoperative metastases (p value = 0.0001 for both groups). CONCLUSION: For both groups of malignant bone tumors systemic chemotherapy as well as adequate surgical therapy are necessary to reduce the rates of local recurrences and to achieve better survival rates.

Adolescent↗

[The Knee Injury and Osteoarthritis Outcome Score--a multifunctional questionnaire to measure outcome in knee arthroplasty].

AIM: It was the purpose of this investigation to create a German version of the Knee Injury and Osteoarthritis Outcome Score (KOOS) and to test its appropriateness in patients with advanced gonarthritis. METHOD: Reliability (test-retest reliability, internal consistency), validity (convergent construct validity and divergent construct validity), sensitivity to change as well as practicability and acceptance of this questionnaire were tested in 90 patients. RESULTS: The test-retest reliability was acceptably high for all subscales, it ranged between r = 0.65 and 0.78 and the questionnaire showed a high internal consistency in almost all of the subscales. The comparison to the results of the questionnaire "Short Form-12" (SF-12) as well as to the patients self-assessment of health status showed high concordance in nearly all subscales, however it was only moderate for the symptom scale. Furthermore the KOOS was able to show significant differences between patients and healthy controls. When testing the sensitivity to change, the KOOS could demonstrate significant improvements within 3 months and the instrument has shown to be practicable with a high acceptance by the patients. CONCLUSION: With the German version of the Knee Injury and Osteoarthritis Outcome Score a multidimensional instrument is available now to measure health status as well as therapeutic effects in patients with knee problems. Modifying the subscale "symptoms" could further optimize this questionnaire in patients with advanced gonarthritis.

Adolescent↗

Heat-shock protein 72 in human osteosarcoma: T-lymphocyte reactivity and cytotoxicity.

Heat-shock proteins (hsp) have been shown to be involved in tumor immunity. The expression of hsp72, the inducible form of the 70-kDa family, is increased in human osteosarcoma and correlates with a good response to neoadjuvant chemotherapy. It is selectively expressed on the surface of osteosarcoma cell lines where it acts as a target molecule for natural killer cells. Because hsps are strongly immunogenic, this study investigates the role of hsps as antigens in human osteosarcoma. Osteosarcoma cells and infiltrating T lymphocytes were isolated from osteosarcoma specimens from 3 patients with high-grade osteosarcoma. Two of the tumors immunohistochemically expressed hsp72, whereas one did not. T-cell lines isolated from both hsp72-positive osteosarcomas had a significantly proliferative response upon stimulation with recombinant human hsp72, whereas the T lymphocytes from the hsp72-negative osteosarcoma did not recognize hsp72. The lines had a significantly proliferative response upon stimulation with autologous osteosarcoma cells and exerted cytotoxicity. Cytotoxicity and proliferation could be increased by heat treatment of the target cell in the hsp72 responsive lines. These results demonstrate that hsp72 is involved in the interaction of T lymphocytes and osteosarcoma cells in a specific group of osteosarcomas expressing hsp72. Because of the cytotoxic potential of these T lymphocytes, induction of hsp72 in osteosarcomas might lead to an increased immune response and rejection of the osteosarcoma.

Coculture Techniques↗

Bioincompatible membranes place patients with acute renal failure at increased risk of infection.

The mortality of critically ill patients with acute renal failure (ARF) requiring hemodialysis remains high (> 50%), even though major improvements in the management of this disorder have been made. Sepsis has been identified as a major cause of death in ARF. Experimental data have suggested that bioincompatible membranes aggravate uremia induced neutrophil dysfunction. In the following two combined prospective, randomized, clinical studies, the effects of the biocompatibility of dialysis membranes on the susceptibility to infection were compared in 72 surgical and medical patients with ARF. The group of patients treated with biocompatible polyacrylonitrile membranes had a significantly lower incidence of bacterial infections and a lower relative and absolute mortality rate due to sepsis, compared to patients treated with bioincompatible cuprophane membranes. These investigations identified bioincompatibility as a factor that adversely affects the prognosis of critically ill patients with ARF.

Acrylic Resins↗

Nonlinear anisotropic diffusion filtering of three-dimensional image data from two-photon microscopy.

Two-photon microscopy in combination with novel fluorescent labeling techniques enables imaging of three-dimensional neuronal morphologies in intact brain tissue. In principle it is now possible to automatically reconstruct the dendritic branching patterns of neurons from 3-D fluorescence image stacks. In practice however, the signal-to-noise ratio can be low, in particular in the case of thin dendrites or axons imaged relatively deep in the tissue. Here we present a nonlinear anisotropic diffusion filter that enhances the signal-to-noise ratio while preserving the original dimensions of the structural elements. The key idea is to use structural information in the raw data-the local moments of inertia-to locally control the strength and direction of diffusion filtering. A cylindrical dendrite, for example, is effectively smoothed only parallel to its longitudinal axis, not perpendicular to it. This is demonstrated for artificial data as well as for in vivo two-photon microscopic data from pyramidal neurons of rat neocortex. In both cases noise is averaged out along the dendrites, leading to bridging of apparent gaps, while dendritic diameters are not affected. The filter is a valuable general tool for smoothing cellular processes and is well suited for preparing data for subsequent image segmentation and neuron reconstruction.

Algorithms↗

COX-inhibitors relieve the immunosuppressive effect of tumor cells and improve functions of immune effectors.

A common phenomenon in cancer patients is a suppressed cell-mediated immunity, characterized by the inability of immune effector cells to mount efficient anti-tumor responses. Immunosuppressive factors, released by the tumor, contribute to this phenomenon and thus to tolerance. Prostaglandins, catalyzed by the cyclooxygenases (COX-1 and COX-2) from arachidonic acid, are one class of these factors. Since at least one of the COX enzymes is often expressed at high level in human cancers, the enzymes were ascribed a causal role in tumor etiology and progression. Non-steroidal antiinflammatory drugs (NSAIDs) like aspirin, which block COX activity, have demonstrated their antitumor effects in preclinical and clinical trials. Pro-apoptotic and anti-angiogenic effects in tumor cells may account for this activity. In addition, by inhibiting the release of prostaglandins from the tumor and by blocking COX activity in immune effector cells, NSAIDs may also bias the function of immune cells towards a more tumoricidal phenotype. We show here that tumor cells inhibit the physiological function of immune cells, and that NSAIDs restore this function. These data contribute to an understanding of the antineoplastic effect ascribed to NSAIDs and support the prophylactic use of these drugs in high-risk patients.

Anti-Inflammatory Agents, Non-Steroidal↗

Wildlife genetics and disease: allozyme evolution in the wild boar (Sus scrofa) caused by a swine fever epidemy.

Enzyme polymorphism at 42 loci was compared before and after a major epidemy of swine fever in wild boars from northern Vosges (France). No change was observed in the 38 monomorphic loci, but allele frequencies at the phosphoglucomutase locus PGM-2* changed significantly. Possible causes for this observation are discussed, and it appears that PGM-2 locus could be a genetic marker of resistance to this viral disease.

Journal Article↗

[Development of a mathematical model for simulation of artificial ventilation].

This article describes a mathematical model for the simulation of artificial ventilation employing only the figures for air pressure and air flow between respirator and lungs. A discussion of methodological aspects of the problem shows that the model of the respiratory system can be reduced to an equivalent circuit diagram comprising only resistances and capacitances. The structure of the mathematical model is oriented to the elements of the real respiratory system, and its modularity permits ready adaptation to a variety of real-life situations. Particular emphasis was placed on the correct parametrization of the model with the aid of data originally collected from physical experiments. Finally, some selected model runs that demonstrate the range of validity and the accuracy of the model are presented.

Airway Resistance↗

Chemical and physical characterization of four interfacial-active rhamnolipids from Pseudomonas spec. DSM 2874 grown on n-alkanes.

Four extracellular glycolipids produced under growth-limiting conditions were isolated from the culture broth of Pseudomonas spec. DSM 2874. After purification by column and thick-layer chromatography they were identified as anionic rhamnolipids. 1H and 13C-NMR studies showed that two of these, beta(beta(2-O-alpha-L-rhamnopyranosyloxy)decanoyl)decanoic acid and beta(beta(2-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosylox y)decanoyloxy) decanoic acid, were identical with compounds described previously, while the other more hydrophilic compounds, beta(2-O-alpha-L-rhamnopyranosyloxy)decanoic acid and beta(2-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosyloxy) decanoic acid, were new compounds. Surface and interfacial activity of the organic crude extract and of the purified components were determined in different aqueous solutions. The pH-dependence of surface and interfacial properties of the two previously described rhamnolipids (4, 20, 23) were examined in Teorell-Stenhagen-buffer (supplemented with 10% NaCl) at pH 3.0 and pH 9.0. All rhamnolipids reduced the surface-tension from 72 to about 30 mN/m and the interfacial-tension from 42 to about 1 mN/m. The critical micelle concentrations were of the order of 5 to 200 mg/l depending on the structure of the molecule.

Alkanes↗

Production of four interfacial active rhamnolipids from n-alkanes or glycerol by resting cells of Pseudomonas species DSM 2874.

In a simple phosphate buffer or a sodium chloride solution resting cells of Pseudomonas spec. DSM 2874 produced up to 15 g/l of different rhamnolipids. The rhamnolipid composition of the organic crude extract depended on the temperature during the cultivation and on the C-source. The optimal sodium chloride concentration for rhamnolipid formation was about 100 mM/l and the optimal phosphate buffer concentration about 65 mM/l. The optimal pH-value for the production of rhamnolipids from n-alkanes or glycerol was in the range pH 6.0-7.2. While rhamnolipid formation with glycerol as the sole C-source showed a wide optimum ranging from 27 degrees up to 37 degrees C, production of rhamnolipids from n-alkanes had a sharp optimum at 37 degrees C. The addition of multivalent cations, different N-sources and EDTA caused an inhibition of rhamnolipid formation, while the n-alkane concentration had no influence. Specific rhamnolipid formation decreased with increasing cell concentration. Various C-sources were suitable for the formation of rhamnolipids by resting cells of Pseudomonas spec. DSM 2874. Yields, which were comparable to those obtained on n-alkanes or glycerol, were found for stearic acid, fatty alcohols and vegetable oils. A study of the time course of glycolipid production of resting cells was carried out in a 20 1-bioreactor with an intensor system and with n-tetradecane as the sole C-source.

Alkanes↗

Marine biosurfactants, I. Screening for biosurfactants among crude oil degrading marine microorganisms from the North Sea.

Three bacterial strains of marine origin were isolated during a screening for biosurfactants among n-alkane degrading microorganisms. One strain-identified as Alcaligenes sp. MM1-produced a novel glucose lipid. In the case of Arthrobacter sp. EK 1 the well-known trehalose tetraester was found as major component. From another pure culture classified as Arthrobacter sp. SI 1, extracellular emulsifying agents with properties indicating high molecular weight substances were detected. Furthermore trehalose corynomycolates were found at up to 2 g/l. The isolated biosurfactants showed good interfacial and emulsifying properties.

Alcaligenes↗

Marine biosurfactants, II. Production and characterization of an anionic trehalose tetraester from the marine bacterium Arthrobacter sp. EK 1.

Within a screening for biosurfactants we could isolate various n-alkanes utilizing marine bacteria which were capable of synthesizing glycolipids. One strain was identified as Arthrobacter sp. EK 1 which produced trehalose lipids. After purification by column and thick layer chromatography the main fraction, an anionic 2,3,4,2'-trehalose tetraester, was obtained. The chain lengths of fatty acids ranged from 8 up to 14, furthermore succinate could be detected. Since the place of substitution of succinate has so far not been cited in literature, a definitive structural elucidation was carried out chemically by hydroboration and by 1H, 2D1H, 13C and 13C-1H correlation NMR measurements. All investigations confirmed the exact position of succinate at C 2 atom of trehalose. After improvement of growth conditions the production of the trehalose tetraester increased up to 4.8 milligrams during a fermentation in 20 l bioreactor under nitrogen limitation.

Animals↗

Marine biosurfactants, III. Toxicity testing with marine microorganisms and comparison with synthetic surfactants.

Eight synthetic and nine biogenetic surfactants were tested on their toxicity. Because of their possible application as oil dispersants against oil slicks on sea, the test organisms used were marine microorganisms (mixed and pure cultures of bacteria, microalgae, and protozoa). Bacterial growth was hardly effected or stimulated, whilst that of algae and flagellates was reduced. All substances tested were biodegraded in sea water. The bioluminescence of Photobacter phosphoreum (Microtox test) was the most sensitive test system used. A ranking shows that most biogenetic surfactants were less toxic than synthetic surfactants. No toxicity could be detected with the glucose-lipid GL, produced by the marine bacterium Alcaligenes sp. MM1.

Animals↗

Regulatory mechanism in glomerular mesangial cell proliferation.

Glomerular mesangial cells have a central function in maintaining structure and function of the glomerular capillary ultrafiltration apparatus. Regardless of the type of glomerular injury, imbalances in the control of mesangial cell replication appear to play a key role in the pathogenesis of progressive renal failure. The available evidence from in vitro and in vivo studies indicates that such regulatory mechanisms include specific soluble and non-soluble extracellular factors and a complex array of receptor-mediated signals which control cell proliferation, survival and apoptosis. This review summarizes results from recent investigations concerning regulation of cell cycle progression in mesangial cells. In addition to results from cell culture studies, descriptive findings on expression and regulation of cell cycle-regulatory proteins and their potential role for altered mesangial cell behaviour in glomerular disease are considered. We believe that better understanding of processes which regulate mesangial cell replication could lead to novel diagnostic as well as therapeutic strategies and, thus, help control better proliferative glomerulonephritis.

Apoptosis↗