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Biomedical subjects

M A Schwarz

Publications and source records attributed to M A Schwarz.

At least 19 recordsLinked to original sources
PubMed1998

Characterization of micelles by capillary electrophoresis.

A practical approach for the characterization of pure micelles, and binary or ternary mixed micelles by capillary electrophoretic methods is presented. Interest is focused on the determination of mobility and composition of the micelles. The investigations are performed with bile salts, phosphatidylcholines and fatty acids. Pure bile salt micelles are characterized with the help of marking and displacement methods. Binary bile salt/phospholipid and ternary bile salt/phospholipid/fatty acid micelles are analyzed using capillary electrophoresis (CE) techniques with standard and improved UV detection, laser-induced fluorescence and electrospray ionization-mass spectrometry (ESI-MS). For both the binary and the ternary systems, only one stable mixed micellar phase is found with a high negative mobility.

Bile Acids and Salts↗
PubMed1998

Interaction between food components and drugs. Part 6: Influence of starch degradation products on propranolol transport.

Interactions between different starch degradation products and propranolol (P) were studies using permeation experiments and affinity capillary electrophoresis (ACE). In the presence of maltooligosaccharides (MO), the transport of P across artificial lipid membranes was retarded. The most intensive interaction with the drug was found in the presence of the not-debranched MO from maize starch. The electrophoretic mobility mu of the drug was decreased in dependence of the MO concentration. However calculation of equilibrium binding constants from the ACE experiments was not possible because of the relatively weak influence of starch degradation products on the electrophoretic behaviour of the drug. With both methods the same tendency in strength of interactions between the different MO and P was found. Molecular parameters of the MO and their viscosity play a role in the interactions and in the decreased permeation of the drug.

Biological Transport↗
PubMed1996

Application of capillary electrophoresis of characterizing interactions between drugs and bile salts. Part I.

Capillary electrophoresis offers a new way of characterizing interactions between different bile salts and drugs. The observed interactions were characterized with modified model functions known from affinity capillary electrophoresis (ACE) an micellar electrokinetic capillary electrophoresis (MECC). The methodical background of both methods is the change of the ionic mobility of the drug caused by partition between phases and aggregation with the bile salt molecules, respectively. This phenomenon is described by two different physicochemical models. A parameter estimation was carried out in order to obtain the partition coefficients KP as well as constants for the aggregate formation KA. Furthermore, an expression about the specific molar volume of the micelles and stoichiometric coefficients can be given.

Atenolol↗
PubMed1996

Characterization of interactions between bile salts and drugs by micellar electrokinetic capillary chromatography. Part I.

PURPOSE: The general properties of micellar electrokinetic capillary chromatography (MECC) were utilized to characterize the strength of interactions between bile salts and biological active substances. METHODS: For that purpose various bile salts were used as micellar pseudostationary phase in the background electrolyte. Furthermore, a physicochemical model was applied and the effective partition coefficients between micellar and water phase were calculated in order to evaluate the strength of interactions between bile acids and the drugs. RESULTS: It was found that the interactions between the selected drugs and bile salts depend both on the lipohilicity of the drugs and on the charge of the components. Only hydrophobic, cationic drugs such as quinine and propranolol are able to interact with these surface active agents. CONCLUSIONS: MECC is a valuable method to characterize interactions such occurring between drugs and bile salts.

Bile Acids and Salts↗
PubMed1996

Inducible nitric oxide synthase expression in cerebrovascular smooth muscle and neutrophils after traumatic brain injury in immature rats.

The inflammatory response after traumatic brain injury (TBI) includes cytokine production, leukocyte infiltration, and microglial activation. Production of nitric oxide by inducible nitric oxide synthase (iNOS) occurs during acute inflammation outside of the CNS and in models of cerebral ischemia, and therefore may contribute to the inflammatory response after TBI. The purpose of this study was to localize and define the time course of iNOS expression after TBI in the immature rat. Immature Wistar rats (age 3.5-4.5 wk) were anesthetized and subjected to percussive trauma to the right parietal cortex. Nontraumatized rats were used as controls (n = 7). At 2, 24, 48, or 168 h (n = 3/group) posttrauma rats were killed by perfusion fixation. Brains were removed, frozen, sectioned, immunostained with antibodies against iNOS and glial fibrillary acidic protein (GFAP, a marker specific for astrocytes), and imaged using fluorescent detection systems. There was no detectable expression of iNOS in control brains. At 2h, minimal cerebrovascular iNOS expression was seen in the peritrauma area. At 24 and 48 h, there was marked peritrauma cerebrovascular iNOS expression that appeared to be restricted to vascular smooth muscle cells and infiltrated leukocytes. Further dual-immunolabeling showed that the leukocytes expressing iNOS were predominantly neutrophils. At 168 h, iNOS expression was no longer detectable. iNOS was not detectable in GFAP-positive cells. The prominent expression of iNOS protein after TBI in cerebrovascular smooth muscle cells and infiltrated neutrophils suggests that iNOS may play a role in cerebrovascular disturbances and secondary brain injury after trauma.

Animals↗
PubMed1995

Interleukin 4 retards dissemination of a human B-cell lymphoma in severe combined immunodeficient mice.

We have examined the antitumor activity of murine interleukin 4 (IL-4) on development of a human B-cell lymphoma (Daudi) in severe combined immunodeficient (SCID) mice. The progression of Daudi cells in SCID mice was followed by histological staining and by flow cytometric analysis of CD20+ cells in spleen, liver, bone marrow, and kidneys. By day 35, CD20+ Daudi cells populate the majority of space in the bone marrow and kidney in vehicle-treated mice. Mice receiving i.p. injections of IL-4, commencing 7 or 14 days after tumor inoculation, exhibit a reduction in tumor burden as well as a decrease in CD20+ cells in both compartments. The antitumor activity of IL-4 does not appear to be due to an antiproliferative effect, since the cytokine does not alter the growth of Daudi cells in vitro, nor does it correlate with any marked cellular infiltrate in tumor-bearing tissues. In 51Cr-release assays, we observed that splenocytes from IL-4-treated mice were capable of lysing YAC-1 but not Daudi cell targets. Our findings demonstrate that: (a) systemic administration of IL-4 retards dissemination of a human B-cell lymphoma in SCID mice; and (b) antitumor activity elicited by IL-4 may not involve a direct effect on proliferation of Daudi cells or on the induction of cytolytic activity.

Animals↗
PubMed1995

Metallothionein protects against the cytotoxic and DNA-damaging effects of nitric oxide.

In inflammatory states, nitric oxide (.NO) may be synthesized from precursor L-arginine via inducible .NO synthase (iNOS) in large amounts for prolonged periods of time. When .NO acts as an effector molecule under these conditions, it may be toxic to cells by inhibition of iron-containing enzymes or initiation of DNA single-strand breaks. In contrast to molecular targets of .NO, considerably less is known regarding mechanisms by which cells become resistant to .NO. Metallothionein (MT), the major protein thiol induced in cells exposed to cytokines and bacterial products, is capable of forming iron-dinitrosyl thiolates in vitro. Therefore, we tested the hypothesis that overexpression of MT reduces the sensitivity of NIH 3T3 cells to the .NO donor, S-nitrosoacetylpenicillamine (SNAP), and to .NO released from cells (NIH 3T3-DFG-iNOS) after infection with a retroviral vector expressing human iNOS gene. There was a 4-fold increase in MT in cells transfected with the mouse MT-1 gene (NIH 3T3/MT) compared to cells transfected with the promoter-free inverted gene (NIH 3T3/TM). NIH 3T3/MT cells were more resistant than NIH 3T3/TM cells to the cytotoxic effects of SNAP (0.1-1.0 mM) or .NO released from NIH 3T3-DFG-iNOS cells. A brief (1 h) exposure to 10 mM SNAP caused DNA single-strand breaks that were 9-fold greater in NIH 3T3/TM compared to NIH 3T3/MT cells. Electron paramagnetic resonance spectroscopy of NIH 3T3 cells revealed a greater peak at g = 2.04 (e.g., iron-dinitrosyl complex) in NIH 3T3/MT than NIH 3T3/TM cells. These data are consistent with a role for cytoplasmic MT in interacting with .NO and reducing .NO-induced cyto- and nuclear toxicity.

3T3 Cells↗
PubMed1995

Retrovirus-mediated gene transfer in lungs of living fetal sheep.

In utero somatic gene transfer may be a useful therapeutic strategy for a variety of inherited disorders. In the present study, we demonstrate transgene expression in the airways of fetal lamb lungs, 2-3 weeks after injection of Moloney murine leukemia retrovirus based vectors containing cDNA for beta-galactosidase (lacZ) or human interleukin receptor antagonist protein (IRAP), into the fluid filled future airspace of fully catheterized twin fetal lambs (104-117 days gestational age; term 147 days). Expression of lacZ or IRAP was limited to the twin that received the respective vector and was apparent, at light microscopic level, in the epithelium and submucosal space of proximal airways, and to a lesser extent, in the respiratory epithelium of the distal airways. These data demonstrate for the first time that transfer of foreign DNA to fetal lung can be accomplished. These findings support the use of retroviral vectors for somatic lung DNA transfer and suggest that inherited disorders such as cystic fibrosis may be approached therapeutically via gene transfer, in utero.

Animals↗
PubMed1994

Cytoplasmic metallothionein overexpression protects NIH 3T3 cells from tert-butyl hydroperoxide toxicity.

Metallothioneins (MT) are ubiquitous low molecular weight metal-binding proteins that may act as antioxidants. We examined the sensitivity of NIH 3T3 cells transfected with a plasmid containing mouse metallothionein-I gene (NIH3T3/MT) to the membrane permeant oxidant, tert-butyl hydroperoxide (tBH). NIH3T3/MT cells had a 4-fold increase in intracellular metallothionein as compared to cells transfected with a plasmid containing an inverted gene (NIH3T3/TM). Newly expressed metallothionein appeared to be localized to the cytoplasm as determined by immunofluorescence and confocal microscopy. NIH3T3/MT cells were 6 times more resistant than NIH3T3/TM cells to the cytotoxic effects of tBH. The antioxidant activity of NIH3T3/MT cells was greater than NIH3T3/TM cells, since exposure to tBH resulted in significantly less: (a) thiobarbituric acid-reactive substances and (b) fluorescence after loading cells with the oxidant-sensitive dye, 2'7'-dichlorodihydrofluorescein diacetate. Furthermore, homogenates of NIH3T3/MT cells were more capable of scavenging in vitro generated phenoxyl radicals as quantified by electron spin resonance detection. In contrast, overexpression of cytoplasmic MT did not protect against tBH-induced DNA damage, suggesting that subcellular location of MT is important for its function and that DNA damage is not a key determinant of cytotoxicity. These data provide direct support for an antioxidant role for MT, since physiologically relevant elevations in cytoplasmic MT interfere with tBH-induced cytotoxic peroxidation.

3T3 Cells↗
PubMed1994

Stimulation of cytolytic activity by interleukin-10.

Interleukin-10 (IL-10), originally identified as an inhibitor of cytokine and monokine synthesis [e.g., IL-2, interferon-gamma (IFN-gamma), and tumor necrosis factor (TNF-alpha)], modulates a wide range of immunologic activities. In the present study we have examined the induction of non-major histocompatibility complex-restricted cytolytic activity in human peripheral blood mononuclear cells (PBMCs). PBMCs incubated with human IL-10 for 3 days were used as effector cells in cytotoxicity (i.e., 51Cr release) assays against a panel of human tumor cells. In a concentration-dependent manner. IL-10 stimulated or potentiated lytic activity against several human tumor cell lines. Induction of cytolytic activities by IL-10 was neutralized by anti-IL-10 monoclonal antibodies but not by antibodies against IFN-gamma or TNF-alpha. Co-incubation of PB-MCs with IL-10 and IL-2 or IL-10 and IFN-alpha augmented cytolytic activity, in particular at lower effector-to-target ratios. IL-2-induced release of TNF-alpha was dramatically reduced by IL-10; however, the expression of lymphokine-activated killer (LAK) activity was not affected. PBMCs preactivated with IL-10 before addition of IL-2 displayed higher levels of LAK activity. Inhibition of IL-2-driven LAK activity by IL-4 is alleviated by IL-10. Finally, IL-10 is not affected by inhibitors of IL-2, such as IL-4 and transforming growth factor-beta. Potential application of IL-10 to anti-tumor therapies is discussed.

Antibodies, Monoclonal↗
PubMed1994

Culture of pulmonary microvascular smooth muscle cells from intraacinar arteries of the rat: characterization and inducible production of nitric oxide.

Pulmonary arterial microvascular smooth muscle function governs many aspects of lung physiology and pathophysiology. Acutely, microvascular smooth muscle cells (SMC) modulate pulmonary vascular resistance; chronically, they contribute to vascular remodeling. Recent work has also suggested a possible immune function for pulmonary smooth muscle through cytokine-stimulated nitric oxide production. To facilitate study of the mechanisms underlying these functions, we have developed methods for isolating pulmonary arterial microvessels from the rat and culturing SMC from these vessels. The pulmonary arterial circulation was filled with a suspension of iron oxide in agar, and a subpleural tissue sample was obtained. The vessels were cleared of surrounding lung parenchyma by partial collagenase digestion, and the iron-containing arteries were separated magnetically. The diameter of the harvested arteries confirmed an intraacinar origin, and the cultured cells expressed smooth muscle isoforms of alpha-actin and myosin but did not take up acetylated low density lipoprotein. To assess a possible immune effector role for these cells, confluent monolayers were stimulated with cytokines and endotoxin. At 24 h, immunofluorescent staining for inducible nitric oxide synthase was prominent within these cells. Nitric oxide production, as measured by nitrite levels in the cell-conditioned medium, was also markedly elevated but reduced by adding NG-monomethyl-L-arginine. We conclude that rat pulmonary arterial microvascular SMC can be obtained by the iron oxide infusion method and that these cells express an inducible nitric oxide synthase after cytokine stimulation.

Amino Acid Oxidoreductases↗
PubMed1991

Interaction of cisplatin with other cytotoxics and non-steroidal anti-inflammatory drugs.

This study investigated a possible interaction between cisplatin, other cytotoxics and non-steroidal anti-inflammatory drugs. Experiments were performed in quadruplicate. Plasma was spiked with cisplatin with or without another cytotoxic or non-steroidal anti-inflammatory drug. The results were analysed by Student's t-test and a p value of less than 0.05 was accepted as statistically significant. No interaction between cisplatin and the other cytotoxics was demonstrated. However, an increase in free cisplatin was noted when mixed with indomethacin (p = 0.019). No interaction with the other non-steroidal anti-inflammatory drugs was demonstrated.

Adult↗
PubMed1990

Reconstituted basement membrane enhances neurite outgrowth in PC12 cells induced by nerve growth factor.

Rat pheochromocytoma cells (PC12) respond to nerve growth factor (NGF) by elaborating neurites. We have studied the effect of extracellular matrix proteins on responsiveness of PC12 cells to NGF. NGF elicited neurite outgrowth in cells plated on collagen, fibronectin, or laminin within 48-72 h. In contrast, cells entrapped in reconstituted basement membrane prepared from the Engelbreth-Holm-Swarm tumor (EHS-BM) responded within 24 h. Cells plated on collagen or fibronectin required a minimal dose of 50 ng/ml NGF to achieve the same effect as cells entrapped in EHS-BM at 1 ng/ml NGF. Neurites displayed by cells plated in EHS-BM were more extensively branched and remained intact up to 21 days following a single administration of NGF.

Adrenal Gland Neoplasms↗
PubMed1989

Modulation of growth factor induced fiber outgrowth in rat pheochromocytoma (PC12) cells by a fibronectin receptor antibody.

Rat pheochromocytoma PC12 cells respond to the binding of nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) by extending neurites in a manner resembling sympathetic neurons. This response requires cell attachment to an appropriate substratum (Fujii et al., J. Neurosci., 2:1157, 1982); attachment factors which function in this capacity include the adhesive proteins fibronectin and laminin. Incubating PC12 cells with a polyclonal antiserum directed against a putative 140-kDa fibroblast cell surface fibronectin receptor (anti-gp140) perturbed spreading but not attachment of the cells to fibronectin and laminin substrates. However, in the presence of anti-gp 140 or its Fab fragments, NGF-stimulated neurite outgrowth was dramatically reduced. The antibody also caused a retraction of previously extended neurites. SDS-PAGE analysis of immunoprecipitates of PC12 cells surface labeled with 125I identified a prominent 120-140-kDa band, suggesting that the site of anti-gp140 action in PC12 cells is also through a fibronectin receptor.

Adrenal Gland Neoplasms↗
PubMed1989

The blood-brain barrier and response of C.N.S. metastases to chemotherapy.

A case demonstrating a differential effect of chemotherapy on a pineal metastasis and parenchymal cerebral metastases is described. At presentation, extensive metastatic small cell carcinoma of the lung was present and CT scanning showed an apparently solitary metastasis in the pineal. The clinical course and serial CT scans showed significant improvement of the pineal tumor and simultaneous development of multiple intra-cerebral metastases. This case confirms that the pineal gland is excluded from the blood-brain barrier, and indicates the clinical importance of the effect of the blood-brain barrier in the responsiveness of CNS metastases to chemotherapy.

Blood-Brain Barrier↗
PubMed1989

Metastatic bone marrow involvement from supraglottic squamous cell carcinoma.

A case of an aggressive supraglottic squamous cell carcinoma, which was managed with neo-adjuvant chemotherapy and radical surgery, is described. The post-operative course was of rapid deterioration and death due to progressive metastatic disease involving bone marrow and liver. This is the first reported case of bone marrow infiltration by squamous cell carcinoma of the head and neck diagnosed ante-mortem. The incidence and pattern of metastatic disease from head and neck tumours is reviewed, and the importance of initial staging in determining the risk of distant metastatic disease is emphasised.

Bone Marrow↗