[Development of a bovine combined Rotavirus-Escherichia coli vaccine].
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Animals↗
Biomedical subjects
B Nagy
Publications and source records attributed to B Nagy.
[Experiences in the production of oil emulsion vaccines].
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Adjuvants, Immunologic↗
Chemotactic activity of bronchoalveolar lavage fluid from children with recurrent obstructive bronchitis.
Boyden's method was used to assess the chemotactic activity of bronchoalveolar lavage (BAL) fluid samples from patients aged 1-6 ys with recurrent obstructive bronchitis when signs of chronic mucosal inflammation were observed bronchoscopically. BAL was performed to reveal features of this mucosal inflammation by analysing the lavagable cells and soluble factors. In comparison with the chemotactic effect of casein, the activity of the fluid proved to be high for polymorphonuclear leukocytes (PMNs), but significantly low for mononuclear cells. After treatment of antibodies to C3 and C5, the activity was decreased considerably, but not to a minimum. Presumably, other chemo-attractants (leukotriens, enzymes) can also be found in the lavage fluid beside macrophage- or serum-derived and locally activated complement components. A comparison of complement components/albumin ratios in BAL fluid with serum complement components/albumin ratios suggested a significant local production and/or concentration of these factors. On the basis of our results, an accumulation of PMNs could be expected in the differential cell count, but an increased influx of macrophages was detected. Other amplifying or inhibitor systems may play an important role in the accumulation of PMNs in vivo.
Bronchitis↗
[The acetylator phenotype affects the antipyrine metabolism inhibiting action of cimetidine].
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Acetylation↗
Membrane defects in Duchenne dystrophy: protease affecting sarcoplasmic reticulum.
Human muscle sarcoplasmic reticulum (SR) yields three major protein bands. The percent distribution of the mean values of the bands from 15 normal human muscles was 55.4, 14.6, and 30.0 for the 100, 55, and 45-kDa mass proteins, respectively. A mean distribution similar to that in normal muscle SR was found in preparations from 7 patients with polymyositis and from 7 patients with myotonic dystrophy. In 12 preparations from patients with Duchenne dystrophy, the protein distribution differed from that of preparations from normal muscle. The 100-kDa mass protein band was decreased, whereas the 55- and 45-kDa mass bands were increased. Protease inhibitors pepstatin A, antipain, and leupeptin, as well as ethyleneglycol-bis(aminoethyl ether)-N,N,N',N'-tetraacetic acid or ethylenediaminetetraacetic acid, significantly reduced this change. However, some of the changes cannot be prevented by the addition of inhibitors and must be expressed in vivo. Neither protease inhibitors nor chelators affected SR preparations from normal muscle. We found a five- to ten-fold increase in calcium-activated neutral protease activity in Duchenne dystrophic muscles that degraded the calcium-adenosinetriphosphatase of SR. The active protease was identified as the cytoplasmic calpain II. The increased activity in Duchenne muscles may explain many reported abnormalities.
Electrophoresis, Polyacrylamide Gel↗
Amino acids derived from Titan tholins.
An organic heteropolymer (Titan tholin) was produced by continuous dc discharge through a 0.9 N2/0.1 CH4 gas mixture at 0.2 mbar pressure, roughly simulating the cloudtop atmosphere of Titan. Treatment of this tholin with 6N HCl yielded 16 amino acids by gas chromatography after derivatization of N-trifluroacetyl isopropyl esters on two different capillary columns. Identifications were confirmed by GC/MS. Glycine, aspartic acid, and alpha- and beta-alanine were produced in greatest abundance; the total yield of amino acids was approximately 10(-2), approximately equal to the yield of urea. The presence of "nonbiological" amino acids, the absence of serine, and the fact that the amino acids are racemic within experimental error together indicate that these molecules are not due to microbial or other contamination, but are derived from the tholin. In addition to the HCN, HC2CN, and (CN)2 found by Voyager, nitriles and aminonitriles should be sought in the Titanian atmosphere and, eventually, amino acids on the surface. These results suggest that episodes of liquid water in the past or future of Titan might lead to major further steps in prebiological organic chemistry on that body.
Amino Acids↗
Protective effects of 2-[(aminopropyl)amino] ethanethiol against bleomycin and nitrogen mustard-induced mutagenicity in V79 cells.
This study examines the effects of the radioprotector 2-[(aminopropyl)amino] ethanethiol (WR-1065) on bleomycin (BLM) and nitrogen mustard- (HN2) induced cytotoxicity, DNA damage, and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster cells. The anti-mutagenic effect of WR-1065 on cis-diamminedichloroplatinum (cis-DDP) and radiation- (XRT) induced HGPRT mutations was also evaluated for comparative purposes. WR-1065 (4 mM) was added prior to exposure of cells to therapy agents. All exposure times were 30 min. and both cell survival and mutagenesis were assayed. WR-1065 was effective in protecting against both effects. The induction of mutants corrected for background by BLM, HN2, cis-DDP, or XRT was linear in all cases. Mutation frequencies without WR-1065 were 78 X 10(-6) per unit BLM, 66 X 10(-7) per microgram HN2, 25 X 10(-7) per microgram cis-DDP; and 87 X 10(-7) per Gy of XRT. With WR-1065, these were reduced to 37 X 10(-6) per unit BLM, 40 X 10(-7) per microgram HN2, 1 X 10(-7) per microgram cis-DDP, and 44 X 10(-7) per Gy of XRT. Mutation protection factors (MPF), a ratio of the corresponding slopes of the mutation induction curves, with and without WR-1065 were: BLM, MPF = 2.8; HN2, MPF = 3.4; cis-DDP, MPF = 7.1; and XRT, MPF = 5.1. Single-strand-break (SSB) formation in DNA by BLM or HN2, assayed by alkaline elution, was protected against by WR-1065. WR-1065 did not induce SSB in control cells. The reduction of the mutagenic effects of agents used in radiation and chemotherapy by radioprotectors may be an important additional benefit for consideration in their use in cancer treatment.
Animals↗
The effect of 2-[(aminopropyl)amino] ethanethiol (WR1065) on radiation-induced DNA damage and repair and cell progression in V79 cells.
The radioprotector 2-[(aminopropyl)amino] ethanethiol (WR1065) was investigated with respect to its ability to affect radiation-induced DNA damage and repair in V79 cells. Studies were performed to evaluate the protector under conditions in which it is known to be effective in reducing the cytotoxic and mutagenic effects of gamma-irradiation. At a concentration of 4 mM, WR1065 protected against the formation of single strand breaks (SSB), as determined by the method of alkaline elution, when it was present during irradiation. The protector appeared, however, to inhibit the subsequent postirradiation repair or rejoining of SSB. While repair was complete within 24 h, the protector reduced the rate of repair by a factor of 3. This inhibitory effect on the rate of repair did not correlate with either measured differences in cell survival or mutagenesis. The radioprotector was also investigated with respect to its ability to affect cell cycle progression. WR1065 present in the growth medium inhibited the progression of cells through S-phase, and cell-doubling time following a 3 h exposure to the protector was increased from 11 to 18 h. These data are consistent with the well characterized property of thiols to inhibit DNA polymerase activity. It was concluded that, while the presence of WR1065 during irradiation reduced SSB-DNA damage, its effect on the subsequent rejoining of these breaks could not be correlated with its observed effect on protecting against radiation-induced mutagenesis. It may be that the inhibition of cell-cycle progression by the protector allowed more time to enhance the fidelity of repair as measured by the protector's ability to protect against radiation-induced mutagenesis.
Animals↗
2-[(Aminopropyl)amino]ethanethiol (WR1065) is anti-neoplastic and anti-mutagenic when given during 60Co gamma-ray irradiation.
We have studied the effect of 2-[(aminopropyl)amino]ethanethiol (WR1065) on the induction of neoplastic transformation using 10T1/2 cells and on mutation at the hypoxanthine guanine phosphoribosyl transferase (HGPRT) locus using Chinese hamster V79 cells. Here we report the first observations that treatment of 10T1/2 cells with 1 mM WR1065 for a total of 35 min during irradiation with 60Co gamma-rays significantly reduces the incidence of neoplastic transformation while having no effect on cell viability. In a similar experiment with V79 cells in which 4 mM WR1065 was used, we found a significant reduction in mutation frequency at the HGPRT locus and significant protection against cell killing. These results suggest that WR1065 acts to modulate both acute damage and sub-lethal processes that lead to mutation and neoplastic transformation. Beyond the purely mechanistic approach of these studies, the potential application of these agents to minimizing the long-term neoplastic effects of radiation or chemotherapeutic agents currently in use for treating potentially curable cancer patients should be further investigated.
Animals↗
Immunoglobulin levels in bronchoalveolar lavage fluid of children with recurrent obstructive bronchitis.
Bronchoalveolar lavage was performed in 22 children with recurrent obstructive bronchitis and the recovered lavage fluid samples were analysed for concentration of IgA, IgG, IgM, IgE and C3. Previously a significant influx of exudate macrophages and persistence of bacteria on the bronchoalveolar surface were detected in these patients and a severe mucosal inflammation was observed bronchoscopically. The relative lavage fluid levels of immunoglobulins to albumin were significantly higher than in serum, indicating a local production of these proteins. The elevated levels of C3 indicated a high activity of the macrophages and the complement system. It is concluded that the mucosal inflammation in patients with recurrent obstructive symptoms cannot be attributed to a deficiency of immunoglobulins either in blood or in bronchial secretions.
Bronchitis↗
Characterization of cells in bronchoalveolar lavage fluid of children with recurrent obstructive bronchitis.
In children 1 to 6 years of age with recurrent obstructive bronchitis bronchoalveolar lavage was performed to obtain material to allow characterization of the cell-types present on the bronchoalveolar surface. Recurrent infections may produce a chronic mucosal inflammation which was observed bronchoscopically in the symptom-free periods, too. Two main components of the lavaged cells were alveolar and NAML macrophages with morphological, cytochemical and functional features of mononuclear phagocytes. It seemed that the persistence of bacteria in the respiratory tract induces an increased influx of macrophages without PMN accumulation. This inflammation may constitute the morphological basis of frequent relapses which sometimes occur without any sign of respiratory infection.
Bronchi↗
Protection against cis-diamminedichloroplatinum cytotoxicity and mutagenicity in V79 cells by 2-[(aminopropyl)amino]ethanethiol.
The effect(s) of the radioprotector 2-[(aminopropyl)amino]ethanethiol (WR1065) on cis-diamminedichloroplatinum(II) (cis-DDP)-induced cytotoxicity and mutagenesis at the hypoxanthineguanine phosphoribosyl transferase locus in V79 Chinese hamster cells was examined. With a standard exposure time of 30 min for both agents, WR1065, at a final working concentration of 4mM, was added to cells either prior to, during, or immediately following treatment with selected doses of cis-DDP. With respect to cell survival, dose modification factors of 2.9, 1.4, and 1.4 were obtained for cells treated under each of these conditions, respectively. The induction of mutants under all conditions was linear as a function of cis-DDP concentration. Mutation frequencies per microgram of cis-DDP were 25 X 10(-7), 1 X 10(-7), 5 X 10(-7), and 11 X 10(-7) for protocols involving no protector present or WR1065 added before, during, or after cis-DDP treatment, respectively. No WR1065-mediated cytotoxicity to cells derived from either wild-type or mutant colonies was observed. These data demonstrate that WR1065, the free thiol of S-2-(3-amino-propylamino)ethyl phosphorothioic acid (WR2721) which is currently being evaluated in clinical trials, affords substantial protection against the cytotoxic and mutagenic effects of cis-DDP, with the most effective protection occurring when the protector is administered prior to cis-DDP treatment. Due to their ability to better protect normal as compared to tumor tissue against acute effects, these protectors have generated considerable interest for use in improving the therapeutic gain of radiation therapy and chemotherapy. The ability of these compounds to also protect against the mutagenic effects of therapy agents may be an important additional benefit for consideration in their use in the treatment of human neoplasia.
Animals↗
The radioprotector WR1065 reduces radiation-induced mutations at the hypoxanthine-guanine phosphoribosyl transferase locus in V79 cells.
N-(2-mercaptoethyl)-1,3-diaminopropane (WR1065) protects against radiation-induced cell killing and mutagenesis at the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus in V79 Chinese hamster lung fibroblast cells. At a concentration of 4 mM, WR1065 was found to be effective in protecting against radiation-induced cell lethality only if present during irradiation, e.g., a dose modification factor (DMF) of 1.9. No protective effect was observed if the protector was added within 5 min after irradiation or 3 h later, e.g., DMFs of 1.0 and 1.1, respectively. The effect of WR1065 on radiation-induced mutation, expressed as resistance to the cytotoxic purine analogue 6-thioguanine (HGPRT), was also investigated. In contrast to the treatment-schedule dependence for protection by WR1065 against cell killing, this agent was effective in reducing radiation-induced mutations regardless of when it was administered. Following a dose of 10 Gy of 60Co gamma-rays, the mutation frequencies observed per 10(6) survivors were 77 +/- 8, 27 +/- 6, 42 +/- 7, and 42 +/- 7 for radiation only, and WR1065 present during, immediately after, or 3 h after irradiation. These data suggest that although a segment of radiation-induced damage leading to reproductive death cannot be modulated through the postirradiation action of WR1065, processes leading to the fixation of gross genetic damage and mutation induction in surviving cells can be effectively altered and interfered with leading to a marked reduction in mutation frequency.
Animals↗
Uranium-bearing stratiform organic matter in paleoplacers of the lower Huronian Supergroup, Elliot Lake--Blind River region, Canada.
The Elliot Lake-Blind River, Ontario, paleoplacer deposits in the basal Matineda Formation, lowermost member of the 2.25-2.45 Ga old Huronian Supergroup, contain organic matter chemically consistent with kerogen. This substance is also referred to as thucholite. Uranium ores and some gold occur here, and these minerals may be in close association with the kerogen. Two uraniferous and auriferous stratiform kerogens, obtained from the Denison Mines Limited's Denison mine and Rio Algom Limited's Stanleigh mine, have been analyzed by combined high-vacuum pyrolysis--gas chromatography--mass spectrometry and by neutron activation. The reflectances of these samples have also been determined. Related samples containing dispersed kerogen have been examined by backscattered scanning electron microscopy. The polymer-like matrix of the two stratiform kerogens consists of aromatic, alkyl aromatic hydrocarbon, and sulphur moieties and contains 20 and 32% uranium with gold abundances in the parts per billion range. The reflectances of the two kerogens are generally higher than those of the dispersed kerogens; the atomic H/C ratios of the former are approximately 0.6 and approximately 0.4. Backscattered scanning electron microscopy and petrographic observations reveal a complex diagenetic history. Stratigraphic position and supportive analytical data suggest that the stratiform kerogens were probably derived from ancient mats of cyanobacteria, subjected to various radiation-induced reactions, and, at least in part, were affected in a manner similar to the surrounding rocks. The latter experienced physical and chemical diagenetic reactions, which often caused repeated mineral fracturing and led to the local development of authigenic carbonates and feldspar. Some of the chemical nature and history of the stratiform kerogens resemble those of the Witwatersrand carbon seam kerogen.
Canada↗
Colonization of infant mice by K99+ Escherichia coli and lack of colonization by Streptococcus faecium M74.
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Animals↗
Inhibition of small intestinal colonization of enterotoxigenic Escherichia coli by streptococcus faecium M74 in pigs.
Colonizing and anti E. coli activity of S. faecium M74 was tested by oral inoculation of cesarean derived, colostrum deprived piglets with Streptococcus faecium M74 and subsequently with a heat stable enterotoxin (ST) producing E. coli (O101 : K30 : K99 : NM). Enterotoxin neutralization and co-culture studies were also performed in vitro. Bacterial counts in 10 cm ileal segments, fluorescein antibody stained cryostat sections, as well as 0.5 micron sections from the ilea of the experimental pigs taken 16 hours post exposure to enterotoxic E. coli (ETEC) all indicated that S. faecium M74 could not colonize the ileum of the newborn pigs, in a single high (7 X 10(8) - 3 X 10(10)) dose either in TSB or in milk suspension, in contrast to the ETEC. However, S. faecium given in milk suspension resulted a marked decrease in ileal colonization of ETEC and in weight loss of piglets. In vitro experiments indicated that neither extracellular nor cell-bound products of S. faecium M74 could neutralise ST, but there was a significant reduction of pH in the TSB cultures of S. faecium that was accompanied by a reduction in ETEC counts of the mixed cultures.
Animals↗
Cell survival after the combined action of manganese (MnCl2) and X-rays in synchronized Chinese hamster cells.
The interactions between the effects of manganese chloride and X-rays were studied in synchronized populations of V79 Chinese hamster fibroblasts. The cells were selected by shaking off asynchronous cultures for detachment of mitotic cells which were plated in petri dishes and exposed to various treatments. Irradiation was carried out with a Philips RT-100 X-ray unit. A final concentration of 0.25 mM MnCl2 was used. The main parameter was the colony forming ability of the surviving cell fraction. When MnCl2 was administered over 1 h, its toxicity was low regardless of the phase of the cell cycle. Administered separately, 2 Gy irradiation produced only a slight decrease in survival, less marked in the S phase. However, the two agents together induced a synergistic inhibition of the surviving fraction in the S phase when the metal was given immediately after irradiation. If manganese was administered 3 h after irradiation the two inhibitory effects apparently remained only additive. It seems that MnCl2 can impair some repair processes starting immediately after irradiation.
Animals↗
The organic aerosols of Titan.
A dark reddish organic solid, called tholin, is synthesized from simulated Titanian atmospheres by irradiation with high energy electrons in a plasma discharge. The visible reflection spectrum of this tholin is found to be similar to that of high altitude aerosols responsible for the albedo and reddish color of Titan. The real (n) and imaginary (k) parts of the complex refractive index of thin films of Titan tholin prepared by continuous D.C. discharge through a 0.9 N2/0.1 CH4 gas mixture at 0.2 mb is determined from x-ray to microwave frequencies. Values of n (approximately equal to 1.65) and k (approximately equal to 0.004 to 0.08) in the visible are consistent with deductions made by ground-based and spaceborne observations of Titan. Many infrared absorption features are present in k (lambda), including the 4.6 micrometers nitrile band. Molecular analysis of the volatile component of this tholin was performed by sequential and non-sequential pyrolytic gas chromatography/mass spectrometry. More than one hundred organic compounds are released; tentative identifications include saturated and unsaturated aliphatic hydrocarbons, substituted polycyclic aromatics, nitriles, amines, pyrroles, pyrazines, pyridines, pyrimidines, and the purine, adenine. In addition, acid hydrolysis produces a racemic mixture of biological and non-biological amino acids. Many of these molecules are implicated in the origin of life on Earth, suggesting Titan as a contemporary laboratory environment for prebiological organic chemistry on a planetary scale.
Aerosols↗