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At least 991 records · Page 55Linked to original sources
PubMed1988

Studies on activation variables in multiple sclerosis.

The study aimed to evaluate the usefulness of some selected immune variables as markers of disease activation, progression and possible etiopathogenesis of multiple sclerosis (MS). Levels of neopterin, a factor known to be released from macrophages and monocytes at increased rates in cellular immune reactions were higher in cerebrospinal fluid (CSF) from patients with MS during exacerbations in comparison with remissions. The elevation in CSF during exacerbations was not reflected in serum. Expression of HLA class II antigens (DR) on activated T lymphocytes in CSF were encountered at elevated percentage in only 10% of patients with MS, against 81% of patients with acute aseptic meningoencephalitis (AM). In patients with AM, the DR expression on CSF T cells was found on both CD8+ and CD4+ cells. There was no correlation between percentage of DR+ T cells in CSF and disability, exacerbation/remission or recent onset of disease in patients with MS. Phenotypic characterization of mononuclear cells in CSF and peripheral blood revealed increased proportion of CD5+ cells in CSF compared to peripheral blood which in MS was not reflected by any changes in CD4+ or CD8+ cells, while in AM the increase of CD5+ cells in CSF was followed by increase of CD4+ cells. A population of CD5+, CD8-, CD4- cells might be postulated to occur in MS CSF. Levels of CD8+ cells in peripheral blood and CSF did not fluctuate in parallel with disease activity as measured as clinical exacerbation. OKB7+, OKM1+ and HLA-DR+ cells differed significantly between CSF and peripheral blood, indicative of a selective passage of cells into the central nervous system (CNS) - CSF compartment. Proliferating cells expressing transferrin receptors (OKT9) were generally few or absent in CSF of patients with MS. MS patients' bone marrow mononuclear cells showed higher spontaneous proliferation both in comparison with cells from bone marrow of control subjects and peripheral blood lymphocytes from MS patients. PHA response of bone marrow mononuclear cells from MS patients was also higher than that from controls. There was, however, no significant difference in proliferative response of peripheral blood lymphocytes between MS patients and controls. Seven of 11 MS patients showed morphological signs of activation in their bone marrow, without correlation to patients' clinical condition. Higher levels of undifferentiated or activated cells, measured as OKT10+ cells were found in peripheral blood of patients with MS compared to controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Biopterins↗
PubMed2002

A review of intensity modulated radiation therapy: incorporating a report on the seventh education workshop of the ACPSEM--ACT/NSW branch. Australasian College of Physical Scientists and Engineers in Medicine.

Intensity modulated radiation therapy (IMRT) is an evolving treatment technique that has become a clinical treatment option in several radiotherapy centres around the world. In August 2001 the ACT/NSW branch of the ACPSEM held its seventh education workshop, the subject was IMRT. This review considers the current use of IMRT and reports on the proceedings of the workshop. The workshop provided some of the theory behind IMRT, discussion of the practical issues associated with IMRT, and also involved presentations from Australian centres that had clinically implemented IMRT. The main topics of discussion were patient selection, plan assessment, multi-disciplinary approach, quality assurance and delivery of IMRT. Key points that were emphasised were the need for a balanced multi-disciplinary approach to IMRT, in both the establishment and maintenance of an IMRT program; the importance of the accuracy of the final dose distribution as compared to the minor in-field fluctuations of individual beams; and that IMRT is an emerging treatment technique, undergoing continuing development and refinement.

Australian Capital Territory↗
PubMed1976

The fluctuation test as a more sensitive system for determining induced mutation in L5178Y mouse lymphoma cells.

Luria-Delbrück fluctuation tests for the determination of the spontaneous mutation rate to ouabain resistance incultured L5178Y mouse lymphoma cells gave values in the range 0.44 to 1.03 X 10(-7) mutants per cell per generation. Addition of very low, non-toxic, levels of EMS (0.1 mM) and MMS (0.012 mM) 30-48 h before plating in selective medium gave a highly significant increase in the number of ouabain-resistant mutants. Methods for the calculation of spontaneous and induced mutation rates are discussed and a method for the computation of induced mutation rates is described. It is suggested that the modified fluctuation test is a simpler and considerably more sensitive assay for mutagens than the conventional experimental design. Some of its limitations are discussed.

Cells, Cultured↗
PubMed1984

Mouse monoclonal antibodies against the idiotype of human B cell non-Hodgkin lymphomas: production, characterization and use to monitor the progress of disease.

Four monoclonal anti-idiotype (Id) antibodies against B cell non-Hodgkin lymphomas have been made by a simple and rapid procedure for hybridoma production that does not use isolated Id-carrying immunoglobulin. Mice were immunized with plasma membranes from the tumor cells. Screening of hybridoma colonies using an autologous T cell line and a cell line bearing the same immunoglobulins as the malignant lymphocytes as well as the capping phenomenon on the patient's own tumor cells, allowed selection of hybridomas producing anti-Id antibodies. These anti-Id antibodies were used to demonstrate variations in the circulating malignant cell population and fluctuations in the level of circulating free Id.

Animals↗
PubMed1990

Pharmacokinetic and biopharmaceutic aspects of once daily treatment with metoprolol CR/ZOK: a review article.

In the development of a new controlled release preparation and its subsequent assessment there are a number of factors that need to be considered both related to the drug itself and to the pharmaceutical preparation. This review describes the biopharmaceutical and pharmacokinetic properties of metoprolol CR/ZOK, a recently introduced formulation of a widely used beta 1-selective adrenoceptor antagonist intended for once daily usage. The metoprolol CR/ZOK preparation provides reproducible dissolution and absorption properties resulting in stable plasma concentrations with minimum fluctuations over a 24-hour dosage interval. This has been shown in extensive studies comprising over 200 healthy volunteers. Considerations for a new drug preparation such as bioavailability and variability in relation to a standard treatment and the clinical significance of taking the drug with food and in increasing doses, are potential concerns that do not seem to be a problem for the therapeutic use of metoprolol CR/ZOK. Furthermore, the pharmacokinetic data achieved in young healthy subjects appear to be relevant for the treatment of patients, as shown by the consistent plasma concentration profiles obtained in elderly and in hypertensive patients.

Biopharmaceutics↗
PubMedDate not supplied

A study of phenobarbital and dilantin in neonatal seizures.

A total of 40 cases of neonatal convulsions of different nonmetabolic aetiological factors were studied. Patients with kernicterus were included in the study. Peak plasma phenobarbital concentrations after incremental loading doses of phenobarbital i.e. 10 mg/kg, 15 mg/kg, and 20 mg/kg were determined. Diphenylhydantoin was added if phenobarbital alone was unable to control seizures. In three patients, a combination of phenobarbital and diphenylhydantoin was used as the initial loading therapy. Increase in the loading dose of phenobarbital was associated with an increase in its peak plasma concentration. Despite increase in the plasma phenobarbital concentration beyond the 'therapeutic' levels suggested by the Western studies, doses of 15 mg/kg and 20 mg/kg of phenobarbital were unable to score over the traditional regimen of 10 mg/kg. Convulsions were controlled in 50% of the patients with any of these three regimens, irrespective of the aetiology. Convulsions were controlled in 7 out of the 9 cases where diphenylhydantoin was added, because of the failure of phenobarbital in controlling the convulsions as a single drug. Convulsions of all the three patients, in whom a combination of phenobarbital and diphenylhydantoin was used by random selection as the initial bolus, were controlled. Seizure effects were difficult to distinguish from drug effects but major side effects were not encountered despite the fluctuating drug levels in the sick neonate.

Dose-Response Relationship, Drug↗
PubMed1998

Spontaneous mutation in a thermoacidophilic archaeon: evaluation of genetic and physiological factors

We used direct selection of pyrE and pyrF mutants to estimate the rates of spontaneous mutation in Sulfolobus acidocaldarius as a function of genetic background and culture conditions. Fluctuation tests were applied to several genetically marked strains, including one isolated as a putative mutator strain, and to cultures grown over a wide range of temperature and other physiological conditions. The results suggested some impact of auxotrophic markers on the apparent rate of mutation, but no obvious pattern of effect of growth conditions, including those that gave evidence of being physiologically stressful.

Journal Article↗
PubMed1980

Thymidine resistance in Chinese hamster V79 cells in vitro.

Thymidine resistance in V79 Chinese hamster cells has been investigated. Phenotypically stable variant resistant lines occurred at a high frequency, and the mutation rate (2.67 x 10(-3) per cell per generation) to 400 micrograms/ml thymidine resistance as measured by the standard Luria--Delbrück fluctuation analysis was extremely high. Populations of cells maintained for extended periods in F-10 medium spontaneously increased in resistance, possibly as a result of selective pressures due to the thymidine present in F-10 medium since this change was not observed in Dulbecco's medium. The degree of resistance for a given variant was correlated with the amount of thymidine employed in its selection. Metabolic cooperation, resulting in the suppression of the resistant phenotype, was demonstrated in artificial mixtures of sensitive and resistant clonal lines. Clones isolated in high levels of thymidine possessed lowered uptake of [3H]thymidine and the depression in uptake was related to the level of resistance of the particular clone. Although thymidine kinase specific activity levels were slightly depressed in variant cell lines, growth rate and uridine uptake were unaffected. We conclude that thymidine resistance is due to a genetically controlled depression of external thymidine uptake.

Animals↗
PubMed2006

Modest changes in dietary intake across the menstrual cycle: implications for food intake research.

Food intake varies across the menstrual cycle in mammals, energy intake usually being greater in the premenstrual phase compared with the postmenstrual phase. Premenstrual increments in energy intake and a preferential selection of carbohydrate have been suggested to be greater in women with premenstrual syndrome (PMS), who may be more sensitive to cyclical hormonal or neurotransmitter fluctuations. This has direct implications for research within populations of women, especially where the primary outcome is diet or a change in energy balance. We aimed to determine whether: the premenstrual intake of energy and macronutrients differed from the postmenstrual intake; the change in intake across the menstrual cycle differed in women with PMS compared with controls; and the change in intake was related to the severity of premenstrual symptoms. We collected 3 d dietary intake data during the postmenstrual and premenstrual phases of the menstrual cycle in thirty-one women with PMS and twenty-seven control women. The consumption of energy and macronutrient intake were similar between the phases of the cycle in women with PMS. Conversely, intakes were usually greater premenstrually in control women, although not all differences were statistically significant. Exceptions were with non-milk extrinsic sugars and alcohol, which were both consumed in greater amounts in the premenstrual phase in women with PMS. Significant correlations were observed between the severity of symptoms and the change in the consumption of these nutrients. These data suggest that a consideration of the menstrual cycle phase and PMS in diet may not be warranted, especially in cross-sectional analysis, although it may need to be taken into account when examining change in intake during dietary interventions.

Adolescent↗
PubMed1996

Mitochondrial ADP/ATP carrier can be reversibly converted into a large channel by Ca2+.

Single-channel current measurements of excised patches with reconstituted purified mitochondrial ADP/ATP carrier (AAC) indicates the presence of a large low cation selective (PK+/PCl- = 4.3 +/- 0.6) channel. The channel conductance has multiple sublevels and varies from 300 to 600 pS. It has low probability of current fluctuations at Vhold up to 80-100 mV of both signs and is reversibly gated at Vhold > 150 mV. The opening of the channel is Ca(2+)-dependent (1 mM Ca2+) and can be reversibly closed on removal of Ca2+. It is strongly pH dependent and closes completely at pHex 5.2. The AAC-specific inhibitor bongkrekate inhibits the channel partially and completely in combination with ADP, whereas carboxyatractylate did not affect the conductance. The effects of these AAC-specific ligands prove that the channel activity belongs to AAC. The AAC-linked conductance can clearly be differentiated from the porin channel, rarely detected in our preparations. The properties of the AAC-linked channel coincide with the mitochondrial permeability transition pore (MTP), which is also affected by the AAC ligands [Hunter, D. R., & Haworth, R. A. (1979) Arch. Biochem. Biophys. 195, 453-459] and resembles the mitochondrial "multiconductance channel" [Kinnally, K. W., Campo, M. L., & Tedeschi, H. T. (1989) J. Bioenerg. Biomembr. 21, 497-506] or "megachannel" [Petronilli, V., Szabo, I., & Zoratti, M. (1989) FEBS Lett. 259, 137-143]. Therefore we conclude that the AAC, when converted into a large unselective channel, is a key component in the MTP and thus is involved in the ischemia-reperfusion damage and cytosolic Ca2+ oscillations. The channel opening in AAC is proposed to be caused by binding of Ca2+ to the cardiolipin, tightly bound to AAC, thus releasing positive charges within the AAC which open the gate.

Animals↗
PubMed2005

Structural changes involved in protein binding correlate with intrinsic motions of proteins in the unbound state.

Protein-protein binding usually involves structural changes that may extend beyond the rearrangements on a local scale, and cannot be explained by a classical lock-and-key mechanism. Several models have been advanced to explain the flexible binding of proteins such as the induced fit mechanism where the ligand is postulated to induce a conformational change at the interaction site upon binding, or the preexisting equilibrium hypothesis that assumes that protein samples an ensemble of conformations at equilibrium conditions and that the ligand binds selectively to an active conformation. We explored the equilibrium motions of proteins that exhibit relatively large (nonlocal) conformational changes upon protein binding using the Gaussian network model and the anisotropic network model of protein dynamics. For four complexes, LIR-1/HLA-A2, Actin/DNase I, CDK2/cyclin, and CDK6/p16(INK4a), the motions calculated for the monomer exhibiting the largest conformational change, in its unbound (free) form, correlate with the experimentally observed structural changes upon binding. This study emphasizes the preexisting equilibrium/conformational selection as a mechanism for protein-protein interaction and lends support the concept that proteins, in their native conformation, are predisposed to undergo conformational fluctuations that are relevant to, or even required for, their biological functions.

Actins↗
PubMed1996

Orientation dependence in homologous recombination.

Homologous recombination was investigated in Escherichia coli with two plasmids, each carrying the homologous region (two defective neo genes, one with an amino-end deletion and the other with a carboxyl-end deletion) in either direct or inverted orientation. Recombination efficiency was measured in recBC sbcBC and recBC sbcA strains in three ways. First, we measured the frequency of cells carrying neo+ recombinant plasmids in stationary phase. Recombination between direct repeats was much more frequent than between inverted repeats in the recBC sbcBC strain but was equally frequent in the two substrates in the recBC sbcA strain. Second, the fluctuation test was used to exclude bias by a rate difference between the recombinant and parental plasmids and led to the same conclusion. Third, direct selection for recombinants just after transformation with or without substrate double-strand breaks yielded essentially the same results. Double-strand breaks elevated recombination in both the strains and in both substrates. These results are consistent with our previous findings that the major route of recombination in recBC sbcBC strains generates only one recombinant DNA from two DNAs and in recBC sbcA strains generates two recombinant DNAs from two DNAs.

Crossing Over, Genetic↗
PubMed1988

Varix of the facial vein.

The differential diagnosis for a mass overlying the angle of the mandible but not attached to it includes lymphatic masses, benign and malignant parotid lesions, cysts, and vascular malformations. Thrombosis of the facial vein is a rare entity that now must be added to the list. This article details the first English-language description of such a thrombosis presenting as a mass. The possible causes are antecedent trauma, infection, or thrombosis of contiguous venous structures. While the diagnosis could be made preoperatively by selective venography or ultrasonography, it most likely will be made by surgical excisions. The preoperative diagnosis may be suggested by the "turkey wattle sign" (i.e., fluctuation in the size of the mass with bending the head downward). In this article the entity and differential diagnosis are reviewed and discussed.

Humans↗
PubMed1997

Stability of CII is a key element in the cold stress response of bacteriophage lambda infection.

Bacteria are known to adapt to environmental changes such as temperature fluctuations. It was found that temperature affects the lysis-lysogeny decision of lambda such that at body temperature (37 degrees C) the phage can select between the lytic and lysogenic pathways, while at ambient temperature (20 degrees C) the lytic pathway is blocked. This temperature-dependent discriminatory developmental pathway is governed mainly by the phage CII activity as a transcriptional activator. Mutations in cII or point mutations at the pRE promoter lead to an over-1,000-fold increase in mature-phage production at low temperature while mutations in cI cause a smaller increase in phage production. Interference with CII activity can restore lytic growth at low temperature. We found that at low temperature the stability of CII in vivo is greatly increased. It was also found that phage DNA replication is blocked at 20 degrees C but can be restored by supplying O and P in trans. It is proposed that CII hampers transcription of the rightward pR promoter, thus reducing the levels of the lambda O and P proteins, which are necessary for phage DNA replication. Our results implicate CII itself or host proteins affecting CII stability as a "molecular thermometer".

Bacteriophage lambda↗
PubMed1992

Exploring the connections between platelet monoamine oxidase activity and behavior. II. Impulsive personality without neuropsychological signs of disinhibition in air force pilot recruits.

Platelet monoamine oxidase (MAO) activity and serum levels of the adrenal androgen metabolite dehydroepiandrosterone sulfate (DHAS) were measured in 18 male air force pilot recruits and 19 randomly selected male conscripts. Personality scales from three inventories were given, and computerized neuropsychological tests were performed: finger tapping and alternation, reaction time, perceptual maze, perspective fluctuation and lexical decision. The pilot recruits had higher scores in sensation-seeking-related scales suggesting disinhibited behavior in the social sphere, interest in sports and activities involving some danger, and a need for change. They also had higher scores on an impulsivity scale which comprises sensation-seeking content. In the neuropsychological tasks, the pilot recruits were faster in finger-tapping alternation and performed more efficiently in the perceptual-maze test than the conscripts. In a linear discriminant analysis, neuropsychological-task performance discriminated significantly between the pilot and conscript groups. In the biochemical measures, the pilot recruits had higher DHAS levels but similar MAO activity levels compared to the conscripts, which is in contrast to what has been found in other sensation-seeking groups in comparison to controls. This result is in accordance with the normal scores in one of the impulsivity scales in the pilot recruits, and with the absence of signs of disinhibition in neuropsychological tasks. It is proposed that only some aspects of the impulsivity concept might be critical for the association with low MAO activity.

Adolescent↗
PubMed1983

Virus-host cell interaction in rat C6 glial cell cultures persistently infected with herpes simplex virus.

The virus-host cell interaction in a rat C6 glial cell line persistently infected with herpes simplex virus type 1 (HSV1) was examined. The C6 cultures infected at an MOI of 10 or 0.01 exhibited virally induced cytopathology and produced infectious virus and viral antigens for 108 and 50 days, respectively. Infectious virus was continually present in the supernatant fluids of persistently infected cultures, with only a minority of the cells having viral CPE or viral antigens at any given time. There was no obvious pattern of periodic cyclical viral replication in these cultures; no predictable regularity in the fluctuations of virus production was evident. 'Cured' cultures were as susceptible to re-infection with HSV1 as previously uninfected cultures; thus, there was no selection of a subpopulation of C6 cells resistant to subsequent challenge with HSV1. The virus recovered from persistently infected cultures was more infectious for C6 cells relative to HeLa cells than was the original virus stock. Significant levels of interferon were not detected in HSV1-infected C6 cultures during either the acute or persistent phases of infection or in 'cured' cultures.

Animals↗
PubMed2006

Predicting effects on aquatic organisms from fluctuating or pulsed exposure to pesticides.

Exposure of aquatic nontarget organisms to pesticides almost always occurs as pulses or fluctuating concentrations. Extrapolation from laboratory to field thus depends on an understanding and ability to simulate effects resulting from these types of exposure. This paper reviews models that may be used to predict effects on aquatic organisms resulting from time-varying exposure to pesticides. We evaluate and compare the theoretical basis of these models and their applicability to the simulation of effects from fluctuating exposures. The many different models rest on only a few basic concepts with differing degrees of mechanistic character. Building on this critical review, we select the most appropriate models and propose modifications. Two process-based models, the threshold hazard model and the modified damage assessment model, represent the optimum descriptions that are available at present. They could facilitate a better understanding of the ecotoxicity of different compound and species combinations and even mixtures of noninteracting compounds. The possibility to model lethal and sublethal effects allows applications in risk assessment, standard setting, and ecological modeling.

Animals↗
PubMedDate not supplied

Spontaneous reactivation of hepatitis B virus replication in HBsAg carriers who seroconverted from HBeAg to anti-HBe.

Twenty one patients with chronic liver disease (CLD), type B, who were persistently positive for anti-HBe after disappearance of HBeAg, were studied for serial measurement of HBV DNA and DNA-P in serum in relation to the elevation of alanine aminotransferase (ALT). Patients were selected and allocated to two groups on the basis of having been seen for at least 3 years and having been found to have either fluctuating, or normal ALT levels during the course of their disease activity. Nine patients have had fluctuating or sustainingly abnormal ALT levels and the remaining 12 have had sustainingly normal ALT levels for at least 3 years follow-up period after anti-HBe seroconversion. In 2 patients, ALT levels were persistently elevated with positive HBV DNA and DNA-P in serum, and in 6, ALT levels were fluctuated between normal range and more than six times the normal, in whom serum HBV DNA and DNA-P became also positive with ALT elevation. In one patient, serum HBV DNA and DNA-P became transiently positive with ALT elevation. On the contrary, 12 patients with normal ALT levels were persistently negative for both HBV DNA and DNA-P in serum. Therefore, we may conclude that in patients with anti-HBe positive CLD, type B, ALT elevation is associated with reactivation of HBV replication.

Adult↗