The effects of salts on the oxygen affinity of hemoglobin.
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Bromides↗
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Mutagenic and chromosome-breaking effects of azide in barley and human leukocytes.
Azide (10-3 M, solution buffered at pH 3) is more effective in inducing mutations in embryonic shoots of seeds germinated between 8 and 16 h than in non-germinated seeds and in seeds germinated between 0 and 8 h and 16 to 28 h. This peak of chlorophyll-deficient seedling mutation frequency coincides with maximum frequencies of seeding lethals and DNA replication in the cells of the embryonic shoot. The mutation data suggest azide may only act on replicating DNA. Azide induced no chromosome-aberration frequencies significantly above controls in (1) embryonic shoots of barley seeds germinated for 8--12 h, (2) microspores of barley and (3) human leukocytes. It appears to be a point-mutation mutagen.
Azides↗
Somatic crossing-over in Glycine max (L.) merrill: activation of dimethyl nitrosoamine by plant seed and comparison with methyl nitrosourea in inducing somatic mosaicism.
The soybean system used for detecting environmental mutagens is analyzed for various types of spots on the leaves of heterozygous y11y11 plants and homozygous y11y11's induced by a nitrosoamine (dimethyl nitrosoamine, DMN) and a nitrosoamide (methyl nitrosourea, MNU). It is shown that the nitrosoamine can be "activated" by the seed (is converted to a true mutagen) without the addition of NADPH or S-9 fraction of the liver homogenate as is necessary in animal tissue culture or bacterial studies. Whereas somatic mosaicism in soybean can be induced with a dose as low as 1.25 ppm of DMN, the upper limit in spot production is reached at around 60 ppm concentration, applied for 0--24 h. Such saturation effect may be due to a limited amount of DMN being converted to true mutagen. MNU, on the other hand, does not show such limitations, perhaps because of its property of being a direct mutagen not necessitating an intermediate step required for converting the promutagen DMN. The frequency of twin spots on Y11y11 leaves increases only slightly by either DMN or MNU, suggesting only a small increase in somatic crossing-over induced by the two chemicals. The yellow spots increase the most, perhaps due to segmental losses carrying Y11 or non-complementary segregation of exchanges involving non-homologous chromosomes. Neither chemical is found capable of mutating y11 to Y11 as seen by the general lack of light green sectors on y11Y11 plants. Usefulness of the soybean system in studying mutagenesis is briefly discussed.
Crossing Over, Genetic↗
Hyperthermic enhancement of chromosome damage and lack of effect on sister-chromatid exchanges induced by bleomycin in Chinese hamster cells in vitro.
Chinese hamster cells, M-3, were treated with BLM (1--4 micrograms/ml) for 30 min to 1 h at 37 degrees or 43 degrees C. After treatment, the cells were reincubated at 37 degrees until recovery. The material treated at 43 degrees showed increased damage expressed as chromosome and chromatid-type breaks and exchanges. Since the amount of BLM entering the cell at 37 degrees is supposedly similar to that which enters the cell at 43 degrees, the enhanced damage is the result of true synergism, and not the facilitation of the drug's entry into the cell.
Animals↗
Genetic toxicology of mitomycin C, actinomycins, daunomycin and adriamycin.
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Bacteria↗
Genetic toxicology of bleomycin.
Bleomycin (BLM), an antibiotic obtained from Streptomyces verticillus, is of significance as an antineoplastic agent. The compound is actually the mixture of some 200 related forms which differ from each other in the amine moiety. The drug, at low concentrations, can cause elimination of bases, particularly thymine. This causes strand breakage of DNA and inhibition of cell growth. The influence of BLM on cell growth may be unrelated to the effects on DNA. In general, mitotically dividing cells show more DNA damage than non-dividing cells. G2 seems to be the most sensitive phase indicating that cell death may not be related to a direct effect of BLM on DNA replication. The antibiotic shows specific effects on chromatin and causes chromosomal damage in all sub-phases of interphase. It can affect early prophase chromosomes also. Suggestion has been made that BLM-induced breakage and cell death are similar to those induced by densely ionizing radiations. Whereas the antibiotic affects the frequency of somatic crossing over and produces micronuclei, the data on mutation induction and production of sister-chromatid exchanges do not permit classifying BLM as a potent inducer of these phenomena. The genetic effects of BLM can be modified quantitatively by thiol compounds, caffeine, hyperthermia and H2O2. It is concluded that the available data do not permit assessment of genetic damage in the offsprings of BLM-treated patients. Such studies are urgently needed, as are the studies to find out the effects of BLM on meiotic phenomena.
Animals↗
Smith-Lemli-Opitz syndrome: Clinical, biochemical, and genetic insights with emerging treatment opportunities.
Smith-Lemli-Opitz syndrome (SLOS), also known as RSH syndrome, is an inborn error of cholesterol biosynthesis first described in 1964. Since then, significant advances have been made in understanding its pathophysiology, both during fetal development and postnatally. Cholesterol is a crucial lipid in the body, especially in the central nervous system, which accounts for nearly 25% of the body's total cholesterol. Cholesterol deficiency in SLOS can lead to congenital malformations and severe neurodevelopmental disabilities. The biochemical and genetic bases of SLOS have been elucidated. Reduced or absent 7-dehydrocholesterol reductase enzymatic activity results not only in cholesterol deficiency but also in accumulation of 7-dehydrocholesterol, 8-dehydrocholesterol, and toxic oxysterol metabolites, which contribute to the pathophysiology of SLOS and correlate variably with the severity of its clinical symptoms. Despite decades of research, the clinical recognition of SLOS remains challenging because of the condition's multisystemic nature and noteworthy phenotypic variability. This review provides an up-to-date summary of major research advances in the study of SLOS with a focus on clinical manifestations and biochemical and genetic findings, which, taken together, facilitate recognition and diagnostic confirmation. Additionally, we recap past and current efforts in therapeutic development and offer guidance for disease management.
Humans↗
The kinetics of anterior tooth display.
A survey has been presented that correlates measurements of upper lip type, sex, race, and age of dentulous patients with the amount of exposure of the maxillary and mandibular anterior teeth with the lips gently parted and in the resting position. Perhaps the most interesting finding was the gradual reduction in the amount of maxillary central incisor exposure with an increase in age, accompanied by a gradual increase in the mandibular tooth exposure. The importance of the amount of mandibular teeth seen in complete dentures has not been sufficiently emphasized in previous literature.
Adolescent↗
Study on cytological effects of carofur -- a new mutagen.
Chinese hamster cells (line V-79) and human leukocytes in vitro and mice of the CBA strain were treated with carofur (also called nifurprazinum), an antibacterial agent of pharmaceutical importance. At concentrations as low as 20 ppm, the in vitro treatments of cells of Chinese hamster and human lymphocytes expressed chromosome aberrations, almost exclusively of deletion type. This effect resembles that of fluorodeoxyuridine but may not necessarily reflect the same basic mechanism involved. When Chinese hamster cells were treated with 5 ppm or more of carofur for 24 hr, a 3-fold increase in the frequency of somatic sister chromatid exchanges was observed. An interesting phenomenon of "centromeric association" was observed in the bone marrow cells of mice treated with carofur, where the centromeres of the acrocentric chromosomes were oriented towards each other in groups of 2's or more.
Animals↗
Somatic mosaicism in plants with special reference to somatic crossing over.
Plant systems in use for the detection of environmental mutagens appear capable of detecting all types of genetic effects which can be studied in animals. The study of somatic mosaicism, however, is better developed in plants than in higher animals. A case is presented here which shows the ability of plant systems in analyzing a host of genetic end points, including chromosome aberrations like deletions, somatic crossing over, numerical inequality, gene conversion, paramutations and point mutations. The systems in general use utilize certain varieties of Tradescantia, Glycine max, Nicotiana tabacum, Antirrhinum majus, Petunia hybrida, and Arabidopsis thaliana. Heterozygous plants or their homozygous counterparts with gene markers affecting chlorophyll development or anthocyanin in floral parts are exploited in these studies. Mutagens produce different frequencies of different types of spots typical of the mode of action of the agent. Analysis of these parameters may be used to predict, at least qualitatively, the kind of genetic damage that might be produced in man. Besides, one can test the validity of interpretation by traditional progeny tests of plants raised from tissue culture from sectors as in Nicotiana and/or by precursor analysis as done in Antirrhinum. The study of mosaicism in plants offers quite inexpensive, rapid, and reliable tests of mutagenicity at least as a preliminary eukaryotic test system.
Biotransformation↗
[Activity of polynucleotide phosphorylase in ribosomal fraction of rat liver].
A method of isolating polynucleotidephosphorylase (PNPase) containing polyribosome fraction from rat liver is described. PNPase is found to be bind to RNA in polyribosomes with weak electrostatic bonds which are easily broken down in a weak alkaline medium with ionic strength more than 0.1 beta-22P-labelled ADP, GDP, UDP and CDP are found among the products of endogenous RNA degradation in the fraction of total polyribosomes in the presence of 32P-orthophosphate. A considerable change in the base composition of PNP-degraded RNA is observed at different incubation times of total polyribosomes with 32P-orthophosphate: G+C//A+U ratio increased from 2.3 to 3.1, and purines/pyrimidines ratio-from 0.47 to 1.06 with the increase of the incubation time. Specific activity of PNP in ribosome fractions obtained under ultracentrifugation of total polyribosomes in succrose density gradient (0.3-1.0 M) increased in the direction from the fraction of heavy polysomes to trimers and dimers and then dropped at the region of monomers (80 S particles). The data obtained give no possibility to determine the type of PNP-bound RNA in polyribomes of rat liver.
Animals↗
[Effect of cyclic-3',5'-AMP on rat liver polynucleotide phosphorylase activity].
Effect of cAMP on the activity of polynucleotide phosphorylase (PNPase) was studied in polyribosome fraction of rat liver tissue. Intraperitonel administration of cAMP or of theophilline into rats distinctly decreased the PNPase activity in the polyribosome fraction. The cAMP (1-10(-4) M) inhibited the enzymatic activity only by 8% in polyribosome fraction in vitro, as it was estimated by the reaction of phosphorolysis of endogenous RNA and polyA added. Any attempts were proved to be uncucessful to reveal cAMP, ATP-dependent proteinkinase in rat liver, responsible for the decrease in the PNPase activity in the polyribosome fraction. The cAMP inhibited the increase in the PNPase activity, coupled with protein biosynthesis in polyribosomes. Moreover, cAMP caused a decrease in the PNPase activity in reaction of polyA phosphorolysis and did not affect the rate of endogenous RNA phosphorolysis in polyribosome fraction, isolated from postmitochondrial fraction after incubation for 15 min at 30 degrees. The 3',5'-cyclo AMP (2-10(-6)-2-10(-4) M) stimulated incorporation of 14C-leucine into acid-insoluble material, when postmitochondrial fraction was incubated under the same conditions. The data obtained suggest that cAMP either inhibits specifically the PNPase synthesis or represses the coupled with protein biosynthesis formation of active "heavy" type of PNPase from less active "light" type.
Animals↗
[The activity of polynucleotide phosphorylase in polyribosomes of regenerating liver of adult rats, liver of newborn rats and in some reinoculated tumours].
Specific activity and level of polynucleotide phosphorylase (PNPase) in polyribosomes of regenerating liver of adult rats, liver of newborn rats and in malignant tumours of rat (sarcoma M-1 and hepatoma 27) were studied. 24 hours after partial hepatectomy the specific activity and level of PNPase in regenerating liver decreased 3--4 times in the fraction of polyribosomes, bound to the endoplasmic reticulum membranes, and remained at a constantly low level in the fraction of free polyribosomes. The PNPase activity also showed a sharp decrease in the fraction of membrane-bound polyribosomes from newborn rats liver and could not be detected either in free or in bound polyribosomes from sarcoma M-1 or hepatoma 27. The PNPase activity in the fraction of bound polyribosomes increased with a decrease in the rate of liver growth (regenerating liver and newborn rats liver), and reached the level normal for adult animals. Possible mechanisms of regulation of the PNPase activity in animal tissue were studied. It was found that a 2-fold administration of cyclic 3,5'-AMP to intact animals (5 mg per 100 g of body weight) with an interval of 8 hours, corresponding to the interval between two peaks of the increase in cyclic 3,5'-AMP concentration following partial hepatectomy, diminished the PNPase specific activity in polyribosomes by 30%. A factor, presumably of protein origin, which induced a release of PNPase from polyribosomes of normal rat liver but did not affect the activity of the liberated enzyme, was detected in the cell sap of sarcoma M-1 and hepatoma 27.
Age Factors↗
Direct observation of the methionine residues of cytochrome c by 13C nuclear magnetic resonance spectroscopy.
The two Cepsilon-methyl methionine groups in cytochrome c have been chemically enriched (45%) with 13C. Their 13C NMR signals have been monitored in both the oxidized and reduced states and under various solution conditions. Methionine residue 80 showed characteristic chemical shift positions for the reduced Fe(II) and cyano-Fe(III) forms. No signal for methionine 80 was observed in the oxidized Fe(III) form due to the paramagnetic effect of the iron atom to which it is bonded, but the position of the methionine 65 signal was shifted, indicating that it is sensitive to the change of oxidation state. Two well resolved signals were observed at pH 11 for the Fe(III) form but only one was resolved at pH 2, indicating that while methionine 80 is definitely displaced from the iron atom at alkaline pH, it may not be in acid conditions.
Cytochrome c Group↗
Form, function and tooth position.
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Dental Stress Analysis↗
How to combine record-making and try-in appointments for complete-denture patients.
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Appointments and Schedules↗
[Animal tissue polynucleotide phosphorylase].
Localization, physico-chemical and catalytic properties and possible biological functions of polynucleotide phosphorylase (PNPase) from animal tissues are discussed. In animal tissue cells PNPase has multiple localization; the major amount of the enzyme is localized in the endoplasmic reticulum ribosomes. In the nuclei PNPase, similar to other endo- and exo-RNAses participates in the processing of precursor molecules of mature forms of RNA, whereas in the cytoplasm it is involved in the destruction of polyribosomes in the polyribosomes of rapidly growing tissues the activity of PNPase is extremely decreased. The mechanisms regulating the PNPase activity in rapidly growing tissues are discussed.
Animals↗