Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By techniques of recombination in vitro, we have constructed a plasmid bearing the repressor gene (cI) of bacteriophage lambda fused to the promoter of the lac operon. Strains carrying this plasmid overproduce lambda repressor. This functional cI gene was reconstituted by joining DNA fragments bearing different parts of that gene. Flush end fusion techniques, involving no sequence overlap, were necessary for the construction; in certain cases, the abutting of the DNA molecules bearing ends generated by different restriction endonucleases creates a sequence at the junction which is recognized by one of the restriction endonucleases.
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PMID:Construction of plasmids carrying the cI gene of bacteriophage lambda. 106 7

Repair and remodeling processes initiated by arterial injury are thought to be critical in the pathogenesis of important vascular disorders. However, how these processes are related to specific types of injury is not well defined. Consequently, we compared arterial responses to several types of injury. Segments of rabbit carotid arteries were injured by intraluminal passage of an inflated embolectomy catheter, by hyperdistending the arteries with sterile saline, or by flushing them briefly with Triton X-100. Ballooning and Triton treatment removed the endothelium while imposing hyperdistending or nonhyperdistending injury on the vessel media. Hyperdistension with sterile saline caused medial injury but only transient and focal endothelial denudation. All modes of injury caused medial damage that was repaired within 2-7 days as assessed by vessel wall DNA content and synthesis and by capacity to contract. In addition, ballooned arteries recovered their capacity to exhibit diameter reductions induced by decreased blood flow once the endothelium had regenerated. The two injuries that caused endothelial denudation, ballooning and Triton treatment, resulted in equal intimal thickening after 6 weeks despite lower short- and long-term rates of cell replication after Triton-induced injury. Only ballooning resulted in chronic turnover of intimal smooth muscle cells after injury. No neointimal proliferation followed hyperdistension with saline despite significant medial injury. These latter findings suggest that even severe medial injury does not lead to intimal proliferation in the absence of endothelial denudation.
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PMID:Structural changes and recovery of function after arterial injury. 154 90

The distribution of the human liver alcohol dehydrogenase, ADH2, and aldehyde dehydrogenase, ALDH2, genotypes in 21 different populations comprising Mongoloids, Caucasoids, and Negroids was determined by hybridization of the amplified genomic DNA with allele-specific oligonucleotide probes. Whereas the frequency of the ADH1(2) allele was found to be relatively high in the Caucasoids, Mexican Mestizos, Brazilian Indios, Swedish Lapps, Papua New Guineans and Negroids, the frequency of the ADH2(2) gene was considerably higher in the Mongoloids and Australian Aborigines. The atypical ALDH2 gene (ALDH2(2)) was found to be extremely rare in Caucasoids, Negroids, Papua New Guineans, Australian Aborigines and Aurocanians (South Chile). In contrast, this mutant gene was found to be widely prevalent among the Mongoloids. Individuals possessing the abnormal ALDH2 gene show alcohol-related sensitivity responses (e.g. facial flushing), have the tendency not to be habitual drinkers, and apparently suffer less from alcoholism and alcohol-related liver disease.
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PMID:Distribution of ADH2 and ALDH2 genotypes in different populations. 173 36

Using newborn rat calvaria, we determined the effects of oxygen tension on bone cell metabolism in vitro. Halved calvaria were incubated in medium either in air or after flushing nitrogen or oxygen and studied for collagen synthesis, calcium uptake, and DNA content. The percentages of DNA content, radioactive proline count in mg of bone tissue, and radioactive proline count combined with counts of medium and bone tissue in the nitrogen-exposed group were less than those of their pair-matched controls. Percent calcium counts per DNA and calcium uptake per mg of tissue were greater in the nitrogen-exposed group than in the pair-matched controls. In contrast, no difference was found in any measurements in the oxygen-exposed group compared with controls. It is concluded that collagen synthesis, in contrast to proline uptake, is not affected by low oxygen, whereas calcium uptake is greatly enhanced. Furthermore, low oxygen tension exerts a greater effect on bone cell metabolism than does the hyperoxic condition.
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PMID:The effect of oxygen tension on collagen synthesis and calcium uptake in newborn rats' calvaria in vitro. 231 96

At weaning, 162 sows were assigned randomly to six treatments (27 in each treatment) according to a 2 X 3 factorial arrangement: two levels of supplementary folic acid (0 and 5 mg/kg of diet) and three treatments to stimulate ovulation (none, flushing and pregnant mare serum gonadotropin [PMSG] injection). All sows were mated twice within 7 d after weaning. Of the 162 animals originally selected, 123 sows were pregnant and used in this trial. The flushing treatment consisted of allowing sows ad libitum access to feed from the day after weaning through the 1st day of behavioral estrus, whereas control animals received 2.4 kg of feed daily. The hormonal treatment consisted of one i.m. injection of 1,250 IU of PMSG the day after weaning. The commercial-type diet used as the control was computed to contain .6 mg folates per kilogram. Folic acid supplementation elevated (P less than .001) serum folates between weaning and 30 d of gestation. Fetuses of sows fed the diet supplemented with folic acid had a higher (P less than .05) total protein concentration than fetuses of control sows, whereas RNA and DNA concentrations and protein:DNA ratio were not affected. The PMSG treatment elevated (P less than .05) ovulation rate, whereas the flushing or folic acid treatments had no effect on this trait. The addition of 5 mg/kg folic acid to the commercial-type diet improved (P less than .05) the survival rate of fetuses during early gestation and tended (P = .096) to increase the number of fetuses presumably living at 30 d of gestation when this treatment was associated with high ovulation rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Survival rate and development of fetuses during the first 30 days of gestation after folic acid addition to a swine diet. 247 Jul 22

Amonafide (benzisoquinolinedione, NSC 308847) is a new synthetic imide antineoplastic agent with DNA intercalative properties that has been evaluated in a phase I clinical trial. The drug was administered as a single intravenous (IV) infusion over 30 to 120 minutes repeated every 28 days. Ninety-five courses of therapy at doses ranging from 18 to 1,104 mg/m2 were administered to 38 patients with refractory solid tumors. Granulocytopenia was dose limiting. Leukopenia was seen in 13 of 31 courses at doses of 690 mg/m2 or greater. Life-threatening granulocytopenia (less than or equal to 250 microliters) was noted in 1/6 patients treated at 800 mg/m2, 1/8 patients treated at 918 mg/m2, and 2/5 patients treated at 1,104 mg/m2. No definite relationship between myelotoxicity and prior treatment status was noted. Rate-of-infusion dependent, nonhematologic toxicities included diaphoresis, flushing, dizziness, and tinnitus, all of which were ameliorated by increasing the duration of drug infusion to 120 minutes. In addition, nausea and vomiting (grades 1 and 2) were seen in 29/56 courses at doses greater than or equal to 519 mg/m2, but were easily controlled by phenothiazine antiemetics. Amonafide plasma and urine concentrations were determined by high-pressure liquid chromatography (HPLC). Plasma concentrations declined biexponetially with a terminal harmonic mean terminal half-life (t 1/2) of 5.5 h. The mean apparent volume of distribution at steady-state and total body clearance were 532 L/m2 and 84 L/h/m2, respectively. Less than 5% of the total dose of amonafide was excreted unchanged in the urine. Antitumor activity has been noted in one patient with non-small-cell lung cancer (one complete response exceeding 29 months duration) and in one patient with prostatic cancer (complete pain relief and improvement in bone scan for 9 months). The recommended dose for phase II trials with this schedule of amonafide is 918 mg/m2 with dose escalation to amonafide is 918 mg/m2 with dose escalation to myelotoxicity.
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PMID:Phase I clinical investigation of amonafide. 254 5

Deficiency of mitochondrial aldehyde dehydrogenase (ALDH I) is an inborn error of metabolism that is responsible for acute alcohol sensitivity (flushing response) observed only in Orientals of Mongoloid origin. Our previous studies using electrophoretic enzyme detection have shown that this deficiency is prevalent among Japanese, Chinese, and other Orientals. We report here the genotyping of ALDH I locus in blood samples of 218 South Korean individuals by means of hybridization analysis with allele-specific oligonucleotide probes and enzymatically amplified human genomic DNA. The results of genotyping are compared with the phenotype analysis in hair roots of the same individuals. Among 62 apparently deficient phenotypes, 58 heterozygote and 4 homozygote deficient genotypes were observed.
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PMID:Genotyping of mitochondrial aldehyde dehydrogenase in blood samples using allele-specific oligonucleotides: comparison with phenotyping in hair roots. 270 32

A much higher incidence of alcohol flushing among Orientals in comparison to Caucasians, i.e., greater than 50% vs 5%-10%, has been attributed to racial differences in alcohol-metabolizing enzymes. A large majority of Orientals are "atypical" in alcohol dehydrogenase-2 locus (ADH2), and their livers exhibit significantly higher ADH activity than the livers of most Caucasians. Approximately 50% of Orientals lack the mitochondrial aldehyde dehydrogenase (ALDH2) activity, and elimination of acetaldehyde might be disturbed. We determined by means of hybridization of genomic DNA samples with allele specific oligonucleotide probes, genotypes of the ADH2 and ALDH2 loci in Japanese alcohol flushers and nonflushers. We found that all individuals with homozygous atypical ALDH2(2)/ALDH2(2) and most of those with heterozygous atypical ALDH1(2)/ALDH2(2) were alcohol flushers, while all subjects with homozygous usual ALDH1(2)/ALDH1(2) were nonflushers. Frequency of the atypical ADH2(2) was found to be higher in alcohol flushers than in nonflushers, but the statistical significance was not established in the sample size examined.
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PMID:Genotype of alcohol dehydrogenase and aldehyde dehydrogenase loci in Japanese alcohol flushers and nonflushers. 271 75

Differences in the pharmacokinetics of alcohol absorption and elimination are, in part, genetically determined. There are polymorphic variants of the two main enzymes responsible for ethanol oxidation in liver, alcohol dehydrogenase and aldehyde dehydrogenase. The frequency of occurrence of these variants, which have been shown to display strikingly different catalytic properties, differs among different racial populations. Since the activity of alcohol dehydrogenase in liver is a rate-limiting factor for ethanol metabolism in experimental animals, it is likely that the type and content of the polymorphic isoenzyme subunit encoded at ADH2, beta-subunit, and at ADH3, the gamma-subunit, are contributing factors to the genetic variability in ethanol elimination rate. The recent development of methods for genotyping individuals at these loci using white cell DNA will allow us to test this hypothesis as well as any relationship between ADH genotype and the susceptibility to alcoholism or alcohol-related pathology. A polymorphic variant of human liver mitochondrial aldehyde dehydrogenase, ADLH2, which has little or no acetaldehyde oxidizing activity has been identified. Individuals with the deficient ALDH2 phenotype do not have altered ethanol elimination rates but they do exhibit high blood acetaldehyde levels and dysphoric symptoms such as facial flushing, nausea and tachycardia, after drinking alcohol. Because acetaldehyde is so reactive, it binds to free amino groups of proteins including a 37 kilodalton hepatic protein-acetaldehyde adduct and may elicit an antibody response. We would predict that individuals who have low ALDH2 activity because of liver disease or because they have the inactive ALDH2 variant isoenzyme might form more protein-acetaldehyde adducts and elicit a greater immune response. These adducts may represent good biological markers of alcohol abuse and may also play a role in liver injury due to chronic alcohol consumption.
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PMID:Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. 306 25

Fertilized oocytes of the inbred genotypes AKR (AK), C57BL/6 (B6), DBA/2 (D2), and CBA (CB) and the hybrid genotypes F1 (female AK X male B6) and F1 (female B6 X male AK) were collected by flushing the oviducts of female mice every 2 h from 2 until 26 h post coitum. Developmental stages of the embryos and DNA content of the pronuclei were estimated by morphological criteria and cytofluorometric measurement of the pronuclei (ethidium bromide-stained DNA), respectively. In all genotypes, S-phase started about 4 h post conception (h.p.c.). The duration of S-phase amounted to 5.9 h (F1 [female B6 X male AK]), 6.4 h (AK), 8.5 h (B6), 9.4 h (F1 [female AK X male B6]), 9.8 h (D2), and 11.4 h (CB). In each of the reciprocal F1 hybrids, the length of S-phase differed from the maternal genotype (p less than 0.01) and resembled closely the paternal genotype (p greater than 0.25). Cleavage from one-cell stage to two-cell stage occurred between 16 and 21 h.p.c.
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PMID:Paternal influence on timing of pronuclear DNA synthesis in naturally ovulated and fertilized mouse eggs. 340 33


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