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PubMed1980

[Assessment of the loss of thyroid hormone during hemodialysis by administration of a hormone tracer in an in vitro experiment (author's transl)].

Several investigators have examined thyroid function in hemodialysis patients. Similar results were obtained: reduced total triiodothyronine and subnormal thyroxine values in serum. This raised the question whether a deficiency in hormones during hemodialysis could be responsible for these findings. The present studies were ade in an attempt to prove or disprove this assumption by determining hormone loss. The loss of thyroxine during hemodialysis was 1.1 microgram. This order of magnitude excludes a hormone deficit caused by dialysis. The assumption that an increased loss of hormone during hemodialysis is the cause of pathologic changes in the serum as compared with the period before dialysis can be considered as disproved.

Humans↗

PubMed1980

[The effect of aminophylline (Euphyllin) on the mechanics of breathing and the gaseous exchange in persons with bronchial asthma (author's transl)].

The physiological effect of intravenous application of aminophylline on the mechanics of breathing and the gaseous exchange in persons with bronchial asthma was studied in 7 out-patients before, during and up to 90 minutes after intravenous injection of 0,48 g of Euphillin, and the data were related to the respective serum levels of the drug. The patients suffered from long-standing bronchial asthma, generally associated with moderate airways obstruction. The bronchodilating effect of Euphyllin could be substantiated for the whole time of the trial solely in respect of the changes in oscillatory impedence; the other parameters showed only temporary changes which had disappeard by the end of the trial although the serum levels of aminophylline were in the therapeutic range (mean +/- SD: 12,5 +/- 3,0 microgram/ml). The data indicate that in some patients with bronchial asthma the effect of Euphyllin on lung function is unpredictable. The suggestion is made to measure the responsiveness of the patient to aminophylline by means of simple lung function tests in order to decide whether or not other bronchodilatory substances should be aded to the therapy.

Adult↗

PubMed1995

In vitro transcription of DNA containing 2-chloro-2'-deoxyadenosine monophosphate.

2-Chloro-2'-deoxyadenosine (cladribine [CldAdo]) represents one of the most promising therapeutic agents for the treatment of pediatric leukemias and adult hairy cell leukemia. We examined whether CldAdo incorporation into DNA inhibited subsequent transcription in vitro using purified phage RNA polymerases. Control (Ade-containing) and 2-chloroadenine (ClAde)-substituted DNA strands that contained a RNA polymerase promoter sequence were synthesized by a modified asymmetric polymerase chain reaction. Complementary (+) and (-) strands were annealed, incubated with phage RNA polymerase, and analyzed with denaturing PAGE. When ClAde was present in both strands, the yield of full-length transcripts (approximately equal to 100 bases) was reduced by approximately equal to 90% relative to control DNA. Transcription was also reduced to a slightly lesser degree when substitutions occurred in only one of two strands. The observed low transcript levels on ClAde-containing DNA were due in part to the presence of the analogue within the promoter region. With gel shift binding assays, we demonstrated that RNA polymerase did not bind as well to ClAde-containing promoters. Polymerase/DNA complex formation was decreased by approximately equal to 80% compared with that on control unsubstituted promoters. In addition, on binding to the substituted promoter, RNA polymerase had an altered conformation that led to enhanced proteolytic clipping by endoproteinase Glu-C. Transcript sequence analysis indicated that SP6 RNA polymerase read through template ClAde residues with no apparent misincorporation into RNA. Our results provide insight into a novel effect of this nucleoside analogue that may explain its cytotoxicity in nondividing cells.

Antineoplastic Agents↗

PubMed1994

Human alpha atrial natriuretic peptide fermentation by using a genetically engineered yeast strain.

The genotype of the recombinant yeast strain Y33::YFD71-3 used in this study is alpha, his, leu, ade and suc. Preliminary batch cultures in shaking flasks showed the expression level of atrial natriuretic peptide (ANP) was 1-2 mg/L. Shaking flask cultures were carried out in YG medium which contained glucose, yeast nitrogen base (YNB), and different amounts of adenine, histidine and leucine. When the growth was limited by adenine, protein secreted from Y33::YFD71-3 cells was increased obviously. Adenine became the limiting substrate when the YG medium was supplemented with 5 g/L of casamino acid (CAA) and the level of ANP expression was influenced by the concentrations of adenine, YNB and leucine in the medium. In fed batch cultures carried out in a RIBE-5 fermenter, the cultures were fed with glucose and a mixture of YNB, CAA, adenine, histidine and leucine to improve cell growth and ANP expression, and the maximum ANP concentration in the culture reached 24.8 mg/L.

Adenine↗

PubMed1995

[Mutation of ade13-1 of the yeast Saccharomyces cerevisiae leads to the absence of growth on a complete medium with glucose and epistatically interacts with mutations in other genes for purine biosynthesis].

Saccharomyces cerevisiae gene ADE13 encodes enzyme adenylosuccinate lyase catalyzing steps 8 and 12 of the de novo purine pathway. The mutation ade13-1 induced by ethyl methanesulfonate leads to a complete loss of enzymatic activity. Stocks with this mutation cannot grow on complete organic media with glucose or fructose as a carbon source, but they can grow on media with glycerol or ethanol. The inhibiting effect of glucose is confirmed by the lack of growth on the medium with glycerol instead of glucose. Three independently obtained ade2 mutations and mutations ade1-p3, ade4, ade5, and ade5,7-33 suppress growth inhibition by glucose; i.e., they are epistatic with respect to this phenotypical expression of mutation ade13-1. The activity of adenylsuccinate lyase is not reconstituted. Mutations ade1-263, ade6, ade7-23, and ade8-21 do not manifest an epistatic effect. It was suggested that purine synthesis genes participate in the control of glycolysis or in the transduction of signal about the carbon source in the medium. The properties of ade mutations found by us were previously unknown. The results of our study contribute to the knowledge about the function of purine synthesis genes in yeasts.

Adenylosuccinate Lyase↗

PubMed1978

Genetic transformation in Rhizobium trifolii.

Markers controlling the synthesis of amino acids and organic bases as well as streptomycin resistance and sensitivity to acriflavine were transformed in Rhizobium trifolii. The results indicate that the str marker was transformed independently of leu, his, ade and trp markers. Co-transformation of leu and utra markers ranged from 3 to 7%, whereas that of thi and acr was 10%.

Acriflavine↗

PubMed1976

[UV-mutagenesis in Bacillus subtilis. VI. Mutagenesis under conditions of experimental delay of post-radiation DNA replication].

To test a suggestion that mutation frequency decline (MFD) in UV-irradiated bacteria starved by nitrogen sources is caused by long delay of the first postradiation cycle of DNA replication, we used a strain 1201-05 of Bacillus subtilis 168 (ade6 met5tsdnaC) which does not synthesize DNA at 42 degrees C. In a suspension of UV-irradiated cells of this strain which is incubated at 42 degrees in liquid deprived by nitrogen sources, a decrease of frequencies of Ade+ and Met+ revertants is observed. This shows that the mechanism responsible for MFD normally operates at higher temperature. Such a level of decline is not observed in a suspension incubated in nutritional medium when the DNA replication is blocked by non-permissive temperature for the same period as in starved cells. On the basis of these facts it is concluded that MFD in suspension of bacteria starved by nitrogen sources can not be caused only by delay of postradiation replication of DNA.

Bacillus subtilis↗

PubMedDate not supplied

[Disseminated encephalomyelitis. A study of 5 cases].

Five cases of acute disseminated encephalomyelitis (ADE) with a follow-up longer than 5 years are presented. The clinical picture, CT images, MR and laboratory tests, specially LCR and evoked potentials presented in a variable form. In two cases the symptoms were preceded by viral infection. The course was acute in one case while the other four evolved in a subacute form during weeks. In two patients a pseudotumoral pattern was observed in the CT and MR images leading to difficulties in the diagnosis. Clinical improvement was accompanied by a partial resolution of the lesions. Steroid treatment improved symptomatology in all the cases. Knowledge of this process may avoid the unnecessary practice of other, more aggressive tests.

Adolescent↗

PubMed1996

Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies.

OBJECTIVE: To determine the ability of various antihypertensive agents to reduce left ventricular hypertrophy, a strong, blood pressure-independent cardiovascular risk factor, in persons with essential hypertension. DATA SOURCES: MEDLINE, DIMDI, RINGDOC, ADES, EMBASE, and review articles through July 1995 (English-language and full articles only). STUDY SELECTION: Meta-analysis of all published articles including only double-blind, randomized, controlled clinical studies with parallel-group design. DATA EXTRACTION: Intensive literature search and data extraction according to a prefixed scheme performed independently by 2 investigators. Reduction of left ventricular mass index after antihypertensive therapy with placebos, diuretics, beta-blockers, calcium channel blockers, or angiotensin-converting enzyme (ACE) inhibitors was the principal parameter. DATA SYNTHESIS: Of 471 identified references describing the effects of antihypertensive drugs on left ventricular hypertrophy, only 39 clinical trials fulfilled the inclusion criteria of our study. We found that the decrease in left ventricular mass index was more marked the greater was the decline in blood pressure (systolic r=0.46, P<.001; diastolic r=0.21, P=.08) and the longer was the duration of therapy (r=0.38, P<.01). After adjustment for different durations of treatment (mean duration of treatment, 25 weeks), left ventricular mass decreased 13% with ACE inhibitors, 9% with calcium channel blockers, 6% with beta-blockers, and 7% with diuretics. There was a significant difference between drug classes (P<.01): ACE inhibitors reduced left ventricular mass more than beta-blockers (significant, P<.05) and diuretics (tendency, P=.08). Similar differences between drug classes were found with regard to effect on left ventricular wall thickness (P<.05). CONCLUSIONS: The database of articles published through July 1995 is small and incomplete, and most of the articles are of poor scientific quality. In this first meta-analysis including only double-blind, randomized, controlled clinical studies, decline in blood pressure, duration of drug treatment, and drug class determined the reductions in left ventricular mass index. The ACE inhibitors seemed to be more potent than beta-blockers and diuretics in the reduction of left ventricular mass index; calcium channel blockers were somewhat in the intermediate range. The ACE inhibitors and, to a lesser extent, calcium channel blockers emerged as first-line candidates to reduce the risk associated with left ventricular hypertrophy.

Adrenergic beta-Antagonists↗

PubMed1977

Synteny between glycinamide ribonucleotide synthetase and superoxide dismutase (soluble).

The auxotrophic mutant ade -C derived from Chinese hamster ovary cell CHO-K1 lacks the enzyme glycinamide ribonucleotide synthetase and requires exogenous supplement of purines for growth. Cells from this mutant were fused with normal human lymphocytes, and the resulting hybrids were isolated in purine-deficient medium. A total of 32 primary clones and 49 secondary clones were analyzed for various isozyme markers. Cytogenetic analysis with chromosome banding was also performed in some hybrid clones. The results provide evidence indicating that glycinamide ribonucleotide synthetase is syntenic with superoxide dismutase (soluble) and is located on human chromosome 21.

Animals↗

PubMed1997

[Seip-Lawrence syndrome associated with polyostotic fibrous dysplasia. Report of a case].

We report the case of a 28-year-old woman attending for hirsutism and diabetes mellitus. Diabetes was a casual finding 2 years before consulting and was treated with diet and antidiabetic drugs. Acromegalic appearance, facial acne, penty, curled and rude hair, hypertrichosis, ade I diffuse goitre, prominent abdomen with umbilical hernia, severe hepatomegaly, prominent muscles and veins with normal genitalia appeared in the physical examination. No other abnormalities were found. Hypophysis, thyroid, suprarenal and ovaric hormonal functional studies were normal. An insulin-resistant diabetes mellitus was found in the metabolic study. Ultrasound and TAC showed severe diffuse hepatomegaly and visceral fat lack. Bone radiographies showed diffuse lesions compatible with polyostotic dysplasia. Subcutaneous, hepatic and bone biopsy revealed lack of fat tissue, hepatic steatosis and osteal fibrosis. Patient s diagnosis was Berardinelli-Seip syndrome, Seip-Lawrence or lipoatrophic diabetes associated with polyostotic fibrotic dysplasia. Case is studies and bibliographic references are reviewed.

Adult↗

PubMed1997

A comprehensive review of sedative and analgesic agents.

The intent of this article is to be a comprehensive, but by no means exhaustive, review of some of the agents used for CS. The major classes and their principal uses are presented: benzodiazepines, for sedation-hypnosis, anxiolysis, and, in the case of midazolam, amnesia; and opiates, for analgesia and sedation. Also included are the miscellaneous items etomidate and propofol, for sedation-hypnosis; ketamine, for sedation and analgesia; and the phenothiazines and butyrophenones. One should consider how the interactions between and among these agents can be used for the benefit of the patient undergoing CS, and also the danger in combining agents and the necessity of constant monitoring. The reporting of ADEs is a recurring theme, the value of which cannot be overemphasized in modern medical practice, not only to satisfy accreditation requirements but also to ensure patient safety and improve therapeutic choices of medications.

Analgesics↗

PubMed1997

[Information model of systemic organization of human mental functions: new approach to the problem of artificial intelligence].

The information model of systemic functions of the human brain reproduces important features of human intelligence: goal planning, prediction of needed results, behavior correction by feedback from the parameters of the results obtained and their comparison with the acceptor of action results. Human behavior imitation in the model is statistically proved by testing the model on a computer. An Adaptron apparatus based on the model quantitatively estimates the parameters of an important mechanism of the brain, namely human intuitive learning. With the Adaptron, the ade-dependent properties and some human intellectual dysfunctions are estimated, which reflect the mechanisms of prediction of future results, the building of memory traces in intuitive learning when the findings coincide with the planned results and the restructure of memory and respective behavior changes when the findings do not coincide with the planned ones.

Artificial Intelligence↗

PubMedDate not supplied

Factors associated with clinical mastitis incidence in French dairy herds during late gestation and early lactation.

A prospective epidemiological survey was conducted in dairy herds in Brittany (France), concerning 139 herd-years. The data were divided into ten 14 herd-year groups (deciles) and three of these were compared using discrimination by barycentric analysis to study herd late gestation and early lactation variables associated with the annual incidence of herd clinical mastitis in the first 60 days of gestation (CMAI). The first decile included herd-years with low CMAI (o to 4.6%), the second decile, herd-years with medium CMAI (11.6 to 14.3%) and the last decile, herd-years with high CMAI (26.3 to 45.5%). Herd data included diet components, milk yield and reproduction parameters, clinical diseases, body condition score, body dirtiness score and circulating biochemical and hematological markers. The high CMAI group had the following characteristics: 1) lower percentages of dried cows supplemented with vitamins 'ADE'; 2) higher levels of plasma ceruloplasmin and higher gamma glutamyl transferase activities (GGT) in the late gestation period; 3) higher percentages of winter calvings (December, January, February). Clinical mastitis risk could be controlled by supplementations with vitamins A, D and E in the late gestation period, because of the potential relationship between oxidative stress and mastitis. Higher GGT activities would be associated with Fasciolasis via common climatic risk factors (rainfall, humidity) for both mastitis and liver flukes. Winter calving and clinical mastitis would be associated with unfavourable hygiene conditions and stress at calving related to high animal density and bad weather conditions. Ceruloplasmin could be a specific predictor for mastitis risk through nutritional, immune and genetic interrelated factors.

Animal Feed↗

PubMed1997

Artemether in moderate to severe malaria: a multicenter trial in India.

154 patients suffering from acute attack of moderate to severe malaria caused by Plasmodium falciparum were treated with 480 mg artemether, administered intramuscularly (i.m.) in six equally divided doses at 12 hour intervals. Results showed a rapid parasite clearance. Mean parasite clearance time (PCT) was found to be 23.65 +/- 1.57 hours. Mean fever clearance time (FCT) was 35.28 +/- 1.7 hours. Adverse drug events (ADE) were mild and self-limiting. Recrudescence rate (RR) among the patients followed up was 4.55%. We conclude that artemether is a safe and effective anti-malarial agent for the treatment of moderate and severe cases of P. falciparum malaria.

Acute Disease↗

PubMed1998

[The influence of space loading suits on interhemispheric asymmetry of the brain in infantile spastic cerebral palsy].

The paper presents the study concerning influence of somatosensory stimulation (single wearing of either space loading costume "PENGUIN" or its modification--"ADELY" costume) on the individual profile of interhemispheral cerebral assymmetry (IPIHCA) in patients with spastic form of infantile cerebral paralysis (ICP). The computer stabilograph analyzed motor arms' asymmetry, sensory asymmetry of visual hemiareas, asymmetry of the position of centre of gravity. It is shown that peculiarities of the realization of the standing position either with visual control or without it both in healthy individuals and in patients depended on initial IPIHCA. Initial stability was higher in healthy individuals than in patients, besides in healthy persons it was higher in right-handers while in patients--in left-handers. There was possibility of changes of both IPIHCA and stability during keeping up vertical position even during single somatosensory stimulation. For elaboration of new criteria of the estimation of the efficiency of treatment in patients with CNS damages, including ICP, it is necessary to take into consideration different influence of somatosensory stimulation on IPIHC in right-handers and left-handers.

Adolescent↗

PubMed1999

N-(2-chloroethyl)-N-nitrosourea tethered to lexitropsin induces minor groove lesions at the p53 cDNA that are more cytotoxic than mutagenic.

Many different N-chloroethyl-N-nitrosourea (CENU) derivatives have been synthesized in an attempt to minimize carcinogenic activity while favoring antineoplastic activity. CENU derivatives linked to the dipeptide lexitropsin (lex) showed significant changes in groove- and sequence-selective DNA alkylation inducing thermolabile N3-alkyladenines (N3-Alkyl-As) at lex equilibrium binding sites. CENU-lex sequence specificity for DNA alkylation was determined using 32P-end-labeled restriction fragments of the p53 cDNA. The adducted sites were converted into single-strand breaks by sequential heating at neutral pH and exposure to piperidine. To establish the mutagenic and lethal properties of CENU-lex-specific lesions, a yeast expression vector harboring a human wild-type p53 cDNA was treated in vitro with CENU-lex and transfected into a yeast strain containing the ADE2 gene regulated by a p53-responsive promoter. p53 mutants were isolated from independent ade- transformants. The results revealed that: (a) CENU-lex preferentially induces N3-Alkyl-A at specific lex equilibrium binding sites, the formations of which are strongly inhibited by distamycin; (b) reactivity toward Gs is still present, albeit to a lesser extent when compared to N-(2-chloroethyl)-N-cyclohexyl-N-nitrosourea and to CENU; (c) 91% of the 49 CENU-lex p53 mutations (45 of 49) were bp substitutions, 29 of which were GC-->AT transitions, mainly at 5' purine G sites; (d) all AT-targeted mutations but one were AT-->TA transversions; (e) the distribution of the CENU-lex mutations along the p53 cDNA was not random, with position 273 (codon 91), where only GC-->AT transitions were observed, being a real (n = 3, P < 0.0002) CENU-lex mutation hot spot; and (f) a shift in DNA alkylation sites between lesion spectra induced by CENU-lex and N-(2-chloroethyl-N-cyclohexyl-N-nitrosourea was associated with an increased lethality and a decreased mutagenicity, whereas no dramatic change in mutational specificity was observed. Hence, it is tempting to conclude that, in this experimental system, N3-Alkyl-A is more lethal than mutagenic, whereas O6-alkylguanine is a common premutational lesion formed at non-lex binding sites. These results suggest that CENU derivatives with virtually absolute specificity for A residues would make targeting of lethal, nonmutagenic lesions at A+T-rich regions possible, and this may represent a new strategy for the development of new chemotherapeutic agents with a higher therapeutic index.

Alkylation↗

PubMed1999

Determinants of physical functioning in coronary patients: response to cardiac rehabilitation.

BACKGROUND: Coronary heart disease is a major cause of disability. There has been little study of the effect of cardiac rehabilitation on measures of self-reported physical functioning. METHODS: Physical functioning was measured using the Medical Outcomes Study-Short-Form Questionnaire. Determinants of physical function were analyzed in 303 patients with coronary heart disease. Response of physical function to a 3-month exercise rehabilitation program was then determined. RESULTS: At baseline, women had lower physical function scores than men, despite similar age and diagnostic distribution. Older patients had lower physical function than younger patients. Aerobic exercise capacity, leg and arm strength, and comorbidity and depression scores were all significant predictors of baseline physical function (r range, 0.46 to -0.22). Physical function score increased significantly after exercise conditioning, with a mean (+/- SD) overall score increase from 66 +/- 23 to 80 +/- 20 on a scale of 0 to 100. The best baseline determinant of a favorable physical function improvement after rehabilitation was a low baseline physical function score. The best training-related correlate of improved physical function score was a decrease in mental depression score. CONCLUSIONS: Self-reported physical function in coronary patients is related to age, sex, fitness, and mood state. Physical functioning improves after cardiac rehabilitation in all age, sex, and diagnostic groups, but particularly in patients with low baseline values. These data support the concept that cardiac rehabilitation effectively prevents and treats cardiac disability.

Adult↗