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Biomedical subjects

C J Nielsen

Publications and source records attributed to C J Nielsen.

At least 37 records · Page 2Linked to original sources
PubMed1983

Age-related changes in reducible crosslinks of human dental pulp collagen.

Coronal pulp of human third molars from patients ranging in age from 16 to 40 yr was analysed for collagen, protein, calcium and reducible crosslink content. Dihydroxylsinonorleucine (DHLNL) was the major crosslink; it decreased with age. Hydroxylsinonorleucine (HLNL) and lysinonorleucine (LNL) appeared in insignificant amounts. Calcium content increased with age. Based on the premise that collagen synthesis is characterized by the presence of reducible crosslinks, the study showed that coronal pulp collagen synthesis decreases with age; this is accompanied by a decrease in collagen concentration in terms of dry weight and total protein between 16 and 30 hr of age.

Adolescent↗
PubMed1983

Subjective symptoms after long term lead exposure in secondary lead smelting workers.

The prevalence of lead induced subjective symptoms was evaluated by a standardised questionnaire in a group of 96 workers employed between nine and 45 years in a secondary lead smelting works. A control group of 96 non-lead exposed subjects, matched for age and sex, were chosen from the Glostrup population study. Blood lead concentrations were in excess of 60 micrograms/100 ml in about 30% of the lead workers. Zinc protoporphyrin levels were found to be higher than 500 mumol/Hb in nearly 18% of the lead workers. The prevalence of fatigue, headache, sleep disturbance, and digestive symptoms (constipation and colic) were not higher in the lead exposed group. The body weight showed no significant difference in the two groups. Nervousness was four times more frequent in the control group. The results indicate that subjective symptoms are useless as indicators of incipient lead poisoning.

Adult↗
PubMed1983

Atypical EEG abnormalities in children with benign partial (Rolandic) epilepsy.

In order to determine the borderlines of the benign partial epilepsy of children with centrotemporal spike foci ('Rolandic epilepsy') 43 patients with epilepsy and spike foci in the centrotemporal region or elsewhere drawn from the EEG files were re-evaluated as adults. The prognosis was equally good whether the spike focus was in the centrotemporal region or elsewhere, and synchronous paroxystic activity did not make the prognosis worse, but focal temporal low frequency activity did. It is suggested that borderline cases exist between 'Rolandic epilepsy' and other age dependent epilepsies.

Adolescent↗
PubMed1982

Absence of peripheral neuropathy in long-term lead-exposed subjects.

The safety of a blood lead concentration of 70 microgram/100 ml as a hygienic border value with regard to development of lead neuropathy was tested in 95 employees, who had been exposed occupationally to lead for more than 9 years. The blood lead concentration was slightly above the border value in nine subjects, while the erythrocyte-Zn-protoporphyrin concentration was significantly elevated in 81 subjects, indicating an abnormal accumulation of metabolically active lead. None of the group showed clinical evidence of peripheral neuropathy, and the vibratory perception thresholds as well as motor conduction data from the median, radial, and common peroneal nerves were normal, as compared with an age-matched control group of 21 non-exposed normal subjects. The amplitude ratio between proximally and distally evoked muscle action potentials was normal in all lead-exposed subjects. These findings suggest that lead-exposed subjects are well protected against peripheral lead neuropathy, when blood lead levels are kept below the hygienic border value.

Adult↗
PubMed1981

A gas chromatographic and mass spectral approach to the analysis of the anticancer drug methyl-G as the trimethylsilyl derivative.

Methyl-G was analyzed by gas chromatography and mass spectrometry after trimethylsilylation. A means of quantitatively measuring methyl-G by gas chromatography of the TMS derivative is presented using the analogous derivative of methylethyl-G as an internal standard. The value of this compound as an internal standard for measurements of methyl-G is discussed based on comparisons of the mass spectral and gas chromatographic properties of their derivatives as well as their similar behavior in the ion exchange method used for partial purification. The latter procedure is discussed in some detail, and the results of applying it to biological samples of human and cell culture origin are presented.

Antineoplastic Agents↗
PubMed1980

Direct quantitative analysis of indicine-N-oxide in cancer patient samples by gas chromatography using the internal standard heliotrine-N-oxide including a mass spectral comparison of their trimethylsilyl derivatives.

Indicine-N-oxide was analyzed quantitatively in biological samples using a direct partial purification method involving acetonitrite precipitation or methanol precipitation followed by ion exchange chromatography. Trimethylsilyl derivatization of the resultant provided either of two derivatives, depending on the reaction conditions used, both of which had good gas chromatographic qualities. Heliotrine-N-oxide was used as the internal standard for this work. Data are presented to show that this is a reliable and useful internal standard based on its behavior in the partial purification method and on the gas chromatographic characteristics of its two derivatives. In addition, both low and high resolution mass spectral data indicate that heliotrine-N-oxide produces two trimethylsilyl derivatives analogous to those produced by indicine-N-oxide under the same conditions. Application of this procedure to urine and blood samples from cancer patients in clinical trials indicates that over 95% of the drug is removed from the circulation and excreted in the urine over the course of 48 h.

Antineoplastic Agents, Phytogenic↗
PubMed1979

The gas chromatographic mass spectrometric analysis of the new antitumor drug indicine-N-oxide utilizing a novel reaction accompanying trimethylsilylation.

Indicine-N-oxide was analyzed by gas chromatography mass spectrometry with nanogram sensitivity after trimethylsilylation. Two different products were produced by altering the conditions of this reaction. Mass spectral evidence is presented to show that one of these was the expected trisubstituted pyrrolizidine product while the other was a trisubstituted pyrrole. The latter derivative is useful for distinguishing between indicine-N-oxide and indicine which dies not form this novel product under the same conditions. Analogous pyrrole and pyrrolizidine products were formed from heliotrine-N-oxide, a compound that can serve as an internal standard from measuring indicine-N-oxide and its metabolites in biological samples. A method for purifying such samples by strong cation exchange chromatography prior to derivatization is also discussed.

Animals↗
PubMed1979

Glucocorticoid receptor inactivation and activation by phosphorylation mechanisms.

The specific glucocorticoid binding capacity of cytosol preparations is rapidly lost on incubation at 25 degrees in the absence of ligand. We have examined this process in cell-free preparations from rat thymus, rat liver and mouse fibroblasts (L 929 cells), and we have found that the unoccupied receptor is inactivated by endogenous enzymes to a form that does not bind steroids. The inactivation can be prevented by inhibitors of phosphatase action such as molybdate, fluoride and glucose-1-phosphate. On the basis of this type of evidence we propose that the receptor activity of cytosol can be rendered inactive by a dephosphorylation process. We have now been able to partially reactivate the receptor in both L cell and rat thymus cytosols in an ATP dependent manner. If fibroblast (L cell) cytosol is preincubated to permit receptor inactivation by endogenous enzyme, further inactivation can be prevented by the addition of 10 mM molybdate and reactivation of the binding capacity can be obtained by adding 5 to 10 mM ATP in addition to molybdate. ATP dependent activation is prevented with EDTA and this block is overcome by added magnesium. ADP, CTP, GTP, and UTP are inactive. After inactivating the glucocorticoid binding capacity of rat thymocyte cytosol by incubation for 45 minutes at 25 degrees, considerable reactivation is obtained by addition of dithiothreitol and ATP. This system does not absolutely require the presence of a phosphatase inhibitor in order to show activation. Thymocyte cytosol can also be activated to a steroid binding state by addition of DTT and heat-treated (90 degrees for 15 min.) cytosol from a variety of cell types. The heat-treated cytosol contains ATP, reducing equivalents, and a relatively small molecular weight heat-stable activator(s) that potentiates the reactivation process. Maximum receptor activation is obtained by adding dithiothreitol, heat-stable factor, ATP, and molybdate to the inactivated thymocyte cytosol.

Adenosine Triphosphate↗
PubMed1977

Reactivation of thymocyte glucocorticoid receptors in a cell-free system.

The specific glucocorticoid binding capacity of the 100,000 X g supernatant from thymocytes becomes rapidly inactivated with a half-life of approximately 4 h at 0 degrees. Following this inactivation, the receptor can be reactivated by a factor (or factors) present in the high speed supernatant of L929 mouse fibroblasts. The L cell activating factor is excluded from Sephadex G-25. It can be separated from the glucocorticoid receptor of L cells by chromatography of Sephadex G-150 where it elutes with the small molecular weight material. The probable molecular weight range for the activating factor is 5,000 to 20,000. Approximately 50% of the activating activity is retained after heating at 90 degrees for 15 min.

Adrenalectomy↗
PubMed1977

Synthesis and biological action of two glucocorticoid alkylating agents.

Two alkylating glucocorticoids have been synthesized in order to test the possibility of alkylating glucocorticoid receptors. The title compounds are 9alpha-fluoro-11beta,16alpha,17alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione 21-[bis(2-chloroethyl)carbamate] 16,17-acetonide (I) and 11beta,17alpha,21-trihydroxypregn-4-ene-3,20-dione 21-[bis(2-chloroethyl)carbamate] (II), prepared from triamcinolone acetonide and cortisol, respectively, through the reaction of the C-21 hydroxyl group with phosgene and di-2-chloroethylamine in the presence of triethylamine. Both compounds are biologically active as inhibitors of the growth of cultured mouse fibroblasts and are able to compete for the specific binding of radiolabeled triamcinolone acetonide to the L929 cell receptor. The bis(2-chloroethyl)carbamate moiety is capable of reacting with nucleophilic groups as evidenced by the colorimetric reaction with 4-(p-nitrobenzyl)pyridine. Both the interaction with the receptor and inhibition of cell growth by these two glucocorticoids are reversible.

Alkylating Agents↗