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Biomedical subjects

M Barker

Publications and source records attributed to M Barker.

At least 109 records · Page 6Linked to original sources

Methylation of DNAase-digestible DNA and of RNA in chromatin from rats treated with dimethylnitrosamine.

After injecting rats with di[14C]methylnitrosamine we have prepared liver chromatin and have examined firstly, the methylation level of the DNAase I-degradable fraction of the DNA and secondly, the level of methylation and the stability of methylated sites in chromatin RNA. Our results show that the level of 7-methylguanine in the degradable DNA is about 1.3 times that of whole DNA; therefore in the 20% or so of the DNA which is undegradable by DNAase I, the level must be very low or zero. Experiments using chromatin from rats injected with unlabelled dimethylnitrosamine plus [3H]thymidine show that the specific activity is similar in the DNAase I degradable and undegradable fractions, suggesting that there is no preferential repair in the latter region. In chromatin RNA, the level of 7-methylguanine is higher than that of whole DNA and decreases fairly rapidly within 30 h after dimethylnitrosamine treatment. Our results indicate that this decrease is due to some type of excision or repair process rather than to normal turnover.

Animals↗

Symptoms and feeding patterns in the first year of life.

With the help of family doctors, mothers and infant welfare sisters, we report an analysis of symptom and food diaries maintained throughout the first twelve months of life on 482 infants. This reveals the existence of extensive symptomatology in the first year of life--most of which was clearly unrelated to ingestion of foods or cow's milk. Our efforts to define the true incidence of cow's milk allergy have been unsuccessful. Altogether, 77 of the 482 diaries have revealed symptomatology at some time in the year which could conceivably have been associated with cow's milk ingestion. But, in only one of these 77 children were withdrawal and challenge tests carried out to determine whether the symptomatology disappeared on withdrawal of cow's milk and reappeared on its reintroduction into the diet. Most of the remaining 76 children had long periods of complete freedom from symptoms whilst taking cow's milk, and the evidence of any association with cow's milk was generally very tenuous. Soya substitutes were introduced in 13 cases, and cow's milk was temporarily discontinued in another 11 cases. Only 16 of these 77 children continued to experience chronic symptoms during the last two weeks of their first year.

Animals↗

Effect of dibutyryl cAMP on cell cycle progression of rat brain tumor cells in vitro.

Autoradiographic and flow microfluorometry analyses have been applied to a study of perturbed cell kinetics in 9L rat brain tumor cells treated with dibutyryl cyclic AMP and theophylline alone and in combination in vitro. At a concentration of 1 mM each, cell growth ceased shortly after the administration of these drugs. The results indicate that cells in S and G2 phase at the time of drug administration can undergo mitosis even though a considerable prolongation of G2 phase was apparent. However, cells in G1 at the time of drug administration was arrested in that phase, whereas those cells in S or G2 were able to complete one mitosis before becoming arrested in the G1 phase. This blocking effect was reversible, and cells resumed proliferation at a normal rate shortly after the removal of these drugs.

Animals↗

Studies on liver chromatin RNA from rats treated with alkylating agents.

We have examined firstly some properties of rat liver chromatin RNA and nuclear sap RNA and secondly the incorporation of [3H]orotic acid into the RNA in vivo in control rats and in rats treated with the alkylating agents, N,N-dimethylnitrosamine or methyl methane sulphonate. Half or more of the nuclear RNA is associated with the chromatin and consists mainly of two species: one is labelled and probably comprises "nascent" RNA, and the other is unlabelled and of lower molecular weight. Neither species is attributable to cytoplasmic contamination. Studies with added polylysine with RNAase A and with DNAase I suggest that both species are ironically bound to protein and that the labelled species is not associated with the part of the chromatin DNA most readily degraded by DNAase I. After dimethylnitrosamine treatment, the amount of unlabelled RNA remains constant but the amount of labelled RNA increases after a low dose, and decreases after a high dose. After methyl methane sulphonate treatment, no change occurs in either species. These results can be explained by changes in extent of association of the DNA and protein within the chromatin complex.

Adolescent↗

Response to CO2 of intrapulmonary chemoreceptors in the emu.

We studied discharge frequencies of 12 intrapulmonary chemoreceptors in the paleopulmonic lung of an emu (Dromiceius novaechollandiae) during unidirectional, artificial ventilation when step changes and static CO2 concentrations were given. Discharge frequency in afferent neurons from the receptors increased as intrapulmonary CO2 decreased. The response of the receptors to various static intrapulmonary CO2 concentrations was similar to that previously demonstrated for the duck and chicken. The median sensitivity of the emu receptors at one-half maximal discharge was 4.6 imp-(sec-0.01 F1CO2)-1. Discharge frequencies altered phasically in nine of 12 receptors when step changes in CO2 of 3.3% at 1.6 Hz were given in the unidirectional gas stream while four of 12 modulated their discharge when the CO2 changes were as rapid as 3.2 Hz. Hence, some receptors can respond to rapid fluctuations in CO2 in their microencironment. We conclude that intrapulmonary chemoreceptors in the paleopulmonic lung of the emu exhibit similar characteristics to those in birds that possess varying amounts of neopulmonic parabronchi, such as the duck and chicken.

Animals↗

The kinetics of cultured human glioma cells: autoradiographic studies.

The kinetics of monolayer cell cultures, derived from brain tumors which had been labeled with 3H-thymidine just prior to surgical removal, have been investigated. Analysis of autoradiographs indicates that: 1. the distribution of cell types in primary cultures is similar to that of the viable areas of the parent tumor in vivo; 2. the first week of culture constitutes a lag phase; and 3. vigorous proliferation commences during the second week of culture. Double labeling of the tritiated cultures with 14C-thymidine indicates that the pulse labeling index (PLI) of primary cultures during the second week is lower than that of the parent tumor and that the PLI of the culture increases during the second week. In contrast, we found that long-term established cultures in our laboratory have a high PLI during the first few days after passage, quickly reach a maximum, and then drop precipitously 1 week after passage. These latter variations in PLI correspond to the following growth pattern: 1. exponential growth; 2. a stationary phase due to medium exhaustion; or 3. a a plateau due to overcrowding. There are indications that some cell types, which have the capacity to divide in the parent tumor, lose this ability after transfer to tissue culture.

Autoradiography↗

Prevention of folate deficiency by food fortification. III. Effect in pregnant subjects of varying amounts of added folic acid.

Maise meal fortified with folic acid was administered to subjects in late pregnancy in a daily dose of either 500 or 300 mug of folic acid. Changes in hematological and folate nutritonal status were compared to those in subjects receiving 300 mug folic acid/day in tablet form, and also in subjects in a previous study who received unfortified maize meal (control group) or meal containing 1,000 mug folic acid/day. In all groups receiving folic acid, red cell and serum folate levels rose progressively, and the rate of rise increased with increasing doses of folic acid. Maize meal containing a daily dose of 500 mug folic acid produced an effect similar to that of 300 mug daily in tablet form. Maize containing 300 mug added folic acid daily was effective in preventing the progression of folate depletion in late pregnancy.

Dose-Response Relationship, Drug↗

Prevention of folate deficiency by food fortification. IV. Identification of target groups in addition to pregnant women in an adult rural population.

In a rural Negro population subsisting on a predominantly maize meal diet, the incidence of folate deficiency was 43.8% in nonanaemic women in late pregnancy, 32.1% in nonpregnant women, and 18.6% in adult males. More than one-third of all subjects older than 60 were deficient. No instance of unequivocal vitamin B12 deficiency was revealed in 431 subjects sampled, and it is considered that the hazards of giving a small daily dose of folic acid in this population are negligible. These findings warrant food fortification with folic acid in this and similar population groups.

Adolescent↗

Prevention of folate deficiency by food fortification. VII. The use of bread as a vehicle for folate supplementation.

Bread fortified to contain a daily dose of 900 mug folic acid was administered to patients in late pregnancy. The patients receiving the bread showed significant rise in red cell folate concentration. The rise was similar to that observed in women receiving a daily dose of 300 mug of folic acid in tablet form. It is concluded that bread may be used as a vehicle for folic acid fortification.

Africa, Southern↗

Chemotherapeutic implications of growth fraction and cell cycle time in glioblastomas.

Four patients received 3H-thymidine 4 to 7 days and vinblastine 4 to 6 hours prior to operation for recurrent malignant gliomas (three glioblastomas and one anaplastic astrocytoma). Tumor biopsies obtained at operation were fixed for routine histological studies and radioautography. The tumors' growth fractions averaged 0.28 with a range of 0.14 to 0.39. The tumor cell cycle time calculated in three patients had a mean duration of 57 hours with a standard deviation of 6 hours. The authors concluded that: 1) single short-term courses of cell-cycle specific chemotherapeutic agents alone will probably fail to achieve either significant reduction in tumor mass or dramatic clinical improvement; 2) cell-cycle phase-specific drugs should be administered to maintain effective blood levels over 2 to 3 days for maximal tumor cell kill. Tumor growth rate appears to correlate with the fraction of proliferating cells rather than the length of the tumor cell cycle. The scientific basis for combination drug and multimodality therapy is discussed.

Biopsy↗

Chemotherapeutic implications of early tumor cell growth in an animal brain-tumor model.

The onset of tumor cell proliferation was determined in an animal brain-tumor model in which tumor cells had been injected into the cerebrum of rats through a hollow stainless steel screw implanted stereotactically. Tritiated thymidine uptake in the DNA at various periods after injection of tumor cells indicated no significant proliferation of tumor cells until 168-192 hours post implantation, after which tritium uptake increased exponentially. Control rats with screws alone or screws through which balanced salt solution had been injected showed an increased uptake at 72 hours, a phenomenon not observed in animals given tumor cells. Our findings suggested that, in the tumor model described, experimental chemotherapy tests should be deferred until at least 7 days post implantation.

Animals↗