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Biomedical subjects

P Brooks

Publications and source records attributed to P Brooks.

At least 109 records · Page 6Linked to original sources

Some restriction endonucleases tolerate single mismatches of the pyrimidine.purine type.

DNAs from phage mutants M13mp18 and M13mp18/MP-1 were used to construct two closed circular heteroduplexes. One of them carried the sequence 5'-CCTGGG-3' 3'-GGGCCC-5' with a T.G mismatch at the position 6248. The other carried the sequence 5'-CCCGGG-3' 3'-GGACCC-5' with a C.A mismatch at the same position. Heteroduplexes were exposed to 7 restriction endonucleases having recognition sites within the sequence 5'-CCCGGG-3' 3'-GGGCCC-5' and to 1 restriction endonuclease having a recognition site within the sequence 5'-CCTGGG-3' 3'-GGACCC-5'. All tested enzymes cleaved at least one mismatch-containing sequence although with reduced efficiency. Smal and Xmal tolerated both mismatch-containing sequences. Aval, Hpall, Mspl, Ncil and Nsplll were able to tolerate only the T.G containing sequence, while BstNl was able to tolerate only the C.A containing sequence. It is inferred that the tolerance displayed by Smal and Xmal depends on the presence of either the original purines or the original pyrimidines in mismatches of both the T.G and C.A type and that all other tested enzymes require the presence of the original purines in mismaches of both types.

Bacteriophages↗

The language of children with spina bifida and hydrocephalus: meeting task demands and mastering syntax.

Children with hydrocephalus are thought to exhibit deficiencies in their linguistic performance, including the production of numerous off-topic utterances and semantically immature responses to linguistically posed problems (e.g., questions, word definitions). The hydrocephalic children included in many previous studies, however, have been mentally retarded. We sought to determine whether these language problems also characterized intellectually average children with hydrocephalus. A second purpose was to evaluate the hypothesis that the language problems of hydrocephalic children occur predominantly on tasks with high cognitive or linguistic demands. A third purpose was to reexamine the claim that despite their semantic-pragmatic deficiencies, the syntax of hydrocephalic children is age appropriate. Our hydrocephalic subjects dealt with the semantic-pragmatic requirements of linguistically posed problems in an age-appropriate manner, and although their performance on these problems declined as task demands increased, the decline was no more than that seen for nondisabled age-matches. The hydrocephalic children did not differ significantly from nondisabled age-matches on measures of productive syntactic maturity.

Child↗

DNA mismatch repair in Xenopus egg extracts: repair efficiency and DNA repair synthesis for all single base-pair mismatches.

Repair of all 12 single base-pair mismatches by Xenopus egg extracts was measured by a physical assay with a sequence containing four overlapping restriction sites. The heteroduplex substrates, derivatives of M13 phage DNA, differed in sequence at the mismatch position only and permitted measurement of repair to both strands. The efficiency of repair varied about 4-fold between the most and least effectively repaired mismatches. Repair was most active with C/A and T/C mismatches but the efficiency varied depending on the orientation of the mismatch. Mismatch-specific DNA repair synthesis was also observed but the extent of repair was not always predictive of the extent of synthesis, suggesting the presence of different repair systems or different modes of mismatch recognition.

Animals↗

Mismatch repair involving localized DNA synthesis in extracts of Xenopus eggs.

Repair of heteroduplex DNA containing G.T or A.C mismatches or containing two tandem unpaired bases occurred in vitro with Xenopus egg extracts as detected by a physical assay. The repair was accompanied by a mismatch-stimulated and mismatch-localized DNA synthesis. Repaired molecules, separated from unrepaired molecules, showed a 20- to 100-fold increase in DNA synthesis in the region of the mismatch compared to regions distant from the mismatch. The remaining unrepaired heteroduplex DNA included molecules that also displayed mismatch-stimulated DNA synthesis in the mismatch-proximal regions. These may represent intermediates in the repair process. The patterns of DNA synthesis suggest that repair begins at some distance from the mismatch and that as much as 1 kilobase or more can be involved in the mismatch-stimulated synthesis.

Animals↗

Immunosuppressive drugs and corticosteroids in the treatment of rheumatoid arthritis.

Rheumatoid arthritis is the most common form of severe inflammatory arthropathy affecting patients at a relatively early age. Although there are a number of drugs which significantly reduce pain and swelling, few alter the development of erosions and progression of joint destruction. A significant number of patients with rheumatoid arthritis develop this progressive disability and will require treatment with corticosteroids or immunosuppressive agents. In this article the use of immunosuppressive drugs and corticosteroids in the treatment of aggressive rheumatoid arthritis is reviewed. Controlled clinical trials have shown that a number of these drugs can play a significant role in reducing pain and swelling and might possibly alter the disease course in rheumatoid arthritis. Side effects of these agents, including the potential for oncogenesis, still pose major problems in their long term use. The risks and benefits of immunosuppressive and corticosteroid drug therapy must be balanced in each patient to whom they are prescribed and reviewed at frequent intervals.

Adrenal Cortex Hormones↗

Effects of aspirin, naloxone and placebo.

This study was designed to examine the effects of aspirin, naloxone and placebo treatment on serum beta-endorphin concentration and joint pain in patients with rheumatoid arthritis (RA). Ten patients with definite or classical RA were studied. All treatments were administered in a randomized sequence. On each study day, the following measurements were carried out at specified time intervals: serum beta-endorphin concentration, serum salicylate concentration and joint pain score on a visual analogue horizontal scale. We conclude that in patients with rheumatoid arthritis suffering from chronic joint pain, serum beta-endorphin does not appear to play a role in pain relief.

Arthritis, Rheumatoid↗

Estrogen therapy arrests bone loss in elderly women.

Although osteoporosis is an age-related disorder, the accelerated bone loss observed in postmenopausal women may be preventable with early diagnosis and adequate estrogen replacement. In a prospective study, we investigated the effect of oral estrogen replacement using conjugated estrogens (Premarin, 0.625 mg) or micronized 17 beta-estradiol (Estrace, 1 mg) versus no estrogen in sequential single-photon bone density measurements over 3-year intervals in 397 postmenopausal women. Estradiol, 1 mg, and conjugated estrogens, 0.625 mg, were equally effective in regarding bone loss. The rate of bone loss was about the same for estrogen users regardless of age (51 to 80 years) and was approximately one third that of nonusers. Among nonusers a uniform accelerated rate of bone loss of 2.5% per year was noted between 56 and 70 years old, whereas between the ages of 51 and 55 years and after age 70 years, the rate of bone loss was significantly less. Ever users over age 65 years showed continued protection from bone loss as long as estrogen therapy was continued. Previous estrogen users who stopped estrogen after age 65 years lost bone more rapidly than women of similar age who had never taken estrogen. Thus to prevent accelerated bone loss in postmenopausal women, we recommend early and continued hormone replacement for life. Estrogen nonusers should be monitored at regular intervals to minimize accelerated bone loss.

Absorptiometry, Photon↗

Thickening of infant feedings for therapy of gastroesophageal reflux.

To assess the effect of thickening of feedings on gastroesophageal reflux and gastric emptying, 20 infants were examined with technetium scintigraphy and detailed behavioral observation after each of a pair of feedings, one with radiolabeled infant formula alone and the other with radiolabeled formula thickened with dry rice cereal. The thickened and unthickened meals were followed by similar amounts of scintigraphically demonstrated gastroesophageal reflux. However, the number of episodes of emesis (1.2 +/- 0.7 vs 3.9 +/- 0.9 per 90 minutes postprandial), the percent of gastric emptying at 30 minutes (17.8% +/- 2.7% vs 22.4% +/- 2.4%), the time spent crying (11.7 +/- 3.1 minutes vs 17.6 +/- 3.8 minutes per 90 minutes), and the total time spent awake (45.2 +/- 5.9 minutes vs 53.1 +/- 4.9 minutes per 90 minutes) were significantly less after the thickened feedings. Because thickening of infant feedings increases the caloric density, decreases emesis, decreases crying time, and increases sleep time in the postprandial period, it is likely to be beneficial in the treatment of infants with gastroesophageal reflux associated with failure to thrive.

Crying↗

Hydroxymethyluracil DNA glycosylase in mammalian cells.

An activity has been purified 350-fold from extracts of mouse plasmacytoma cells that forms 5-hydroxymethyluracil (alpha-hydroxythymine) and apyrimidinic sites with phage SPO1 DNA, which contains this base in place of thymine. This DNA glycosylase presumably functions to eliminate hydroxymethyluracil, a major thymine-derived DNA lesion produced by ionizing radiation and oxidative damage. The enzyme has no cofactor requirement and is active in EDTA. Neither intermediate formation nor hydrolysis of hydroxymethyl-deoxyuridine or hydroxymethyldeoxyuridine monophosphate was detected. The enzyme does not cleave apyrimidinic sites in DNA. It does release uracil from the uracil-containing DNA of phage PBS2, but this activity is less than 2% of the predominant uracil DNA glycosylase activity of the cell, which is separated by phosphocellulose chromatography. The major uracil DNA glycosylase does not release hydroxymethyluracil from SPO1 DNA. The hydroxymethyluracil glycosylase is also separated upon phosphocelluose chromatography from a thymine glycol DNA glycosylase activity that is accompanied by an apyrimidinic endonuclease activity.

Animals↗

Sublingual absorption of micronized 17beta-estradiol.

The sublingual absorption rates, the sustained effects, te biologic activity, and the metabolism of micronized 17beta-estradiol (E2) were measured in 10 postmenopausal women. E2 (0.5 mg) was administered in a single sublingual dose to five of the patients. An alternate-day schedule with the same dosage was used for the other five patients. In the single-dose study, a twenty-six fold increase in serum E2 and a ninefold increase in serum estrone (E1) concentrations were observed 1 hour after the sublingual deposition of E2 (0.5 mg). Serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were significantly decreased within 6 hours. The rise in E2 was early and peaked in the first 2 hours. The rise in E1 was slower and progressive, reaching its maximum thirteenfold increase at 4 hours, and remained two and one half times the baseline of 29 pg/ml at 24 hours, whereas E2 returned to the baseline level of 24 pg/ml. When micronized E2 was given in a dosage of 0.5 mg sublingually every other night, increased circulating levels of estrogens continued to be elevated at a minimum two and one-half fold baseline level for the week of study.

Absorption↗

The reliability of a Survey Psychiatric Assessment Schedule for the elderly.

The Survey Psychiatric Assessment Schedule (SPAS) was used in a survey of elderly people living at home and in institutions to examine its reliability in determining mental state. A psychiatrist assessed the same subjects using the Geriatric Mental State Schedule (GMSS) and classified psychiatric disorder into three broad groups: organic disorders, schizophrenia and paranoid disorders, and affective disorders and psychoneuroses. The agreement between the psychiatrist's classification of mental state and the classification derived from SPAS was found to be satisfactory for organic disorders and less satisfactory for functional disorders. The limitations of this method of identifying psychiatric illness are examined.

Aged↗