Search PubMedSearch

Biomedical subjects

P Singer

Publications and source records attributed to P Singer.

At least 109 records · Page 6Linked to original sources

Resolving arguments about the sanctity of life: a response to Long.

Thomas Long has argued that there is an irreconcilable metaphysical difference between the views of those who, like ourselves, believe that on quality-of-life grounds it is sometimes justifiable to end the life of a severely handicapped infant, and those who, like Paul Ramsey, reject this view. Because of this metaphysical difference, Long considers it impossible for our arguments to refute Ramsey's position. We disagree.

Persons with Disabilities

Unilateral onychodystrophy secondary to nail biting.

Whether or not nail biting is a sign of underlying psychiatric disorders is the subject of controversy. We report here a case of nail biting that was unusual in its pattern and severity, and occurred in a patient with previously diagnosed psychiatric disease. The literature regarding psychiatric disease associated with self-inflicted nail disease is reviewed.

Humans

Promoter search by Escherichia coli RNA polymerase on a circular DNA template.

Using the rapid-mixing/photocross-linking technique developed in our laboratory, we have investigated the kinetics of interaction between Escherichia coli RNA polymerase and pAR1319, a recombinant plasmid DNA containing the bacteriophage T7 A2 early promoter. By monitoring the time-dependent density of bound RNA polymerase along the relaxed circular DNA molecule using this technique, we have been able to demonstrate kinetic evidence for linear diffusion of RNA polymerase along DNA in a different system from that previously described (Park, C. S., Hillel, Z., and Wu, C.-W. (1982) J. Biol. Chem. 251, 6950-6956). The nonspecific association rate constant kon was measured to be 7.7 x 10(4) M-1 s-1 at a DNA chain concentration of 22.4 nM. By taking advantage of the fact that rapid mixing displaces bound protein molecules from DNA, but leaves them within the domain of the DNA, the rate of intradomain binding of RNA polymerase to pAR1319 DNA was determined to be 8.2 s-1. Since the plasmid is described by a radius of gyration of 0.22 microns, the intradomain concentration of base pairs could be calculated. Using this concentration (180 microM), the rate constant for intradomain nonspecific association of RNA polymerase to pAR1319 DNA was estimated to be 4.6 x 10(4) M-1 s-1. In addition, a mathematical model has been used to fit the other two important rate constants to the experimental data: koff, which describes the dissociation of RNA polymerase from nonspecific binding sites, and D1, the one-dimensional diffusion coefficient of the enzyme along the DNA molecule. In this model, the circular DNA molecule is described as a ring of interconnected binding sites which together comprise a DNA "domain." RNA polymerase, which enters the domain via three-dimensional diffusion and binds to each site, is allowed to diffuse linearly between adjacent sites and three-dimensionally on and off the DNA molecule. The rate equations for the time-dependent occupancy of each site by RNA polymerase could be written, based on general principles. By solving the resulting family of differential equations, koff and D1 were determined to be 0.3 s-1 and 1.5 x 10(-9) cm2 s-1, respectively.

DNA, Circular

Changes of N-6 and N-3 fatty acids in liver from spontaneously hypertensive (SHR) and normotensive rats after diets supplemented with alpha-linolenic or eicosapentaenoic acids.

In spontaneously hypertensive (SHR) and normotensive rats (WKY), diets supplemented with n-3 fatty acids of different chain length (alpha-linolenic acid, LNA-C 18:3, n-3 with linseed oil and eicosapentaenoic acid, EPA-C 20:5, n-3 with cod liver oil) were fed over a period of 22 weeks. A diet with commercially available pellets served as control. After the LNA-rich diet the augmentation of LNA was most pronounced in liver triglycerides (TG) and free fatty acids (FFA), whereas the increase of EPA was most marked in phosphatidylethanolamine (PE) and phosphatidylcholine (PC) when compared with the controls. Docosahexaenoic acid (DHA) was decreased mainly in neutral lipids. Of the n-6 fatty acids linoleic acid (LA) appeared significantly depressed in TG and FFA, but increased in phospholipids. Arachidonic acid (AA), however, was lower in all lipids. In SHR and WKY fed the EPA-rich diet EPA and DHA were significantly higher as compared to the controls on a pellet diet. On the contrary, LNA was not detectable in all lipid classes. LA and AA were markedly depressed. Docosenoic acids were significantly increased. The p/s-ratio did not reflect the changes in the 20:5/20:4- and n-3/n-6-ratios. The data indicate a differential effect of dietary n-3 fatty acids of different chain length on the supply of other n-3 fatty acids. Moreover, after an LNA-rich diet divergent alterations of LA in neutral lipids and phospholipids occurred. The results are dissimilar to those obtained in adipose tissue. Blood pressure was not influenced by the diets in either SHR or WKY.

Animals

Attitudes of Australian neonatal paediatricians to the treatment of extremely preterm infants.

A questionnaire survey was carried out to identify areas of consensus or disagreement in the attitudes and practices of Australian neonatal paediatricians with regard to the treatment of extremely preterm infants. Considerable variation was found in the estimated chances of survival and disability among respondents. The majority of neonatal paediatricians advocated prompt resuscitation and initiation of neonatal intensive care at birth, although all believed life-support treatment should be withdrawn in those instances where medical complications develop resulting in near certainty of death or life with total incapacity. The predominant view was for parents to be involved in the decision-making process for withdrawal of life-support and for the neonatal intensive care policy to be made known to the parents. Information from this survey which raised concerns included the variability in the estimate of the potential for survival, the lack of relevance of the law to everyday practices in the neonatal intensive care units, the small minority of respondents who felt that life-and-death decisions should be made by medical staff alone, and the reluctance of some neonatal paediatricians to inform parents about the policies of their unit.

Adult

Glucose and leucine uptake in the hypoglossal nucleus after hypoglossal nerve transection with and without prevented regeneration in the Sprague-Dawley rat.

We studied [14C]2-deoxyglucose and [14C]leucine uptake in the rat hypoglossal nucleus after hypoglossal nerve transection and when regeneration was prevented by placing a nylon ligature around the nerve proximal to the cut. Glucose and leucine uptake increased after nerve transection in both the animals with nerve transection alone and with the ligature. Both the glucose and leucine uptake increased more in animals with the ligature. The glucose and leucine uptakes returned to normal at 30 and 45 days, respectively, after transection alone and at 60 days in animals in whom regeneration was prevented with a ligature. This suggests that there is a more powerful stimulus to regeneration when regeneration is prevented but that some mechanism turns the process off after a fixed time.

Animals

[Changes in blood pressure and serum lipids with fish diets in patients with mild essential hypertension].

14 male patients with moderate essential hypertension were treated in the cross-comparison with a mackerel and herring diet, respectively, for two weeks. The mackerel diet contained double as much eicosapentaenic (EPA) and docosahexaenic acid (DHA) as the herring diet which served as control. In the serum triglycerides particularly DHS, in the cholesterol esters above all EPA were enriched. In the phospholipids the increase of the two fatty acids was approximately the same. At the end of the mackerel period the serum triglycerides, the total and LDL-cholesterol, the activity of the lecithin-cholesterol-acyl-transferase (CALT) and the serum sodium were significantly decreased. On the other hand, the HDL-cholesterol and the uric acid in the serum significantly increased. Under influence of the herring diet the parameters mentioned appeared only slightly changed. After the mackerel diet also a significantly lower systolic blood pressure was found. The systolic and diastolic blood pressure during a standardized psychophysiological stress test was more diminished at the end of the mackerel period than after the herring diet. The plasma renin activity (PRA) was increased after the mackerel diet. Its increase under the stress test could no more be proved at the end of the mackerel diet. In similar way the stress-conditioned increase of thromboxane B2 could no more be observe both after mackerel and after herring diet. When the results should confirm themselves in long-term studies, a mackerel diet in practicable dosage can be recommended as non-medicamentous treatment of moderate hypertension.

Blood Pressure

Comparative study of the blood pressure effects of four different vegetable fats on young, spontaneously hypertensive rats.

Following the suckling period, four groups of male four-week-old spontaneously hypertensive rats (SHR) were fed semisynthetic diets with 14% (by weight) of either sunflower seed oil [46% 18:2(n-6); linoleic acid (LA)-rich], linseed oil [62.5% 18:3(n-3) + 12.9% 18:2(n-6); alpha-linolenic acid (LNA)-rich], evening primrose oil [9.2% 18:3(n-6) + 71% 18:2(n-6); gamma-linolenic acid (LNA)-rich] or hydrogenated palm kernel fat [1.5% 18:2(n-6); polyunsaturated fatty acid (PUFA)-deficient], respectively, up to an age of 18 wk. All diets enriched with PUFA provoked an attenuation of hypertension development. The effect was lowest in the LA-rich group and highest in the gamma-LNA-rich group. Differences in fatty acid composition of renal phospholipids between groups reflect the fatty acids present in the respective dietary fats. Renomedullary production of PGF2 alpha was significantly reduced in alpha-LNA-rich and slightly diminished in gamma-LNA-rich fed rats. Aortic formation of 6-keto-PGF1 alpha and TXB2 was increased in animals fed the gamma-LNA-rich diet. Thus, the attenuation of hypertension development cannot be explained only by changes in prostanoid formation. Other mechanisms possibly involved should be pursued.

Animals

Long-term effect of mackerel diet on blood pressure, serum lipids and thromboxane formation in patients with mild essential hypertension.

Twelve male patients with mild essential hypertension were put on a diet supplemented with 2 cans of mackerel/day (= 2.2 g daily of eicosapentaenoic acid, EPA, C20:5 n-3 and 2.8 g daily of docosahexaenoic acid, DHA, C22:6 n-3) for 2 weeks within an isocaloric regimen and then with 3 cans/week (= 3.3 g/week, equivalent to 0.47 g daily of EPA and 4.2 g/week, equivalent to 0.69 g daily of DHA) for 8 months with a subsequent period of 2 months on normal diet. Eleven male hypertensives matched for age, body weight index, blood pressure and serum lipids with no change in their nutritional habits served as controls. After the first dietary period (2 weeks) a significant decrease of serum triglycerides (TG), total and LDL-cholesterol, blood pressure and thromboxane B2 (TxB2) was found, whereas HDL cholesterol and potassium in erythrocytes were significantly increased. During the second dietary period (8 months) providing the lower dose of EPA, serum lipids and the other biochemical parameters returned to the initial values. Blood pressure, however, remained significantly lower and rose to the basal levels only after the third period (2 months) on normal diet. In the control group no alterations could be seen. The data suggest a dose-related differential effect of dietary EPA on serum lipids, lipoproteins, TxB2 and blood pressure in subjects with mild hypertension.

Adult

Serum triglycerides and HDL cholesterol from SHR after evening primrose oil and other polyunsaturated fats.

Spontaneously hypertensive rats (SHR) were fed diets enriched with evening primrose (EPO), sunflower (SO) and linseed oils (LO) as well as palm kernel fat (PKF), the latter being deficient in polyunsarated fatty acids (PUFA). In SHR fed EPO serum triglycerides were lowest and HDL1 cholesterol was highest as compared to the other groups of animals. Total cholesterol was not different. The data suggest that - as with blood pressure - serum lipids and lipoproteins might be influenced most effectively by EPO in comparison to other polyunsaturated fats.

Administration, Oral

Different changes of n-6 and n-3 fatty acids in adipose tissue from spontaneously hypertensive (SHR) and normotensive rats after diets supplemented with linolenic or eicosapentaenoic acids.

In spontaneously hypertensive (SHR) and normotensive rats of the Wistar-Kyoto (WKY) and Wistar-Schönwalde (WSCHOE) strain, diets supplemented with n-3 fatty acids of different chain length (alpha-linolenic acid, LNA--C 18:3, n-3 with linseed oil and eicosapentaenoic acid, EPA--C 20:5, n-3 with cod liver oil) were fed over a period of 22 weeks. After the LNA-rich diet, among the long-chain n-3 fatty acids EPA in epididymal adipose tissue remained unchanged, whereas docosapentaenoic (DPA) and docosahexaenoic acids (DHA) fell. The n-6 fatty acids linoleic (LA) and arachidonic acid (AA) both appeared decreased. After the EPA-rich diet, all n-3 fatty acids, i.e. not only EPA, DPA and DHA, but also LNA were augmented when compared with controls fed commercially available pellets. Among the n-6 fatty acids LA was extremely depressed, whereas AA appeared increased. The p/s-ratio was elevated after the LNA-rich diet, but decreased after the EPA-rich diet. The data indicate a differential effect of dietary n-3 fatty acids of different chain length on the supply of other n-3 fatty acids, of LA and AA as well as on the p/s-ratio in adipose tissue of rats. Blood pressure was not influenced by either diet in either SHR or in both normotensive strains of rats.

Adipose Tissue