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Biomedical subjects

R Smith

Publications and source records attributed to R Smith.

At least 1,387 records · Page 77Linked to original sources

Dependence on lipid structure of the coil-to-helix transition of bovine myelin basic protein.

In aqueous solution bovine myelin basic protein has a close-to-random coil structure that is partially transformed to helix on interaction with lipids. Circular dichroism spectra have been used to follow this conformational transition which, with phospholipids, decreases in the order phosphatidylglycerol, phosphatidic acid approximately equal to phospholipids, decreases in the order phosphatidylethanolamine. There appears to be a strong correlation between the extent of alpha-helix formation and the degree of penetration of the hydrophobic region of the bilayer, as assessed by other methods. Cholesterol mixed in bilayers with phosphatidylserine has little effect on the protein secondary structure. Although basic protein binds strongly to cerebroside and to cerebroside sulphate, two of the other major myelin lipids, the intrinsic chirality of these lipids precludes assessment of their effect on the protein conformation. No significant changes in the circular dichroism spectra accompany the protein association with either of the zwitterionic bilayer-forming lipids, phosphatidylethanolamine and phosphatidylcholine. This seems to exclude extensive penetration into bilayers of these lipids and hence to exclude appreciable hydrophobic interactions; on the other hand, it is argued that little evidence exists for ionic attractions to these lipids. The optical activity of peptides derived from the basic protein by cleavage at the 42-43 and 88-89 peptides bonds (with cathepsin D) and at the 115-116 bond (with a skatole derivative) has also been measured in an attempt to locate the helix-forming regions within the primary structure.

Animals↗

Clinical usefulness of urinary 3-methylhistidine excretion in indicating muscle protein breakdown.

Urinary excretion of the post-translationally modified amino-acid 3-methylhistidine, derived from the contractile proteins actin and myosin, was measured in patients with conditions associated with nitrogen loss. The ratio of 3-methylhistidine:creatinine excretion, a measure of the fractional catabolic rate of myofibrillar protein was increased in severe injury, thyrotoxicosis, neoplastic disease, prednisolone administration, and sometimes Duchenne muscular dystrophy. In myxoedema, osteomalacia, and hypothermia the ratio was decreased; and starvation, elective operations, and rheumatoid arthritis had little effect. Provided that the diet is meat free, measurement of urinary 3-methylhistidine may provide useful information on the cause of protein loss.

Adolescent↗

Computed tomography brain scans in long term survivors of childhood acute lymphoblastic leukemia.

There have been varying frequencies cited for the occurrence of abnormal brain CT scans in leukemic patients and conflicting evidence about the significance of these abnormalities and their relationship to sanctuary therapy. Our study of CT brain scans in 26 long survivors of acute lymphoblastic leukemia showed an overall prevalence of 35% abnormal scans. There was no statistically significant difference between the number of abnormal scans in patients given radiotherapy as part of their CNS prophylaxis and those receiving only intrathecal methotrexate. Because the children in each treatment group were evenly matched with respect to other treatment variables possibly relevant to the causation of abnormal brain scans, a strong case is made for more rigorous design of such studies, preferably in a prospective fashion, looking simultaneously at other parameters of brain structure and function.

Adolescent↗

The relative amounts of the collagen chains alpha 1(I), alpha 2 and alpha 1(III) in the skin of 31 patients with osteogenesis imperfecta.

1. The relative amounts of type III and type I collagen, determined as the ratio of their constituent alpha 1(III) and alpha 1(I) chains, have been measured by interrupted electrophoresis of pepsin extracts of skin collagen from 31 patients with osteogenesis imperfecta of varying severity, and from six clinically unaffected family members. In 18 patients the ratio of the alpha 1(I) to alpha 2 chains of type I collagen has also been measured. 2. In the 15 patients with osteogenesis imperfecta classified as mild or the 18 with type I disease the ratio alpha 1(III)/alpha 1(I) was significantly increased (P less than 0.001) and the ratio alpha 1(I)/alpha 2 significantly decreased (P less than 0.005) compared with age-matched control subjects. 3. In three infants with lethal (type II) osteogenesis imperfecta the ratio alpha 1(III)/alpha 1(I) was normal, contrasting with the high ratio observed by others in fibroblast cultures from some apparently similar patients. 4. The ratio of alpha 1(I)/alpha 2 and of alpha 1(III)/alpha 2(I) was increased in both clinically normal parents of a child with severe disease, and in the mother of two children with osteogenesis imperfecta (one lethal and one severe) the ratio alpha 1(III)/alpha 1(I) was increased. 5. In the remaining patients with severe bone deformity (types III and IV) the relative amounts of the different collagen chains varied. 6. These data support previous suggestions that mild or type I osteogenesis imperfecta results from a generalized inability to form sufficient type I collagen, the predominant collagen of adult bone, and imply that in many cases this may result from defective production of the alpha 1(I) chain rather than of the alpha 2 chain. Some patients with severe disease demonstrate a similar defect; but in the remainder other abnormalities of collagen or connective tissue maturation are presumably involved.

Adolescent↗

Delayed cerebral embolization of a shotgun pellet with fatal consequences.

A case of shotgun pellet embolization to the middle cerebral artery is presented. Embolization occurred approximately 36 hours following successful resuscitation of blood pressure, respirations, and neurologic function in a 21-year-old man who had sustained a massive chest wound. The diagnosis of pellet embolization was made within 8 hours of the onset of neurologic deficits; however, fatal cerebral infarction had occurred before surgery could be undertaken. Seven similar cases are briefly reviewed and it is concluded that low velocity and low kinetic energy missiles are more likely to embolize, and that left lower extremity injuries are more frequently involved in embolization. In all cases of shotgun trauma to the chest cerebral embolization of pellets should be considered at any sign of neurologic change and skull films obtained. Surgical intervention is necessary before cerebral infarction.

Adult↗

Mexiletine in plasma by high pressure liquid chromatography.

We report here a novel high pressure liquid chromatographic (HPLC) technique for use in therapeutic monitoring of the primary amine antiarrhythmic drug mexiletine in plasma samples. Mexiletine and its structural analogue, the internal standard Ko 768, are extracted with heptane after alkalinization of the sample. The extracts are evaporated to dryness, reconstituted, and injected into a liquid chromatograph equipped with an octadecylsilane reversed phase column using an acetonitrile/acetate buffer mobile phase. Detection is by ultraviolet absorption at 254 nm. The method is linear from 0.2 to 5.0 microgram/ml; the coefficient of variation ranges from 5 to 10% within the therapeutic range. The drug is stable for at least 99 days in samples stored at -20 degrees C. Our HPLC results showed good agreement with a popular gas liquid chromatographic method (14), and there are few incidents of interference from common drugs. The method is convenient for any laboratory equipped with standard liquid chromatographic equipment and is suitable for automation.

Chemical Phenomena↗