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Biomedical subjects

C Sutherland

Publications and source records attributed to C Sutherland.

At least 37 records · Page 2Linked to original sources

Holistic physicians and family practitioners: similarities, differences and implications for health policy.

Although loosely defined, holistic or alternative medicine has been viewed by most observers as fundamentally at odds with mainstream biomedical approaches. Convergence or integration of the two are seen as highly unlikely. We attempt to assess the potential for such integration empirically through a survey of physicians, members of the American Holistic Medical Association (N = 340) and a comparison group of family practitioners (N = 142). Although social origins of the two groups are similar, they differ in their completion of residency training and a variety of practice characteristics. While the groups differ in the predicted directions in their evaluation and utilization of holistic techniques and in their attitudes toward the nature of medical practice, there is a good deal of overlap. Personal experiences, especially those in the area of religion/spirituality and psychotherapy differ sharply between the groups. Policy concerned with fostering cooperation or convergence between holistic and mainstream medicine should differentiate between clinical attitudes and behaviors (which appear to be more compatible than has been suggested), and the personal world views of physicians (which appear to be much further apart).

Adult

Activation of smooth muscle myosin Mg2+-ATPase by native thin filaments and actin/tropomyosin.

Application of the myosin competition test (Lehman, W., and Szent-Györgyi, A. G. (1975) J. Gen. Physiol. 66, 1-30) to chicken gizzard actomyosin indicated that this smooth muscle contains a thin filament-linked regulatory mechanism. Chicken gizzard thin filaments, isolated as described previously (Marston, S. B., and Lehman, W. (1985) Biochem. J. 231, 517-522), consisted almost exclusively of actin, tropomyosin, caldesmon, and an unidentified 32-kilodalton polypeptide in molar ratios of 1:1/6:1/26:1/17, respectively. When reconstituted with phosphorylated gizzard myosin, these thin filaments conferred Ca2+ sensitivity (67.8 +/- 2.1%; n = 5) on the myosin Mg2+-ATPase. On the other hand, no Ca2+ sensitivity of the myosin Mg2+-ATPase was observed when purified gizzard actin or actin plus tropomyosin was reconstituted with phosphorylated gizzard myosin. Native thin filaments were rendered essentially free of caldesmon and the 32-kilodalton polypeptide by extraction with 25 mM MgCl2. When reconstituted with phosphorylated gizzard myosin, caldesmon-free thin filaments and native thin filaments exhibited approximately the same Ca2+ sensitivity (45.1 and 42.7%, respectively). The observed Ca2+ sensitivity appears, therefore, not to be due to caldesmon. Only trace amounts of two Ca2+-binding proteins could be detected in native thin filaments. These were identified as calmodulin (present at a molar ratio to actin of 1:733) and the 20-kilodalton light chain of myosin (present at a molar ratio to actin of 1:270). The Ca2+ sensitivity observed in an in vitro system reconstituted from gizzard thin filaments and either skeletal myosin or phosphorylated gizzard myosin is due, therefore, to calmodulin and/or an unidentified minor protein component of the thin filaments which may be an actin-binding protein involved in regulating actin filament structure in a Ca2+-dependent manner.

Actins

Vascular smooth muscle caldesmon.

Caldesmon, a major actin- and calmodulin-binding protein, has been identified in diverse bovine tissues, including smooth and striated muscles and various nonmuscle tissues, by denaturing polyacrylamide gel electrophoresis of tissue homogenates and immunoblotting using rabbit anti-chicken gizzard caldesmon. Caldesmon was purified from vascular smooth muscle (bovine aorta) by heat treatment of a tissue homogenate, ion-exchange chromatography, and affinity chromatography on a column of immobilized calmodulin. The isolated protein shared many properties in common with chicken gizzard caldesmon: immunological cross-reactivity, Ca2+-dependent interaction with calmodulin, Ca2+-independent interaction with F-actin, competition between actin and calmodulin for caldesmon binding only in the presence of Ca2+, and inhibition of the actin-activated Mg2+-ATPase activity of smooth muscle myosin without affecting the phosphorylation state of myosin. Maximal binding of aorta caldesmon to actin occurred at 1 mol of caldesmon: 9-10 mol of actin, and binding was unaffected by tropomyosin. Half-maximal inhibition of the actin-activated myosin Mg2+-ATPase occurred at approximately 1 mol of caldesmon: 12 mol of actin. This inhibition was also unaffected by tropomyosin. Caldesmon had no effect on the Mg2+-ATPase activity of smooth muscle myosin in the absence of actin. Bovine aorta and chicken gizzard caldesmons differed in several respects: Mr (149,000 for bovine aorta caldesmon and 141,000 for chicken gizzard caldesmon), extinction coefficient (E1%280nm = 19.5 and 5.0 for bovine aorta and chicken gizzard caldesmon, respectively), amino acid composition, and one-dimensional peptide maps obtained by limited chymotryptic and Staphylococcus aureus V8 protease digestion. In a competitive enzyme-linked immunosorbent assay, using anti-chicken gizzard caldesmon, a 174-fold molar excess of bovine aorta caldesmon relative to chicken gizzard caldesmon was required for half-maximal inhibition. These studies establish the widespread tissue and species distribution of caldesmon and indicate that vascular smooth muscle caldesmon exhibits physicochemical differences yet structural and functional similarities to caldesmon isolated from chicken gizzard.

Actins

Motor activity changes and conditioned taste aversions induced by administration of scopolamine in rats: role of the area postrema.

Three experiments examined the effects of centrally and peripherally acting scopolamine (scopolamine hydrochloride-SHC) or only peripherally acting scopolamine (scopolamine methyl nitrate-SMN), on motor activity levels and the ability of these agents to induce taste aversions. In Experiment 1 rats were injected with isotonic saline, 1 mg/kg SHC, or 1 mg/kg SMN. SHC produced significant increases in stabilimeter activity (p less than 0.025) and in rearing response frequency (p less than 0.01), whereas SMN resulted in significantly less activity (p less than 0.025). Both agents induced strong conditioned taste aversions to saccharin (p less than 0.01). Experiment 2 examined the role of the area postrema in mediating these drug induced behavioral changes. Sham lesioned and area postrema lesioned rats were given saline, SHC or SMN (1 mg/kg for both drugs) and examined for changes in activity, rearing response frequency and induction of taste aversions to saccharin. SHC again produced significant increases in activity (p less than 0.01), whereas SMN produced decrements in activity (p less than 0.05). However, the brain lesion did not consistently alter the effects of these drugs on activity but it did reduce the amount of the decrement observed in rearing responses in SMN treated rats. The brain lesion also altered the ability of the drugs to induce taste aversions. Both SMN and SHC produced strong taste aversions in the sham lesioned rats (p less than 0.01) but no significant aversions were observed in the area postrema lesioned rats. Experiment 3 examined the ability of the brain lesion to alter the effects of SMN by using a within groups design. Area postrema lesions were found to attenuate but not abolish, the inhibitory effects of SMN on both activity levels and rearing responses (p less than 0.03). The results of these experiments suggest that in the absence of the chemically-sensitive area postrema both SMN and SHC fail to induce taste aversions and the inhibitory effect of SMN on spontaneous activity is attenuated.

Animals

Harvey-ras oncogene restriction fragment alleles in familial melanoma kindreds.

Unique and uncommon BamHI allelic restriction fragments of the Ha-ras locus have been reported in the genomes of patients with cancer and of three affected members of a familial melanoma kindred (Krontiris et al., 1986). Analysis of the BamHI and Msp/HpaII restriction fragments of peripheral blood leucocyte DNA from the members of two families with hereditary melanoma (HM)/familial dysplastic naevus syndrome (DNS) revealed that the only Ha-ras allele common to four affected members of one kindred and two from a second kindred, was the 6.7kb allele which is found in 66% of the normal population. This allele was found equally in affected and non-affected family members, and in one affected case was inherited from an unaffected homozygous parent. It was absent in two affected sisters in a third kindred. In the first kindred the karyotype of all three melanoma sufferers was 46XX 9qh+, while six unaffected members had a normal karyotype. BamHI polymorphism of the Ha-ras gene does not identify the affected members in the HM/DNS families studied.

Alleles

Phosphorylation of bovine cardiac C-protein by protein kinase C.

C-protein, a thick filament-associated protein, has been isolated from bovine myocardium and found to be a substrate in vitro of the Ca2+- and phospholipid-dependent protein kinase (protein kinase C). Incorporation of approximately 1.6 mol Pi/mol C-protein was observed. This phosphorylation was dependent on both Ca2+ and a phospholipid (L-alpha-phosphatidyl-L-serine was used). Phosphate incorporation specifically into C-protein was verified by SDS-polyacrylamide gel electrophoresis and autoradiography and was almost exclusively into serine residues (86.9%), with only a small amount of phosphothreonine (13.1%) and no phosphotyrosine being detected. Two-dimensional thin-layer electrophoresis of a chymotryptic digest of phosphorylated C-protein indicated site specificity of phosphorylation. Cardiac C-protein is known to be a substrate of cAMP-dependent protein kinase both in vitro and in vivo (Jeacocke, S.A. and England, P.J. (1980) FEBS Lett. 122, 129-132). Isolated bovine cardiac C-protein was rapidly phosphorylated, to the extent of 5 mol/mol, by the purified catalytic subunit of cAMP-dependent protein kinase. Phosphorylation catalyzed by these two protein kinases was not additive, suggesting that the sites phosphorylated by protein kinase C are also phosphorylated by cAMP-dependent protein kinase. Chicken cardiac muscle has also been shown to contain a Ca2+, calmodulin-dependent protein kinase which phosphorylates C-protein (Hartzell, H.C. and Glass, D.B. (1984) J. Biol. Chem. 259, 15587-15596). The physiological role of cardiac C-protein may therefore be subject to regulation by multiple protein kinases.

Amino Acids

Conditioned taste aversions induced by 1-5-hydroxytryptophan are mediated by the area postrema.

Previous studies have shown that injections of 5-HTP can induce conditioned taste aversions when paired with a novel taste. Adult male albino rats received either lesions of the area postrema or were subjected to a sham lesion procedure. All rats were adjusted to a 23 1/2 hr/day water deprivation schedule and on the conditioning day were given a 0.15% saccharin solution for 1/2 hr. After drinking the saccharin fluid 9 area postrema lesioned and 10 sham lesioned rats were injected i.p. with 25 mg/kg 1-5-hydroxytryptophan. Similarly 10 area postrema lesioned and 6 sham lesioned rats were injected with the vehicle solution. A two-bottle choice test between the saccharin solution and water was given to all animals on the third and fourth days after the conditioning day. The sham lesioned rats injected with the 1-5-hydroxytryptophan exhibited a strong aversion to the saccharin taste whereas the vehicle injected sham lesioned rats showed an equal preference for the two fluids. The difference in group mean saccharin preference ratio was significant (p less than .01). Both area postrema lesioned groups exhibited saccharin preference ratios that were comparable to and not significantly different from the sham lesioned animals injected with the vehicle solution. These results show that an intact area postrema is necessary for induction of conditioned taste aversions with 1-5-hydroxytryptophan.

5-Hydroxytryptophan

Dying of cancer. Factors influencing the place of death of patients.

An analysis of factors influencing the place of death of patients seen by two medical oncology units is reported. There were 1295 recorded deaths of patients from the Royal Prince Alfred Hospital, Sydney, and 688 from The Royal North Shore Hospital of Sydney during 1979-1981; the places of death were known in 1724 instances (87%). Of these, 73% of patients died in hospital, 9% died in terminal nursing care (TNC) institutions, and the remainder at home. Factors influencing the place of death were the place of residence, age, home circumstances-social support, diagnosis, and interval from first contact with the medical oncology unit. Our data indicate that a complex interrelation of these factors determines the place of death. Improvements in community services may allow more patients with cancer to die at home or in TNC institutions, but a substantial proportion of these will still die in major hospitals. Therefore, there is a need for the improvement of palliative care services in these institutions.

Adult

Photoreactivating enzyme from Escherichia coli: appearance of new absorption on binding to ultraviolet irradiated DNA.

The photoreactivating enzyme, PRE, monomerizes pyrimidine dimers in DNA in a light requiring reaction (lambda greater than 300 nm). However, the purified PRE from E. coli has no well-defined absorption band for lambda greater than 300 nm. Using absorption difference spectroscopy, we show that when PRE is mixed with ultraviolet-irradiated DNA, new absorption appears in the spectral region required for catalysis. There is a concomitant decrease in the absorption of the mixture for wavelength less than 300 nm. The hyperchromicity for lambda greater than 300 nm is true absorption, not an artifact due to light scattering. Both the hyperchromicity (lambda greater than 300 nm) and hypochromicity (lambda less than 300 nm) can be reversed by irradiation of 365 nm with identical first-order kinetics. We estimate the molar extinction coefficient of the new absorption to be 6900 +/- 1400 at 350 nm. We conclude that the PRE from E. coli does not possess a distinct "chromophore" which by itself is entirely responsible for the absorption of photoreactivating light. Instead, new absorption results when PRE binds its substrate, dimer-containing DNA.

DNA, Bacterial