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Biomedical subjects

L R Jones

Publications and source records attributed to L R Jones.

At least 127 records · Page 7Linked to original sources
PubMed1990

Managing somatization phenomena in primary care.

Patients communicating psychological distress in the form of somatic symptoms and seeking medical care for them pose difficult diagnostic and treatment dilemmas for the primary care physician. Somatization may be conceptualized as an illness-focused behavior style, with multiple etiologies, rather than a single psychiatric disorder. Somatizing behavior is associated with emotional distress, cognitive-perceptual abnormalities, and socially learned illness behaviors. Although recognition of the somatizing patient begins with thorough medical evaluation, assessment should also include careful examination of social history and the affective meaning of symptoms. Management strategies will vary according to the etiology of the psychiatric diagnosis associated with physical symptoms; however, the essential element is provision of a long-term supportive relationship with a physician, who provides effective monitoring of physical and mental health status, appropriate emotional support, and reassurance concerning symptoms.

Humans↗
PubMed1990

Intralumenal sarcoplasmic reticulum Ca(2+)-binding proteins.

The sarcoplasmic reticulum (SR) controls the level of intracellular Ca2+ in cardiac and skeletal muscle by storing and releasing Ca2+. A set of intralumenal SR Ca(2+)-binding proteins has been identified that may serve important roles in SR Ca2+ storage and mobilization. The most prominent of these SR proteins, calsequestrin, is discretely localized to junctional SR. Other intralumenal proteins are more widely distributed throughout the SR. All of these intralumenal SR Ca(2+)-binding proteins are acidic, stain blue with dye Stains-All, and appear to be substrates for casein kinase II. The biochemistry and cell biology of lumenal SR proteins may conform to a paradigm now emerging from the study of endoplasmic reticulum proteins.

Amino Acid Sequence↗
PubMed1989

Secondary structure of detergent-solubilized phospholamban, a phosphorylatable, oligomeric protein of cardiac sarcoplasmic reticulum.

The structure of phospholamban, a 30-kDa oligomeric protein integral to cardiac sarcoplasmic reticulum, was probed using ultraviolet absorbance and circular dichroism spectroscopy. Purified phospholamban was examined in three detergents: octyl glucoside, n-dodecyloctaethylene glycol monoether (C12E8) and sodium dodecyl sulfate (SDS). Ultraviolet absorption spectra of phospholamban reflected its aromatic amino acid content: absorption peaks at 275-277 nm and 253, 259, 265 and 268 nm were attributed to phospholamban's one tyrosine and two phenylalanines, respectively. Phospholamban phosphorylated at serine 16 by the catalytic subunit of cAMP-dependent protein kinase exhibited no absorbance changes when examined in C12E8 or SDS. Circular dichroism spectroscopy at 250-190 nm demonstrated that phospholamban possesses a very high content of alpha-helix in all three detergents and is unusually resistant to denaturation. Dissociation of phospholamban subunits by boiling in SDS increased the helical content, suggesting that the highly ordered structure is not dependent upon oligomeric interactions. The purified COOH-terminal tryptic fragment of phospholamban, containing residues 26-52 and comprising the hydrophobic, putative membrane-spanning domain, also exhibited a circular dichroism spectrum characteristic of alpha-helix. Circular dichroism spectra of phosphorylated and dephosphorylated phospholamban were very similar, indicating that phosphorylation does not alter phospholamban secondary structure significantly. The results are consistent with a two-domain model of phospholamban in which each domain contains a helix and phosphorylation may act to rotate one domain relative to the other.

Adenosine Triphosphatases↗
PubMed1989

Phospholamban phosphorylation in intact ventricles. Phosphorylation of serine 16 and threonine 17 in response to beta-adrenergic stimulation.

Phospholamban is the major membrane protein of the heart phosphorylated in response to beta-adrenergic stimulation. In cell-free systems, cAMP-dependent protein kinase catalyzes exclusive phosphorylation of serine 16 of phospholamban, whereas Ca2+/calmodulin-dependent protein kinase gives exclusive phosphorylation of threonine 17 (Simmerman, H. K. B., Collins, J. H., Theibert, J. L., Wegener, A. D., and Jones, L. R. (1986) J. Biol. Chem. 261, 13333-13341). In this work we have localized the sites of phospholamban phosphorylation in intact ventricles treated with the beta-adrenergic agonist isoproterenol. Isolation of phosphorylated phospholamban from 32P-perfused guinea pig ventricles, followed by partial acid hydrolysis and phosphoamino acid analysis, revealed phosphorylation of both serine and threonine residues. At steady state after isoproterenol exposure, phospholamban contained approximately equimolar amounts of these two phosphoamino acids. Two major tryptic phosphopeptides containing greater than 90% of the incorporated radioactivity were obtained from phospholamban labeled in intact ventricles. The amino acid sequences of these two tryptic peptides corresponded exactly to residues 14-25 and 15-25 of canine cardiac phospholamban, thus localizing the sites of in situ phosphorylation to serine 16 and threonine 17. Phosphorylation of phospholamban at two sites in heart perfused with isoproterenol was supported by detection of 11 distinct mobility forms of the pentameric protein by use of the Western blotting method, consistent with each phospholamban monomer containing two phosphorylation sites, and with each pentamer containing from 0 to 10 incorporated phosphates. Our results localize the sites of in situ phospholamban phosphorylation to serine 16 and threonine 17 and, furthermore, are consistent with the phosphorylations of these 2 residues being catalyzed by cAMP- and Ca2+/calmodulin-dependent protein kinases, respectively.

Adenosine Triphosphatases↗
PubMed1989

Purification of phospholamban from bovine cardiac muscle with organic solvents.

Phospholamban (PLB), an integral membrane protein of cardiac sarcoplasmic reticulum, was extracted from bovine cardiac muscle with an acidic chloroform/methanol mixture. A combination of gel permeation and ion-exchange chromatographies in organic solvents allowed the purification of PLB. The intensive use of organic solvents throughout the isolation yielded a highly purified and intact protein that can be phosphorylated by cAMP protein kinase. The ease of purification and the high yield obtained (2.5 mg/100 g of fresh tissue) show that organic solvents can be very useful in the extraction and purification of hydrophobic membrane proteins.

Amino Acid Sequence↗
PubMed1989

High molecular weight proteins purified from cardiac junctional sarcoplasmic reticulum vesicles are ryanodine-sensitive calcium channels.

The cardiac high molecular weight proteins/ryanodine receptors were purified to homogeneity from junctional sarcoplasmic reticulum membranes and shown to exhibit large conductance calcium channel activity. High molecular weight proteins were solubilized from junctional sarcoplasmic reticulum in zwitterionic detergent and purified by size-exclusion chromatography followed by sucrose density gradient centrifugation. The purified proteins exhibited an apparent Mr = 400,000-350,000, and bound [3H]ryanodine with a Kd of 4.6 nM and a Bmax of 140-280 pmol/mg protein. High molecular weight proteins demonstrated divalent cation channel activity after incorporation into planar lipid bilayers. Two channel types were identified. Large conductance channels had a slope conductance of 96 +/- 13 pS and a Erev of 42 +/- 9 mV (n = 5); small conductance channels had a slope conductance of 5.5 +/- 1 pS [1.0 microM cis CaCl2; 50 mM trans Ba(OH)2]. Reducing cis calcium from 1 microM to 1 nM reduced the large conductance channel open time from 7 +/- 1% to 0.1% (holding potential, -100 mV). Adding ATP (1 mM) to the cis chamber increased channel open time from 6 +/- 1% to 52 +/- 4% (holding potential, -100 mV); 10 nM ryanodine increased and 100 microM ryanodine decreased percent of open time of the 96 pS channel, without altering unitary channel conductance. The large conductance channel was similar to the calcium release channel detected in native canine cardiac junctional sarcoplasmic reticulum vesicles. Our data suggest that the ryanodine receptor, the calcium-release channel, and the high molecular weight proteins are all identical proteins containing allosteric regulatory sites for calcium, ATP, and ryanodine.

Adenosine Triphosphate↗
PubMed1989

Physician interpretation of illness behavior.

Determining factors in physician recognition of emotional factors in the illness presentation of their patients was examined by stepwise multiple regression analysis, utilizing 18 predictor variables, in a sample of 101 randomly selected internal medicine inpatients. Self-report measures of patients' psychological symptoms failed to explain a significant percentage of the variance in physician assessment of emotional factors in illness. Physician assessment of severity of medical illness, patient satisfaction with present medical care, and age predicted 58 percent of the variance in physician ratings of emotional factors in illness. Physicians attributed greater emotional morbidity to patients judged to have less severe medical illness and to be less satisfied with their care. Using only patient variables as independent predictors, number/frequency of symptoms and race accounted for 16 percent of the variance in physicians' ratings. These results suggest that physician expectations about normative illness behavior, more than mental status characteristics documented by patient self-report measures, determine the recognition of significant emotional factors in illness presentation.

Adult↗
PubMed1989

Illness coping strategies and hypochondriacal traits among medical inpatients.

The Illness Coping Strategies scale (ICS) is an 18-Likert-item scale developed to examine illness appraisal and coping by medical patients more comprehensively than instruments which screen for hypochondriacal traits in this population. This study has examined the association of hypochondriacal traits with illness coping strategies addressed by the ICS among 101 randomly selected inpatients drawn from a general medicine unit of a teaching general hospital. Despite the exclusion of patients with substance abuse or organic mental disorder, or referral for psychiatric consultations, hypochondriacal traits were prevalent in this inpatient sample. Five factor-derived subscales of the ICS (disease vigilance, limit activity, overresponsiveness, self-treatment and obsessive worry) were extracted, and internal consistency and test-retest reliabilities were determined. Multiple regression analysis on a composite measure of hypochondriasis revealed that the five ICS factor scales accounted for 26 percent of the variance. Patients with a high hypochondriacal index had associated high scores on symptom vigilance, limit activity and obsessive worry subscales, suggesting that these illness coping strategies may represent an important aspect of hypochondriacal illness presentation. The self-treatment subscale appeared to act as a suppressor variable, contributing to the prediction of the hypochondriacal index by extracting self treatment aspects from the other illness coping factors. Illness coping responses found to be associated with hypochondriacal traits in this study were rather passive strategies which promoted increased vigilance and concern about symptoms while providing few opportunities to reduce uncertainty regarding health status.

Adaptation, Psychological↗
PubMed1988

Phospholamban forms Ca2+-selective channels in lipid bilayers.

Phospholamban is the major membrane protein of the heart phosphorylated in response to beta-adrenergic stimulation. A role for phospholamban in the control of Ca2+ transport by the sarcoplasmic reticulum has been postulated, but the mechanism is incompletely understood. Structural characterization of the purified protein suggests that it is capable of forming a membrane-spanning pore (Simmerman, H. K. B., Collins, J. H., Theibert, J. L., Wegener, A. D., and Jones, L. R. (1986) J. Biol. Chem. 261, 13333-13341). The experiments described here tested the hypothesis that canine cardiac phospholamban, isolated in the fully dephosphorylated state, forms ion channels in lipid bilayers. Phospholamban purified by two different methods formed channels that were permeable to cations, exhibited spontaneous openings and closings, and were selective for Ca2+ over K+. Dihydropyridine drugs and ryanodine did not affect channel activity. The putative membrane-spanning portion of the molecule, residues 26-52, also formed channels in the bilayer. The putative regulatory portion of the molecule, residues 2-25, did not. The results suggest that phospholamban may regulate sarcoplasmic reticulum Ca2+ flux by acting as a Ca2+ channel.

Adenosine Triphosphatases↗
PubMed1988

Complete amino acid sequence of canine cardiac calsequestrin deduced by cDNA cloning.

cDNA cloning was used to deduce the complete amino acid sequence of canine cardiac calsequestrin, the principal Ca2+-binding protein of cardiac junctional sarcoplasmic reticulum. Cardiac calsequestrin contains 391 amino acid residues plus a 19-residue amino-terminal signal sequence. The molecular weight of the mature protein, excluding carbohydrate, is 45,269. Cardiac calsequestrin is highly acidic, and a striking feature is the enrichment of acidic residues (60%) within the 63 carboxyl-terminal residues. No part of the sequence contains EF hand Ca2+-binding structures. The photo-affinity probe 3-(trifluoromethyl)-3-(m-[125I]iodophenyl)diazirine was used to localize the Ca2+-regulated hydrophobic site to amino acid residues 192-223. The cardiac and skeletal muscle isoforms of calsequestrin (Fliegel, L., Ohnishi, M., Carpenter, M. R., Khanna, V. K., Reithmeier, R. A. F., and MacLennan, D. H. (1987) Proc. Natl. Acad. Sci. U. S. A. 84, 1167-1171), although the products of different genes, are 65% identical, are acidic, and share one glycosylation site. However, cardiac calsequestrin has several unique features. First, it has a 31-amino acid extension at its carboxyl terminus (residues 361-391), which contains 71% acidic residues and a second glycosylation site. Second, its mRNA contains a second open reading frame with the capacity to code for a 111-amino acid protein. Third, contrary to the restricted expression of the fast skeletal isoform, cardiac calsequestrin mRNA is present in both cardiac and slow skeletal muscle, but not in fast skeletal muscle. We conclude that the deduced amino acid sequence of cardiac calsequestrin is consistent with its ability to bind large amounts of Ca2+ (40 mol of Ca2+/mol of calsequestrin). The protein probably binds Ca2+ by acting as a charged surface rather than by presenting multiple discrete Ca2+-binding sites.

Amino Acid Sequence↗
PubMed1988

Structural and functional comparison of a 22 kDa protein from internal human platelet membranes with cardiac phospholamban.

We have shown that a platelet 22 kDa phosphoprotein is similar to the cardiac regulator phospholamban, in that both are phosphorylated by cAMP- and calmodulin-dependent protein kinases, and that both can be phosphorylated simultaneously by these two classes of protein kinases to yield an additive stimulation of the respective Ca2+ pumps (Adunyah, S.E. and Dean, W.L. (1987) Biochim. Biophys. Acta 930, 401-409). However, whereas phosphorylation of phospholamban increases the affinity of the cardiac Ca2+-ATPase for Ca2+, phosphorylation of the platelet 22 kDa protein increased the Vmax of the pump. In addition, antibodies raised against canine phospholamban did not crossreact with the human platelet 22 kDa protein. Finally, it was not possible to dissociate the platelet protein into lower-molecular-weight subunits by boiling in sodium dodecylsulfate which is characteristic of cardiac phospholamban. These results show that although phosphorylation of low-molecular-weight membrane-associated regulator proteins in cardiac muscle and platelets appears to stimulate the respective Ca2+ pumps, these proteins have different chemical and physical properties.

Blood Platelets↗
PubMed1988

Ca2+ binding effects on protein conformation and protein interactions of canine cardiac calsequestrin.

Calsequestrin is a Ca2+-binding protein located intraluminally in the junctional sarcoplasmic reticulum (SR) of striated muscle. In this study, Ca2+ binding to cardiac calsequestrin was assessed directly by equilibrium dialysis and correlated with effects on protein conformation and calsequestrin's ability to interact with other SR proteins. Cardiac calsequestrin bound 800-900 nmol of Ca2+/mg of protein (35-40 mol of Ca2+/mol of calsequestrin). Associated with Ca2+ binding to cardiac calsequestrin was a loss in protein hydrophobicity, as revealed with use of absorbance difference spectroscopy, fluorescence emission spectroscopy, and photoaffinity labeling with the hydrophobic probe 3-(trifluoromethyl)-3-(m-[125]iodophenyl)diazirine. Ca2+ binding to cardiac calsequestrin also caused a large change in its hydrodynamic character, almost doubling the sedimentation coefficient. We observed that cardiac calsequestrin was very resistant to several proteases after binding Ca2+, consistent with a global effect of Ca2+ on protein conformation. Moreover, Ca2+ binding to cardiac calsequestrin completely prevented its interaction with several calsequestrin-binding proteins, which we identified in cardiac junctional SR vesicles for the first time. The principal calsequestrin-binding protein identified in junctional SR vesicles exhibited an apparent Mr of 26,000 in sodium dodecyl sulfate-polyacrylamide gels. This 26-kDa calsequestrin-binding protein was greatly reduced in free SR vesicles and absent from sarcolemmal vesicles and was different from phospholamban, an SR regulatory protein exhibiting a similar molecular weight. Our results suggest that the specific interaction of calsequestrin with this 26-kDa protein may be regulated by Ca2+ concentration in intact cardiac muscle, when the Ca2+ concentration inside the junctional SR falls to submillimolar levels during coupling of excitation to contraction.

Animals↗
PubMed1988

Hypochondriacal traits in medical inpatients.

Hypochondriacal traits were examined in 100 general medical inpatients, and correlates of these traits were examined from four perspectives: (1) emotional distress; (2) affective inhibition; (3) learned social behavior; and (4) symptom misinterpretation. In contrast to previous studies of hypochondriasis in general medical populations, this study examined patients' illness perceptions and presentation in relationship to objective health status as assessed by their treating physicians. Data concerning the illness being treated and associated illness behavior were obtained from patients and their treating physicians. Results suggested that hypochondriacal traits of "disease phobia," disease conviction, bodily preoccupation, perceptions that one's illness is more severe than the physician's assessment, and illness presentation disproportionate to demonstrable organic disease were quite prevalent. On multiple regression analyses, correlates pertaining to emotional distress appear to be preeminent in the prediction of hypochondriacal traits. However, variables pertaining to learned social behavior also provided further understanding of hypochondriacal traits in medical inpatients beyond that explained by emotional distress.

Adult↗
PubMed1988

Mental health training of primary care physicians: an outcome study.

It is well documented that primary care physicians encounter many patients in their practices who suffer psychiatric morbidity, especially affective, anxiety and substance abuse disorders. These physicians have been unable to effectively address the needs of these patients, over half of whom receive care exclusively in the primary care sector. Five years after implementing a curriculum to train family practice physicians to assume a comprehensive psychiatric role with patients in their practices, the authors undertook an outcome evaluation. The focus was on psychiatric disorder recognition, diagnosis, documentation, and management, including referral. It was hoped that biopsychosocial and community mental health orientations emphasized during training would be incorporated into the subsequent primary care practices of physicians in the study. In the research design, physician-generated diagnoses were compared with DIS/DSM-III diagnoses; physician interviews and chart audits enabled processes of care delivery to be evaluated. Unexpectedly, physicians were not found to assume an appropriately active or comprehensive mental health role in their practices following the training intervention. Of ninety-four DIS-generated diagnoses in the study population of fifty-one patients, 79 percent were unrecognized. Patients were assumed to function well emotionally, and psychiatric dimensions of patient complaints were not examined in the majority of cases. The physicians did diagnose and treat a number of patients with mental symptoms who were not identified by the DIS. These patients had high, but sub-diagnostic, DIS symptom counts. Most received a diagnosis of adjustment disorder in response to medical illness. Though this finding underscores shortcomings of present psychiatric nosology when applied in the general medical setting, the foremost consideration was the large number of DIS-identified patients with serious psychopathology, needing active assessment and intervention, who were unrecognized, undiagnosed or untreated. Implications of these findings for the psychiatric training of primary care physicians are examined.

Curriculum↗
PubMed1987

Smooth-muscle endoplasmic reticulum contains a cardiac-like form of calsequestrin.

It is proposed that smooth-muscle endoplasmic reticulum contains calsequestrin and that this protein in smooth muscle resembles cardiac calsequestrin more than the skeletal-muscle form. This proposal is based on seven similarities between the smooth-muscle protein and cardiac calsequestrin. Proteins with an Mr of 55,000 can be extracted from the membranes of smooth muscle and of cardiac muscle using 100 mM Na2CO3. The protein from smooth muscle binds to phenyl-Sepharose in the absence of Ca2+ and is released by 10 mM CaCl2, as has been observed for cardiac calsequestrin. The protein from smooth muscle comigrates with the cardiac calsequestrin on Laemmli-type SDS-polyacrylamide gel electrophoresis. The protein of Mr 55,000 from smooth muscle and cardiac calsequestrin both strain blue with the carbocyanine dye Stains-all. Both proteins present similar one-dimensional Cleveland peptide maps although minor differences might exist. From an analysis of subcellular membranes separated by sucrose gradient centrifugation it is concluded that the protein with Mr 55,000 from the smooth muscle is confined to the endoplasmic reticulum, the same subcellular structure from which, in heart muscle, calsequestrin can be isolated. Antibodies raised against canine cardiac calsequestrin bind to a protein of similar Mr in smooth-muscle endoplasmic reticulum. In addition to the calsequestrin, three other extrinsic proteins with an Mr of 130,000, 100,000 and 63,000, stain blue with Stains-all and occur in the endoplasmic reticulum of smooth muscle.

Animals↗