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Biomedical subjects

T E Nelson

Publications and source records attributed to T E Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1997

Carnosine is a novel peptide modulator of intracellular calcium and contractility in cardiac cells.

Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease and systemic inflammatory states such as sepsis. Accumulating evidence indicates that contractile failure is associated with dysregulation of myoplasmic calcium levels. In a search for biochemical causes for contractile dysfunction, we found that the dipeptide carnosine improves cardiac contractility and tested the possibility that carnosine plays a role in the regulation of intracellular calcium. Carnosine increased contractility in a dose-dependent manner (1-10 mM) in isolated perfused rat hearts. and it also increased free intracellular calcium levels in isolated myocytes. Carnosine increased myocyte tension via calcium release from the ryanodine receptor calcium release channel in skinned myocardial fibers and increased open-state probability and dwell time of the isolated ryanodine receptor calcium release channel in lipid bilayers. In addition. we report that carnosine sensitizes the contractile proteins so calcium. These results suggest a novel role for carnosine as a modulator of intracellular calcium and contractility in cardiac tissue.

Animals↗
PubMed1997

Malignant melanoma: Mayo Clinic experience.

To present the Mayo Clinic experience with treatment of melanoma of the trunk and extremities, we reviewed previous Mayo Clinic studies on the management of malignant melanoma and summarized the survival data and treatment-related outcome. A prospective trial involving elective lymph node dissection in 171 patients with malignant melanoma showed no advantage in overall survival and disease-free survival in the group whose nodes were removed. In an assessment of the treatment variables, a Cox stepwise multiple regression analysis showed a strong correlation of lesion thickness and level of invasion with survival. Another study of 535 patients with melanomas that involved the trunk and extremities, who were treated at the Mayo Clinic between 1971 and 1980, showed an overall survival of 83%. Patients with thin lesions (less than 0.76 mm thick) had a 98% 5-year survival, whereas patients with lesions 4 mm thick or thicker had only a 45% 5-year survival. Because the Mayo Clinic prospective randomized study showed no benefit for patients with melanoma who undergo immediate or delayed lymphadenectomy in the trunk and extremities, we do not perform elective lymph node dissection; however, close follow-up of patients is instituted, and lymph node dissection is performed when nodal involvement is first suspected.

Humans↗
PubMed1997

Changes in ryanodine-induced contractures by stimulus frequency in malignant hyperthermia susceptible and malignant hyperthermia nonsusceptible dog skeletal muscle.

Elective diagnosis of malignant hyperthermia depends on halothane and caffeine contracture testing of biopsied skeletal muscle. Ryanodine-induced contractures may provide greater sensitivity and specificity for malignant hyperthermia (MH) diagnosis. This study investigated the effects of ryanodine concentration and stimulus frequency to distinguish between MH susceptible (MHS) and MH non-susceptible (MHN) dogs. Increasing ryanodine concentrations (1, 2.5 and 5 microM) increased peak isometric contracture tension, but similar responses in MHS and MHN muscle precluded use for diagnosis. Time to tension onset and to peak tension decreased with increasing ryanodine concentration, and these times were shorter in MH skeletal muscle. Increasing stimulus frequency (0.1, 0.5 and 1 Hz) decreased the time to tension onset and to peak tension, but the effect was greater in MHN muscle which decreased the difference between MHN and MHS muscle responses. When ryanodine contracture tension onset time was selected to detect MHS muscle, combinations of either 0.1 Hz and 1 microM ryanodine or 0.5 Hz and 1 microM ryanodine reduced the probabilty of a false diagnosis to less than 1%. Similar studies performed on human muscle might identify optimal stimulus frequency and ryanodine concentration for detecting MH in patients.

Animals↗
PubMed1996

Dantrolene sodium can increase or attenuate activity of skeletal muscle ryanodine receptor calcium release channel. Clinical implications.

BACKGROUND: Dantrolene sodium (DS) is a direct-acting skeletal muscle relaxant whose only known action is to block calcium release from intracellular storage sites. The exact site of action for DS is unknown, but its efficacy in treating and preventing anesthetic-induced malignant hyperthermia (MH) is well established. METHODS: Single ryanodine (Ry1) receptor calcium release channels were incorporated into a planar lipid bilayer for electrophysiologic recording and for subsequent analysis of the channel's gating and conductance properties. The cellular effects of low DS concentrations were investigated by isometric contracture tension responses in biopsied MH human and dog muscle fascicles and in normal, single fibers from human vastus lateralis muscle. RESULTS: Two concentration-dependent DS effects on the isolated Ry1 receptor were discovered, suggesting at least two different binding sites. At nanomolar concentrations, DS activated the channel by causing three-to fivefold increases in open-state probability and dwell times. At micromolar concentrations, DS first increased then reduced activity in the channels; with the dominant effect being reduced activity. A 20 nm concentration of DS produced significant contracture tension in human muscle from one MH subject and caused potentiation of twitch in muscle from another MH patient. Halothane contracture in MH dog muscle was followed by an additional increase in tension when treated with 20 nm DS. Other investigations on chemically skinned, human fibers showed that calcium loaded in the sarcoplasmic reticulum was partially released by nM DS. CONCLUSIONS: The study results suggest that at least two binding sites for DS exist on the Ry1 receptor calcium channel. A low-affinity (microM) site is associated with reduced channel gating and open-state dwell time and may relate to the established pharmacologic muscle relaxant effect of DS. The proposed high-affinity (nM) DS binding site activates the channel, producing Ca2+ release to the myoplasm, which, under environmentally adverse conditions, could damage genetically predisposed MH muscle. Such a phenomenon, if it occurs in DS treated MH patients, could generate a recrudescence of the syndrome.

Animals↗
PubMed1996

Evaluation of suspected osteoid osteoma.

A technique of computed tomography with intravenous contrast has proven useful in the differentiation between osteoid osteoma and other similar appearing lucent lesions of bone in 6 cases. The clinical evaluation of benign appearing radiolucent lesions of long bones has been greatly improved by the use of modern imaging techniques. The differential diagnosis often is narrowed to osteoid osteoma and osteomyelitis based on plain radiographs, computed tomography, or magnetic resonance imaging. The enhancement of the lucent center of the lesion was plotted against time. The rapid uptake of contrast medium by the osteoid osteoma was in sharp contrast to the much slower enhancement in osteomyelitis. The establishment of a preoperative diagnosis enabled the surgeon to excise the lesion without a biopsy. Histologic review verified the preoperative diagnosis in all cases.

Adolescent↗
PubMed1996

Carnosine: a novel peptide regulator of intracellular calcium and contractility in cardiac muscle.

Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease and inflammatory disorders such as sepsis. Recent research indicates that contractile failure is associated with dysregulation of cytoplasmic calcium levels in the myocyte. However, the specific biochemical alterations responsible for calcium dysregulation remain unclear. In a search for mechanisms which might explain the altered calcium regulation in cardiac cells during ischemia and sepsis, we discovered new roles for an intracellular peptide which regulates intracellular calcium and contractility in myocardial cells. The intracellular peptide carnosine improves contraction in the isolated rat heart and increases free intracellular calcium levels. It stimulates calcium release from the ryanodine calcium-release channel, inhibits calcium uptake by the sarcoplasmic reticulum calcium pump, and sensitizes the contractile proteins to calcium. We believe that this peptide represents a new intracellular messenger system for the regulation/modulation of intracellular calcium. Changes in levels of carnosine may play a role in the altered contractility seen during critical illness.

Animals↗
PubMed1994

A clinical grading scale to predict malignant hyperthermia susceptibility.

BACKGROUND: The diagnosis of an acute malignant hyperthermia reaction by clinical criteria can be difficult because of the nonspecific nature and variable incidence of many of the clinical signs and laboratory findings. Development of a standardized means for estimating the qualitative likelihood of malignant hyperthermia in a given patient without the use of specialized diagnostic testing would be useful for patient management and would promote research into improved means for diagnosing this disease. METHODS: Using the Delphi method and an international panel of 11 experts on malignant hyperthermia, a multifactor malignant hyperthermia clinical grading scale comprising standardized clinical diagnostic criteria was developed for classification of existing records and for application to new patients. RESULTS: This scale ranks the qualitative likelihood that an adverse anesthetic event represents malignant hyperthermia (malignant hyperthermia event rank) and that, with further investigation of family history, an individual patient will be diagnosed as malignant hyperthermia susceptible (malignant hyperthermia susceptibility rank). The assigned rank represents a lower bound on the likelihood of malignant hyperthermia. The clinical grading scale requires the anesthesiologist to judge whether specific clinical signs are appropriate for the patient's medical condition, anesthetic technique, and surgical procedure. CONCLUSIONS: The malignant hyperthermia clinical grading scale is recommended for use as an aid to the objective definition of this disease. It use may improve malignant hyperthermia research by allowing comparisons among well-defined groups of patients. This clinical grading system provides a new and comprehensive clinical case definition for the malignant hyperthermia syndrome.

Adult↗
PubMed1993

The Albrecht nursing model for home healthcare: predictors of health status outcomes in working adults.

The health profile of American adults is heavily influenced by lifestyle behaviors. Therefore, working adults have a unique opportunity to take personal action to decrease their risk of cancer, heart disease, and other chronic illnesses and to improve their health status outcomes. Health status outcomes of working adults were evaluated through this quantitative study. Four structural variables (demographics, psychologic status, social status, and economic status), two modifying variables (access and cost), and three process variables (preventive care, including exercise/nutrition/stress management; client involvement; and family involvement) were examined as to their relationship to health status outcomes (client perception of health, amount of exercise, body mass index, and percent body fat). Results support the importance of the variables in the Albrecht nursing model in explaining health status outcomes in working adults. These factors may therefore be suitable targets for interventions to encourage healthy lifestyle behaviors at home. Nursing administrators, occupational health nurses, and home health nurses can use these findings to guide effective planning for wellness programs in the home and work setting.

Adult↗
PubMed1993

The use of MRI in the diagnosis of benign and malignant bone and soft tissue tumours.

Two hundred and thirty four suspected primary bone and soft tissue tumours were investigated using plain films and MRI. The MR appearance of 200 of these tumours was assessed with respect to the intensity of the lesion, the homogeneity of the tumour, the presence or absence of a capsule or lobulation, whether the tumour was whorled or not and whether it contained either fluid or blood. Apart from benign lipomas and some malignant myxoid liposarcomas, however, it seemed virtually impossible to tell one tumour from another and in many cases to differentiate a benign lesion from a malignant tumour using MRI alone. We recommend that the workup of a suspected soft tissue tumour should be initially by MR scanning and that the workup of a suspected malignant bone tumour should be plain films followed by an MRI scan.

Adult↗
PubMed1992

[3H]ryanodine as a probe of changes in the functional state of the Ca(2+)-release channel in malignant hyperthermia.

The defect in malignant hyperthermia (MH) alters the binding of [3H]ryanodine to the Ca(2+)-release channel by increasing its apparent affinity for the binding site. In sarcoplasmic reticulum (SR) membranes from both normal and mutant pigs the apparent Kd is dependent on a number of parameters. Adenosine 5'-(beta,gamma-methylene)triphosphate, ionic strength, and Ca2+ each increase the apparent affinity of the binding site for [3H]ryanodine. Equilibrium and kinetic evaluation of the binding of [3H]ryanodine to these membranes demonstrates that the MH defect in pigs increases the apparent affinity of the membranes for [3H]ryanodine by increasing the amount of high affinity relative to low affinity binding sites. Both the association and dissociation of [3H]ryanodine with all three types of membranes (normal, heterozygous MH, homozygous MH) are characterized by two or more components, with the relative ratios of these components altered by the MH defect. These findings suggest that the observed Kd is the weighted average of the binding of ryanodine to two or more interconvertible states of the channel. Dilution of [3H]ryanodine bound to normal membranes at high Ca2+ into low Ca2+ solutions enhances the rate of dissociation. This conversion occurs to a much lesser extent with MH membranes, suggesting that the MH defect may alter the rate at which the high affinity form of the protein converts to the low affinity form.

Animals↗
PubMed1992

Halothane effects on human malignant hyperthermia skeletal muscle single calcium-release channels in planar lipid bilayers.

Malignant hyperthermia (MH) may be life-threatening when genetically predisposed individuals are administered triggering anesthetic agents that are believed to produce intracellular calcium release. To test this theory, the effects of halothane on normal and MH human skeletal muscle calcium-release channels were studied. Single calcium-release channels were incorporated from isolated sarcoplasmic reticulum membrane vesicles into a planar lipid bilayer, and halothane effects on the conductance and gating properties were measured by electrophysiologic techniques. Among the subjects studied, seven were MH-susceptible, and 13 channels were recorded from this group. Five subjects were negative for MH, and 10 channels were recorded from this group. Among the 13 channels recorded from the MH group, 7 were affected by halothane, which increased the probability of the channel to change from the inactive, closed state to an open state. This effect of halothane to increase open-state probability was associated with an overall increase in channel conductance. Thus, halothane affected the activation/inactivation process of the halothane-sensitive calcium-release channel from MH muscle as well as the gating properties of the MH calcium-release channel, as evidenced by the increased conductance. In 6 of the 13 channels recorded from MH muscle, halothane (2.2-17.6 microM) was without effect on these properties of the channel. Halothane (2.2-17.6 microM or 0.0057-0.0456 vol%) also had no measurable effect on the 10 channels from the negatively diagnosed subjects. Results of this study support a defect in the ryanodine-sensitive calcium-release channel from MH human muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Channels↗
PubMed1992

Protein kinase C-mediated enhancement of NMDA currents by metabotropic glutamate receptors in Xenopus oocytes.

1. N-Methyl-D-aspartate (NMDA) receptors were expressed in Xenopus oocytes injected with rat brain RNA. The modulation of NMDA-induced currents was examined by activating protein kinase C (PKC) either directly (using phorbol esters) or indirectly (via metabotropic glutamate agonists). 2. Bath application of the PKC activator, 4-beta-phorbol-12,13-dibutyrate (PDBu) resulted in a two-fold increase in the NMDA-evoked current at all holding potentials examined (-80 to 0 mV). The inactive (alpha) stereoisomer of phorbol ester was ineffective. 3. The increase was observed under conditions that eliminate the oocyte's endogenous calcium-dependent chloride current, which often contributes to the NMDA response in oocytes. 4. The PDBu effect was specific to the NMDA subclass of glutamate receptors in that no increase was observed in the responses to two other glutamate agonists, kainate and AMPA (alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid). 5. Stimulation of PKC by activation of metabotropic receptors via either quisqualate or trans-ACPD (trans-1-aminocyclopentane-1,3-dicarboxylic acid) also led to an increase in NMDA currents. 6. Both methods of enhancement induced transient effects. PDBu effects lasted 10-45 min, depending upon both dose and length of application. Quisqualate and trans-ACPD effects were shorter, lasting less than 10 min under these conditions of application. 7. Both methods of enhancement were blocked by the PKC inhibitor, staurosporine. In addition, the phorbol ester-induced enhancement of NMDA responses occluded further enhancement by quisqualate. 8. The results suggest a role for metabotropic glutamate receptors in modulation of NMDA-mediated processes.

Animals↗
PubMed1991

Malignant hyperthermia in dogs.

Malignant hyperthermia (MH) is an anesthetic agent-induced hypermetabolic state. Human beings and several other animal species, including dogs, have been described to be genetically predisposed to development of MH. The halothane-triggered MH syndrome was characterized in genetically predisposed dogs, and in vitro contracture sensitivity of biopsied gracilis muscle exposed to halothane and caffeine was quantitated. Within 1 hour of halothane administration, each MH-susceptible dog developed rapid increases in CO2 production and rectal temperature. Reversal of the hypermetabolic state was achieved when halothane was discontinued and dantrolene sodium was given i.v. Biopsied gracilis muscle from MH-susceptible dogs had abnormal in vitro contracture responses to halothane and caffeine. These findings were consistent with those observed for MH-susceptible human beings and pigs in which a loss in regulation of muscle cell Ca(+)+ is believed to be the primary etiologic event for induction of MH.

Animals↗
PubMed1991

Annexin VI is associated with calcium-sequestering organelles.

Annexin VI is a member of a Ca(2+)-dependent, phospholipid-binding protein family. Although functions for this annexin have been proposed from in vitro studies, most remain controversial. Díaz-Muñoz et al. (J Biol Chem 265:15894, 1990) demonstrated that annexin VI modified, in a Ca(2+)-dependent manner, the gating behavior of the sarcoplasmic reticulum Ca(2+)-release channel, reconstituted into artificial bilayers, by increasing both the open probability and the mean open time. This effect was specific to the trans chamber, which represents the luminal side of the sarcoplasmic reticulum. In agreement with those findings, we show herein that annexin VI produced no effect on Ca(2+)-uptake or -release by intact heavy sarcoplasmic reticulum vesicles (analogous to the cis chamber). We also used monospecific antibodies to evaluate the subcellular localization of annexin VI by immunofluorescent microscopy. Studies in rat skeletal muscle suggest that annexin VI is present surrounding individual myofibrils. Double immunolocalization studies with cultured muscle cells (chick myotubes) using anti-annexin VI and anti-SR Ca(2+)-ATPase antibodies demonstrated superimposable staining patterns. In non-muscle tissue (normal rat kidney (NRK) cells), a punctate, perinuclear anti-annexin VI staining pattern was observed. Collectively, these data suggest that annexin VI may play a regulatory role in the Ca(2+)-release/uptake cycle in the sarcoplasmic reticulum as well as in non-muscle organelles, a key process in stimulus-response systems.

Animals↗