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Biomedical subjects

S Jameson

Publications and source records attributed to S Jameson.

At least 19 recordsLinked to original sources

An analysis of risk assessment tools for falls in the elderly.

The authors entered into a collaborative project with the staff of a visiting nurse service to evaluate the utility of a risk assessment inventory (RAI) in identifying factors that lead to falls in elderly persons receiving home care. Although no clear pattern emerged among personal factors, the majority of patients who experienced a fall used one or more assistive devices for ambulation.

Accidental Falls

Strategy for isolating and sequencing biologically derived MHC class I peptides.

The presentation of MHC class I peptides at cell surfaces and the subsequent cytolytic T-lymphocyte response are critical components of the mammalian immune response. However, the identification and sequencing of such peptides present a considerable analytical challenge since > 10,000 peptides at 10(-15)-10(-18) M concentrations are often present in the mixture. We describe a two-dimensional chromatography approach in conjunction with tandem mass spectrometry to sequence and identify such peptides. After immunoaffinity concentration, and subsequent acetic acid release of MHC class I peptides from MHC protein complex, the peptides are subjected to reversed phase HPLC, where they are separated based on their hydrophilic-hydrophobic character. These coarse fractions are then loaded onto a specially designed membrane preconcentration-capillary electrophoresis cartridge (mPC-CE) and subsequently subjected to on-line mPC-CE-MS analysis. The second dimension of chromatography by CE separation affords resolution of peptides based on their charge/mass (to a first approximation) ratio. Ultimately peptides are sequenced using mPC-CE-tandem mass spectrometry (mPC-CE-MS-MS). We describe the strategy for sequencing < 60 femtomoles of a peptide obtained from 3.10(9) Kb-derived EL-4 cells.

Amino Acid Sequence

Rapid loading of large sample volumes, analyte cleanup, and modified moving boundary transient isotachophoresis conditions for membrane preconcentration-capillary electrophoresis in small diameter capillaries.

Using a removable membrane preconcentration (mPC) cartridge, large sample volumes can be loaded prior to final assembly of the mPC capillary electrophoresis (CE) capillary. For narrow-bore (< or = 25 microns ID) uncoated mPC-CE capillaries, applied to peptide analysis, efficient moving boundary transient isotachphoresis (tITP) conditions at the onset of electrophoresis are described. The enhancement of mPC-CE-mass spectrometry (MS) technology afforded by rapid sample loading and modified moving boundary tITP conditions are demonstrated by analysis of major histocompatibility complex (MHC) class I peptides that were derived from a Kb precipitation of mouse EL-4 cells. Furthermore, we demonstrate the structural characterization of these immunologically significant molecules by mPC-CE-tandem mass spectrometry (mPC-CE-MS/MS).

Amino Acid Sequence

A randomized controlled clinical study to quantify the effect of small changes in the design of pacing electrodes on threshold voltages.

A double-blind randomized study of three pacing leads, identical in all ways except for the surface of their electrodes, is presented. The leads were implanted in 30 patients. Ten patients (Group A) received a standard Laserdish lead (dish electrode with laser pores), 10 patients (Group B) received a platinum-iridium coated modified Laserdish electrode, and 10 patients (Group C) received a platinum-iridium coated dish electrode identical to that in Group B except for the absence of laser pores. All leads were implanted by the same operator via the subclavian vein and all patients received an Optima MPT pulse generator. Direct measurement at implantation of pacing threshold and endocardial electrograms showed no significant difference between the three groups (mean +/- standard deviation voltage thresholds 0.30 +/- 0.06 V at 0.5 ms and 0.21 +/- 0.05 V at 1.0-ms pulse durations, R wave amplitude 7.6 +/- 3.2 mV). Significant differences (P = 0.001) were found in threshold impedances at implant (Group A 940 omega, Group B 782 omega, Group C 673 omega). Ten further measurements of voltage threshold were made over the next 2 years. Overall, at a pulse duration of 1.0 ms, a significantly reduced (P < 0.025) threshold voltage was found for both the electrode with pores and platinum-iridium coating compared with pores alone (20%), and with pores and platinum-iridium coating compared with the coating alone (18%). There was no significant difference between using platinum-iridium alone or pores alone. We have shown that a controlled randomized study, using electrodes that are identical except for the characteristics being assessed, can enable effects of small differences in electrode design to be quantified.

Double-Blind Method

Growth regulation of human glioblastoma T98G cells by insulin-like growth factor-1 and its receptor.

The interaction of insulin-like growth factors (IGFs) with the IGF-1 receptor is an important step in the control of cell proliferation and development. In particular, IGF-1 and IGF-2 are key regulators of central nervous system development, and may modulate the growth of glial tumors. We have investigated the growth factor regulation of the human glioblastoma cell line T98G. These cells growth arrested in serum-free medium at 34 degrees C, despite their secretion of substantial amounts of bioactive IGF-1. To be stimulated to divide, growth-arrested cells required the addition of platelet-derived growth factor (PDGF) or its equivalent, 1% serum. Cell proliferation in serum-free medium could also be obtained by shifting the cells to a temperature of 39.6 degrees C. Treatment of growth-arrested cells with PDGF or temperature shift was accompanied by a transient increase in the expression of the mRNA for the IGF-1 receptor. Transfection with a plasmid constitutively expressing the full cDNA for the human IGF-1 receptor allowed autonomous growth in serum-free medium at 34 degrees C. By contrast, growth induction by growth factors or temperature shift was abrogated by transfection of the cells with a plasmid expressing a 300 bp segment of mRNA antisense to the IGF-1 receptor mRNA. Cloning in soft agar was also inhibited by expression of antisense IGF-1 receptor mRNA. These results demonstrate that the IGF-1 receptor is strictly required for the growth of T98G glioblastoma cells. Moreover, the autocrine interaction of IGF-1 with its receptor regulates both autonomous and anchorage-independent growth of these cells.

Base Sequence

Peptide-induced changes in class I heavy chains alter allorecognition.

Class I molecules of the MHC are intimately involved in the development and function of CD8+ T cells. Small peptides, derived from endogenous proteins, bind within the Ag binding groove created by the beta-pleated sheets and alpha-helices of the alpha 1 and alpha 2 domains of the class I molecule. This peptide-MHC complex has been shown to influence allorecognition by CD8+ T cells. However, the precise role of peptide in alloantigen recognition remains unclear. We have previously shown that conformational changes induced in the class I molecules can be identified as specific alterations in serologic epitopes. These results suggested that alloreactive T cells may detect structural changes in MHC based on the nature of the peptide binding to the class I protein. Here, we have shown that, in at least some instances, alloreactivity may not depend on the recognition of a precise self-peptide but on an epitope on the class I molecule influenced by the peptide. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic effect on T cell development, self-tolerance, and alloreactivity.

Amino Acid Sequence

Zinc status in pregnancy: the effect of zinc therapy on perinatal mortality, prematurity, and placental ablation.

Zinc is present in and indispensable to all forms of life. Zinc is essential for the normal growth of human beings, and zinc proteins have been shown to be involved in the transcription and translation of the genetic material. Zinc deficiency has been incriminated in infertility, abortions, malformations, fetal intrauterine growth retardation, premature and postmature births, perinatal death, and abnormal deliveries with dystocia and placental ablation. Risk groups for developing zinc deficiency, which in turn might modify the expression of the underlying disease, are found among those with insufficient food intake, especially in protein malnutrition; abnormal mucosal uptake, as in celiac disease; abnormal intestinal losses, as in steatorrhea and inflammatory bowel disease; abnormal renal excretion, as in diabetes with insufficient metabolic control; alcoholism; and treatment with diuretic drugs. Zinc deficiency could be identified by means of fasting serum or plasma samples or the more laborious estimation of zinc in leucocytes or monocytes if sampling and handling is carefully performed and if stressful situations and acute-phase reactions as fever, delivery, or abortion are avoided. Zinc therapy in identified low-zinc groups has given favorable results and has reduced the frequencies of premature birth, placental ablation, perinatal death, and postmaturity. It is suggested, as we did in 1980, that these data are compatible with the presence of a zinc-deficiency syndrome in pregnancy, which includes increased maternal morbidity, abnormal taste sensations, abnormally short or prolonged gestations, inefficient labor, atonic bleeding, and increased risks to the fetus such as malformations, growth retardation, prematurity, postmaturity, and perinatal death.

Female

Statistical data support prediction of death within 6 months on low levels of coenzyme Q10 and other entities.

Ninety-four consecutive hospital patients aged over 50 years were included in a cross-sectional study. Serum samples were analyzed for coenzyme Q10, alpha-tocopherol, and free cholesterol levels. Patients who died within a follow-up period of 6 months or had congestive heart failure or severe myalgia, and/or received cytostatic or lipid-lowering drug therapy showed significantly lower free cholesterol-related coenzyme Q10 values. Prospective controlled clinical trials will determine whether coenzyme Q10 has a potential to protect patients from such complications and become a useful therapy.

Adult

Endocardial pacemakers in children: lead length and allowance for growth.

Permanent endocardial pacing in small children is feasible but is limited by two problems: sufficient extra lead has to be left within the heart to allow for growth and the excess has to be coiled behind the pacemaker, limiting the benefit from smaller generators. The required intravascular lead length in 120 children and adults was measured on posteroanterior chest X ray and was correlated with standing height. Measurements were made from the mid-point of the left clavicle to the apex of the right ventricle in a curve simulating the usual endocardial lead position. In 60 children, aged 2.0-15.9 years, intravascular lead length (range 15.5-29.0 cm) correlated well with height (0.83-1.70 m), r = 0.91. In 60 adults, mean age 54.9 years, intravascular lead length (25.5-35.6 cm) also correlated well with height (1.45-1.85 m), r = 0.71. In 20 adults the excess extravascular lead length, measured during pacemaker implantation via the subclavian route, was 15.1-33.7 cm and was inversely correlated with height. A child's eventual adult height can be predicted and, using our data, the extra length of lead necessary to allow for growth can be computed. Available endocardial pacing leads are usually 58- to 64-cm long. The excess extravascular lead is a major practical difficulty in children. Shorter leads would avoid the problem of excess lead and facilitate long-term pacing in small children.

Adolescent

Peptide-induced conformational changes in class I heavy chains alter major histocompatibility complex recognition.

Small peptides, derived from endogenous proteins bind within the antigen binding groove created by the beta-pleated sheets and alpha helices of the alpha 1 and alpha 2 domains of the class I molecule of the major histocompatibility complex (MHC). However, the precise role of peptide in class I MHC conformation remains unclear. Here, we have shown that, in at least some instances, changes induced in the MHC molecule by the binding of distinct peptides can be identified as specific alterations in serological epitopes expressed on the class I protein. The nature of specific peptides expressed by class I-bearing cells may, therefore, have a dramatic influence on T cell development, self-tolerance, and alloreactivity.

Amino Acid Sequence

Ham-2 corrects the class I antigen-processing defect in RMA-S cells.

The murine major histocompatibility complex (MHC) contains two genes (Ham-1 and Ham-2) that encode members of a super-family of ATP-dependent transport proteins. These genes are believed to mediate the transport of peptide antigen from the cytoplasm into the lumen of the endoplasmic reticulum for binding by MHC class I molecules. Evidence for such a function has come from the rescue of class I surface expression by a cloned copy of the human homologue of Ham-1, PSF-1, in a human cell line that is defective in antigen processing. A mutant murine cell line, RMA-S, has an identical antigen-processing-defective phenotype. Here we show that expression of a cloned copy of the Ham-2 gene in RMA-S cells results in recovery of the ability to process and present class I-restricted antigens to cytotoxic T lymphocytes, and in partial recovery of class I surface expression. Processing defects for classical (H-2 K and D) and non-classical (Qa1 and HMT) class I molecules are corrected by Ham-2. These data indicate that both MHC-linked transporter genes are probably required for class I antigen processing, and that the functional transporter in this pathway may consist of a Ham-1/Ham-2 heterodimer.

ATP Binding Cassette Transporter, Subfamily B, Mem

Complications associated with retained pacemaker leads.

Retention of functionless pacemaker leads may occur following mechanical or infective problems (potentially or definitely infected) or after electrical failure of the lead. One hundred nineteen patients with a pacemaker lead (or leads) retained between 1970 and 1990 were reviewed retrospectively. Lead retention after an intervention dictated by potential or definite infection of the pacing system resulted in complications in 27 of 53 patients (51%), which in 22 patients (42%) were major (septicemia, superior vena cava syndrome, and further surgery under general anesthesia for recurrent "infective" problems) including three deaths. Complications were less likely if lead retention occurred after electrical failure with three minor and two major (surgery under general anesthesia, superior vena cava syndrome) complications in 66 patients (P less than 0.001). Bacteriology of swabs taken at the time of retention in the patients with potential or definite infection was unhelpful in predicting future complications: 8/18 patients (44%) whose swabs were negative had complications of which 5/18 (28%) were major. In our experience retention of functionless pacemaker leads after an intervention dictated by potential or definite infection of the pacing system, is associated with significant morbidity and mortality and should be avoided.

Adolescent

Atrial antitachycardia pacing in patients with supraventricular tachycardia: clinical experience with the Intertach pacemaker.

During a 3-year period, 22 patients with recurrent supraventricular tachycardia have been treated with antitachycardia pacemakers (Intermedics Intertach, 262-12, n = 17, and Intertach II, 262-16, n = 5). Eighty-two percent were female, the mean age was 44 +/- 14 years; 86% had atrioventricular node reentrant tachycardia. Symptoms had occurred over 11.8 +/- 7.1 years, with 3.6 hospital admissions per patient, despite 4.7 +/- 2.1 antiarrhythmic drugs. Following pacemaker implantation, during a follow-up of 14.8 +/- 11.5 months, only two patients have been readmitted to a hospital because of supraventricular tachycardia (mean 0.1 per patient). One patient is taking an antiarrhythmic agent, and four are taking beta adrenergic blocking agents. Thus, 23% are taking cardioactive drugs (it was anticipated that two patients would continue on drugs after pacemaker implantation). There have been no serious complications. Atrial antitachycardia is thus an effective therapy in carefully selected patients with recurrent supraventricular tachycardia, reducing hospital admissions for supraventricular tachycardia and reducing the need for antiarrhythmic drugs.

Adrenergic beta-Antagonists

Do electrode and lead design differences for permanent cardiac pacing translate into clinically demonstrable differences? (Comparison of sintered platinum and activated vitreous and porous carbon electrodes).

A randomized prospective study was undertaken to compare the electrical performances of three permanent, endocardial, tined pacing leads with different electrode designs--sintered platinum, vitreous carbon, and porous carbon. Ninety-nine patients received one of the leads (S80 31; 423S 32; S100 36). Acute R wave amplitude and ST elevation of the native endocardial electrogram, voltage threshold, impedance, and current flow at four pulse durations (0.25-1.0 msec) were measured. Voltage thresholds were measured noninvasively at each of four pulse durations at 2 days and 1, 3, and 6 months after implantation. No significant differences were found in sensing properties, or current flow at threshold at 0.5 msec pulse duration. The 423S lead had a significantly higher impedance at threshold and both a higher impedance and lower current flow at 5 V. No significant differences in threshold voltages were found between the three leads at any pulse duration, at any of the assessed times after implantation. Six-month thresholds for the S80, 423S, and S100 leads were 1.18 +/- 0.35, 1.17 +/- 0.29, and 1.06 +/- 0.38 V respectively at 0.5 msec pulse duration. Differences between 'high performance' pacing leads need to be of a greater order of magnitude before they can be exploited to give any real clinical advantage to patients.

Aged