Biomedical subjects

S M Jones

Publications and source records attributed to S M Jones.

At least 19 recordsLinked to original sources

PubMed1992

Reduced contractile responses to forskolin and a cyclic AMP analogue in myocytes from failing human ventricle.

Myocytes were isolated from the right or left ventricles of failing and non-failing human hearts. Contractile responses to increasing concentrations of Ca2+, isoprenaline, forskolin and dibutyryl cyclic AMP (a lipophilic analogue of cyclic AMP) were determined. Responses were correlated with the age of the patient, and the severity of failure as defined by New York Heart Association class of symptoms (NYHA), left ventricular ejection fraction (LVEF), left ventricular end diastolic pressure (LVEDP) and dose of diuretics prescribed (diuretic class). The maximum contraction amplitude in high Ca2+ did not change with either age or severity of failure (n = 31-40 patients). Responses to isoprenaline (relative to Ca2+ in the same cell, isoprenaline/calcium ratio) decreased with increasing age (P < 0.001, n = 38), and increasing severity of disease (NYHA, P < 0.001, n = 38; LVEF, P < 0.001, n = 34; LVEDP, P < 0.001, n = 30; diuretic class, P < 0.01, n = 36). The decrease in forskolin/calcium ratio also correlated with age (n = 17, P < 0.005) and increasing severity (NYHA, P < 0.002, n = 17; LVEF, P < 0.05, n = 15; LVEDP, P < 0.02, n = 14; diuretic class, P < 0.05, n = 15). Multiple regression indicated that the contribution of age was greater than that of disease severity for both isoprenaline and forskolin responses. The dibutyryl cyclic AMP/calcium ratio did not change significantly with the age of the patient (P > 0.1, n = 13), or severity as defined by LVEDP (P = 0.05-0.1, n = 12) but did decrease with increasing NYHA class (P < 0.01, n = 13) or diuretics (P < 0.02, n = 12) or with low LVEF (P < 0.002, n = 12). Overall, neither forskolin nor dibutyryl cyclic AMP produced maximum responses greater than isoprenaline in myocytes from failing hearts. Where the response to isoprenaline was not limited by the appearance of arrhythmias, forskolin or dibutyryl cyclic AMP could give a significant (but small) increase in contraction over that with isoprenaline alone. These results provide evidence for a post-receptor defect in addition to beta-adrenoceptor desensitisation in myocytes from failing human heart.

Adult↗

PubMed1992

Expression of CYP2E1 during human fetal development: methylation of the CYP2E1 gene in human fetal and adult liver samples.

The expression and regulation of cytochrome P450IIE1 (CYP2E1) in adult and fetal human liver has been investigated. Three mRNA transcripts of 1.9, 2.7 and 3.8 kb were detected in all adult liver samples after hybridization with a full length cDNA to CYP2E1 whereas no expression was detected in 12 fetal liver samples studied. Similarly, expression of CYP2E1 was not detected in 11 placental samples (10-17 weeks gestational age) or in two full-term placental samples. CYP2E1 expression was not detected in fetal liver, kidney, lung, placenta (18 weeks gestational age) or liver (6 weeks gestational age) obtained at termination of pregnancy where maternal alcohol abuse had been established. Southern blot analysis of the cytosine methylation status of the CYP2E1 gene revealed substantial methylation of the 3' region of the gene in both adult and fetal human liver samples. No differences were observed in the methylation pattern of fetal liver samples between the gestational ages 12 and 17 weeks. Two small DNA fragments detected by the 5' end of the CYP2E1 cDNA were cleaved by the restriction enzyme HpaII in adult liver DNA but not in the fetal liver DNA samples. Methylation of specific 5' residues in the CYP2E1 gene may be responsible for the lack of transcription of the CYP2E1 gene in fetal liver.

Alcoholism↗

PubMed1992

Nucleotide and predicted amino acid sequence of a cDNA clone encoding part of human transketolase.

Transketolase is a key enzyme in the pentose-phosphate pathway which has been implicated in the latent human genetic disease, Wernicke-Korsakoff syndrome. Here we report the cloning and partial characterisation of the coding sequences encoding human transketolase from a human brain cDNA library. The library was screened with oligonucleotide probes based on the amino acid sequence of proteolytic fragments of the purified protein. Northern blots showed that the transketolase mRNA is approximately 2.2 kb, close to the minimum expected, of which approximately 60% was represented in the largest cDNA clone. Sequence analysis of the transketolase coding sequences reveals a number of homologies with related enzymes from other species.

Amino Acid Sequence↗

PubMed1992

Comparison of autoantibodies to the collagen-like region of C1q in hypocomplementemic urticarial vasculitis syndrome and systemic lupus erythematosus.

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an apparent autoimmune disorder that resembles SLE. We previously showed that C1q precipitins in HUVS sera are IgG autoantibody to human C1q. We have compared HUVS anti-C1q autoantibody to a similar autoantibody in the serum of some patients with SLE. As with anti-C1q autoantibody in SLE sera, the HUVS autoantibody binds only to the collagen-like region (CLR) of C1q. In both HUVS and SLE, IgG2 is the predominant subclass of IgG autoantibody and IgM autoantibody to C1q is uncommon. In both diseases, anti-C1q autoantibodies bind preferentially to surface-adsorbed C1q or CLR fragments compared to these antigens in solution. Finally, when HUVS or SLE autoantibodies were added to CLR-coated wells already bound, respectively, by SLE or HUVS autoantibodies, no increases in CLR binding were observed, suggesting that HUVS and SLE autoantibodies to C1q bind to the same CLR epitope(s).

Autoantibodies↗

PubMed1992

Behavioral changes in pediatric intensive care units.

OBJECTIVE: The purposes of this study were to compare the frequency and severity of manifestations of anxiety, depression, delirium, and withdrawal in pediatric patients hospitalized in intensive care unit vs ward settings and to evaluate the impact of preexisting psychopathologic disorders on the expression of these symptoms. RESEARCH DESIGN: Prospective patient series. SETTING: Tertiary care pediatric center. PATIENTS: Forty-three subjects aged 6 to 17 years hospitalized in either the pediatric or cardiovascular intensive care unit (n = 18) or on the general wards (n = 25) were recruited to participate. Subjects were excluded if their parents were unavailable for diagnostic interview or if they could not answer interview questions themselves. SELECTION PROCEDURES: Consecutive sample. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The Hospital Observed Behavior Scale, developed for this study, was used to describe objectively subjects' manifestations of anxiety, depression, delirium, and withdrawal. The Diagnostic Interview for Children and Adolescents and Diagnostic Interview for Children and Adolescents-Parents were used to determine the presence of preexisting psychopathologic disorders. As measured by the Hospital Observed Behavior Scale, subjects in the intensive care unit exhibited apprehension, anxiety, detachment, sadness, and weeping more often than did patients in the ward. Behavior was also significantly influenced by severity of illness, duration of hospitalization, number of previous hospitalizations, and presence of a preexisting anxiety or mood disorder. We found the Hospital Observed Behavior Scale to have good interrater reliability. CONCLUSIONS: Our data indicate that critically ill children in the intensive care unit, children with prolonged or repeated hospitalizations, and children with preexisting anxiety and mood disorders are at greater risk than other hospitalized pediatric patients for psychological trauma and/or behavior problems that may warrant psychiatric intervention. The Hospital Observed Behavior Scale is a reliable tool to quantitate behaviors in hospitalized children.

Adolescent↗

PubMed1992

Plasma progesterone levels in the pregnant female rat-kangaroo (Bettongia gaimardi).

Plasma progesterone levels were measured in female bettongs (small macropodid marsupials) under two natural regimes: (1) during "delayed" gestation (initiated by removal of pouch young, RPY) and (2) during the pregnancy prior to pouch vacation when a young still occupies the pouch (i.e., during lactation). Basal levels of progesterone were 0.15-0.5 ng/ml. There was a transient peak of progesterone (0.7 ng/ml) early in gestation at Day 4 RPY. After Day 6 RPY, progesterone levels remained elevated (1.2-1.5 ng/ml) until they dropped sharply to basal levels on the day of birth. This pattern of progesterone secretion during delayed gestation is similar to that seen in other marsupials, such as the tammar wallaby. There was no significant difference between the progesterone profiles of the two experimental groups. We deduce, then, that lactation had no effect on corpus luteum function (as assessed by plasma progesterone levels) in the pregnant bettong.

Analysis of Variance↗

PubMed1992

Isolated ventricular myocytes from failing and non-failing human heart; the relation of age and clinical status of patients to isoproterenol response.

Single cardiac myocytes were isolated from the ventricles of failing and non-failing human hearts. The contraction amplitude, time-to-peak shortening and time to 50% and 90% relaxation were measured in cells stimulated at 0.2 Hz at 32 degrees C. The effects of increasing extracellular calcium and isoproterenol were investigated using cumulative concentration/response curves. Maximum contraction amplitude in high calcium or velocities of contraction or relaxation were not impaired in cells from failing hearts. Beta-adrenoceptor function in a single cell was assessed by the maximum contraction amplitude in the presence of isoproterenol relative to that with high calcium in the same cell (isoproterenol/calcium ratio). A decrease in the isoproterenol/calcium ratio correlated positively with an increase in the isoproterenol EC50 (concentration for half-maximal effect) for a cell (P less than 0.02, n = 39). The isoproterenol/calcium ratio in left ventricular myocytes decreased with increasing severity of disease, correlating with failure as defined by New York Heart Association class (P less than 0.001, n = 26 patients), left ventricular ejection fraction (P less than 0.001, n = 24), left ventricular end diastolic pressure (P less than 0.05, n = 21) and amount of diuretics prescribed (P less than 0.001, n = 26). In right ventricular myocytes, only increasing NYHA class correlated with decreasing isoproterenol/calcium ratios. There was a correlation of the isoproterenol/calcium ratio between right and left ventricular cells from patients with ischemic heart disease (P less than 0.05), n = 11). Beta-adrenoceptor subsensitivity occurred in mitral valve disease, ischemic heart disease, congenital abnormalities and congestive cardiomyopathy, but not in the right ventricle of patients with myocarditis. The isoproterenol/calcium ratio correlated negatively with the age of the patient (P less than 0.001, n = 26, left ventricle). Multiple regression indicated that the maximum contraction amplitudes in either high isoproterenol or high calcium declined significantly with age only, but that both age and severity of disease contributed to the decrease in isoproterenol/calcium ratio. Time-to-peak tension in isoproterenol, as well as relaxation times in high calcium also decreased with the age of the patient. Analysis of variance showed that between-patient variation was significantly greater than between-cell for most of the parameters measured. Beta-adrenoceptor desensitisation may be detected in individual myocytes from failing hearts, and this relates more to the severity of disease and the age of the patient rather than the etiology of heart failure. A decline in absolute contractility of muscle cells with age was detected.

Adolescent↗

PubMed1992

Altered macrophage antigen-presenting cell function following Friend leukemia virus infection.

To investigate the mechanism by which Friend leukemia virus (FV) causes immunosuppression, the ability of peritoneal macrophages to mediate antigen-specific T-cell activation following FV infection was examined. Decreased IL-2 production was observed when antigen-primed T cells were cultured with antigen-pulsed macrophages from mice infected with FV, compared to T cells cultured with macrophages from control mice. Macrophages from FV-infected mice demonstrated decreased phagocytic and pinocytic activity, suggesting that antigen uptake may be impaired in these cells. In addition, FV-infected mice had decreased numbers of MHC class II positive macrophages compared to uninfected controls, as measured by immunofluorescence. The alterations in antigen uptake and class II expression observed in macrophages from FV-infected mice may be the result of infection of these cells by FV, which was demonstrated by in situ hybridization using a FV-specific probe. The ability of FV to infect and modulate the functions of macrophages may account, at least in part, for the immunosuppression observed in FV-infected mice.

Animals↗

PubMed1992

Survival of virulent and attenuated strains of Brucella abortus in normal and gamma interferon-activated murine peritoneal macrophages.

Virulent Brucella abortus 2308 was phagocytized more readily than attenuated strain 19 following opsonization and survived at significantly higher levels in normal murine peritoneal macrophages and in macrophages treated with gamma interferon. Activation of macrophages with gamma interferon greatly inhibited intracellular replication of strain 2308 but did not result in its elimination. These data support the hypothesis that persistent infection of the host requires the ability of antibody-opsonized B. abortus to survive in activated macrophages.

Animals↗

PubMed1992

Polyethylene wear in uncemented knee replacements.

Isolated wear of the polyethylene tibial component led to failure in five of a series of 108 uncemented porous-coated knee replacements. The clinical features included pain, effusion and instability with progressive varus deformity. In all cases there was extensive wear on the medial side of the polyethylene surface of the prosthesis. The mechanism of such wear is complex, being due in part to the unconstrained nature of the joint and the incongruity of its surfaces. Other design characteristics may have contributed.

Adult↗

PubMed1992

Arcaine blocks N-methyl-D-aspartate receptor responses by an open channel mechanism: whole-cell and single-channel recording studies in cultured hippocampal neurons.

Arcaine, a putative competitive antagonist at the polyamine site on the N-methyl-D-aspartate (NMDA) receptor complex, not only inhibits polyamine enhancement of NMDA-induced [3H]dizocilpine (MK-801) binding but also depresses binding in the absence of polyamines. In the present experiments, we investigated the mechanism of this latter effect in whole-cell and single-channel recordings from cultured rat hippocampal neurons. Arcaine produced a concentration-dependent block of NMDA-evoked inward currents (KD, 61 microM at -60 mV) but not those induced by kainate, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, or gamma-aminobutyric acid. The arcaine block was strongly voltage dependent and was almost completely relieved at positive holding potentials. Analysis of the voltage dependence indicated that the arcaine acceptor site appeared to sense 67% of the transmembrane electric field. In support of an open channel blocking mechanism, arcaine, like Mg2+, prevented dizocilpine from blocking the NMDA receptor channel. Moreover, increasing the dizocilpine concentration partially overcame the arcaine effect, indicating a competitive interaction between arcaine and dizocilpine. Spermine, which in our preparation usually produced only an arcaine-like voltage-dependent block of NMDA currents at high concentrations (greater than 100 microM), had no effect on the block by arcaine at lower concentrations. In single-channel recordings, arcaine caused a concentration- and voltage-dependent decrease in apparent channel amplitude. Assuming a simple model of open channel block, we estimate the arcaine binding and unbinding rates as 4.4 x 10(8) M-1 sec-1 and 1.8 x 10(4) sec-1, respectively, which are comparable to the rates for open channel block by Zn2+ and substantially faster than those of Mg2+. These results indicate that arcaine inhibits NMDA-induced [3H]dizocilpine binding by blocking the open NMDA receptor channel, an action that is independent of the polyamine site.

Animals↗

PubMed1992

IgG autoantibody to the collagen-like region of Clq in hypocomplementemic urticarial vasculitis syndrome, systemic lupus erythematosus, and 6 other musculoskeletal or rheumatic diseases.

We previously found that the Clq precipitin in sera from patients with hypocomplementemic urticarial vasculitis syndrome is an IgG autoantibody to Clq. We report here a prevalence study of this autoantibody in 162 patients with musculoskeletal or rheumatic diseases including hypocomplementemic urticarial vasculitis syndrome, systemic lupus erythematosus (SLE), and rheumatoid arthritis uncomplicated by vasculitis. The autoantibody, which binds only to the collagen-like region of Clq, was found almost exclusively in hypocomplementemic urticarial vasculitis syndrome (100%) and SLE (35%) sera. Our results support the idea that among rheumatic diseases, anti-Clq autoantibody develops in disorders characterized by immune complex mediated injury, particularly of cutaneous and glomerular microvasculature.

Alleles↗

PubMed1991

Lower extremity motor evoked potentials in multiple sclerosis.

Transcranial magnetic stimulation was performed on 25 patients with definite multiple sclerosis. Motor evoked potentials were recorded from the anterior tibial muscle. Central motor conduction time was calculated using the equation (F + M-1)/2 by stimulation of the common peroneal nerve. Motor evoked potentials were capable of detecting subclinical pyramidal tract lesions in multiple sclerosis. In patients with multiple sclerosis, the incidence of abnormality of motor and somatosensory evoked potentials was similar. Central motor conduction time was correlated with overall and pyramidal tract subscores on the Kurtzke Disability Status Scale and the Scripps Neurological Rating Scale. Central motor conduction time abnormalities correlated best with the presence of a Babinski's sign but also correlated significantly with weakness and hyperreflexia.

Adult↗

PubMed1991

Canine carrageenin-induced acute paw inflammation model and its response to nonsteroidal antiinflammatory drugs.

A quantitative method for testing antiinflammatory agents in beagles has been developed, based on measurement of paw inflammation induced by a local injection of carrageenin. Carrageenin [0.5 mL of 2% (wt/vol) in saline] was injected into the plantar region of the hindpaws of pentobarbital-anesthetized beagles. Paw pressure changes registered from a water-filled balloon held on the top of the paw by a light adhesive tape wrapping were monitored for 240 min. In control dogs given 0.5% (wt/vol) methylcellulose (10 mL/kg orally) just before carrageenin, paw pressure increased significantly (p less than 0.05) over eightfold, from 2.9 +/- 0.8 mm Hg (mean +/- SEM, n = 29 paws) at 75 min to 26.0 +/- 3.5 mmHg at 240 min. The increase in paw pressure was significantly inhibited by the cyclooxygenase inhibitors, ibuprofen, indomethacin, and orpanoxin, and partially inhibited by the lipoxygenase inhibitor, phenidone, administered orally before carrageenin injection. Thus this model, with further characterization, could provide a convenient, quantitative way of assessing the efficacy of nonsteroidal antiinflammatory agents in dogs.

Animals↗

PubMed1991

Usefulness of scanning procedures for diagnosis of fever of unknown origin in children.

During a 5-year study period, 109 patients were referred to a large children's hospital for evaluation of prolonged fever of unknown origin, defined as temperature greater than or equal to 38 degrees C (100.4 degrees F) for 3 weeks or longer and negative findings on initial examination. A two-phase protocol of outpatient followed by inpatient diagnostic studies was instituted for most patients. Confirmed diagnoses were achieved in just 36 of these children (33%) in the following disease categories: infectious, 24 (22%); autoimmune, 7 (6%); and neoplastic, 2 (2%). Scanning or special procedures and the number with positive results (in parentheses) were as follows: abdominal ultrasonography, 43 (8); abdominal computed tomography, 14 (3); indium scan 11 (5); gallium scanning, 4 (1), upper gastrointestinal tract series, 13 (2); technetium bone scanning 15 (2); bone marrow examination, 16 (1); and cranial computed tomography, 7 (0). These studies rarely led to an unsuspected diagnosis. It appears most appropriate in evaluating fever of unknown origin in children to obtain only basic laboratory studies such as a complete blood cell count, urinalysis and culture, chest radiograph, tuberculin skin test, and, in the older child, an antinuclear antibody titer. When these test results are negative, almost all children can be observed clinically for progression of illness or a focus that might then direct specific diagnostic procedures.

Adolescent↗

PubMed1991

Contractile responses of myocytes isolated from patients with cardiomyopathy.

Single cardiac myocytes isolated from failing and non-failing human ventricles were superfused at 32 degrees C and electrically stimulated at 0.2 Hz. Their contraction amplitude and velocities of contraction and relaxation were continuously during challenge with isoprenaline or high extracellular calcium. Action potentials were monitored with intracellular microelectrodes, and calcium transients followed using the fluorescent dye fura-2. Changes in contractility were correlated with severity of disease, as defined by New York Heart Association class, dose of diuretics, left ventricular ejection fraction and left ventricular end-diastolic pressure. Beta-adrenoceptor desensitization was detected in these cells as a decreased response to isoprenaline relative to that of calcium in the same cell. Significant correlations were obtained between reduction of beta-adrenoceptor sensitivity and all four indicators of disease severity. No correlation between the maximum contraction amplitude in high extracellular calcium and severity of disease was observed, the same was true for contraction and relaxation velocity in high calcium. Some significant decline in contractility with age of the patient was noted. Analysis with respect to aetiology of disease showed a subpopulation with dilated or hypertrophic cardiomyopathy where relaxation of the single cells was impaired. This was related to a prolonged calcium transient and action potential. Isoprenaline accentuated the lengthened second phase of relaxation, whereas high extracellular calcium reduced it. These interventions had similar effects on action potential duration. The actions of isoprenaline and calcium were similar on cells from failing and non-failing human hearts and on normal guinea-pig myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗

PubMed1991

The right ventricular outflow tract as an alternative permanent pacing site: long-term follow-up.

The long-term characteristics of the right ventricular outflow tract have been assessed as an alternative permanent pacing site to the right ventricular apex. Thirty-three consecutive patients requiring ventricular pacing were randomized to be paced from one of the two sites. Pacing was performed using a screw-in lead, and a programmable pacemaker was used to facilitate threshold testing. There was no significant difference in the lead positioning time or any acute implant measurement (e.g., threshold at 0.5 msec 0.4 +/- 0.2 V for both sites, P = 0.99). Chronic measurements were also comparable during follow-up (mean 73 months) with a mean threshold at most recent follow-up of 0.15 +/- 0.2 msec (apex) and 0.13 +/- 0.21 msec (outflow tract) at 5 V, P = 0.81. There was only one pacing related complication, a lead dislodgment (outflow tract) in a pacemaker twiddler. Overall, both sites were highly satisfactory.

Aged↗

PubMed1991

Day case permanent pacing.

We have previously reported our preliminary experience of day-case permanent pacing in the United Kingdom. The study has now been extended to 50 patients with follow-up of 22 +/- 4 months. During the study period, all patients referred for permanent pacing, either to the senior author, or as in-hospital transfers, were considered for the study. Forty two percent of patients considered fulfilled inclusion and exclusion criteria, resulting in a total of 50 patients being randomized either to day case or conventional in-patient management. In the first month postimplantation, one patient in each group developed a complication requiring revision of system. Only one further pacing related complication occurred over the follow-up period, percutaneous extrusion of a fixation sleeve with spontaneously healing of the wound. This was in a day-case patient. Mean duration of in-patient stay was 5.7 hours in day-case patients, compared with 70.0 hours in those managed conventionally. Postimplantation local physician consultation rates were equal in both groups. Questionnaires were used to determine the relative acceptability to patients of the two management protocols; on a ten point score of acceptability, the mean score for both groups was 8.8. The difference in cost per patient using day-case management was approximately 430 ($817) pounds. We conclude that day-case permanent pacing in the United Kingdom is feasible, acceptable to patients, and has considerable economic benefits.

Aged↗