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Biomedical subjects

R Sutton

Publications and source records attributed to R Sutton.

At least 181 records · Page 10Linked to original sources
PubMed1991

Properties of ATPase activity associated with peroxisomes of rat and bovine liver.

1. Peroxisomes were isolated from bovine and rat liver by use of differential and density gradient centrifugations. 2. In the final density gradient (Nycodenz) a distinct peak of ATPase activity codistributed with the peroxisome marker catalase and was well separated from the bulk of the ATPase activity and from markers for other subcellular organelles. 3. The peroxisome-associated ATPase had a pH optimum of 7.5 and was inhibited by N-ethylmaleimide, by N,N'-dicyclohexylcarbodiimide and by 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole, but was unaffected by up to 30 microM n-tributyltin chloride. 4. Prolonged incubation with oligomycin at high concentrations indicated that 50% of peroxisomal ATPase was resistant to this inhibitor. The oligomycin-sensitive ATPase activity required at least a four-fold higher ratio of inhibitor to protein for inhibition than mitochondrial ATPase did. It was concluded that oligomycin-sensitive and oligomycin-resistant ATPase may be associated with liver peroxisomes.

Adenosine Triphosphatases↗
PubMed1991

Methodology of head-up tilt testing in patients with unexplained syncope.

Prolonged 60 degree head-up tilt has been shown to be valuable in the investigation of unexplained syncope, diagnosing neurally mediated bradycardia/hypotension or malignant vasovagal syndrome. To evaluate the methodology of tilt testing, the following were examined: reproducibility of results, tilt duration, angle of tilt, method of tilt support and effect of age in patients and control subjects. Seventy-one patients with recurrent unexplained syncope underwent 60 min of 60 degree tilt; 53 (75%) had an abnormal test with vasovagal syncope at 24 +/- 10 min (mean +/- SD). Tilting to 60 degrees resulted in an abnormal test in only 2 (7%) of 27 control subjects without cardiovascular symptoms (p less than 0.001); and 5 (15%) of 34 patients with syncope and documented conduction tissue disease (p less than 0.001). Of 15 youthful fainters, 3 (20%) had vasovagal reactions as did 1 (8%) of 12 asymptomatic youthful control subjects. These 12 control subjects also underwent tilting with a saddle support and 7 (67%) had vasovagal reactions. It is concluded that the duration of tilting at 60 degrees should be 45 min (mean time to syncope +2 x SD in the 53 patients with abnormal results). Twenty percent of patients with an abnormal tilt test may not demonstrate syncope with repeat tilting. Saddle tilt testing in unexplained syncope may result in a loss of specificity. Tilting at less than 60 degrees results in a loss of sensitivity. Head-up tilt may be less useful in youthful subjects with vasovagal syncope than in other subjects.

Aged↗
PubMed1991

Transfection with SV40 gene of human pancreatic endocrine cells.

At present, only islet cell lines of animal origin have been successfully generated (e.g. RIN, HIT). A fully differentiated human beta cell line would be advantageous for diabetes research. We now report the generation of a human endocrine pancreatic cell line obtained by transfection using a plasmid containing the early region of SV40 viral DNA. Viral integration and transcription was assessed by Southern and Northern blotting. This cell line has been growing continuously for more than 2 years and maintains several of the characteristics of the parental cells from which they were generated. The presence of Neuron Specific Enolase, Protein Gene Product 9.5, cytokeratin, microvilli, cytoplasmic electrodense granules and the secretion of insulin, glucagon and somatostatin supports the neuroendocrine origin of this cell line. However, hormone production progressively decreased and finally stopped at passage 8. Flow cytometric analysis showed that HLA expression in this cell line is readily induced by IFN-gamma and modulated by TNF-alpha. The establishment of this human endocrine cell line indicates the feasibility of immortalizing human islets by transfection with viral oncogenes. To obtain a fully differentiated cell line it may be necessary to use other DNA constructs which immortalize the cells without fully transforming their phenotype.

Antigens, Viral, Tumor↗
PubMed1991

The incidence of malignant vasovagal syndrome in patients with recurrent syncope.

We reviewed 322 patients with recurrent syncope between 1984 and 1988. Investigation included limited intracardiac electrophysiological study in all cases with programmed extra-stimulus studies in 48 cases. In 93 patients (29%), all investigations were normal, (including negative extrastimulus in 30). In the other 229 cases syncope was explained by AV-block (n = 111, 34%), sinus node disease (n = 68, 21%), carotid sinus syndrome (n = 32, 10%) and inducible sustained tachyarrhythmia (n = 18, 6%). Prolonged 60 degrees head-up tilt was performed in 71 out of 93 patients with unexplained syncope, and reproduced vasovagal syncope and presenting symptoms in 53 (75%), or 16% of the whole population reported. These patients were diagnosed as having malignant vasovagal syndrome. Positive tilts were significantly less common in a group of 27 subjects of similar age without a history of syncope (7%), and a random sample of 37 patients with atrioventricular block (n = 16), sick sinus syndrome (n = 18) and inducible tachyarrhythmia (n = 3), (19%, 11% and 0% respectively, P less than 0.01). From this retrospective review it appears, therefore, that tilt testing is a valuable provocative tool for vasovagal syncope and may reduce the number of syncopal patients that remain undiagnosed, although these early observations do not allow an exact appraisal of the sensitivity and specificity of the tilt test.

Arrhythmias, Cardiac↗
PubMed1991

Cardiac pacing.

Sixty-seven recent publications in the field of cardiac pacing are reviewed under the headings of underlying mechanisms, temporary pacing, reports of therapy, pacing technology, and complications. The reference list is annotated, and papers considered of particular importance are highlighted. This review offers an appraisal of the recent advances in this highly technologic field, with particular emphasis on clinical problems, and is divided into five sections. The first covers the underlying mechanisms that lead to the need for pacing and the changes in hemodynamics and the neuroendocrine system that pacing imposes. The second examines two aspects of temporary pacing. The third gives a wide view of reports of therapy, and the fourth gives a clinical view of advances in pacing technology. The final section covers complications of pacing therapy.

Arrhythmias, Cardiac↗
PubMed1991

Dual chamber pacing aborts vasovagal syncope induced by head-up 60 degrees tilt.

To determine if pacing might prevent syncope in cardioinhibitory 'Malignant Vasovagal Syndrome' (also known as 'Neurally-Mediated Bradycardia/Hypotension'), a study of dual chamber pacing during head-up 60 degrees tilt was undertaken. Paired invasive tilts were performed in 10 patients who had a history of recurrent syncope, normal routine investigations including electrophysiological study and prior tilt-induced vasovagal syncope. Vasovagal reactions of identical severity were produced by prolonged 60 degrees head-up tilt on consecutive days in seven out of 10 patients. On day 2, without pacing, seven patients had tilt-induced vasovagal reactions and six became syncopal during the reaction. On day 3, with temporary DVI pacing with rate hysteresis, seven patients had tilt-induced vasovagal reactions and 1 patient was syncopal. Syncope was aborted in the other five patients. DVI pacing significantly improved cardiac index (CI) (one +/- 0.2 to 1.6 +/- 0.3 L/min/m2, P less than 0.01) and mean arterial blood pressure (MABP) (30 +/- 11 to 48 +/- 12 mmHg, P less than 0.01) during vasovagal reactions on day 3 compared with day 2. The mean period of time that patients could tolerate in the tilted position after the onset of the tilt-induced vasovagal reaction was significantly prolonged by pacing from 0.9 +/- 1.2 to 3.2 +/- 1.6 min (P less than 0.01). Dual chamber pacing may abort syncope in 85% of patients with cardioinhibitory malignant vasovagal syndrome. Pacing may prolong consciousness sufficiently during a vasovagal reaction to allow injury to be avoided.

Adult↗
PubMed1991

Natural history of sinus node chronotropy in paced patients.

The natural history of chronotropic incompetence is not clear. To assess this, we evaluated corrected sinus node recovery time (cSNRT) and sinus node chronotropy at rest and during exercise in two groups of syncopal patients with sinus node disease. Group A comprised patients with resting bradycardia but normal cSNRT and group B had resting bradycardia and prolonged cSNRT (greater than 1000 ms). An additional two groups (C and D) were studied. Group C comprised patients with complete AV (CAVB) and no evidence of sinus node disease and group D were asymptomatic controls of similar age. At diagnosis, patients with symptomatic bradycardia but normal cSNRT and no evidence of carotid sinus syndrome (group A) had resting bradycardia and impaired peak heart rate (PHR-I) on exercise compared to controls (P less than 0.001 and P less than 0.05, respectively), but no reduction in exercise duration. At follow-up group A patients demonstrated an increase in resting rate that was significantly slower than the controls (P less than 0.01). Peak heart rate (PHR-II) also remained significantly slower (P less than 0.05). There was no difference in exercise duration between groups A and D at follow-up. Group B was further subdivided according to follow-up findings of preservation of atrial activity in seven patients (group B-1) and junctional rhythm without any atrial activity in four patients (group B-2). Retrospective analysis showed no significant difference in resting heart rate at initial examination but group B-2 showed a significantly lower peak heart rate on exercise compared with B-1 (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Voltage-activated calcium and potassium currents in human pancreatic beta-cells.

1. The whole-cell configuration of the patch clamp technique was used to study inward and delayed outward currents in beta-cells isolated from human pancreatic islets. 2. The delayed outward current activated at about -20 mV and increased linearly with further depolarization. The instantaneous current-voltage (I-V) relation, measured by tail current analysis, reversed at -70 mV. This is close to the K+ equilibrium potential and suggests the outward current is carried primarily by potassium ions. In support of this idea, outward currents were abolished when internal K+ was replaced by the impermeant cation N-methyl-D-glucamine (NMG). 3. The voltage dependence of K+ current activation could be fitted by a sigmoidal function with a mid-point at +1 mV. K+ currents showed voltage-dependent inactivation which was half-maximal at -25 mV. 4. Inward currents were studied after outward currents were suppressed by replacing internal potassium with NMG. In 5 mM [Ca2+]o, the inward current activated between -50 and -40 mV, had a peak amplitude at -10 mV and reversed at potentials positive to +60 mV. The voltage dependence of inward current activation was sigmoidal with half-maximal activation at -10 mV in 5 mM [Ca2+]o and at -22 mV in 5 mM [Ba2+]o. 5. Inward currents were unaffected by tetrodotoxin (TTX), but could be blocked by cadmium ions. Barium was also capable of carrying inward current. This pharmacology is consistent with inward currents flowing through Ca2+ channels. 6. The inactivation of the inward current was dependent on calcium entry. In two-pulse experiments, the voltage dependence of inactivation was U-shaped, and resembled that of the calcium current. Barium currents showed little inactivation. 7. In two-pulse experiments the degree of inward current inactivation during the test pulse was related to the amount of calcium entry during the first pulse. Calcium entering at more positive potentials was less effective at producing inactivation. 8. Calcium and barium currents also showed a slow, voltage-dependent inactivation when the holding potential was changed between -100 and -40 mV. This inactivation developed with a time course of seconds. 9. The Ca2+ and K+ currents described here are similar to those reported for rodent beta-cells and indicate the rodent beta-cell provides a good model for that of man.

Action Potentials↗
PubMed1991

How and when to investigate syncope.

Recurrent syncope is a distressing phenomenon and may be very difficult to treat where the cause remains obscure. A methodical approach to investigation will often be fruitful when proper emphasis is given to thorough clinical assessment and simple investigations. Where these are normal, head-up tilt testing will often diagnose 'malignant vasovagal syndrome'.

Electrocardiography↗
PubMed1990

Pregnancy and offspring after adjuvant chemotherapy in breast cancer patients.

A retrospective review of 227 consecutive breast cancer patients who were 35 years of age or younger and who had been given doxorubicin-containing adjuvant chemotherapy was conducted to determine the frequency of pregnancy and its effect on the clinical course of the disease. Also, the status of the newborn was evaluated. There were 33 pregnancies in 25 patients (10 pregnancies were terminated, 2 patients had spontaneous abortions, and 19 patients gave birth to full-term offspring without fetal malformation). Two patients were still pregnant at the time of this report. The median interval between the completion of chemotherapy and pregnancy was 12 months. Eight patients who became pregnant experienced temporary amenorrhea during chemotherapy. Of the 25 patients who became pregnant, recurrent disease subsequently developed in 7 and 3 died. A patient's disease-free and overall survival status was not adversely effected by pregnancy. These data illustrate that in a sizeable fraction of patients 35 years of age or younger treated with adjuvant doxorubicin-containing therapy, ovarian function remained intact and subsequent pregnancy did not affect the disease-free or overall survival of the patients.

Abortion, Incomplete↗
PubMed1990

Reduction of vinblastine neurotoxicity in mice utilizing a collagen matrix carrier.

Vinblastine sulfate (VLB) suspended within a collagen matrix (CM) as a diffusion limiting drug delivery vehicle was examined in vitro, as well as in mouse subcutaneous and brain tumor models. Against RIF-1 and KHT subcutaneous tumors, there was enhancement of antitumor activity with intratumoral (i.t.) delivery of VLB when it was combined with CM and/or epinephrine (epi) provided as a vasoactive agent to limit diffusion of VLB away from the injection site. Furthermore, in pharmacokinetic studies an 3-fold enhancement of tumor exposure to drug (AUC) with the CM-formulation was observed relative to the administration of free VLB i.t. Craniotactic injection of VLB into mouse brain in doses from 0.2 to 2 mg/kg revealed that the CM association markedly reduced the acute toxicity of VLB in normal mouse brain. Furthermore, mice with stereotactically implanted KHT brain tumors treated with 0.2 mg/kg VLB in CM had less tumor present in the brain histologically compared to the free VLB and untreated control groups.

Animals↗
PubMed1990

DDDR pacing.

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Atrioventricular Node↗
PubMed1990

Recurrent symptoms after ventricular pacing in unexplained syncope.

We report clinical and hemodynamic data in two cases of recurrent syncope. Both patients received permanent demand ventricular pacing (VVI) for unexplained syncope. Both patients experienced recurrent syncope after pacemaker implantation. They later underwent 60 degrees head-up tilt testing, initially noninvasively and then with hemodynamic profile. A vasovagal response to tilt occurred with bradycardia and was complicated by the onset of ventricular pacing and retrograde atrioventricular conduction (RAVC) with hemodynamic deterioration and rapid reproduction of syncope. Limited intracardiac electrophysiological study (EPS) excluded atrioventricular (AV) conduction disease, sinus node disease, and carotid sinus syndrome, and confirmed RAVC. Both patients were upgraded to dual chamber pacing, DDI mode, with 50/80 rate hysteresis. One patient was asymptomatic at repeat tilt testing; the other experienced continued symptoms due to the vasodepressor component of vasovagal syncope. Cardiac pacing alone is ineffective treatment for this phenomenon, and no proven therapy is presently available. Ventricular pacing applied to patients with unexplained syncope may lead to an increase in or continuation of symptoms rather than an amelioration. There is a need for full investigation of such patients, which must include tilt testing, to allow for the most accurate diagnosis possible and guide the most appropriate therapy.

Aged↗
PubMed1990

Pacing in atrial arrhythmias.

The history of pacing to control the atrial arrhythmias of sinoatrial node disease (SND) is reviewed and is demonstrated to have become more physiological in recent years. The importance of atrial stimulation is emphasized especially in the context of the natural history of SND. The role of single and dual chamber rate responsive pacing for correction of chronotropic incompetence is outlined and guidelines are proposed for the management of the different types of SND presentation.

Arrhythmias, Cardiac↗
PubMed1990

Mechanisms of impaired excretion of a fluid load after cardiac denervation in dogs.

The influence of cardiac innervation on the renal response to volume expansion was investigated. Systemic hemodynamic, plasma hormone, and renal clearance measurements were made before, during, and after intravenous administration of 1,000 ml 0.9% saline over 10 min to six control and six cardiac-denervated, chloralose-anesthetized mongrel dogs. Volume expansion resulted in a two- to threefold rise in plasma atrial natriuretic peptide (ANP) concentrations and a 50% rise in glomerular filtration rate (GFR) in both groups. Plasma renin activity (PRA) and plasma arginine vasopressin remained higher throughout in cardiac-denervated compared with control dogs. The marked increases in urine flow rate and sodium and free water clearances seen in the controls were attenuated or abolished after cardiac denervation. These differences were due to the influence of higher PRA and vasopressin in these animals compared with the controls, rather than differences in hemodynamic responses operating via GFR or in direct humoral responses via ANP secretion.

Animals↗
PubMed1990

HLA DR, DP, DQ induction in human islet beta cells by the cytokine combination IFN-gamma + TNF-alpha.

Human islet beta cells do not express HLA Class II normally, yet, in the diabetic pancreas, beta cells are selectively positive for Class II and this may facilitate their recognition by T cells. It has been demonstrated that human beta cells can be induced to express Class II when cultured with IFN-gamma + TNF-alpha or IFN-gamma + TNF-beta. To assess whether or not they can be induced to express the products of the Class II subregions, DR, DP and DQ, human islet cultures from 10 pancreas were supplemented with the combination of IFN-gamma + TNF-alpha using MoAbs specific for DR, DP and DQ products, and antibodies to insulin and glucagon. The combination IFN-gamma + TNF-alpha (100-1000 U/ml each) was able to induce the expression of the three subregions in both beta and alpha cells. The induction of subregion expression followed the hierarchy DR greater than DQ greater than or equal to DP. The capability of beta cells to express all three Class II subregions supports the possibility that these cells can present their self antigens to T cells.

Gene Expression Regulation↗