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J V Jones

Publications and source records attributed to J V Jones.

At least 73 records · Page 4Linked to original sources
PubMed1989

A substrate amplification system for enzyme-linked immunoassays. II. Demonstration of its applicability for measuring anti-DNA antibodies.

We have recently described a substrate amplification system, based on the method of Self, which increases the sensitivity of alkaline phosphatase (AP)-dependent enzyme-linked immunosorbent assays (ELISA) by a factor of 30-50. This increase is achieved by having AP, the primary enzyme, produce an activator for a secondary enzyme-substrate system, within which marked amplification occurs. We have now demonstrated that this amplification method can be applied to the measurement of human antibodies to DNA. The sensitivity is greater by a factor of 10 than the conventional method, which uses p-nitrophenyl phosphate (p-NPP) as substrate. On replicate assays the method is reproducible, with a coefficient of variation of less than 0.1. This great increase in sensitivity should be of value in conserving specimens of serum and in screening monoclonal antibodies.

Alkaline Phosphatase↗
PubMed1989

Differentiation and investigation of primary versus secondary hypertension (Cushing reflex).

Hypertensive encephalopathy is a rare complication of severe or malignant hypertension. When treated promptly it is potentially reversible without leaving long-term neurologic damage. It can be difficult to differentiate from cerebrovascular accidents or uremia. Acute elevations of intracranial pressure cause acute elevations of blood pressure--the Cushing reflex. This association is less clear for chronic elevations of intracranial pressure, which could occur with tumors. In patients with hypertensive encephalopathy, there are usually diffuse neurologic signs, evidence of visual upset, variable alterations in conscious level, and often a history of rather gradual onset and more systemic symptoms beforehand. The optic fundi show the characteristic hemorrhages, exudates and papilledema, while the urine usually contains protein red cells and casts. Early treatment is mandatory but need not be by the parenteral route, and any blood pressure reduction should be gradual. Vigorous antihypertensive therapy under such circumstances can lead to problems with relative hypotension and underperfusion of vital organs such as the brain, the heart and the kidneys.

Animals↗
PubMed1989

Lack of correlation between HLA types and anti-idiotypic production in family members of a lupus patient.

Correlations of anti-single-stranded (ss) DNA, anti-F(ab')2, and anti-idiotypes to HLA types of 16 healthy family members of a lupus patient were studied. High levels of anti-ss DNA (63%) and anti-F(ab')2 (69%) were detected. Of the 12 family members who expressed HLA-DR2 antigen, 8 had anti-ss DNA and anti-F(ab')2 antibodies. One out of 3 family members who shared the same HLA phenotypes, A1B8DR2, of the proband had high levels of anti-idiotype directed against the proband's F(ab')2 anti-DNA. Though a high prevalence of A1B8DR2, of anti-ss DNA, and of anti-F(ab')2 in healthy family members of a lupus patient was found, anti-idiotypes against anti-DNA were not dependent on HLA-A, B, Dr.

Antibodies, Anti-Idiotypic↗
PubMed1989

Ventricular arrhythmia in untreated newly presenting hypertensive patients compared with matched normal population.

There is evidence to suggest that hypertensive patients are at increased risk of sudden death. However, to date this evidence is restricted to treated hypertensives and it is not clear whether this risk is due to the hypertension itself, its treatment, or its long-term consequences. This study has investigated, by 24-h ambulatory electrocardiography, a total of 58 newly diagnosed hypertensive patients who have never previously been treated and compared the first 50 of them with 50 matched control subjects. The results show that there is an increased prevalence of ventricular arrhythmia in hypertensive patients, compared with normal controls, and that this arrhythmia is present from the outset and thus not dependent on treatment or the development of long-term complications. Multivariate analysis showed that age (positive correlation) and potassium (negative correlation) made the most important independent contributions to the prevalence of arrhythmia in these patients, but even so only accounted for about 33% of the observed arrhythmia. This suggests that the precursors of arrhythmia in hypertension are multifactorial. One other factor appeared to make an important contribution to ventricular arrhythmia in these patients. In contrast to recent evidence from the study of treated hypertensives, the prevalence of ventricular arrhythmia was significantly lower in patients exhibiting electrocardiographic evidence of left ventricular hypertrophy. However, left ventricular hypertrophy did also appear to sensitize the myocardium to the arrhythmogenic effect of low serum potassium levels. These findings may help to explain some of the previous confusion surrounding treatment, hypertension and ventricular arrhythmia.

Adult↗
PubMed1989

The contribution of atrial systole to mitral diastolic blood flow increases during exercise in humans.

1. The change in the relative contribution of the early passive and later active phases of transmitral flow to left ventricular filling was studied using Doppler echocardiography in ten normal male subjects during mild exercise. 2. The peak velocity of passive flow increased during exercise by a mean of 16% whereas peak velocity of active flow increased by a mean of 89%. Hence the ratio of the peak velocities decreased in a linear fashion with a correlation coefficient of r = -0.95. 3. The ratio of the Doppler-derived velocity-time integrals (equivalent to the ratio of flow) of the two phases of transmitral flow also showed a significant negative linear correlation of r = -0.97. 4. Active atrial transport (atrial systole) progressively increases its contribution to overall transmitral blood flow with increasing heart rate during mild exercise. This effect is mainly mediated by an increase in flow velocity which is related to increased atrial contractility.

Adult↗
PubMed1989

Combined anti-arrhythmic therapy with class 1 and class 3 drugs.

This study was designed to investigate the differences in efficacy between 3 different combinations of amiodarone and a class 1 anti-arrhythmic drug (one from each class). The purpose was to determine whether the known differing electrophysiological properties of class 1 drugs result in any particular one making a superior combination with the class 3 drug amiodarone. Eight patients were studied in a randomized single blind cross-over trial. Amiodarone and flecainide proved to be the superior combination producing a significantly greater reduction in mean ectopic counts/24 hours than the amiodarone/mexilitene combination (1,286 vs 3,243; P less than 0.05) or the amiodarone/disopyramide combination (3,795; P less than 0.05). All 3 combinations reduced mean ectopic counts from the baseline value (8,729), but this was only significant for amiodarone/flecainide (P less than 0.01) and amiodarone/mexilitene (P less than 0.05). In addition the amiodarone/flecainide combination produced a significant reduction in complex forms of arrhythmia with ventricular tachycardia abolished in all cases, which was not achieved by any other combination.

Adult↗
PubMed1988

Effects of acute and chronic beta-adrenoceptor blockade on baroreflex sensitivity in humans.

To determine whether beta-adrenoceptor blockade lowers blood pressure by potentiating arterial baroreflex sensitivity (BRS), we compared the effect of acute i.v. and chronic oral beta-blockade on the BRS (phenylephrine technique) of 51 subjects with essential hypertension. Subjects were randomly assigned in a double-blind protocol to one of atenolol, metoprolol, pindolol or propranolol. There was an increase in BRS, unrelated to changes in heart rate, after both acute and chronic beta-blockade. This effect was most evident in younger and less hypertensive subjects. Decreases in blood pressure after 5-months' treatment were unrelated to increases in BRS, indicating that the hypotensive action of these drugs is not dependent upon augmented baroreflex control of heart rate. Only propranolol, of the 4 beta-blockers, increased BRS significantly after acute and chronic treatment. The acute effect of propranolol was significantly different from that of i.v. metoprolol (P less than 0.008) but the effect of long-term treatment with propanolol was not significantly different from that of the other 3 beta-blockers. We conclude that the impaired reflex regulation of heart rate can be improved in younger and mild-to-moderate hypertensive patients by beta-adrenoceptor blockade. Further studies, involving larger numbers and perhaps fewer drugs are needed to determine the relative importance of lipophilicity and beta 1- or beta 2-receptor selectivity in mediating the increase in baroreflex sensitivity seen with treatment.

Adolescent↗
PubMed1988

Consequences of impaired arterial baroreflexes in essential hypertension: effects on pressor responses, plasma noradrenaline and blood pressure variability.

In 62 untreated patients with essential hypertension, arterial baroreflex sensitivity (BRS) for heart rate, i.e. the change in pulse interval in response to a phenylephrine-induced increase in blood pressure, was compared with (1) haemodynamic changes during mental arithmetic, a reaction time test, isometric and bicycle exercise; (2) plasma noradrenaline (PNA) concentrations at rest, and during bicycle exercise and; (3) the variability of ambulatory intra-arterial blood pressure. Subjects with diminished BRS showed the following responses: (1) higher mean arterial blood pressure (MAP) during all four stimuli; (2) a greater pressor response to cycling; (3) tended to have higher PNA concentrations during bicycle exercise and; (4) greater variation in ambulatory blood pressure. Furthermore, an increased pressor response to the reaction time test and increased ambulatory blood pressure variability was seen in younger subjects with reduced BRS. When subjects were subgrouped according to their WHO stage of hypertension, there were significant inverse relationships between BRS and the pressor responses to mental arithmetic, the reaction time test and cycling, and with ambulatory blood pressure variability only in those subjects without ECG or radiographic evidence of left ventricular enlargement (WHO stage I hypertension; n = 42). None of these correlations were present in subjects with one or both of these clinical findings (WHO stage II; n = 20). Pressor responses to the four laboratory stimuli and ambulatory blood pressure variability were similar in both groups, despite significantly higher arterial pressure and significantly lower BRS in WHO stage II subjects. These results suggest that differing mechanisms may be responsible for the regulation of blood pressure variation in these two groups. The arterial baroreflex can buffer acute changes in blood pressure in subjects with WHO stage I hypertension, but this ability is attenuated with progressive reduction of BRS. With the development of clinically evident cardiac adaptation to hypertension (WHO stage II), the contribution of the arterial baroreflex to the regulation of blood pressure is no longer detectable and the influence of cardiac and somatic afferents to reflex circulatory adjustments to activity may predominate.

Adult↗
PubMed1988

Factors influencing blood pressure and heart rate variability in hypertensive humans.

We examined the influence of baroreceptor reflex sensitivity (the increase in pulse interval in response to a phenylephrine-induced increase in blood pressure), age, blood pressure, and beta-adrenergic receptor blockade on the variability of blood pressure and heart rate in essential hypertension. Fifty-six subjects were studied before treatment; intra-arterial blood pressure was recorded outside the hospital for 24 hours. Variability was defined (from all beats occurring while subjects were awake) as the standard deviation about the average waking value for mean arterial pressure (MAP) or pulse interval. The correlation (r) between baroreceptor reflex sensitivity and blood pressure variability was -0.47 (p less than 0.0002). Baroreceptor reflex sensitivity was the only independent determinant of blood pressure variability on multiple regression analysis. Thirty subjects were restudied after 5 months of beta-adrenergic receptor blockade. Ambulatory blood pressure was lower during treatment, whereas pulse interval, its variability, and baroreceptor reflex sensitivity were higher. Blood pressure variability was unchanged. The variability of MAP was inversely correlated with baroreceptor reflex sensitivity before (r = -0.42, p less than 0.02) and during (r = -0.45, p less than 0.02) treatment, but it was unrelated to the average ambulatory MAP or to the variability of pulse interval either before or during beta-blockade. Sixteen subjects whose average waking ambulatory blood pressure was 140/90 mm Hg or less were not treated. This group of borderline hypertensive subjects had less variable MAP than did the remaining 40 subjects (12.4 +/- 2.3 [SD] vs 14.5 +/- 2.5 mm Hg; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1987

A substrate amplification system for enzyme-linked immunoassays. Demonstration of its general applicability to ELISA systems for detecting antibodies and immune complexes.

Self recently described a substrate system for alkaline phosphatase (AP)-dependent ELISAs which markedly increased sensitivity, compared to using p-nitrophenyl phosphate. This increase is achieved by having AP, the primary enzyme, produce an activator for a secondary enzyme-substrate system, within which marked amplification occurs. We adapted this technique to study antibodies to casein, bovine serum albumin, ovalbumin, and cardiolipin in the sera of patients with systemic lupus erythematosus (SLE) and normal individuals. The new substrate system yielded titres 30-50-fold higher than those with p-nitrophenyl phosphate (Sigma 104, p-NPP). In addition, when used in a solid-phase C1q binding assay we were able to use a 1 : 100,000 dilution of AP-conjugated anti-human IgG with the amplified substrate, compared to the 1 : 1000 dilution needed with p-NPP. This system is extremely valuable because of its flexibility. It can either be very sparing of limited samples, or if the added sensitivity is not needed, 100-fold less AP conjugate may be used. Thus rare or expensive conjugates can be significantly conserved.

Animals↗
PubMed1987

Pressor responses to laboratory stresses and daytime blood pressure variability.

We studied 56 patients with essential hypertension to determine whether responses to standardized laboratory mental and physical challenges accurately reflect blood pressure variability during routine daily activities. Four activities were performed in the laboratory: mental arithmetic, a reaction time test, isometric exercise, and submaximal bicycle exercise. Blood pressure was measured directly from a brachial artery catheter. We then recorded intra-arterial ambulatory blood pressure away from hospital over 24 h. A frequency histogram was constructed from all cardiac cycles when subjects were awake. Variability of ambulatory blood pressure was defined as the standard deviation about the mean waking value. The increase in mean arterial pressure (MAP) during each of these four challenges correlated significantly with the variability of mean arterial pressure (highest correlation: reaction time test, r = 0.53, P less than 0.00001; lowest correlation: mental arithmetic, r = 0.26, P less than 0.03), and five subjects who were highly reactive to all four challenges also demonstrated increased blood pressure variability. We therefore conclude that these commonly used laboratory tests can give some information about the behaviour of blood pressure in daily life in some subjects, but overall the variance in blood pressure variability that can be accounted for by the pressor response to these standardized challenges is low.

Activities of Daily Living↗
PubMed1987

Antibody producing capacity to the bacteriophage phi X174 in yersinia arthritis.

Antibody production in response to the primary immunogen bacteriophage phi X174 was investigated in 14 patients with previous yersinia arthritis (YA) and in 15 controls. HLA-B27 occurred in 10 patients with YA and in three controls. After primary and secondary immunisation the antibody responses were essentially similar both in patients with YA and controls. Consequently our results suggest that antibody response to a foreign antigen does not differ between patients with YA and a normal control population. In addition, there was no difference in peak antibody responses between individuals with HLA-B27 and those without HLA-B27.

Adult↗
PubMed1987

Antibody producing capacity to the bacteriophage phi X174 in rheumatoid arthritis.

A study of antibody production in response to a primary immunogen, the bacteriophage phi X174, was performed in 27 patients with rheumatoid arthritis and 15 controls. All patients produced a primary (IgM) response to initial immunisation. The frequency distribution of peak antibody titres after secondary immunisation showed a marked difference between the patients and controls, with 10 patients having peak titres below 5000. The IgG component of the antibody response expressed as a percentage of total phage antibody on the 10th day after secondary immunisation was less in the patients than in the control group. There was no correlation between antibody titres and indices of disease activity, rheumatoid factor titres, or the presence of DRw4, DRw3, and DRw2. After secondary immunisation the patients with rheumatoid arthritis were treated with D-penicillamine, azathioprine, levamisole, or maintained on a non-steroidal anti-inflammatory drug. Assessment of response to tertiary immunisation again showed an impairment of antibody production in the rheumatoid group receiving non-steroidal anti-inflammatory drugs compared with the controls. None of the drugs, D-penicillamine, azathioprine, or levamisole, produced further suppression or augmentation of antibody production in response to the immunogen.

Adult↗