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J Chambers

Publications and source records attributed to J Chambers.

At least 37 records · Page 2Linked to original sources
PubMed1990

Purification and N-terminal characterization of Chinchilla villidera alpha-1-antitrypsin.

1. Chinchilla, Chinchilla villidera, alpha-1-antitrypsin has been purified to homogeneity and partially characterized according to mol. wt, amino acid and carbohydrate composition and N-terminal amino acid sequence (30 residues). 2. The mol. wt is between 52,000 and 55,000 as determined by PAGE or sedimentation equilibrium. 3. The best alignment between chinchilla, human and baboon alpha-1-antitrypsin amino acid sequences offsets the chinchilla sequence 6 positions vs the primate structures. 4. This alignment suggests potential importance of the sequence His-Glu-Gln-Glu-His at positions 11-15. 5. Additionally, the segment Leu-Ala-Glu-Phe-Ala, positions 25-29, is strictly conserved. 6. Shorter N-terminal sequences available for rat and rabbit alpha-1-antitrypsin appear to follow the offset alignment vs the primate structures.

Amino Acid Sequence↗
PubMed1990

Epithelial integrin alpha 6 beta 4: complete primary structure of alpha 6 and variant forms of beta 4.

The integrin alpha 6 beta 4 is a heterodimer predominantly expressed by epithelia. While no definite receptor function has yet been assigned to it, this integrin may mediate adhesive and/or migratory functions of epithelial cells. We have determined the complete primary structure of both the alpha 6 and beta 4 subunits from cDNA clones isolated from pancreatic carcinoma cell line libraries. The deduced amino acid sequence of alpha 6 is homologous to other integrin alpha chains (18-26% identity). Antibodies to an alpha 6 carboxy terminus peptide immunoprecipitated alpha 6 beta 4 complexes from carcinoma cells and alpha 6 beta 1 complexes from platelets, providing further evidence for the association of alpha 6 with more than one beta subunit. The deduced amino acid sequence of beta 4 predicts an extracellular portion homologous to other integrin beta chains, and a unique cytoplasmic domain comprised of greater than 1,000 residues. This agrees with the structures of the beta 4 cDNAs from normal epithelial cells (Suzuki, S., and Y. Naitoh. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:757-763; Hogervost, F., I. Kuikman, A. E. G. Kr. von dem Borne, and A. Sonnenberg. 1990. EMBO [Eur. Mol. Biol. Organ.] J. 9:765-770). Compared to these structures, however, the beta 4 cDNAs that we have cloned from carcinoma cells contain extra sequences. One of these is located in the 5'-untranslated region, and may encode regulatory sequences. Another specifies a segment of 70 amino acids in the cytoplasmic tail. Amplification by reverse transcription-polymerase chain reaction of mRNA indicated that multiple forms of beta 4 may exist, possibly due to cell-type specific alternative splicing. The unique structure of beta 4 suggests its involvement in novel cytoskeletal interactions. Consistent with this possibility, alpha 6 beta 4 is mostly concentrated on the basal surface of epithelial cells, but does not colocalize with components of adhesion plaques.

Amino Acid Sequence↗
PubMed1990

Intraventricular septal hypertrophy in type 1 diabetic patients with microalbuminuria or early proteinuria.

To investigate whether the slightly increased blood pressure that occurs in early diabetic renal disease is associated with hypertensive left ventricular hypertrophy, M-mode echocardiograms were recorded in 11 non-diabetic control subjects and four groups of Type 1 diabetic patients. These were 15 patients without microvascular complications, 10 with microalbuminuria, 12 with early persistent proteinuria, and 8 with established renal impairment. Mean blood pressure was 133/80 mmHg (uncomplicated patients), 143/85 mmHg (microalbuminuria), 147/92 mmHg (early proteinuria) and 158/85 mmHg (renal impairment). Mean intraventricular septal width in the uncomplicated diabetic patients was 9.8 (SE 1.2) mm which did not differ from non-diabetic control subjects. Mean septal width was significantly greater in the other groups (microalbuminuria, 12.7 (1.1) mm, p less than 0.02; proteinuria, 12.0 (0.7) mm, p less than 0.05; renal impairment, 15.5 (1.8) mm, p less than 0.001). Left ventricular mass increased progressively between groups and was significantly increased in those with renal impairment (140 (21) vs 103 (5) g m-2 in uncomplicated patients, p less than 0.05). Septal width in the diabetic population not receiving antihypertensives (n = 37) was significantly correlated with systolic blood pressure (r = 0.45, p less than 0.005) which was the only variable independently related to septal width and ventricular mass. It appears that the slight increase in blood pressure that occurs in microalbuminuria and early proteinuria is frequently associated with hypertensive left ventricular hypertrophy.

Adult↗
PubMed1990

Is accurate rate response programming necessary?

Exercise capacity and general well-being are improved by appropriately programmed rate responsive pacemakers when compared to fixed rate units. Ten patients had activity sensing DDDR units implanted for combined AV block and sinus node incompetence. Ten patients had Sensolog activity sensing VVIR units implanted for complete heart block. The effects of over and under programming of rate response in both dual and single chamber activity sensor rate adaptive pacemakers has been assessed subjectively by visual analog scales and specific activity questionnaires and objectively by graded treadmill testing and the performance of standardized daily activities. Patients were randomly programmed to absent rate response (VVI in the Sensolog group), hyporesponsive (DDD in the dual chamber group), appropriate response (VVIR, DDDR according to Manufacturer's instructions) and over responsive (VVIR+, DDDR+) in a double-blind crossover design. Thirty percent of patients demanded early crossover from VVI, 30% from DDDR+ and 50% from VVIR+. Perception of Exercise Capability was similar to objective exercise treadmill times which were shorter in VVI than in VVIR or VVIR+ (P less than 0.05) or control subjects (P less than 0.001). There was no difference between any dual chamber mode or control subjects. General well-being was poorest in DDDR+ and VVIR+ modes despite objective improvement in exercise capacity. Symptoms were least in VVIR and DDDR and all but one patient chose appropriate programming as their overall preferred mode. Thus, even inaccurate rate response programming results in similar and improved exercise capacity compared to absent rate response but overprogramming is unacceptable to most patients, confirming that appropriate programming and sensor specificity is critical in rate responsive pacing.

Arrhythmia, Sinus↗
PubMed1990

Limitations of Doppler ultrasound in the assessment of the function of prosthetic mitral valves.

Pressure half time has been assumed to be a relatively flow-independent measure of orifice area, but it may also be influenced by atrial and ventricular factors. Pressure half time and peak left ventricular inflow velocity were measured by continuous wave Doppler ultrasound in 164 patients with normally functioning Carpentier-Edwards, Björk-Shiley, and Starr-Edwards mitral prostheses. Pressure half time was shorter in the Björk-Shiley than in the other value types and peak transmitral velocity was highest in the Starr-Edwards prostheses. These differences, however, were partly explained by coexistent differences in transmitral flow. Filling time accounted for 19% and stroke volume for 15% of the variance in pressure half time compared with only 5.6% for prosthetic design and 0.4% for annulus diameter when each of these variables was considered alone. The design of the prosthesis explained 18% of the variance in peak transmitral velocity, while cardiac output and annulus diameter did not contribute significantly. With Doppler ultrasound it is impossible to define reliable normal ranges for prosthetic function independently of atrial and ventricular function. Formulas for orifice area based on peak transmitral velocity and flow seem more likely to reflect the behaviour of normally functioning prostheses than those based on pressure half time.

Blood Flow Velocity↗
PubMed1989

Crystal structure and stability of a DNA duplex containing A(anti).G(syn) base-pairs.

The synthetic dodecanucleotide d(CGCAAATTGGCG) has been analysed by single-crystal X-ray diffraction techniques and the structure refined to R = 0.16 and 2.25 A resolution, with the location of 94 solvent molecules. The sequence crystallizes as a full turn of a B-DNA helix with ten Watson-Crick base-pairs and two adenine-guanine mispairs. The analysis clearly shows that the mismatches are of the form A(anti).G(syn). Thermal denaturation studies indicate that the stability of the duplex is strongly pH dependent, with a maximum at pH 5.0, suggesting that the base-pair is stabilized by protonation. Three different arrangements have been observed for base-pairs between guanine and adenine and it is likely that A.G mismatch conformation is strongly influenced by dipole-dipole interactions with adjacent base-pairs.

Adenine↗
PubMed1989

A randomised double-blind crossover study of isosorbide mononitrate and nifedipine retard in chronic stable angina.

In order to evaluate and compare the efficacy and safety of nifedipine retard and isosorbide-5-mononitrate as monotherapy in the treatment of stable angina, 18 patients with abnormal exercise electrocardiograms and angiographically proven coronary arterial disease were studied in a randomised placebo controlled double-blind crossover study comparing isosorbide 20 mg twice a day, sustained released isosorbide 40 mg once daily and nifedipine 20 mg twice a day each given for two weeks. Patients were assessed subjectively by counting the frequency of anginal attacks and glyceryl trinitrate consumed and objectively by maximal symptom-limited treadmill stress tests performed at "trough" therapeutic blood levels on the last day of each treatment period. There were no significant differences in all parameters between entry and run-out placebo. Compared to placebo, all three active treatments showed significant improvement in exercise time to 1 mm ST segment depression, amount of maximum ST segment depression and exercise duration. All three active treatments also significantly reduced the consumption of glyceryl trinitrate and frequency of anginal attacks. There were no significant differences between active treatments. Thus similar clinical improvements were produced by nifedipine retard and isosorbide, both being shown to be equally effective starting therapy for the treatment of patients with stable angina pectoris. Although anginal frequency was reduced by one third and exercise time increased residual symptoms and exercise ischaemia suggest that nifedipine retard and isosorbide may be more clinically useful in combination therapy. Neither demonstrated tolerance after two weeks of therapy.

Aged↗
PubMed1989

Colour flow Doppler mapping in the assessment of prosthetic valve regurgitation.

Two hundred Carpentier-Edwards, Björk-Shiley, and Starr-Edwards prostheses in 173 patients were examined. Sixteen (16%) in the aortic and 24 (25%) in the mitral position were associated with clinical signs of regurgitation. A phased array system (Hewlett-Packard A77020A) with a 2.5 MHz duplex and 1.9 MHz continuous wave transducer was used. Colour flow mapping showed trivial transvalvar regurgitation in 23 (53%) metal aortic prosthesis, and only nine (20%) metal mitral prostheses. This difference was probably attributable to shielding of the left atrium by the metal components. Colour mapping confirmed abnormal regurgitation in all aortic prostheses with early diastolic numbers, but regurgitation was also shown in 25 (29%) with no diastolic murmur. Abnormal mitral regurgitation was found in 13 (54%) patients with a pansystolic murmur, but also in six (8%) with no systolic murmur. Two patients, thought on clinical grounds to have mild mitral regurgitation, had unexpectedly large jets on colour flow mapping. About one in three prostheses had paraprosthetic leaks, 65 (79%) of which were small with a jet area less than 20% of the area of the receiving chamber. The development of new paraprosthetic leaks led to the diagnosis of bacterial endocarditis in two patients. In eight patients regurgitation was first diagnosed with continuous wave Doppler, but was afterwards shown with colour mapping and in a further 10 regurgitation could only be shown by continuous wave Doppler. Colour flow mapping was less sensitive than continuous wave Doppler in detecting regurgitation,but seemed able to distinguish normal transvalvar from paraprosthetic regurgitation. Further studies in the natural course of paraprosthetic leaks and a comparison of the transoesophageal and transthoracic approaches in the assessment of mitral prostheses are needed.

Aortic Valve Insufficiency↗
PubMed1989

Effect of partial agonist activity on the side effects of beta-blockade in patients with chronic stable angina.

Some side effects of the beta 1-adrenoceptor blocker atenolol may result from depression of cardiac output at rest. They may, therefore, be reduced by the use of drugs with beta 1-partial agonist activity, such as epanolol. We compared once-daily atenolol 100mg and epanolol 200mg in 20 patients reporting side effects while taking atenolol for chronic stable angina. A double-dummy, double-blind, crossover design was used to assess side effects by use of visual analogue scales and interviews, and antianginal efficacy by treadmill exercise tests and diary cards. In a comparison with atenolol, no significant differences in exercise time (686 +/- 11 seconds vs 685 +/- 10 seconds, maximum ST depression (1.02 +/- 0.09mm vs 1.07 +/- 0.08mm), time to 1mm ST depression (8.4 +/- 1.9 minutes vs 9.0 +/- 2.0 minutes), or days without angina (median 100% in both) were shown. All visual analogue scores were higher with epanolol (subjective energy 58.3 +/- 1.7 vs 54.3 +/- 1.5, well-being 61.8 +/- 1.8 vs 58.6 +/- 1.5 and warmth of extremities 68.4 +/- 3.6 vs 62.0 +/- 3.1). Although these differences did not attain statistical significance, 11 patients expressed a preference for epanolol and only 6 for atenolol. We conclude that, in this study, epanolol is as effective as atenolol as an antianginal agent for chronic stable angina. It improved the side effect profile in some but not all patients.

Adrenergic beta-Agonists↗
PubMed1988

Determinants of primary success in elective percutaneous transluminal coronary angioplasty for significant narrowing of a single major coronary artery.

Clinical and angiographic characteristics, procedural details and outcome were analyzed in 2,677 consecutive patients who underwent elective single-artery, single-lesion percutaneous transluminal coronary angioplasty (PTCA) between December 1980 and May 1987. Primary success was achieved in 2,479 (93%) patients. The primary success rate was significantly lower during the first period, when nonsteerable systems were used (73%), than in later periods (94%) (p less than 0.0001), when steerable and low-profile systems became available. Univariate analysis revealed the following variables as predictors of lower primary success: totally obstructed arteries (p less than 0.0001), presence of calcium in the narrowing (p = 0.002), prior myocardial infarction (p = 0.005), stenoses located in the right coronary artery (p = 0.02), narrowings between 90 and 99% in diameter (p = 0.02) and patients older than 60 years of age (p = 0.07). Multivariate analysis revealed the following 4 independent predictors of lower primary success: 100% obstruction (p less than 0.0001), calcium (p = 0.005), previous myocardial infarction (p = 0.029) and patients older than 60 years of age (p = 0.036). With present technology, single-narrowing elective PTCA can be performed with a high success rate in most patients. Although total occlusion, presence of calcium, older age and history of myocardial infarction influence the outcome unfavorably, PTCA can still be performed with acceptable primary success rates.

Adult↗
PubMed1988

Balloon inflation following injection of contrast material through the distal lumen of the USCI balloon catheter.

We report on four patients in whom we observed inflation of the balloon following injection of contrast material into the distal lumen during percutaneous transluminal coronary angioplasty. This is a rare technical problem. However, inadvertent balloon inflation may cause transient occlusion of the proximal coronary artery and in one case was associated with acute occlusion of a vessel that had been dilated. Management involves prompt deflation of the balloon.

Adult↗
PubMed1988

Optimisation of total urinary aldosterone estimation: comparison with other laboratory methods for assessment of mineralocorticoid status.

We have demonstrated that conventional methods for measuring total urinary aldosterone (TUA) may markedly and inconsistently underestimate aldosterone output, since under the conditions usually employed (pH 1.0), the hydrolysis of aldosterone conjugates in urine is incomplete. The use of more acidic hydrolysis conditions (pH 0.2) overcomes this problem. However free aldosterone may be damaged at this pH. Therefore to accurately measure TUA output, it is necessary to isolate the undamaged aldosterone chromatographically and to correct for procedural losses based on the recovery of aldosterone tracer added to the urine prior to hydrolysis. We compared a number of laboratory estimates of aldosterone status (including urinary free aldosterone) with the 24-h urinary sodium output in normal subjects, since this provides a good bioassay of aldosterone. Sodium output correlated best with "optimised" 24 h TUA, i.e. hydrolysed at pH 0.2, (r = -0.589, P less than 0.001), and with plasma aldosterone (r = -0.504, P less than 0.005). Both aldosterone in random urine specimens and plasma renin activity correlated poorly with 24-h sodium output. Therefore, while the measurement of optimised TUA excretion provides the best index of aldosterone activity, assay of aldosterone in random specimens of plasma, which is more convenient for patient and laboratory, may be adequate for many clinical purposes.

Adult↗
PubMed1988

Doppler echocardiography in massive left atrial thrombus before and after successful thrombolysis.

A 65-year-old female, presenting 32 weeks after mitral valve replacement with malaise and weight loss, was found to have a massive left atrial thrombus. She was treated successfully with streptokinase 1,000,000 units followed by anticoagulation with heparin then warfarin. The Doppler ultrasound recordings of left ventricular inflow were biphasic on admission but had resumed a normal appearance 11 days afterwards when clot retraction had occurred. We suggest that thrombolysis should be considered as alternative therapy in patients thought too frail for surgery.

Aged↗
PubMed1988

Effect of changes in heart rate on pressure half time in normally functioning mitral valve prostheses.

To test the validity of a relation between the pressure half time and the diastolic time interval, previously shown in a pulse duplication system, eight patients with prosthetic mitral valves and permanent pacemaker systems were studied. Recordings were made from the apex by continuous wave or pulsed Doppler echocardiography at heart rates between 75 and 150 beats/min. The pressure half time was found to be closely correlated with the diastolic time interval although there was individual variation and in three prostheses the pressure half time attained a plateau when the diastolic time interval was more than 300 ms. It is likely that the orifice area is the main controller of pressure half time where there is stenosis of the prosthesis, but that other factors such as ventricular or atrial compliance and the diastolic time interval may modify or obscure the effect of orifice area in normally functioning prosthetic valves.

Blood Pressure↗
PubMed1988

The application of molecular genetics to detection of craniofacial abnormality.

Congenital malformations such as secondary cleft palate can be exclusively monogenic or polygenic, but most cases have a multifactorial origin involving both environmental and genetic factors, making genetic analysis difficult. The new techniques of molecular genetics have allowed the successful chromosomal localization of mutant genes in disorders that show a simple Mendelian segregation, whether autosomal dominant (e.g. Huntington's disease), autosomal recessive (cystic fibrosis) or X-linked (Duchenne muscular dystrophy). Recently, a large Icelandic family (over 280 members) with X-linked secondary cleft palate and ankyloglossia (tongue-tied) has been used as a model to localize the mutant gene associated with this craniofacial clefting. The gene has been sub-chromosomally localized to Xq13-q21.1, using anonymous probe DXYS1; a LOD score of 3.07 was obtained. We are preparing cosmid libraries from DNA from mouse cell lines containing only the relevant part of the human X chromosome, introduced by chromosome-mediated gene transfer. Cosmids that contain human X-chromosome sequences will be isolated and analysed for overlapping sequences and RFLPs (restriction fragment length polymorphisms) and the regions further defined by pulsed-field gel electrophoresis and the identification of coding sequences. This should give data on the location and structure of a gene involved in the craniofacial development of the human palatine shelves. This gene, and its protein product, will identify one component of the pathway that causes nonfusion of the palate. In the long term, the understanding of the expression of this sex-linked gene for secondary cleft palate and ankyloglossia will provide a model for the molecular identification of other genes regulating processes in craniofacial development whose expression is hidden in phenotypic, polygenic complexity.

Cleft Palate↗