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Biomedical subjects

K Blake

Publications and source records attributed to K Blake.

At least 55 records · Page 3Linked to original sources
PubMed1989

Complement-independent neutralising monoclonal antibody with differential reactivity for strains of human cytomegalovirus.

A mouse monoclonal antibody with complement-independent neutralising activity against cytomegalovirus (CMV) and reactive with the 86 kilodalton (kDa) viral glycoprotein H is described. Neutralisation tests against a range of different strains of CMV showed significant crossreactivity, but clear differences were evident between the two prototype viruses AD169 and Davis, and particularly between AD169 and several low-passage recent clinical isolates; CMV present in urine was neutralised weakly if at all.

Animals↗
PubMed1989

Sequence specific inhibition of in vitro translation of mutated or normal ras p21.

Antisense methylphosphonate-modified oligomers (ONMP) complementary to 8 nucleotides spanning the twelfth amino acid codon of human c-Ha-ras have been synthesized to explore their inhibitory effect on ras p21 translation. The ONMP Ras 0, perfectly complementary to the specific target region in normal c-Ha-ras, inhibits cell-free translation of p21 from a normal c-Ha-ras mRNA template in a dose-dependent manner. At 200uM Ras 0, p21 translation is inhibited by almost 90% in a rabbit reticulocyte lysate; at 100uM, p21 is reduced by over 60%. Ras I and Ras II contain, internally, a single and double base mismatch, respectively. The inhibitory activity of these ONMPs is reduced in proportion to the number of mismatches. When the target mRNA encodes the activated c-Ha-ras differing by a single nucleotide at the twelfth amino acid codon from normal c-Ha-ras, the magnitude of the inhibitory effect of Ras I increased significantly because Ras I is now perfectly complementary to its target mRNA. In turn, Ras 0, now only partially complementary, is considerably less effective at the same concentrations. Therefore, the inhibitory effect is exquisitely sensitive to the extent of the sequence complementarity between the antisense ONMP and the targeted mRNA.

Amino Acids↗
PubMed1989

Modulation of ras expression by anti-sense, nonionic deoxyoligonucleotide analogs.

Anti-ras oligodeoxyribonucleoside methylphosphonates (ONMP's) complementary to the initiation codon region have been synthesized to explore their efficacy and specificity on ras-p21 translation. ONMP (IC-0) precisely complementing the first initial 11 nucleotides of the Balb-ras initiation codon region acts in a dose-dependent manner to inhibit p21 translation by a rabbit reticulocyte lysate. At 100 microM, IC-0 inhibits the cell-free translation of p21 close to completion. The two control oligomers containing one or two nucleotide mismatches were significantly less effective than IC-0 at the equivalent concentration. In living cells, a perfectly matched ONMP directed against the initiation codon region inhibited Ha-ras p21 expression by 90% at a concentration of 50 microM.

Animals↗
PubMed1988

Long-segment coronary ulcerations in survivors of sudden cardiac death.

Angiographically irregular coronary stenoses usually represent plaque rupture with or without superimposed thrombi. Long-segment coronary stenoses with diffuse irregularities (type IIB morphology) have been shown to be more prevalent than focal irregular lesions (type IIA morphology) in survivors of cardiac arrest without acute myocardial infarction. To further understand the pathogenetic importance of type IIB morphology, the clinical and angiographic characteristics in 59 such patients were analyzed. Type IIB lesions accounted for 63% of all type II lesions. Type IIB patients were older than type IIA patients (p less than 0.05). There was a tendency for type IIB morphology to be associated with more extensive disease than other types of lesion morphology (p less than 0.10). Type IIB morphology probably reflects more advanced atherosclerosis. Platelet microemboli may precipitate spasm and/or acute ischemic ventricular tachyarrhythmias. It is possible that long-segment coronary ulcerations are associated with a higher risk for local coronary thromboembolism, and hence with sudden death, than focal lesions.

Aged↗
PubMed1988

Angiographic coronary morphology in survivors of cardiac arrest.

Autopsy studies in victims of sudden coronary death revealed intramyocardial platelet aggregates with microscopic myonecrosis downstream from ruptured atherosclerotic plaques. Ruptured plaques usually manifest angiographically as irregularly bordered (type II) lesions. To investigate the possible pathogenic role of ruptured plaques in arrhythmic death, we analyzed clinical, angiographic, and electrophysiologic data from 49 survivors of cardiac arrest without acute myocardial infarction. All patients had greater than or equal to 50% stenoses of greater than or equal to one coronary artery; 16 had type II morphology, and 33 did not. Type II morphology was more prevalent in patients without inducible sustained monomorphic ventricular tachycardia (11 of 22 or 50%) than in those with it (five of 27 or 19%), p less than 0.05, and patients without akinetic or dyskinetic segments (eight of 14 or 57%) than in those with them (eight of 34 or 24%), p less than 0.06. Thus type II morphology is more prevalent in patients without a demonstrable anatomic and/or electrophysiologic substrate for reentrant ventricular tachycardia, indirectly implicating ruptured plaques in the pathogenesis of cardiac arrest in this subset of patients.

Aged↗
PubMed1988

Mechanism of depolarization in the ischaemic dog heart: discrepancy between T-Q potentials and potassium accumulation.

1. To study the origin of ischaemic myocardial depolarization, the diastolic surface potential - T-Q depression-was correlated with subepicardial extracellular K+ accumulation during serial episodes of widespread ischaemia in open-chest dogs, and in isolated, blood-perfused canine hearts. Placement of the reference electrode on a small island of non-ischaemic myocardium simplified the interpretation of the T-Q potentials. 2. In some experiments, changes in resting potential in the ischaemic zone were recorded using a 'contact' monophasic action potential (MAP) electrode. The change in MAP resting potential was linearly related to T-Q depression for a wide range of experimental conditions (R greater than 0.98). T-Q depression is therefore a linear index of depolarization in superficial myocardial cells. 3. The validity of T-Q depression as a 'measure' of local cellular depolarization was further tested by infiltration of isotonic KCl into the superficial myocardium subjacent to the ischaemic zone electrode. Resulting T-Q depression was 2- to 3-fold larger than the maximum values obtained in ischaemia; and the ratio of T-Q depression to the amplitude of the accompanying monophasic potential was consistent with the assumption that KCl had fully depolarized the underlying myocardium (delta Vm = 89 mV). KCl prevented (i.e. occluded) further changes in the T-Q potential during ischaemia. KCl did not have these effects if it was introduced at sites more remote from the electrode (greater than 4 mm). 4. Ischaemic T-Q depression was drastically accelerated by increasing the heart rate from 90 to 180 beats/min and was further accelerated by arterial infusion of CaCl2. These effects were most striking during the first minute of ischaemia. 5. In contrast, the above manoeuvres produced little acceleration of subepicardial K+ accumulation. After CaCl2 infusion, large ischaemic potentials, severe conduction impairment, and arrhythmias could be observed when K+ activity was almost normal (aK = 4.0-4.5 mM). 6. T-Q depression was larger in vivo than in isolated hearts, both absolutely and relative to K+ accumulation. 7. Based on the reproducible amplitude of ischaemic epicardial potential-estimates of cellular depolarization (delta Vm) could be obtained, which were compared with the concurrent change in K+ electrode potential (delta EK) for each experimental condition. 8. Estimated depolarization was nearly identical to delta EK in isolated hearts under basal conditions. However, depolarization significantly exceeded delta EK during rapid pacing, CaCl2 infusion, or during paced occlusions performed in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Electropharmacology of flestolol for supraventricular tachycardia without associated structural heart disease.

Flestolol is an ultrashort-acting beta-blocking drug with a half-life of 6.9 minutes. Its antiarrhythmic efficacy was studied in 21 patients with spontaneous and inducible supraventricular tachycardia: atrioventricular (AV) nodal tachycardia in 6 patients and orthodromic AV reciprocating tachycardia in 15. It increased the effective refractory period of the AV node in all patients with AV nodal tachycardia (fast pathway, p less than 0.02; slow pathway, p less than 0.01), but did not alter the anterograde (n = 8) or retrograde (n = 9) refractory periods of accessory pathways. Flestolol prevented initiation of tachycardia by causing block in anterograde AV nodal conduction. It was more effective in patients with AV nodal tachycardia (5 of 6) than in those with AV reciprocating tachycardia (4 of 15, p less than 0.03). In patients in whom it was ineffective, the mean tachycardia cycle length increased by 54 ms because of an increase in AH interval (p less than 0.0001, n = 11). The cycle length of tachycardia induced 30 minutes after infusion was similar to the cycle length in the control state (354 vs 355 ms, n = 16). Flestolol's kinetics permitted clinically indicated electropharmacologic testing of a second antiarrhythmic drug in 8 patients and control of ventricular rate until arrhythmia surgery in 1 patient with incessant tachycardia. No hypotension or toxicity occurred. Our findings indicate that flestolol's principal antiarrhythmic effects are on the AV node, similar to the effects of other beta-blocking drugs. Its ultrashort duration of action is an advantage during electropharmacologic testing.

Adrenergic beta-Antagonists↗
PubMed1986

Effect of diltiazem on ischemic myocardial depolarization and extracellular K+ accumulation.

Diltiazem retards ischemic arrhythmias and reduces cellular depolarization, as inferred from recordings of T-Q segment depression (delta T-Q). To explore this further, we correlated delta T-Q with the extracellular K+ electrode potential (delta EK) during serial ischemic trials. delta T-Q and delta EK were uniform in control trials, but decreased markedly in trials that immediately followed diltiazem infusion (0.5 mg/kg). delta EK at 2 min of ischemia was reduced from 11.8 +/- 1.3 to 7.4 +/- 1.2 mV; while delta T-Q was reduced from 7.2 +/- 0.5 to 4.4 +/- 0.7 mV. The effect of diltiazem on ischemic depolarization is largely, but not entirely explained by reduction of delta EK.

Animals↗
PubMed1986

Rate dependence of ischaemic myocardial depolarisation: evidence for a novel membrane current.

Depolarisation of ischaemic myocardial cells is at least partly due to loss of cellular potassium. Whereas most manifestations of ischaemia vary with heart rate potassium loss, however, reportedly does not. Cellular depolarisation was therefore correlated with extracellular potassium activity during serial coronary artery occlusions in Langendorff perfused canine hearts. Occlusions in sinus rhythm (92(11) beats X min-1) were alternated with rapidly paced occlusions (180 beats X min-1). For each occlusion cellular depolarisation was estimated from TQ depression and compared with the simultaneous increase in potassium electrode potential, delta EK. Although potassium accumulation accounted for most of the estimated depolarisation at slow heart rates, a potassium independent mechanism predominated during rapid pacing. The potassium independent mechanism was especially important in the first minute of ischaemia when pacing increased depolarisation by 324%, with little increase in delta EK. It appears that ischaemia induces a rate sensitive depolarising membrane current, which worsens conduction and promotes arrhythmias.

Action Potentials↗
PubMed1984

Indium 111 WBC scan in local and systemic fungal infections.

We describe two patients-one with a systemic fungal infection and one with a localized form-who had strikingly abnormal indium 111 leukocyte (WBC) scans. The patient with systemic disease had an abnormal WBC scan before lesions became clinically apparent.

Aspergillosis↗
PubMedDate not supplied

The social isolation of young men with quadriplegia.

This article describes the results of a study undertaken to identify perceptions of possible social isolation among individuals who become quadriplegic as young adults. Two focus group sessions were held with 4 male participants in each group. All the young men were between the ages of 19 years and 35 years, and all had been disabled for more than 3 years. The results showed that the participants felt challenged by the environment and their resources but did not experience the feelings associated with social isolation as defined by Goffman (1963). The participants, however, identified important socially isolating stressors based on the human needs described by Maslow (1970) as existing in a hierarchy. The results of the study suggest that people with disabilities need interpersonal techniques that enable them to feel a sense of security and control of their time; rehabilitation nurses are ideally suited to assist clients in developing such techniques.

Activities of Daily Living↗
PubMedDate not supplied

Studies on platelets contained in eluates following filtration leukapheresis.

Platelets eluted from nylon fiber filters after filtration leukapheresis have been studied. The platelet yield from 61 routine donations was 1.25 +/- 0.18 x 10(11), (mean +/- SEM) corresponding to 1.78 x 10(10) per 500 ml blood processed. Filtered platelets labeled with radiochromate demonstrated reduced recovery in vivo 15 minutes after infusion (38.5 +/- 1.7%) when compared to the control value (68.5 +/- 6.8, p less than 0.001). The survival of those platelets remaining in the circulation after 15 minutes did not however differ from the control value. ADP (10 micrometer, 1 mM), adrenaline (100 micrometer) and collagen (7.25 mg/ml) added in vitro induced less aggregation of filtered platelets than normal control platelets and electron microscopy revealed structural abnormalities. It is concluded that recipients of granulocyte transfusions obtained by filtration leukapheresis are unlikely to be benefited by the platelets contained in these transfusions.

Blood Platelets↗