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Biomedical subjects

N J Johnson

Publications and source records attributed to N J Johnson.

At least 55 records · Page 3Linked to original sources
PubMed1991

Arrhythmias induced by device antitachycardia therapy due to diagnostic nonspecificity.

New technology has produced automatic cardioverter-defibrillators capable of delivering antitachycardia pacing, as well as low and high energy shocks and backup bradycardia pacing. These expanded treatment options have led to a wider range of clinical applications for such devices, including the treatment of ventricular tachycardias with longer cycle lengths, which may overlap the cycle lengths of some supraventricular arrhythmias. The diagnostic capability of these devices, although improved, has not advanced sufficiently to ensure reliable discrimination between all supraventricular and ventricular arrhythmias. Two cases are presented in which device-mediated pacing therapy, triggered by supraventricular arrhythmias, induced ventricular tachycardia requiring additional therapeutic intervention. This report illustrates the therapeutic versatility and some of the potential pitfalls, of the recently developed devices and reviews the status of automatic arrhythmia identification technology.

Adult↗
PubMed1991

Use of the Glu-Glu-Phe C-terminal epitope for rapid purification of the catalytic domain of normal and mutant ras GTPase-activating proteins.

The C-terminal catalytic domain (residues 704-1047) of the human ras GTPase-activating protein (GAP) has been engineered so as to incorporate the tripeptide, Glu-Glu-Phe, at its C terminus. This motif is recognized by the commercially available YL1/2 monoclonal antibody to alpha-tubulin and has previously been used for the immunoaffinity purification of HIV enzymes engineered to contain this epitope (Stammers, D. K., Tisdale, M., Court, S., Parmar, V., Bradley, C., and Ross, C. K. (1991) FEBS Lett. 283, 298-302). The engineered GAP catalytic domain (GAP-344) was obtained in high yield and purity from Escherichia coli extracts by means of a single affinity column of immobilized YL1/2, eluted under mild conditions with the dipeptide, Asp-Phe. The protein had similar activity to that previously described for full-length GAP, suggesting that the addition of the epitope did not grossly affect the activity. R903K and L902I mutants of GAP-344 were constructed, and the immunoaffinity purification procedure allowed their rapid characterization. The R903K mutant had less than 3% the activity of the normal protein, whereas the L902I substitution had less than 0.5% of normal activity, suggesting an important role for Leu-902 and Arg-903, residues absolutely conserved among GAP-related proteins. This work exemplifies the general utility of the C-terminal Glu-Glu-Phe motif for the rapid purification of proteins whose function is not altered by C-terminal modification.

Amino Acid Sequence↗
PubMed1989

5-Bromo-2'-deoxyuridine incorporation into DNA in hepatic VX2 tumor-bearing rabbits.

The halogenated pyrimidine 5-bromo-2'-deoxyuridine (BrdUrd) possesses both radiosensitizing and antimetabolite effects through its incorporation as a thymidine analog in replicating DNA. To evaluate the regional advantage for treatment of hepatic malignancy by hepatic arterial infusion, BrdUrd was infused into either the hepatic artery (HA) or a central vein (iv) in 26 rabbits with intrahepatic VX2 tumor. After a 24-hr constant rate infusion of 10, 20, or 40 mg/kg/24 hr, the percentage BrdUrd incorporation into the DNA of bone marrow, duodenal mucosa, liver, and hepatic VX2 tumor was measured by gas chromatography/mass spectrometry methods. VX2 tumor BrdUrd incorporation was greater by HA than by iv routes (P less than 0.001). At doses of 10 and 20 mg/kg/day, HA to iv BrdUrd incorporation ratios for VX2 tumor significantly exceeded those for bone marrow and duodenum (P less than 0.05). At appropriate dose rates, hepatic arterial administration of BrdUrd provides a regional advantage for DNA BrdUrd incorporation in the rabbit intrahepatic VX2 tumor.

Animals↗
PubMed1989

Acute treatment of reflux oesophagitis: a multicentre study to compare 150 mg ranitidine twice daily with 300 mg ranitidine at bedtime.

A randomized, double-blind, clinical trial was undertaken to compare 150 mg ranitidine b.d. with 300 mg ranitidine nocte in the treatment of reflux oesophagitis. Endoscopy data were evaluable for 336 patients after 8 weeks of treatment. At this time 75% of patients who received 150 mg ranitidine b.d., and 73% of those who received 300 mg nocte, had healed or showed endoscopic improvement to grade I oesophagitis. At 12 weeks these rates had increased to 89 and 88%, respectively. Oesophageal biopsies from 258 patients at 8 weeks showed histological improvement in 44 and 47% of those treated with 150 mg ranitidine b.d. and 300 mg ranitidine nocte, respectively. After 12 weeks histological improvement was apparent in 57 and 54% of biopsies from each group, respectively. Symptom severity and frequency was reduced to a similar extent by both treatments. Adverse events were reported by 15 patients. A 300-mg bedtime dose of ranitidine was found to be a well-tolerated, effective alternative to twice daily treatment in reflux oesophagitis.

Adult↗
PubMed1989

Acute treatment of reflux oesophagitis: a multicentre trial to compare 150 mg ranitidine b.d. with 300 mg ranitidine q.d.s.

H2-receptor antagonists administered in conventional dosage regimens fail to heal a significant proportion of patients with moderate or severe reflux oesophagitis. We have compared the effects of a higher dose of ranitidine (300 mg q.d.s.) with the currently recommended dosage regimen (150 mg b.d.) in 138 patients suffering from reflux oesophagitis. After 4 weeks of treatment 29% of patients who received 150 mg ranitidine b.d., and 63% of patients who received 300 mg ranitidine q.d.s. had complete endoscopic healing of their lesions (P less than 0.0001). After 8 weeks these proportions had increased to 54% and 75%, respectively (P less than 0.01). After 4 weeks of treatment, compete symptomatic relief had been achieved in 46% of patients who received 150 mg ranitidine b.d. and in 67% of patients who received 300 mg ranitidine q.d.s. (P less than 0.05). After 8 weeks these proportions were 64% and 84%, respectively (P less than 0.05). Both dosage schedules were well-tolerated. We conclude that more rapid symptom relief and healing in reflux oesophagitis can be achieved with 300 mg ranitidine q.d.s. than with 150 mg ranitidine b.d.

Acute Disease↗
PubMed1989

Developmental changes in the electrophysiological properties and the beta-adrenergic receptor-effector complex in atrial fibers of the canine coronary sinus.

beta-Adrenergic stimulation induced delayed afterdepolarizations and triggered activity in atrial fibers of adult but not young canine coronary sinus. However, sensitivity to beta-adrenergic agonists with respect to maximum diastolic potential was identical at both ages, and delayed afterdepolarizations and triggered activity did occur in response to ouabain. Age-dependent lengthening of the action potential duration and plateau also were seen and were greater in the adult than the young. beta-Adrenergic receptor density and affinity and the stimulatory guanine nucleotide regulatory protein (Gs) were similar in adult and young tissues. In contrast, the inhibitory guanine nucleotide regulatory protein (Gi) was 2.5-fold greater in adult (15 fmol/mg) than in young (6.0 fmol/mg) tissues. Basal- and forskolin-stimulated adenylate cyclase activities were greater in adult than young coronary sinus although the increment in isoproterenol-stimulated adenylate cyclase activity in young tissue was greater when compared either with basal levels or expressed as a percentage of maximal catalytic activity. Both the traditional effector pathway of beta-adrenergic action, involving the stimulation of adenylate cyclase activity, and developmental changes in the action potential plateau may contribute to the developmental changes in delayed afterdepolarizations and triggered activity.

Action Potentials↗
PubMed1988

Tissue-specific pharmacodynamics of 5-bromo-2'-deoxyuridine incorporation into DNA in VX2 tumor-bearing rabbits.

The thymidine analog 5-bromo-2'-deoxyuridine (BrdUrd) is felt to exert its cytotoxic effects primarily through incorporation into DNA. We have evaluated the incorporation of BrdUrd into the DNA of relevant normal tissues (bone marrow, gut mucosa, and liver) and tumor in rabbits with the VX2 tumor growing intrahepatically. Using constant i.v. infusions, steady state plasma drug concentrations ranging from 0.4 to 65.4 microM were maintained for 24 h and tissues were harvested and processed so that a sensitive gas chromatography/mass spectrometry (GC/MS) method could be used to analyze the thymine and 5-bromouracil content of hydrolyzed DNA. In all tissues, DNA incorporation showed saturating effects as plasma BrdUrd concentration was increased and, BrdUrd incorporation as a function of plasma concentration could be fitted to a Langmuir-like equation generating tissue-specific pharmacodynamic parameters: Imax for percentage thymine replacement at infinite plasma BrdUrd concentrations, and C50 for the arterial BrdUrd concentration generating incorporation that is Imax/2. At all plasma concentrations of BrdUrd the incorporation into DNA of bone marrow was greater than that observed in VX2 tumor. However, BrdUrd labeling index (with a BrdUrd monoclonal antibody) was greater in tumor than bone marrow. Thus, pharmacodynamic differences in incorporation do not result solely from cytokinetic differences between tissues. This model may prove useful in evaluating the pharmacodynamics of incorporation in studies using hepatic arterial infusion and biochemical modulation to improve selectivity.

Animals↗
PubMed1988

Patients with heart rhythm disturbances: variables associated with increased psychologic distress.

The spectrum of psychologic distress in patients with serious heart rhythm disturbances (HRD) has not been well defined. A survey of personal and clinical background data and general psychologic status was made of 136 patients with serious HRD defined as sustained or symptomatic ventricular tachycardia or fibrillation. Two questionnaires were used: the SCL-90-R, a standard self-report symptom inventory of present psychologic status, and a functional capacity and occupational status questionnaire developed by us. Of the 105 respondents, 89 completed both questionnaires, the results of which form the basis of this report. The patients with HRD were found to have significantly elevated SCL-90-R scores reflective of an increase in overall psychologic distress (Global Severity Index, Positive Symptom Distress Index, and Positive Symptom Total) as well as significantly higher scores on the specific constructs. Within the HRD population, univariate analysis revealed three variables significantly correlated with increased psychologic distress: (1) requiring long-term antiarrhythmic medication, (2) being forced to modify work status, and (3) having more advanced cardiac impairment. Patients who had two or more of these variables, termed risk factors, reported significantly more symptoms and greater psychologic distress than those with zero or one risk factor. We conclude that patients with serious HRD have greater psychologic distress than do normal subjects. Within the HRD group, patients requiring long-term medical treatment for their arrhythmia, those forced to modify work status, and those with more advanced cardiac impairment are at greater risk for emotional sequelae, and patients with two or more of the identified risk factors are more likely to have elevated psychologic distress.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Analysis of bromodeoxyuridine incorporation into DNA: comparison of gas chromatographic/mass spectrometric, CsCl gradient sedimentation, and specific radioactivity methods.

A sensitive new method for the quantitation of 5-bromodeoxyuridine (BrdUrd) incorporated into DNA by GC/MS analysis of enzymatically released Thy and bromouracil (BrUra) is presented. The hydrolysis procedure was characterized and found to give uniform results when sample size was 1-10 micrograms DNA and incubation time for DNA digestion was between 40 min and 16 h. Samples of DNA containing 3H-labeled BrdUrd were analyzed in parallel by the GC/MS technique and by specific radioactivity and buoyant density measurements, in order to compare the three methods. The GC/MS procedure gave values for percentage replacement of Thy by BrUra which were higher than those obtained by specific activity and lower than those obtained by buoyant density. This GC/MS method can detect 1% replacement in a 1-microgram DNA sample, equivalent to approximately 10(5) cells or 0.1 mg tissue, and will permit sensitive and quantitative analysis of the presence of this chemotherapeutic agent/radiosensitizer in cellular DNA from biopsy samples of normal or tumor tissue.

Animals↗
PubMed1986

Probabilistic methods in matching census samples to the National Death Index.

The National Death Index (NDI) of the National Center for Health Statistics is a powerful tool for identifying deaths in epidemiologic studies. The NDI will generate a list of possible matches for every input record according to the NDI matching criteria. The task of determining a true or correct match out of the list of possible matches becomes formidable when a large number of records are being investigated. In the National Longitudinal Mortality Study nearly one million Census records are being matched to the NDI, thus requiring an efficient and accurate method to screen out the false positive matches. In a pilot study to the larger mortality follow-up, Census Bureau files containing 226,000 person records were matched to the 1979 NDI. The results of this match were used to generate a probabilistic method to separate the possible matches into categories of true positives, false positives and those of questionable status requiring manual review of the Census record and the death certificate. Of the 5542 possible matches about one-third were ultimately determined to be true positives and two-thirds false positives. The probabilistic method was validated by replications on subsets of the data and promises to save considerable time in review of records in the large national study of mortality.

Computers↗
PubMed1986

Occupational stress within the paramedic profession: an initial report of stress levels compared to hospital employees.

We report a study of occupational stress in 374 paramedics. Results indicate that this profession experiences a high degree of job-related stress relative to other medical personnel. In a component analysis of this stress the results show that job stress manifests itself as job dissatisfaction, organizational stress, and negative patient attitudes, but not as frequently as somatic distress.

Adult↗
PubMed1986

Triggered activity as a cause of bigeminy.

Standard microelectrode techniques were used to study bigeminal rhythms occurring during otherwise stable triggered activity in ouabain-toxic canine Purkinje fibers. The basis for the bigeminy appeared to be an alternans phenomenon in the delayed afterdepolarizations that induced the triggered activity, as well as in the maximal diastolic potential. The occurrence of bigeminy, previously thought to result from reentry, from single delayed afterdepolarizations coupled to a triggered action potential or from parasystole, can also be considered a manifestation of sustained triggered activity.

Action Potentials↗
PubMed1984

Estrogen treatment increases the oral component of apomorphine-induced stereotypy.

Twelve weeks after surgery, sham operated intact and ovariectomized (OVX) female rats were treated for 3 days with either estradiol benzoate (50 micrograms/kg per day) or the oil vehicle. They were then tested for apomorphine-induced stereotypy 24 or 72 h after the last steroid injection. The data was collected and analysed in terms of both stereotypy ratings and individual behavioural responses. Estradiol, in those animals tested 72 h after estrogen, increased the frequency of oral behaviour in intact and in OVX groups. One possible explanation for the results is that estradiol may exert an anti-dopaminergic effect in the nigrostriatal system.

Animals↗
PubMed1984

Effects of stereoisomers of estradiol on food intake, body weight and hoarding behavior in female rats.

The effects of 17-alpha and 17-beta estradiol on food intake, body weight and hoarding behavior in ovariectomised rats were investigated. For five days, ten animals received subcutaneous injections of both isomers (10 micrograms/kg/day) in a counterbalanced design. Hoarding tests were conducted on the last three days of each 5-day injection period. 17-Alpha estradiol significantly reduced food intake but was without effect on body weight. 17-Beta estradiol reduced food intake significantly more than the alpha form and also significantly reduced body weight. These differential effects suggest that stereoisomers of estradiol may be acting on separate regulatory systems. The treatments did not change hoarding activity compared to pre-treatment levels.

Animals↗
PubMed1983

Comparative effects of estradiol stereoisomers on pimozide-induced catalepsy, locomotor activity and body-weight in the rat.

The effects of 17-alpha and 17-beta estradiol were compared at three dose levels on locomotor activity, pimozide-induced catalepsy, and changes in body weight. At 10 micrograms/kg/day they increased locomotor activity to a similar degree but at 5 and 1 microgram/kg/day the beta form was mor effective. However the alpha isomer failed to potentiate catalepsy, or reduce body weight, even at the highest dose whereas 17-beta estradiol did both. From these and other results it is suggested that estradiol might act on intracellular receptors and not by changing catecholamine metabolism.

Animals↗
PubMed1983

Acute and chronic effects of estrogen treatment on pimozide-induced catalepsy in the rat.

The effects of acute (3 days) and chronic (3 weeks) estrogen treatment on pimozide-induced catalepsy in ovariectomized female rats is described. Bar and grid tests were used to evaluate the cataleptic response to a 4 mg/kg dose of pimozide. Bar data showed that acute estrogen treatment (10 microgram/kg/day) significantly potentiated catalepsy when rats were tested 24 hours after the hormone but not if a dose-test interval of 48 hours was used. In the chronic phase catalepsy was significantly increased in both hormone treated groups (24 and 48 hours after estrogen). The grid data showed a qualitatively similar trend but did not reach significance in either the acute or chronic test phase. The difference between the two test phases may arise from the operation of independent factors in each case: the acute phase effect resulting from a central action of estrogen while the chronic data might be more typical of a metabolic effect. These, and other, possibilities are discussed.

Animals↗