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Biomedical subjects

A L Johnson

Publications and source records attributed to A L Johnson.

At least 19 recordsLinked to original sources

Subcellular fractionation of rat cerebellum: separation of synaptosomal populations and heterogeneity of mitochondria.

A crude mitochondrial fraction (M) derived from manually disrupted cerebellar tissue and enriched in choline acetyltransferase (ChAT) activity was fractionated by centrifugation in discontinuous and continuous sucrose gradients. Further purification of 'cholinergic' synaptosomes was achieved (relative specific activity (RSA) of ChAT greater than 3), but the overlap with other synaptosomal populations was still considerable. Hand-homogenized cerebella processed through the full fractionation procedure described here and in previous papers yielded preparations enriched in certain neuronal structures and a fraction in which 'heavy' free mitochondria was concentrated. To characterize these preparations the activities of two transmitter enzymes (CHAT and glutamate decarboxylase, GAD) and 6 mitochondrial enzymes (succinate dehydrogenase (SDH), glutamate dehydrogenase (GDH), monoamine oxidase, citrate synthase, fumarase and GABA-aminotransferase) were determined. The distribution of the transmitter enzymes was clearly different in the preparations containing various neuronal structures. The GAD:ChAT RSA ratio was 2.4 for the glomerulus particles, 1.3 for the molecular layer fragments, 0.6 for the myelinated axon segments, and 0.2 for the 'cholinergic' synaptosomes. The mitochondrial enzyme profile of the preparations comprising mainly neuronal structures differed markedly from that of the 'free' mitochondrial fraction. Notably the latter was greatly enriched in GDH (RSA 5.6), whereas the SDH:GDH RSA ratio was relatively high in the former preparations. Nevertheless there were notable differences in the enzyme profile of the fractions of predominantly neuronal origin indicating that the enzyme composition of mitochondria of neuronal processes is not uniform.

Animals

Distribution of tryptophan and tyrosine in unipolar affective disorders as defined by multicompartmental analysis.

As requirements for tryptophan for synthesis of protein and 5-hydroxytryptamine were comparable in rat brain, during depletion of tryptophan there could be competition between the two pathways for the amino acid. This implied that tryptophan should be rate-limiting for protein synthesis and this was found in the short term when concentrations of the amino acid were reduced in rats. Multicompartmental studies of tryptophan and tyrosine in controls and patients subject to unipolar depression defined two main pools of the amino acid provisionally assigned to extracellular and intracellular spaces. For tyrosine, mean values for the extracellular space were comparable to those of controls. The concentration of tyrosine was low in the intracellular space in both depressed and recovered patients, but the raised fractional clearance rates for this compartment during depression had returned to normal on remission. Plasma tryptophan concentrations were significantly reduced in depression with intermediate values after recovery. This suggested that the procedure used may have been mildly stressful and that this had evoked an idiosyncratic response to the stress in the depressed patients, which was characterized by inability to maintain concentrations of this amino acid in plasma. The findings for both amino acids may have a bearing on the aetiology of unipolar affective disorder.

Adult

Multicompartmental analysis of amino acids. III. Tyrosine in affective disorder.

Multicompartmental studies of tyrosine in patients suffering from affective disorders and controls gave estimates of 2 major pools of amino acid, together with the associated fractional clearance rates and fluxes. The 2 pools were considered provisionally to represent extracellular and intracellular tyrosine. The concentration of tyrosine in plasma (representing the extracellular pool) and fractional clearance rates from this compartment were normal in ill and recovered patients. The observed abnormalities were confined to the intracellular compartment and consisted of low concentrations of tyrosine in both depressed and recovered patients. In addition, fractional clearance rates from the intracellular compartment were raised in the depressed patients but had returned to normal after recovery. A comparison of these data with those of a similar study of tryptophan described previously suggested that alterations in compartmental volume or dietary differences could not explain the 2 sets of findings. The disturbances in tryptophan metabolism in unipolar affective disorder had led to reduced amounts of this amino acid in the extracellular space. In contrast, the concentration of tyrosine in this compartment was normal, presumably as a result of a metabolic adjustment to the lower amounts found in the intracellular pool. The presence of illness-dependent and illness-independent alterations in tyrosine metabolism in unipolar affective disorder, together with the earlier findings for tryptophan, may have a bearing on the aetiology of the illness.

Adult

Self-recording of blood pressure in the management of hypertension.

The efficacy of self-recording of blood pressure in the management of hypertension was assessed in a randomized clinical trial involving 140 persons who had been receiving antihypertensive therapy for a year or more, but whose diastolic blood pressure had remained at 95 mm Hg or higher. To control for the increased attention implicit in self-recording, which might affect blood pressure, the patients were assigned at random to one of the four groups: self-recording and monthly home visits, self-recording only, monthly home visits only, and neither self-recording nor monthly home visits. This design also permitted assessment of the effect of home visits. During the 6-month experiment no significant differences were apparent between the groups in either compliance or diastolic blood pressure. However, both self-recording and monthly home visits produced a reduction in blood pressure among patients who admitted to difficulty remembering to take their pills; a reduction was not seen among patients who said they had no such difficulty. This confirmed an earlier observation suggesting that this easily identified group of patients may be the most responsive to intervention programs.

Adult

Increased absenteeism from work after detection and labeling of hypertensive patients.

A study of hypertension in an industrial setting allowed us to confirm and explore an earlier retrospective finding that the labeling of patients as hypertensive resulted in increased absenteeism from work. After screening and referral, we found that absenteeism rose (mean +/- 1 S.E.) 5.2 +/- 2.3 days per year (P less than 0.025); this 80 per cent increase greatly exceeded the 9 per cent rise in absenteeism in the general employee population during this period. The main factors associated with increased absenteeism were becoming aware of the condition (P less than 0.01) and low compliance with treatment (P less than 0.001). Subsequent absenteeism among patients unaware of their hypertension before screening was not related to the degree of hypertension, whether the worker was started on therapy, the degree of blood-pressure control achieved or exposure to attempts to promote compliance. These results have major implications for hypertension screening programs, especially since absenteeism rose among those previously unaware of their condition, regardless of whether antihypertensive therapy was begun.

Absenteeism

Multicompartmental analysis of amino acids: II. Tryptophan in affective disorder.

Two of the tryptophan pools in the body and their associated fluxes, as defined by multicompartmental analysis, were studied in patients with unipolar affective disorder, bipolar patients (manic) and control subjects. The 2 pools were tentatively associated with extra- and intra-cellular compartments. The investigations were performed fasting and may have been mildly stressful. Under these conditions the concentration of tryptophan in plasma and perhaps amounts in the extracellular space were reduced in unipolar depression, with intermediate values after recovery. Some model parameters were lower in females than in males. The results in unipolar affective disorder were interpreted in terms of a previously presented hypothesis that this illness may result in an idiosyncratic response to stress in which patients are unable to maintain normal amounts of tryptophan in the body. In manic patients extracellular levels of tryptophan were unchanged but intracellular and total quantities of 'freely available' tryptophan may have been reduced.

Adult

Infection of the uterine cervix with Chlamydia trachomatis.

For identification of those variables in the history and in the clinical and routine laboratory examination that are most likely to indicate infection of the uterine cervix with Chlamydia trachomatis, 284 women attending a venereal disease clinic were studied, were studied, of whom 58 (20.4%) yielded the organism from the cervix. Women with chlamydial cervical infection showed no distinctive symptoms. Although associations were found between the presence of C. trachomatis and cervical discontinuity, purulent cervical exudate, and inflammatory changes in cervical cytology, these signs were not pathognomonic of chlamydial infection since they were also seen in some women infected with other microorganisms. There was a significant relationship between the presence of antibodies, detected by immunofluorescence, and the recovery of C. trachomatis in cell culture. There were no associations between ethnic group, history of sexually transmitted disease, method of contraception, phase in the menstrual cycle, or numbers of sexual contacts and infection with C. trachomatis.

Adolescent

Effect of hospitalization on weight of psychiatric patients.

The hypothesis that patients hospitalized for long periods and receiving psychotrophic drugs increase in weight is tested, and it was discovered that women patients were somewhat heavier than their 'standard' weights. This, however, was not due to hospitalization or drug effects. Contrary to expectation, the ratio of observed/'standard' weight frequently observed in affective disorder patients, we discovered puzzling higher mean ratios in men with this illness. This paper shows that small research projects can be carried out by nurses who are actively involved in patient care. It also demonstrates that small scale investigations, replicating locally some other research, testing its validity in a different setting are eminently worthwhile.

Adult

Is pancreatogram interpretation reliable?--a study of observer variation and error.

Observer variation in the interpretation of endoscopic pancreatograms has been examined by asking four experienced observers to assess 40 sets of well-documented radiographs (from 20 patients with cancer and 20 with pancreatitis), both without ("blind") and with clinical details, each on three occasions. Individual consistency for "blind" diagnoses ranged from 61% to 78%, increasing significantly with clinical information. Overall diagnostic accuracy with clinical information varied from 52% to 83% for cancer, and from 87% to 95% for pancreatitis. However, unanimous and correct opinions were given by the four observers for only 53% of all cases, even when clinical details were provided. Clinical information changed the radiographic diagnosis in 43% of assessments, 83% of these changes leading to improved accuracy. ERCP gives direct information about the major pancreatic and biliary duct systems and often provides an accurate diagnosis. Caution must be exercised in relying upon radiological appearances alone.

Diagnosis, Differential

Falls in the elderly related to postural imbalance.

Two hundred and forty-three elderly people aged 60 to 96 years were questioned about their falls, and their sway was measured. For comparison sway was also measured in 63 younger subjects. Sway increased with age and was higher in women at all ages. There was no difference in sway between those with no history of falls and those who fell only because of tripping. In both sexes sway was significantly increases in people who fell because of loss of balance and in women whose falls were due to giddiness, drop attacks, turning the head, and rising from bed or a chair. This suggests that there is a physiological decline in postural control with advancing age and also a decline due to disease of the central nervous system.

Accidents, Home

Improvement of medication compliance in uncontrolled hypertension.

38 hypertensive Canadian steelworkers who were neither compliant with medications nor at goal diastolic blood-pressure six months after starting treatment were allocated either to a control group or to an experimental group who were taught how to measure their own blood-pressures, asked to chart their home blood-pressures and pill taking, and taught how to tailor pill taking to their daily habits and rituals; these men were also seen fortnightly by a highschool graduate with no formal health professional training who reinforced the experimental manoeuvres and rewarded improvements in compliance and blood-pressure. Six months later, average compliance had fallen by 1.5% in the control group but rose 21.3% in the experimental group. Blood-pressures fell in 17 of 20 experimental patients (to goal in 6) and in 10 of 18 control patients (to goal in 2).

Antihypertensive Agents