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Biomedical subjects

N M Johnson

Publications and source records attributed to N M Johnson.

At least 19 recordsLinked to original sources
PubMed2005

The Caenorhabditis briggsae genome contains active CbmaT1 and Tcb1 transposons.

The maT clade of transposons is a group of transposable elements intermediate in sequence and predicted protein structure to mariner and Tc transposons, with a distribution thus far limited to a few invertebrate species. We present evidence, based on searches of publicly available databases, that the nematode Caenorhabditis briggsae has several maT-like transposons, which we have designated as CbmaT elements, dispersed throughout its genome. We also describe two additional transposon sequences that probably share their evolutionary history with the CbmaT transposons. One resembles a fold back variant of a CbmaT element, with long (380-bp) inverted terminal repeats (ITRs) that show a high degree (71%) of identity to CbmaT1. The other, which shares only the 26-bp ITR sequences with one of the CbmaT variants, is present in eight nearly identical copies, but does not have a transposase gene and may therefore be cross mobilised by a CbmaT transposase. Using PCR-based mobility assays, we show that CbmaT1 transposons are capable of excising from the C. briggsae genome. CbmaT1 excised approximately 500 times less frequently than Tcb1 in the reference strain AF16, but both CbmaT1 and Tcb1 excised at extremely high frequencies in the HK105 strain. The HK105 strain also exhibited a high frequency of spontaneous induction of unc-22 mutants, suggesting that it may be a mutator strain of C. briggsae.

Amino Acid Sequence↗
PubMed2000

Ontogenetic changes in characteristics required for endothermy in juvenile black skipjack tuna (Euthynnus lineatus).

To characterize better the development of endothermy in tunas, we assessed how the abilities to generate heat and to conserve heat within the aerobic, slow-twitch (red) myotomal muscle using counter-current heat exchangers (retia) change with size in juvenile black skipjack tuna (Euthynnus lineatus) above and below the hypothesized minimum size for endothermy of 207 mm fork length (FL). Early juvenile scombrids (10-77 mm FL) collected off the Pacific coast of Panama were raised to larger sizes at the Inter-American Tropical Tuna Commission Laboratory at Achotines Bay, Panama. Evidence of central and lateral rete blood vessels was found in E. lineatus as small as 95.9 mm FL and 125 mm FL, respectively. In larger E. lineatus juveniles (up to 244 mm FL), the capacity for heat exchange increased with fork length as a result of increases in rete length, rete width and the number of vessel rows. The amount (g) of red muscle increased exponentially with fork length in both E. lineatus (105-255 mm FL) and a closely related ectothermic species, the sierra Spanish mackerel Scomberomorus sierra (151-212 mm FL), but was greater in E. lineatus at a given fork length. The specific activity (international units g(-)(1)) of the enzyme citrate synthase in red muscle, an index of tissue heat production potential, increased slightly with fork length in juvenile E. lineatus (84. 1-180 mm FL) and S. sierra (122-215 mm FL). Thus, total red muscle heat production capacity (red muscle citrate synthase activity per gram times red muscle mass in grams) increased with fork length, primarily because of the increase in red muscle mass. Below 95.9 mm FL, E. lineatus cannot maintain red muscle temperature (T(m)) above the ambient water temperature (T(a)) because juveniles of this size lack retia. Above 95.9 mm FL, the relationship between T(x) (T(m)-T(a)) and FL for E. lineatus diverges from that for the ectothermic S. sierra because of increases in the capacities for both heat production and heat retention that result in the development of endothermy.

Animals↗
PubMed1999

Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: a pilot study.

Pulmonary sarcoidosis is a disease in which the pathological processes are distributed along lymphatic pathways, particularly those around the bronchovascular bundles. Delivery of disease-modulating drugs by the inhaled route is therefore an attractive option. The aim of this study was to determine the efficacy of inhaled fluticasone propionate 2 mg x day(-1) in adults with stable pulmonary sarcoidosis. Forty-four adult patients (22 from each centre) were enrolled from outpatient clinics in two London teaching hospitals in a two centre, double-blind, randomized, placebo-controlled trial. Primary end points were home recordings of peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Secondary end points were symptom scores, use of rescue bronchodilator medication, and clinic values for PEFR, FEV1, FVC, forced mid-expiratory flow (FEF25-75%), diffusion capacity of the lung for carbon monoxide (DL,CO), and total lung capacity (TLC). Symptom scores of cough, breathlessness and wheeze were lower in the active treatment group, but this did not reach statistical significance, and a general health perception assessment (Short Form (SF)-36) showed a difference between active and placebo treatment. No significant differences were found between the two groups in any physiological outcome measure. No new adverse reactions were detected. The results of this pilot study do not show an objective benefit of inhaled fluticasone propionate in pulmonary sarcoidosis where the disease is stable and is controlled without the use of inhaled corticosteroids.

Administration, Inhalation↗
PubMed1994

Specific detection of Mycobacterium paratuberculosis DNA associated with granulomatous tissue in Crohn's disease.

The role of mycobacteria, specifically Mycobacterium paratuberculosis, in Crohn's disease has aroused considerable controversy for many years. Using the ultra sensitive polymerase chain reaction some studies have reported detection of M paratuberculosis DNA in as many as 65% of Crohn's disease patients but also in patients without disease. Other studies have been negative for both groups. We therefore designed a double blind control trial to investigate the presence of mycobacterial DNA in age, sex, and tissue matched paraffin wax embedded tissues from 31 Crohn's disease tissues, 20 diseased gut control tissues, and 10 ulcerative colitis tissues. The specimens were coded and analysed blind with three separate polymerase chain reactions (PCR) based on DNA sequences specific for M paratuberculosis (IS900), M avium (RFLP type A/1) (IS901), and the Mycobacterium genus (65 kDa gene, TB600). The number of granulomata and presence of acid fast bacilli in each Crohn's disease tissue was also investigated. The sensitivity of the system was determined using similarly prepared gut tissue from an animal infected with M paratuberculosis. Four of 31 Crohn's disease tissues and none of the 30 control and ulcerative colitis derived tissues amplified M paratuberculosis DNA. Crohn's disease tissues containing granulomata were significantly more likely to amplify M paratuberculosis specific DNA on PCR than the non-Crohn's disease tissues (p = 0.02). All the positive Crohn's disease tissues contained granulomata, and none contained acid fast bacilli. Equivalent numbers of Crohn's and non-Crohn's disease tissues amplified the region of the 65 kD gene on PCR for non-specific mycobacterial DNA (11/31 and 9/30 respectively). No sections produced an amplified product with the IS901 PCR. These results suggest that few Crohn's disease gut biopsy sections contain M paratuberculosis DNA in association with granulomata. The absence of such DNA in any control and ulcerative colitic tissue strengthens the case for it having a specific association, which may be pathogenic, with Crohn's disease in this minority of patients.

Adult↗
PubMed1993

Mycobacterium tuberculosis DNA in tissue affected by sarcoidosis.

OBJECTIVE: To investigate the prevalence of Mycobacterium tuberculosis DNA in granulomatous tissues from patients with sarcoidosis and from controls matched for age, sex, and tissue by using the polymerase chain reaction. DESIGN: Single blind control trial. SUBJECTS: 16 patients with sarcoidosis who had undergone diagnostic biopsy of lung, skin, or lymph node and 16 patients with squamous cell carcinoma or Hodgkin's disease to act as controls. In addition, four lung specimens infected with M tuberculosis were included as positive controls. RESULTS: M tuberculosis DNA was present in sarcoid tissues containing granulomas from seven of the 16 patients and one of the 16 matched controls. Two of the four specimens known to be infected with M tuberculosis were positive in the controlled experiment. CONCLUSION: These figures suggest that M tuberculosis DNA is detected as readily in patients with sarcoidosis as in patients with frankly tuberculous tissues and imply that M tuberculosis may be linked to the cause of sarcoidosis.

Base Sequence↗
PubMed1993

Study into the ability of healthy people of small stature to satisfy the sampling requirements of breath alcohol testing instruments.

In a previous study (Gomm et al., 1991) people with a variety of respiratory diseases were tested and criteria defined for assessing their ability to provide samples for Breath Alcohol Testing Instruments. This study investigated the possible problems which may be encountered by healthy people of small stature--5ft 5in (166cm) or less--who do not suffer from a respiratory disease. This study followed the same pattern as the earlier work in that lung function (Forced Expiration Volume in One Second (FEV1) and Forced Vital Capacity (FVC)) was measured by spirometry, and Peak Expiration Flow Rate (PEFR) was measured using a Wright peak flow meter. Following the lung function measurements the subjects were requested to provide samples for Breath Alcohol Testing Instruments used by the Police in Great Britain. As with the previously reported work (Gomm et al., 1991), this study found that the FEV1 and FVC gave the most reliable indication of a person's capability of satisfying the sampling requirements of Breath Alcohol Testing Instruments, but on this occasion the PEFR also provided a good confirmatory indication. Because there were no subjects with interstitial lung diseases the values determined by this study on 48 healthy adults indicate that a healthy person of small stature should be capable of supplying a suitable breath sample if their FEV1, FVC and PEFR are greater than 2.31, 2.61 and 330 l/min respectively.

Adult↗
PubMed1992

Detection of mycobacterial DNA in sarcoidosis and tuberculosis with polymerase chain reaction.

The cause of sarcoidosis is unknown. However, the histological similarity between the disorder and tuberculosis suggests that mycobacteria might contribute to the pathogenesis of sarcoidosis. We have used the polymerase chain reaction (PCR) to detect mycobacterial DNA in clinical samples from patients with sarcoidosis. 104 patients were included in the study (62 referred for possible tuberculosis and 20 for possible sarcoidosis, and 22 control patients who had undergone bronchoscopy for other reasons). Bronchoalveolar lavage samples, bronchial washings, and tissue specimens (1 from each patient) underwent assay by PCR as well as bacteriological, histological, and cytological examination. We used two PCR reactions: in the first the complex-specific insertion sequence IS986/IS6110 was used to specifically detect DNA from Mycobacterium tuberculosis complex bacteria; in the second, conserved sequences of the mycobacterial groEL gene were used to detect DNA from mycobacteria other than M tuberculosis. The PCR was more sensitive than culture for diagnosis of tuberculosis. However, the false-positive PCR rate for M tuberculosis was 9%. M tuberculosis DNA was found in half the sarcoidosis patients, and non-tuberculosis mycobacterial DNA in a further 20%. The findings that a significant proportion of the sarcoidosis patients in this study have mycobacteria in their lungs and that most of these mycobacteria belong to M tuberculosis complex suggest an aetiological role for mycobacteria in sarcoidosis.

Base Sequence↗
PubMed1992

Tumour necrosis factor production by alveolar macrophages in pulmonary sarcoidosis and tuberculosis.

Tumour Necrosis Factor alpha (TNF/Cachectin) is a cytokine produced mainly by macrophages, which has been shown to cause endothelial cell damage, pyrexia and weight loss, clinical features of tuberculosis, but not of sarcoidosis which is in many other respects a similar disease. 1,25 di-hydroxy Vitamin D and gamma interferon, factors which are present in vivo in both tuberculosis and sarcoidosis, enhance the ability of macrophages to release TNF in vitro. We have studied the ability of pulmonary alveolar macrophages (PAM) harvested by broncho-alveolar lavage (BAL) to produce TNF in response to stimulation with E. coli endotoxin lipopolysaccharide (LPS). 25 patients undergoing bronchoscopy and BAL were studied: 9 with sarcoidosis, 7 with tuberculosis (TB) and 9 (non-neoplastic) disease controls. TNF was assayed by Enzyme Linked Immunosorbent Assay (ELISA) in lavage fluid and cell culture supernatants. No TNF was detected in lavage fluid from any of the groups. PAMs from control patients released no detectable TNF spontaneously, but released 59 +/- 31 units after LPS stimulation. Cells from patients with sarcoidosis and tuberculosis released TNF spontaneously in vitro (TB 226 +/- 106 units; Sarcoidosis 293 +/- 176). TNF release by these cells was not increased further by addition of an optimal concentration of LPS. Thus, the pulmonary macrophages of patients with sarcoidosis and tuberculosis released significantly more TNF than those of controls.

Adult↗
PubMed1991

Isotretinoin and lung function in systemic sclerosis.

During an open prospective study of the synthetic retinoid isotretinoin in ten patients with systemic sclerosis, one patient developed an eosinophilic pleural effusion and two patients were noticed to have asymptomatic deterioration in pulmonary function tests. The pulmonary function of all treated patients was then compared retrospectively with a similar control group of patients not treated with isotretinoin. There was a significantly greater decrease in the 1-s forced expiratory volume and transfer coefficient in the patients with systemic sclerosis being treated with isotretinoin in comparison to the untreated control patients. Studies of lung function in patients treated with isotretinoin for other indications are required.

Adult↗
PubMed1991

Study into the ability of patients with impaired lung function to use breath alcohol testing devices.

A subject who fails to provide an adequate breath sample for a breath alcohol measuring device under the provisions of Road Traffic Act 1988 may be charged with refusing to supply a sample unless the police officer believes the person is genuinely unable to do so. Subjects who are confronted with this situation may approach their general practitioner or chest physician for advice on whether they are medically able to provide adequate breath samples to satisfy the breath testing devices. There is currently no guidance available for medical practitioners concerning respiratory performance or lung function which will impair the use of such breath testing devices. This paper describes experiments with human volunteers suffering from respiratory illnesses and their ability to provide adequate breath samples to satisfy the requirements of the breath alcohol testing devices used in Great Britain. It was found that the most suitable parameters for determining whether a subject was capable of using a breath alcohol testing device were spirometry measurements of Forced Expired Volume in one second (FEV1) and Forced Vital Capacity (FVC). In this study subjects with a FEV1 less than 2.0 litres and a FVC less than 2.6 litres were generally unable to use all the devices.

Adolescent↗
PubMed1991

The effect of salbutamol on breath alcohol testing in asthmatics.

Subjects suffering from asthma can occasionally experience difficulty in providing adequate breath samples for evidential breath alcohol testing devices and may therefore resort to the use of bronchodilators such as salbutamol to improve their respiration. Experiments showed that although salbutamol caused bronchodilation it did not affect breath alcohol levels of asthmatics who have been drinking. The blood:breath alcohol ratios obtained from asthmatics were within the normally recorded range before and after use of salbutamol. We conclude that the use of salbutamol by asthmatics does not affect the reliability of measurements made by evidential breath alcohol testing devices.

Adult↗
PubMed1989

Tumour necrosis factor in bronchopulmonary secretions of patients with adult respiratory distress syndrome.

Tumour necrosis factor (TNF) concentrations were measured in the bronchopulmonary secretions of 5 patients with the adult respiratory distress syndrome. Each patient underwent fibreoptic bronchoscopy and bronchopulmonary aspiration, and control samples were obtained in an identical manner from 24 patients who underwent bronchoscopy for other reasons (8 had tuberculosis, 6 had sarcoidosis, and 10 had haemoptysis but no abnormal findings). Aspirated fluid was assayed for the presence of TNF by use of an enzyme-linked immunosorbent assay. In the 5 patients with adult respiratory distress syndrome, TNF concentrations exceeded 500 U/ml (12.5 ng/ml), whereas in the control samples no TNF was detected.

Bronchoalveolar Lavage Fluid↗