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Biomedical subjects

G J Gibson

Publications and source records attributed to G J Gibson.

At least 19 recordsLinked to original sources
PubMed1992

Cleavage of type VIII collagen by human neutrophil elastase.

In this report, the susceptibility of type VIII collagen to human neutrophil elastase is compared to other extracellular matrix components. Type X collagen is degraded to specific fragments at a substrate to enzyme ratio of 5:1 after 20 h at room temperature, but type VIII collagen is almost completely degraded after only 4 h incubation at a substrate to enzyme ratio of 50:1 and partly degraded after only 15 min. Laminin, merosin and types I, III, IV and V collagen exhibit no susceptibility to neutrophil elastase under the latter conditions, while fibronectin is degraded.

Collagen↗
PubMed1992

Correction of human mucopolysaccharidosis type-VI fibroblasts with recombinant N-acetylgalactosamine-4-sulphatase.

A full-length human N-acetylgalactosamine-4-sulphatase (4-sulphatase) cDNA clone was constructed and expressed in CHO-DK1 cells under the transcriptional control of the Rous sarcoma virus long terminal repeat. A clonal cell line expressing high activities of human 4-sulphatase was isolated. The maturation and processing of the human enzyme in this transfected CHO cell line showed it to be identical with that seen in normal human skin fibroblasts. The high-uptake precursor form of the recombinant enzyme was purified from the medium of the transfected cells treated with NH4Cl and was shown to be efficiently endocytosed by control fibroblasts and by fibroblasts from a mucopolysaccharidosis type-VI (MPS VI) patient. Enzyme uptake was inhibitable by mannose 6-phosphate. After uptake, the enzyme was processed normally in both normal and MPS VI fibroblasts and was shown both to correct the enzymic defect and to initiate degradation of [35S]sulphated dermatan sulphate in MPS VI fibroblasts. The stabilities of the recombinant enzyme and enzyme from human fibroblasts appeared to be similar after uptake. However, endocytosed enzyme has a significantly shorter half-life than endogenous human enzyme. The purified precursor 4-sulphatase had a similar pH optimum and catalytic parameters to the mature form of 4-sulphatase isolated from human liver.

Alkaline Phosphatase↗
PubMed1992

Hurler syndrome: a patient with abnormally high levels of alpha-L-iduronidase protein.

Mucopolysaccharidosis type I (MPS I: McKusick 25280) is a clinically heterogenous lysosomal storage disorder which is caused by a variable deficiency in alpha-L-iduronidase activity (alpha-L-iduronide iduronohydrolase, EC 3.2.1.76). Cultured fibroblasts from an MPS I patient (cell line 2827) with a severe clinical phenotype (Hurler syndrome) have been characterized using immunochemical and biochemical techniques. Using a specific immunoquantification assay, we have demonstrated that cell line 2827 had an alpha-L-iduronidase protein content (189 ng/mg of extracted cell protein) at least six times greater than the mean level found in normal control fibroblasts (30 ng/mg of extracted cell protein). This was the only MPS I cell line, from a group of 23 MPS I patients, that contained greater than 7% of the mean level of alpha-L-iduronidase protein detected in normal controls. Cell line 2827 had very low alpha-L-iduronidase activity toward the fluorogenic substrate 4-methylumbelliferyl-alpha-L-iduronide, and a radiolabeled disaccharide substrate derived from heparin. Maturation studies of alpha-L-iduronidase in cell line 2827 showed apparently normal levels of alpha-L-iduronidase synthesis with delayed processing to the mature form. Subcellular fractionation experiments demonstrated alpha-L-iduronidase protein in lysosomal-enriched fractions isolated from cell line 2827, suggesting a normal cell distribution and supporting the proposed delayed processing. It is proposed that the MPS I patient described has an alpha-L-iduronidase gene mutation which affects both the active site and post-translational processing of the enzyme. This mutation must be structurally conservative because it does not result in instability either during maturation or in the lysosome.

Cells, Cultured↗
PubMed1992

Phrenic neuropathy in association with diabetes.

We report the case of a 51-year-old man who presented with breathlessness on exertion and orthopnoea in association with Type 2 diabetes mellitus. Investigation showed bilateral diaphragmatic paralysis due to phrenic neuropathy. There was no evidence of neuropathy or microvascular disease elsewhere. Phrenic neuropathy may be an important, albeit rare, complication of diabetes and diaphragmatic function should be considered in any patient with unexplained breathlessness and orthopnoea.

Diabetes Mellitus, Type 2↗
PubMed1992

Neuromuscular disease, respiratory failure and cor pulmonale.

Respiratory muscle weakness is an uncommon cause of chronic respiratory failure and a rare cause of cor pulmonale. The problem may not be apparent unless specific physical signs are sought or appropriate investigations performed. We present three patients who presented diagnostic difficulty for prolonged periods until the presence of respiratory muscle weakness was considered. Once the diagnosis was established treatment with nocturnal nasal intermittent positive pressure ventilation produced a dramatic improvement in symptoms and allowed a return to a near normal lifestyle.

Adult↗
PubMed1992

Neutrophilic alveolitis in Sweet's syndrome.

In a case of Sweet's syndrome (acute febrile neutrophilic dermatosis) neutrophilic alveolitis was found by lung biopsy. Pulmonary disease in this condition may be underrecognised yet, like the dermatological features, it responds rapidly to corticosteroids.

Aged↗
PubMed1992

Variability of inspired oxygen concentration with nasal cannulas.

BACKGROUND: The likely values of inspired oxygen concentration (FIO2) of patients with chronic obstructive pulmonary disease breathing via nasal cannulas have not been assessed previously. METHODS: Seven patients with chronic obstructive lung disease and seven healthy subjects were studied while breathing oxygen via nasal cannulas or fixed performance (Venturi) or uncontrolled (MC) oxygen masks. Breath to breath values of FIO2 were calculated by extrapolation from expired oxygen and carbon dioxide concentrations on the basis of the oxygen-carbon dioxide relationship and on the assumption of a respiratory exchange ratio (R) of 0.8. RESULTS: In both groups of subjects the average values of FIO2 with nasal cannulas at 1 and 2 l min-1 were of a similar order to those achieved with 24.5% and 28% Venturi masks, but variations within and between subjects in both groups breathing via nasal cannulas were considerable and similar to those found with MC masks. In the seven patients with chronic obstructive lung disease breathing via nasal cannulas at 2 l min-1 the average FIO2 varied from 23.7% to 34.9%. CONCLUSIONS: "Typical" values of FIO2 quoted with nasal cannulas can mislead. The results confirm that this mode of oxygen delivery is unsatisfactory if precise control of inspired oxygen is desired.

Aged↗
PubMed1991

Human and sheep growth-plate cartilage type X collagen synthesis and the influence of tissue storage.

Direct comparison of type X collagen synthesized by human, sheep and chick growth-plate cartilage has shown that the human type X collagen is similar to the chick in both its molecular mass, containing component alpha-chains of 59 kDa with helical regions of 45 kDa, and apparent absence of disulphide-stabilized aggregates, whereas the sheep type X collagen has slightly larger alpha-chains (63 kDa) accounted for by a longer helical region (49 kDa) that contains cystine residues essential for the formation of the high-molecular-mass aggregates found with this species. Type X collagen from all three species showed heterogeneity in primary collagen structure as revealed by Staphylococcus aureus V8 proteinase-generated peptide maps. Collagen synthesis by growth-plate cartilage in culture, particularly synthesis of type IX and X collagen, was shown to be very sensitive to prior storage and suggests caution in the interpretation of changes detected when examining collagen synthesis by growth plates in culture.

Aging↗
PubMed1991

alpha-L-iduronidase in normal and mucopolysaccharidosis-type-I human skin fibroblasts.

alpha-L-Iduronidase synthesis and maturation were analysed in fibroblasts from normal controls and from alpha-L-iduronidase-deficient mucopolysaccharidosis-type-I (MPS-I) patients. Fibroblasts were radiolabelled with [3H]leucine and alpha-L-iduronidase was isolated from cell lysates or culture medium by monoclonal-antibody affinity chromatography. Pulse-chase labelling of normal control fibroblasts showed that alpha-L-iduronidase was synthesized as an 81 kDa precursor and processed within 24 h via intermediates of 76 kDa and 70 kDa to a 69 kDa species. The incorporation of radiolabel into alpha-L-iduronidase in fibroblasts from three of four MPS-I patients was at levels that were either very low or undetectable. Fibroblasts from one MPS-I patient, however, exhibited levels of incorporation of radiolabelled amino acid into alpha-L-iduronidase similar to those shown by normal control fibroblasts, despite having undetectable alpha-L-iduronidase enzyme activity. The maturation of alpha-L-iduronidase in fibroblasts from this patient was delayed compared with normal controls and showed accumulation of the 76 kDa intermediate, as well as the major 69 kDa, form of the enzyme.

Antibodies, Monoclonal↗
PubMed1991

A specific fluorogenic assay for N-acetylgalactosamine-4-sulphatase activity using immunoadsorption.

A method combining immune capture and enzyme detection by fluorochemistry has been developed for the diagnostic assay of N-acetylgalactosamine-4-sulphatase (4-sulphatase). The procedure uses a monoclonal antibody 4-S 4.1 to immunoadsorb 4-sulphatase specifically from complex protein samples containing other sulphatases, and 4-methylumbelliferyl sulphate to detect captured 4-sulphatase. The assay provides an accurate and simple method for the diagnosis of Maroteaux-Lamy syndrome (Mucopolysaccharidosis type VI).

Antibodies, Monoclonal↗
PubMed1991

A video system for investigating breathing disorders during sleep.

A system has been developed for investigating breathing during sleep that superimposes physiological signals on a video image of the patient, with the combined image plus sound recorded on video tape for later analysis. Signals normally displayed include oxygen saturation, airflow, chest wall motion, electroencephalogram, and electrooculogram; but others can be recorded if desired. The information is displayed on a timebase appropriate for the recognition and analysis of respiratory events during sleep. In addition, use is made of normally invisible video lines to record the analogue voltage waveforms so that on replay this information can be displayed on a fast timebase for analysing the more rapidly changing waveforms of electrophysiological signals. The system allows detailed polysomnography to be performed in the normal ward setting with the subject monitored overnight by the nursing staff. Subsequent analysis of the synchronised video, audio, and analogue signals allows measurement of the conventional indices obtained by polysomnography and aids their interpretation.

Humans↗
PubMed1991

Successful treatment of Bacillus cereus infection with ciprofloxacin.

Bacillus cereus is rarely a pulmonary pathogen but may cause pneumonia in immunocompromised patients. A patient with bronchiectasis and no recognisable immunodeficiency had this organism isolated during two infective exacerbations, once from respiratory secretions and once by blood culture. Ciprofloxacin treatment was effective on both occasions.

Adult↗
PubMed1991

Value of nocturnal oxygen saturation as a screening test for sleep apnoea.

The sensitivity and specificity of overnight recording of arterial oxygen saturation (SaO2) in routine clinical practice was evaluated in 41 subjects who were being investigated for possible sleep apnoea-hypopnoea syndrome. SaO2 was measured with an ear probe oximeter (Biox IIa) and chart recorder during an "acclimatisation" night immediately before a detailed polysomnographic study. The recordings were classified by two observers as positive, negative, or uninterpretable. Twelve of the 41 patients had the obstructive sleep apnoea syndrome when defined in terms of an apnoea-hypopnoea index greater than 15 events an hour on the second night. The sensitivity of nocturnal SaO2 on the acclimatisation night when the diagnostic criterion was an apnoea-hypopnoea index of greater than 5, greater than 15, and greater than 25/h was 60%, 75%, and 100% respectively. Corresponding values for specificity were 95%, 86%, and 80%. Oximetry alone therefore allowed recognition of a moderate or severe sleep apnoea syndrome. In routine practice an appreciable number of equivocal results is likely and repeat oximetry or more detailed polysomnography will then be required if clinical suspicion is high.

Evaluation Studies as Topic↗
PubMed1991

Symptomatic benefit of supplemental oxygen in hypoxemic patients with chronic lung disease.

We have compared the symptomatic benefit of air and oxygen at rest in hypoxemic patients with chronic obstructive airway disease (COAD) or interstitial lung disease (ILD). A total of 12 severely disabled patients with COAD (mean +/- SEM, PaO2, 50.3 +/- 3.7 mm Hg) and 10 with ILD (PaO2, 48.0 +/- 3.1 mm Hg) received 28% oxygen and air by Venturi face mask, each gas on two occasions, in a double-blind randomized fashion. SaO2 increased (p less than 0.01) in both groups during oxygen breathing: COAD, 85.1 +/- 2.3% versus 93.1 +/- 1.4%; ILD, 85.5 +/- 1.7% versus 94.7 +/- 0.9%. The patients with COAD stated that air helped their breathing on 15 of 24 occasions and that oxygen helped on 22 of 24 occasions (p less than 0.05). In the patients with ILD the values were 6 of 20 and 13 of 20 occasions, respectively (p less than 0.05). In both groups of patients the severity of breathlessness recorded on a 100-mm visual analog scale was significantly (p less than 0.05) lower during oxygen breathing: COAD, 29.6 +/- 4.5 versus 45.6 +/- 6.0; ILD, 30.2 +/- 5.1 versus 48.1 +/- 4.4. Ventilation measured by magnetometers was significantly lower during oxygen breathing in the patients with COAD (8.2 +/- 1.0 versus 9.3 +/- 1.1 L/min; p less than 0.05), but the difference between oxygen and air in patients with ILD was not statistically significant (9.3 +/- 1.3 versus 11.2 +/- 1.6 L/min; p greater than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Air↗
PubMed1991

Breathing during sleep in patients with myotonic dystrophy and non-myotonic respiratory muscle weakness.

Sleep apnoea and hypopnoea have been reported in myotonic dystrophy, but it is unclear whether this is simply attributable to the respiratory muscle weakness which is common in this condition. We therefore investigated whether breathing and oxygenation during sleep were more abnormal in patients with myotonic dystrophy than in patients with non-myotonic muscle weakness. Seven subjects were studied in each of three groups: normal controls, myotonic dystrophy and non-myotonic weakness. Patients in the latter group were chosen to represent a similar range of severity of respiratory muscle weakness to those with myotonic dystrophy. Detailed polysomnography was performed; the severity of breathing disorders during sleep was quantified in terms of the frequencies of apnoea and hypopnoea and the degree of arterial desaturation. The myotonic patients showed more frequent apnoea and hypopnoea and more severe desaturation than the other two groups; the results in the non-myotonic patients were generally intermediate. The results suggest that abnormal breathing during sleep is common in myotonic dystrophy and is not due solely to the direct effects of respiratory muscle weakness. Somnolence, which is a well recognized symptom of myotonic dystrophy, was not clearly attributable to the sleep apnoea/hypopnoea syndrome nor to abnormal sleep architecture in the myotonic patients.

Adult↗
PubMed1991

Analysis of N-acetylgalactosamine-4-sulfatase protein and kinetics in mucopolysaccharidosis type VI patients.

A sensitive and specific, monoclonal antibody-based immunoquantification assay has facilitated determination of the N-acetylgalactosamine-4-sulfatase (4-sulfatase) protein content in cultured fibroblasts from normal controls and mucopolysaccharidosis type VI (MPS VI) patients. The assay enabled the quantification of 4-sulfatase protein by using a panel of seven monoclonal antibodies and has shown that fibroblasts from 16 MPS VI patients contained less than or equal to 5% of the level determined for normal controls. Fibroblasts from the most severely affected patients contained the lowest levels of 4-sulfatase protein, usually with few epitopes detected, while fibroblasts from mildly affected patients had higher levels of 4-sulfatase protein, with all seven epitopes detected. The pattern of epitope expression is proposed to reflect the conformational changes in the 4-sulfatase protein that arise from different mutations in the 4-sulfatase gene. Immunoquantification in combination with a specific and highly sensitive 4-sulfated trisaccharide-based assay of enzyme activity in these MPS VI patient fibroblasts enabled the determination of residual 4-sulfatase catalytic efficiency (kcat/Km). The capacity of fibroblasts to degrade substrate (catalytic capacity) was calculated as the product of 4-sulfatase catalytic efficiency and the content of 4-sulfatase in fibroblasts. One patient, 2357, with no clinical signs of MPS VI but with reduced 4-sulfatase activity and protein (both 5% of normal) and dermatansulfaturia, had 5% of normal catalytic capacity. The other 15 MPS VI patient fibroblasts had 0%-1.4% of the catalytic capacity of fibroblasts from normal controls and were representative of the spectrum of MPS VI clinical phenotypes, from severe to mild.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1991

Human N-acetylgalactosamine-4-sulphatase: protein maturation and isolation of genomic clones.

N-Acetylgalactosamine-4-sulphatase (EC 3.1.6.1, G4S) is composed of a 57 kDa species in human liver that dissociates into 43 kDa and 8 kDa subunits under reducing conditions and, when deficient, causes the lysosomal storage disorder, mucopolysaccharidosis type VI. We isolated genomic clones containing the G4S first exon, including the leader peptide and the amino terminus of the 43 kDa polypeptide. Amino-terminal amino acid sequences of the 43 kDa and 8 kDa subunits indicated that the 8 kDa component is linked to the 43 kDa polypeptide by a single disulphide bond, does not contain the mannose-6-phosphate lysosomal targeting signal and is at the carboxyl terminus of G4S.

Amino Acid Sequence↗