PubMed HealthSearch

Biomedical subjects

R J Davies

Publications and source records attributed to R J Davies.

At least 19 recordsLinked to original sources

The interaction of 2,6,8-triaminopurine with poly(uridylic acid).

Equilibrium dialysis measurements have shown that poly(uridylic acid) binds 2,6,8-triaminopurine in a strongly cooperative manner to form a stable 2 : 1 complex at pH 7.8, 0.15 M Na+. The thermal dissociation of the complex has been characterized by ultraviolet absorbance versus temperature profiles. From the variation of Tm with the concentration of uncomplexed triaminopurine at this temperature, the partial molar enthalpy and entropy of formation of the complex have been calculated as --87 (+/- 2) kJ/mol of triaminopurine and --236 (+/- 7) J/mol of triaminopurine per K, respectively. In terms of Tm, the complex is approximately 4 degrees C more stable than the corresponding 2 : 1 complex of poly(U) with 2-aminoadenine. This stabilization is attributed to the existence of an additional hydrogen-bonding interaction, in the poly(U)-triaminopurine complex, between the 8-amino group of 2,6,8-triaminopurine and O(2) of the uracil moiety which is base paired with it in Hoogsteen fashion.

Adenine

The complexing of guanine nucleosides by poly(inosinic acid).

Under conditions where it is single-stranded (pH 7.0, 0.05 M Na+), poly(inosinic acid) complexes guanosine and 2'-deoxyguanosine in a strongly cooperative process that ultimately results in gel formation. The binding isotherm for formation of the poly(I).deoxyguanosine complex at 3.5 degrees C shows that it contains approximately one molecule of deoxyguanosine bound per IMP residue of the poly(I). This is compatible with the complex having a structure similar to that of the four-stranded secondary structure of poly(I) in which two of the poly(I) strands are replaced by helical arrays of deoxyguanosine molecules. The complex is laevorotatory at wavelengths longer than 300 nm. Optical rotation and ultraviolet absorbance versus temperature profiles show that on thermal dissociation the complex undergoes a co-operative helix-coil transition with Tm in the range 10--20 degrees C.

Deoxyguanosine

The mass spectra of 8-azapurines.

The mass spectra of 8-azaadenine, 8-azahypoxanthine, 2,6-diamino-8-azapurine, 8-azaxanthine and 8-azaguanine are all characterized by intense molecular ion peaks. Fragmentation pathways are advanced to account for the other ions observed in the mass spectra and are supported by metastable transitions, accurate mass measurements and deuterium labelling studies. 8-azaadenine and 8-azahypoxanthine fragment initially by elimination of nitrogen from the molecular ion, but this is a minor process with the other compounds. In many respects the electron impact induced fragmentation of the 8-azapurines is analogous to that of the corresponding purine derivatives.

Aza Compounds

The in vitro effect of toluene diisocyanate on lymphocyte cyclic adenosine monophosphate production by isoproterenol, prostaglandin, and histamine: a possible mode of action.

Toluene diisocyanate (TDI) significantly inhibits the rise in intracellular cyclic 3',5'-adenosine monophosphate (cAMP) that follows in vitro incubation of human lymphocytes with 6.7 x 10(-3) M isoproterenol and 1 x 10(-6) M prostagladin E1 (p less than 0.05). TDI has no significant effect on th production of lymphocyte cAMP following incubation with histamine (1 x 10(-3) M). The inhibitory action of TDI is greatest at a concentration of 3.3 x 10(-4) M and diminishes as the TDI concentration is increased or decreased. TDI also caused four- to fivefold stimulation of lymphocyte cAMP, an effect that is maximal at 1 x 10(-3) M, a concentration which has no significant inhibitory effect on stimulation of cAMP by isoproterenol or prostagladin E1. Conversely, 3.3 x 10(-4) M TDI, which inhibits cAMP production by isoproterenol and prostaglandin, has little stimulatory effect itself on cAMP production. This evidence suggests that TDI might induce obstructive airways disease through pharmacologic mechanisms and that TDI may be acting as a partial agonist.

Asthma

Electrical assessment of functional lactase activity in conscious man.

Using an electrical technique for measuring transjejunal potential differences (PDs) in conscious man, we have estimated the electrogenic absorption of the hexoses liberated by hydrolysis of lactose which was infused into the jejunum of one normal control and 21 patients with diarrhoea. The results were compared with jejunal lactase levels determined from biopsy specimens taken from the recording site immediately after infusion. The PD evoked by 100 mM lactose was very significantly lower in patients with lactase levels below 4 units (lactase deficient) compared with subjects with normal lactase levels. There was also a significant correlation (r = 0.87, P less than 0.005) between the magnitude of the lactose potential (expressed as the ratio of the maximum glucose transfer potential) and the mucosal lactase level in the hypolactasic subjects but not in patients with normal lactase levels. Thus, in the subjects with lactase deficiency, the electrogenic transfer of hexose is clearly limited by the rate of lactose hydrolysis. Unlike other assessments of functional lactase activity, the electrical test provides a specific index of jejunal function and, moreover, can be adapted to investigate the possible disorders of small intestinal motility and secretion associated with hypolactasia.

Adolescent

Progressive airway obliteration in adults and its association with rheumatoid disease.

Six patients with rapidly progressive airway obliteration in the absence of chronic bronchitis or emphysema are reported. Because this pattern of lung disease is very uncommon and five of the six patients had classical rheumatoid arthritis an association between the two diseases is suggested. The patients presented with rapidly developing breathlessness, and râles and a high-pitched mid-inspiratory squeak were heard over the lung fields. Chest radiographs showed distended lungs but were otherwise normal. Tests of lung fuction showed airflow obstruction, most marked at low lung volumes, with air trapping. The carbon monoxide gas transfer coefficient, maximum static recoil pressure and static compliance were normal. In spite of treatment with antibiotics, bronchodilators and corticosteroids, five died in respiratory failure five to 18 months after first becoming breathless. Post-mortem examination in four patients showed an obliterative bronchiolitis but no mucous gland hypertrophy or significant emphysema.

Adult

Atopic disorders and adult coeliac disease.

A history of asthma, hay fever, and flexural eczema was significantly more common in patients with adult coeliac disease (A.C.D.) than in normal controls. Autoantibodies were also more common in A.C.D. First-degree relatives of A.C.D. patients were more likely than controls to have atopic disorders. A deficiency of local mucosal immunity due to abnormal IgA responses may underly this association between A.C.D. and atopy.

Adult

Bakers' asthma.

Bronchial provocation tests by "occupational" exposure to flour provoked dual asthmatic reactions accompanied by rhinitis in two atopic bakers engaged in the manufacture of bread and pies. Ingestion tests with uncooked flour produced no reactions. Skin prick tests with aqueous extracts of flour produced positive immediate reactions in both bakers, and negative reactions in nine of ten atopic asthmatic control subjects with no occupational exposure to flour. Intracutaneous tests, performed in one precipitin negative baker, gave dual responses. Precipitating antibodies to an aqueous extract of flour were found in the unconcentrated serum of the other baker, and not in ten control subjects.

Adult

Bacterial precipitins and their immunoglobulin class in atopic asthma, non-atopic asthma, and chronic bronchitis.

In a study of groups of patients with atopic (extrinsic) asthma, non-atopic (intrinsic) asthma, and chronic bronchitis, no difference could be detected in the numbers having precipitating antibodies against species specific antigens from Staphylococcus aureus or Streptococcus pneumoniae compared to suitably matched control subjects. Precipitating antibodies against species specific antigens from Haemophilus influenzae, demonstrated in this investigation by double diffusion in agar gel, were found much more frequently in patients with chronic mucopurulent or obstructive bronchitis (50%) than in either asthmatic subjects (6%) or normal controls (6%) (P = less than 0.0005). While the precipitating antibody demonstrated in these patients against the extracts of Str. pneumoniae and Staph. aureus was in the IgG class alone, IgM and IgA antibody were detected against the species specific but not the non-species specific antigens of H. influenzae. These results underline the importance of H. influenzae as an infecting agent in chronic bronchitis and suggest that the finding of precipitins against the species specific H1 and H2 antigens of this bacterium denotes infection either concurrently or in the recent past. There is no evidence to suggest from this study that infection with Staph. aureus, Str. pneumoniae or H. influenzae is any more common in asthmatics as a group compared to controls or between patients with the non-atopic (intrinsic) and atopic (extrinsic) form of the disease.

Adolescent