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Biomedical subjects

H Jones

Publications and source records attributed to H Jones.

At least 163 records · Page 9Linked to original sources
PubMed1987

REV 2871 (CHBZ): a potent antiallergic agent with a novel mechanism of action. I. Activity profile as an inhibitor of mediator release.

REV 2871 (CHBZ) and its putative metabolite REV 3579-Z (also designated in the literature as RHC 3579-Z) were shown to be potent and orally effective inhibitors of passive cutaneous anaphylaxis (PCA) in the rat (ED50 = 12 mg/kg). The activity profiles of CHBZ, REV 3579-Z and disodium cromoglycate (DSCG) were compared as inhibitors of histamine release (HR) in vitro from rat mast cells, human basophils, and guinea pig lung slices. CHBZ was a potent inhibitor of both immunologic and non-immunologic HR (I50 2-20 microM from rat mast cells). The activity profile of CHBZ as an inhibitor of HR from rat mast cells differed from that of DSCG and REV 3579-Z in the following respects: increasing inhibition of HR with increasing preincubation time; irreversibility of the inhibition; lack of tachyphylaxis and cross-tachyphylaxis to DSCG; potentiation of the inhibition of antigen-induced release of histamine (AIR) by DSCG; and inhibition of HR induced by dextran + phosphatidyl serine, compound 48/80, ionophore A23187 and platelet activating factor (PAF). In the human basophil model, CHBZ was: a potent inhibitor (I50 = 25 microM) of anti-IgE-induced release (AbIR), whereas DSCG and REV 3579-Z had no effect on AbIR; more potent as an inhibitor of AbIR than ionophore-induced release, whereas the reverse was true for proxicromil; an inhibitor of PAF-induced release, whereas proximcromil stimulated it; and potentiative with proxicromil for inhibition of AbIR. In the guinea pig lung slice model, CHBZ inhibited AIR (I50 = 800 microM) whereas DSCG and REV 3579-Z did not (I50 greater than 300 microM). We conclude that CHBZ is an orally effective antiallergic agent whose mechanism of action as an inhibitor of mediator release is different from DSCG and proxicromil.

Animals↗
PubMed1987

The neuroleptic malignant syndrome.

A fatal case of the neuroleptic malignant syndrome in a young lady with paranoid schizophrenia. Cardiovascular collapse was due to profound hyperkalaemia secondary to rhabdomyolysis. We advise immediate estimation of serum potassium in all suspected cases.

Adult↗
PubMed1987

Laryngeal paraganglioma.

Paraganglioma is an uncommon tumor of the larynx. The diagnosis and management of laryngeal paragangliomas remain problematic for the clinician. A recent experience with this uncommon tumor provides a forum for a discussion of laryngeal paraganglioma.

Female↗
PubMed1986

Angiotensin-converting enzyme inhibitors: new orally active 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones possessing antihypertensive activity.

The preparation of a series of 1,4-thiazepine-2,5-diones, 1,4-thiazine-2,5-diones, and 1,4-benzothiazepine-2,5-diones and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) in vitro and in vivo were examined. These compounds are assumed to act as prodrugs since they undergo rapid ring-opening reactions to give the corresponding biologically active free SH compounds when incubated with rat plasma or when treated with aqueous 0.1 N HCl or phosphate buffer (pH 7.4). The thiazepines 23-25 and 30 are potent inhibitors of ACE when administered po to rats and are comparable in potency to captopril (1). The most active thiazines in rats, po, were 42 and 45. Of the benzothiazepines studied, 22a was the most active in inhibiting ACE in the conscious normotensive rat, ID50 = 0.15 mg/kg, po. The acute antihypertensive effects of oral administration of a number of these compounds on mean arterial pressure and heart rate were studied in spontaneously hypertensive rats (SHR) maintained on a sodium-deficient diet.

Administration, Oral↗
PubMed1986

Effect of dietary protein intake on albumin homeostasis in nephrotic patients.

Animals with experimental renal disease maintained on diets restricted in protein develop less severe renal lesions and less proteinuria than do animals maintained on a normal or high protein diet. To determine whether restriction of dietary protein will reduce urinary albumin excretion in patients with established nephrosis and whether such dietary restriction will result in decreased albumin pools, we performed paired studies on nine nephrotic patients. They were fed sequential diets with a protein content of 1.6 and then 0.8 g/kg body wt, each for 2 weeks. Caloric intake remained constant at 35 Kcal/kg. In six patients the high protein diet was fed first; in three the order of dietary administration was reversed. Urinary albumin excretion was reduced on the low protein diet in all patients regardless of dietary order. Both the renal clearance of albumin and the fractional renal albumin clearance were reduced significantly on the low protein diet. The rate of albumin synthesis was greater on the high protein diet, but so was the rate of albuminuria. Despite the higher rate of albumin synthesis during the period of high protein intake, serum albumin concentration and plasma albumin mass were both less than during the period of low protein intake. Thus, dietary protein restriction in patients with established nephrosis results in decreased urinary albumin excretion in excess of any reduction in creatinine clearance. Total albumin mass is preserved and plasma albumin mass is actually increased during the period of dietary protein restriction. Protein restriction may be feasible in nephrotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Peripheral counter-urbanization: findings from an integration of census and survey data in Northern Scotland.

"This paper systematically relates local survey data to national census data in an investigation of one peripheral form of counter-urbanization now regarded as widely present in developed countries. The recent growth and spatial distribution of long-distance English migration to the Highlands and Islands of Scotland is described, and then 'explained' through multivariate analysis of cross-sectional data and through the stated motivations and characteristics of surveyed migrants to some of the remoter, rural parts of the region. The study reveals the importance of environmental and quality of life considerations." (summary in FRE, GER)

Behavior↗
PubMed1986

Diabetes and autonomic neuropathy: an immunological association?

Lymphocytic infiltration of autonomic ganglia found at autopsy and a strong clinical association with iritis suggests that diabetic autonomic neuropathy might have an immunological basis. We measured levels of circulating immune complexes, complement (C3, C4), complement breakdown products (C3d), and insulin antibodies in diabetics with autonomic neuropathy and a history of iritis (n = 17), compared to diabetics of similar age and duration with autonomic neuropathy but no history of iritis (n = 20), and with uncomplicated insulin-dependent diabetics (n = 23), together with normal controls (n = 26). We found higher levels of circulating immune complexes in patients with autonomic neuropathy (irrespective of iritis) compared to normal controls, and differences in C3d levels suggesting complement activation. C4 levels were unexpectedly normal in the diabetics with autonomic neuropathy, in contrast to the uncomplicated insulin-dependent diabetic controls. Insulin antibody levels showed no difference between the three groups of diabetics. These findings suggest that immunological mechanisms may be implicated in the aetiology of diabetic autonomic neuropathy and that further studies are indicated.

Adult↗
PubMed1986

The influence of vagotomy on the respiratory effects of injected phenyl diguanide in anaesthetized rabbits.

The effects of intravenous injections of phenyl diguanide (PDG) on pattern of breathing were studied before, immediately after, and some time after bilateral cervical vagotomy in anaesthetized rabbits. The characteristic tachypnoea observed in the intact animals could not be produced for several minutes after bilateral vagotomy, but after 15 min could be elicited again. This sequence of events was not essentially modified by cutting the glossopharyngeal nerves nor by injection of local anaesthetic into the pericardial sac. We suggest that the respiratory effects of PDG in the rabbit, previously considered to originate mainly from peripheral receptors, including those of the lungs, has a considerable central component which has previously been obscured by the short-term effects of vagotomy.

Anesthesia, General↗
PubMed1986

Repetition of accidents in young children.

Data from the Oxford Record Linkage Study have been used to describe rates of accident repetition for children aged under 5 years. As reflected by hospital admissions, accident rates for children who have already had one accident were approximately twice those of children of the same age and sex who had previously been accident free.

Accident Proneness↗
PubMed1986

Pharmacist involvement in the Concord Hospital clinical review programme.

Drug audits have continued at Concord Hospital and the Pharmacy Department now contributes to the Clinical Review Programme on a frequent basis. Drug audits are descriptive observational studies which provide information as a tool for discussion, and the opportunity to review prescribing habits. From this very simple beginning the pharmacy has progressed to a series of more complex criteria based audits.

Adult↗
PubMed1985

Histamine-induced excitation of spontaneously active medullary neurones in the rat brain is mediated by H2-receptors. A microiontophoretic study using H1- and H2-agonists and antagonists.

The effects of histamine, applied by microiontophoresis onto spontaneously-active medullary neurones were investigated in the rat. Histamine caused current-dependent excitation of these neurones, an action that is at variance with previous studies in the cat. The nature of the receptor mediating these effects was examined using a number of agonists with differing potencies at peripheral H1- and H2-receptors. The precursor of histamine, L-histidine and the metabolite, N-telemethylhistamine did not mimic the effects of histamine while the H2-agonist, 4-methylhistamine caused similar but weaker excitation. The extent of excitations produced by the H1-agonists, 2-pyridylethylamine, 2-methylhistamine and 2-thiazolylethylamine could be related to their activity at H2-receptors. Metiamide was ineffective in antagonising responses to histamine and related agonists as was mepyramine. The H2-antagonist ranitidine, however, proved a good antagonist of responses to histamine and the H1- and H2-agonists, despite an unrelated excitatory action which may be linked to inhibition of cholinesterase. It is concluded that the excitatory effects of microiontophoretically-applied histamine and the agonists on medullary neurones in the rat is probably a result of activation of H2-receptors.

Animals↗
PubMed1985

Synthesis and antiallergic activities of 1,3-oxazolo[4,5-h]quinolines.

A series of new 1,3-oxazolo[4,5-h]quinolines has been prepared. These compounds were tested as inhibitors of antigen-induced release of histamine (AIR) in vitro from rat peritoneal mast cells (RMC) and as inhibitors of IgE-mediated passive cutaneous anaphylaxis in the rat (PCA). After several modifications of the original lead, the most potent compound of the series was determined to be 5-chloro-1,3-oxazolo[4,5-h]quinoline-2-carboxylic acid methyl ester (4a). It has an IC50 of 0.3 microM in the RMC assay and an ED50 (intraperitoneal) of 0.1 mg/kg in the PCA test, which is 10 times and 60 times more potent than disodium cromoglycate (DSCG), respectively. Of greater importance, it is orally active (ED50 = 0.5 mg/kg) as an inhibitor of the PCA test.

Animals↗
PubMed1985

[1,4]Benzoxazine-2,3-diones as antiallergic agents.

The synthesis of a series of [1,4]benzoxazine-2,3-diones and a new class of compounds, benzobisoxazinetetrones, is described. These compounds were evaluated for their effect in the rat mast cell (RMC) test passively sensitized in vitro with rat antiovalbumin serum and for their effect in inhibitory passive cutaneous anaphylaxis (PCA) in the rat. Some of these compounds are of the same potency level as disodium cromglycate in the RMC test and some are effective orally in PCA.

Animals↗
PubMed1985

Angiotensin-converting enzyme inhibitors. New orally active antihypertensive (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives.

A variety of N-substituted (mercaptoalkanoyl)- and [(acylthio)alkanoyl]glycine derivatives was synthesized and their ability in inhibiting the activity of angiotensin-converting enzyme (ACE) was examined in vitro and in vivo. The acylthio derivatives prepared are assumed to act as prodrugs since they are much less active than the corresponding free SH compounds in vitro and can be expected to act in vivo only after conversion to the free sulfhydryl compounds. A number of these compounds are potent ACE inhibitors that lowered blood pressure in Na-deficient, conscious spontaneously hypertensive rats (SHR), a high renin model. One of the most active members of the series was (S)-N-cyclopentyl-N-[3-[(2,2-dimethyl-1-oxopropyl)thio]-2-methyl-1 -oxopropyl]glycine (REV 3659-(S), pivopril). Structure-activity relationships are discussed.

Administration, Oral↗
PubMed1985

Angiotensin converting enzyme inhibitors. (Mercaptoaroyl)amino acids.

A series of (mercaptoaroyl)amino acids and related compounds was synthesized and tested for ability to inhibit angiotensin converting enzyme (ACE). The most active compound was N-(3-chloro-2-mercaptobenzoyl)-N-cyclopentylglycine, having an in vitro I50 = 0.28 microM. Substitution of the aromatic 3-position by small polar groups enhanced ACE inhibitory activity, whereas bulky groups diminished it. Alteration of the beta relationship between the mercaptan and amide carbonyl or masking of the thiol by acylation reduced activity. Replacement of the thiol by nitro, hydroxy, or carboxy gave compounds lacking ACE inhibitory activity.

Amino Acids↗