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Biomedical subjects

J T Allen

Publications and source records attributed to J T Allen.

At least 37 records · Page 2Linked to original sources
PubMed1993

The investigation of UDPGlucose and UDPGalactose concentration in red blood cells of patients with classical galactosaemia.

UDPGlucose (UDPGlc) and UDPGalactose (UDPGal) are nucleotide sugars formed via the galactose metabolic pathway and are essential cofactors for the incorporation of galactose and glucose into complex glycoproteins and glycolipids. It has been proposed that in classical galactosaemia, where the enzyme galactose-1-phosphate uridyl transferase is deficient, the reaction product UDPGal is reduced leading to the long-term complications associated with the disease. We have measured the concentration of UDPGal and UDPGlc in red blood cells by high performance liquid chromatography (HPLC) in 16 children and 15 adult galactosaemics and compared the results with 30 and 27 control children and adults, respectively. The results indicate that UDPGal levels were found to be significantly reduced in galactosaemic patients and UDPGlc/UDPGal ratios significantly increased.

Adolescent↗
PubMed1993

Allosteric modulation of ligand binding to [3H](+)pentazocine-defined sigma recognition sites by phenytoin.

The allosteric modulation of sigma recognition sites by phenytoin (diphenylhydantoin) has been demonstrated by the ability of phenytoin to stimulate binding of various [3H] sigma ligands, as well as to slow dissociation from sigma sites and to shift sigma sites from a low- to a high-affinity state. Phenytoin stimulated the binding of the sigma 1- selective ligand [3H](+)pentazocine in a dose-dependent manner. Stimulation of binding at a final concentration of 250 microM phenytoin was associated with a decrease in the KD. The affinities of the sigma reference compounds caramiphen, dextromethorphan, dextrophan, (+)3-PPP and (+)SKF-10,047 were three- to eight-fold higher, while the affinities of benzetimide, BMY-14802, carbetapentane, DTG and haloperidol were unchanged in the presence of 250 microM phenytoin. The relative sensitivity of sigma compounds to allosteric modulation by phenytoin is not a property of all sigma ligands, and may provide an in vitro basis for distinguishing actions of sigma compounds and predicting sigma effects in vivo.

Allosteric Regulation↗
PubMed1991

Membrane transport of amino acid enantiomers in protoscoleces of Echinococcus granulosus (Cestoda).

Protoscoleces of Echinococcus granulosus absorb both L- and D-alanine. Concentration ratios exceed 1 with values for D-alanine exceeding those for the L-isomer, suggesting that both are absorbed by active mechanisms. Uptake of both isomers involves both diffusion and carrier-mediated components. Values for the diffusion component (Kd) for L- and D-alanine were 0.21 and 0.38 nmol mg-1 protein/1.5 min mM-1 respectively, and values for Kt, the transport constants, 0.17 mM and 0.21 mM respectively. Uptake of both isomers was inhibited competitively by a number of other amino acids.

Alanine↗
PubMed1991

Inherited metabolic diseases in the sudden infant death syndrome.

All sudden, unexpected infant deaths presenting during a two year period within a defined geographical area in Avon and north Somerset were investigated for inherited metabolic disease. Of 95 deaths, 88 were classified as cases of sudden infant death syndrome (SIDS). In addition to the normal postmortem investigations, samples of cerebrospinal fluid, urine, vitreous humour, and skin were collected for metabolic studies. No abnormal organic acid metabolites were found in the fluids from the 88 cases of SIDS. Fatty acid oxidation was assessed in skin fibroblasts from 70 cases of SIDS, but no examples of medium chain acyl CoA dehydrogenase (MCAD) deficiency were found. One case with abundant glycogen in the liver was subsequently diagnosed as having glycogen storage disease type 1c. These findings suggest that the incidence of MCAD deficiency and other metabolic diseases in SIDS is much lower than previously claimed.

Acyl-CoA Dehydrogenase↗
PubMed1990

Pharmacologic profile of NPC 168 (naltrexone phenyl oxime), a novel compound with activity at opioid receptors.

NPC 168 (naltrexone phenyl oxime) was synthesized as a novel opioid antagonist and evaluated in several in vitro and in vivo assays. NPC 168 inhibited binding to the mu, delta and kappa subtypes of the opioid receptor with nanomolar potencies. The potency of NPC 168 to antagonize morphine-induced analgesia was slightly less than that of naltrexone and nalmefene following either intraperitoneal (ED50 = 0.07 mg/kg) or oral (ED50 = 0.82 mg/kg) administration. The duration of action of NPC 168 was approximately 8 hr following subcutaneous administration, compared to 4 hr for nalmefene, to antagonize oxymorphonazine-induced analgesia. The long duration of action of NPC 168 was substantiated by pharmacokinetic data that demonstrated rapid uptake and slow clearance of NPC 168 from brain. NPC 168 (5, 10 and 20 mg/kg) also inhibited cumulative 6-hr food intake in rats that were deprived of food for 24 hr, but chronic administration of this compound to rats over a three-week period resulted in a marginal reduction in cumulative body weight gain. NPC 168 at doses of up to 10 mg/kg did not produce a conditioned taste aversion. However, NPC 168 was slightly more toxic than either naltrexone or nalmefene when administered parenterally, and as toxic as nalmefene when administered by the oral route. These data demonstrate that NPC 168 is a novel opioid antagonist with a longer duration of action than either naltrexone or nalmefene.

Animals↗
PubMed1989

Prenatal diagnosis of disorders of galactose metabolism.

Of three clinically significant galactose disorders, there is only a real need and experience of prenatal diagnosis in classical galactosaemia. Prenatal diagnosis for this disorder may be carried out by galactose-1-phosphate uridyl transferase assay in cultured amniotic fluid cells or in chorionic villus biopsies and by galactitol estimation in amniotic fluid supernatant. Although the long-term outcome of patients treated on a galactose-restricted diet is recognized to be unsatisfactory, prenatal diagnosis is only rarely performed with a view to terminating the affected pregnancy.

Female↗
PubMed1984

An isolated rat liver model for the evaluation of thermal techniques to quantify perfusion.

An isolated, thermally regulated, perfused rat liver model system is presented. The model was developed to evaluate thermal methods to quantify perfusion in small volumes of tissue. The surgically isolated rat liver is perfused with an isothermal oxygenated Krebs-Ringer bicarbonate buffer solution via the cannulated portal vein. A constant-pressure head variable-resistance scheme is utilized to control the total flow to the liver. Total flow is quantified by hepatic vein collection. The spatial distribution of perfusion within the liver is determined using two independent methods. In the first method, radio-labelled microspheres are injected into the portal vein, and the regional flow distribution is determined from the relative radioactivity of each section of tissue. In the second method, the tissue is thermally perturbed, and the time constant of the tissue temperature recovery is measured. The regional distribution is determined from the relative time constants of each section of tissue. Both methods require the measurement of total liver flow to determine the absolute perfusion at each point. Results obtained by the two methods were well correlated (0.973). The rat liver system offers a stable, controllable, and measurable perfusion model for the evaluation of new perfusion measurement techniques.

Animals↗
PubMed1984

The simultaneous measurement of thermal conductivity, thermal diffusivity, and perfusion in small volumes of tissue.

An improved technique is presented for the "in-vivo" determination of thermal conductivity, thermal diffusivity, and perfusion using a self-heated spherical thermistor probe. In the presence of flow, solution of the time-dependent, probe-tissue coupled thermal model allows the measurement of "effective" thermal conductivity and "effective" thermal diffusivity, which represent the thermal properties of the perfused tissue. Perfusion can be quantified from both "effective" thermal properties. In the presence of flow, it has been shown that the transient power responses does not follow t-1/2 as has been previously assumed. An isolated rat liver preparation has been developed validate the measurement technique. Radioactive microspheres are used to determine the true perfusion from the total collected hepatic vein flow. Experimental data demonstrates the ability to quantify perfusion in small volumes of tissue.

Animals↗
PubMed1983

Clinical trials with canine distemper vaccines in exotic carnivores.

Two types of killed canine distemper virus (CDV) vaccine and a modified-live CDV vaccine were clinically evaluated in four species of exotic carnivores. In 16 trials in which 13 red pandas (Ailurus fulgens) were given the killed vaccine, only 1 animal had a virus-neutralization titer that exceeded 1:100. A red panda given modified-live CDV vaccine deemed safe for gray foxes and ferrets died of bacterial pneumonia 16 days later. There was no pathologic evidence of canine distemper in that panda. The same modified-live vaccine proved to be immunogenic and safe in 12 bush dogs (Speothos venaticus), 5 maned wolves (Chrysocyon brachyurus), and 3 fennec foxes (Fennecus zerda) in which virus-neutralization titers often exceeded 1:512 and persisted for several months after vaccination.

Animals↗
PubMed1983

Toxicity of a vitamin D steroid to laying hens.

Two experiments were conducted with 56-week-old or 104-week-old Leghorn hens to determine if feeding vitamin D steroids in excess of requirement levels caused any marked affects on eggshell quality. In the first experiment caged hens had reduced feed consumption, egg shell quality, and egg production as early as 6 weeks after initially consuming a basal diet supplemented with 6.8 micrograms 1 alpha-hydroxycholecalciferol (1 alpha-OH-D3)/kg. The second experiment confirmed the previous results and showed that extensive weight loss occurred with continued feeding of 10 or 15 micrograms 1 alpha-OH-D3/kg diet. No adverse affects were observed in either experiment when the level of 1 alpha-OH-D3 supplementation was 5.0 micrograms/kg diet or less. No toxic effects were observed when the hormone precursor 25-OH-D3 was supplemented to diets at 6 or 12 micrograms/kg. It is suggested that the pathological effects observed are related to the potent calcium homeostatic properties of 1 alpha-OH-D3 that at elevated levels may cause aberrations in circulating calcium.

Animals↗
PubMed1981

Hypothenar hammer syndrome.

The hypothenar hammer syndrome is a distinct entity of digital ischemia caused by the repetitive compression of the distal ulnar artery against the hook of the hamate. Definite diagnosis should most likely rely on selective arteriography. Primary resection with anastomosis and cervicodorsal sympathectomy have both been proposed as treatment. Early recognition of the syndrome is important.

Brachial Artery↗
PubMed1980

Comparison of amino acid concentrations in amniotic fluid from fetal neural tube defective and normal pregnancies.

Amniotic fluid collected during the second trimester of pregnancy was analysed for amino acid and protein concentrations. The composition of amniotic fluid from pregnancies complicated by fetal anencephaly or spina bifida was investigated for variance from normal amniotic fluid. In spina bifida the hydroxy amino acids were raised whilst the branched chain amino acids were lower in concentration. In anencephaly the total amino acid and the protein concentrations were raised, and a wider range of concentrations for most of the amino acids was apparent.

Amino Acids↗
PubMed1980

Transfer coefficients of radionuclides secreted in milk of dairy cows.

This study simulated experimentally the transfer of radionuclides to milk of dairy cows on a worst-case situation using various radionuclides known to emanate from nuclear power stations and which have been detected on particulates. Two lactating Holstein cows were administered orally one gelatin capsule containing 10 radionuclides in water-soluble form per day for 14 consecutive days. Milk samples were collected and aliquots analyzed in a germanium lithium-drifted detector coupled to a 2048-multichannel gamma-ray analyzer to measure small amounts of complex mixtures of radionuclides. The transfer coefficients of the radionuclides were calculated when their secretion in milk reached or approached a plateau of concentration. The radionuclides and their transfer coefficients to milk were: chromium51 less than .01%; manganese54 .033 +/- .005%; cobalt60 .01 +/- .002%; iron59 .0048 +/- .002%; zinc65 .31 +/- .07%; selenium75 .29 +/- .1%; antimony125 .011 +/- .003%; iodine131 .88 +/- .05%; and cesium137 .79 +/- .08%.

Animals↗