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Biomedical subjects

J F Collins

Publications and source records attributed to J F Collins.

At least 145 records · Page 8Linked to original sources
PubMed1984

Variability in lung collagen amounts after prolonged support of acute respiratory failure.

In order to identify correlates of fibrosis in acute respiratory failure, autopsies were performed on 16 patients who died after an episode of more than two weeks' duration, and the left lower lung lobe was obtained for biochemical measurements. The average amount of lobar collagen in one group of patients was nearly three times that in another group. Both groups had been mechanically ventilated for the same length of time and could not be distinguished by primary diagnosis. However, the group with increased collagen had received nearly twice the level of positive end-expiratory pressure and had received an inspired oxygen fraction of more than 0.4 for twice as long as the normal collagen group. Examination of complications and other aspects of therapy did not reveal clearcut differences between the groups. Examination of the same clinical data in a group of patients who had survived an episode of similar duration indicated that survivors differed from the high collagen group in inspired oxygen levels.

Adolescent↗
PubMed1984

Clinical evaluation of the effectiveness of three dentifrices in relieving dentin sensitivity.

It has been reported that sensitive dentin is present in no less than one of seven normal patients with a higher incidence among postperiodontal therapy patients. Numerous agents have been developed to relieve this sensitivity without any being universally acceptable. Two new dentifrices, Protect and Protect with fluoride were compared clinically with Sensodyne to determine the relative ability of these three products to relieve both thermal and tactile sensitivity in sensitive dentin. Double blind analyses were completed and results compared using appropriate statistical tests for each hypothesis tested. The three dentifrices relieved both tactile and thermal sensitivity, but there was no statistical difference at 8 weeks between the three agents. There was a difference in the time it took the dentifrices to achieve a statistically significant reduction in dentin sensitivity.

Adult↗
PubMed1984

Elastolytic activity of peripheral blood monocytes.

Human peripheral blood monocytes have been purified by Ficoll-Hypaque density gradient centrifugation and adherence to plastic dishes, and assayed for elastolytic activity using insoluble [3H]elastin. Approximately 5-10 micrograms of elastin are solubilized at pH 7.5 per mg protein per h. The specific activity in monocytes varies between 3 and 15% of that of neutrophils obtained at the same time from the same subjects. The enzymatic activity derives principally from monocytes. Lymphocytes purified by Sephadex G-10 gel filtration chromatography exhibit only trace elastolytic activity, while neutrophils comprise 1% or less of the cell population. Monocyte elastolytic activity is inhibited by alpha-1-antitrypsin and Succinyl-Ala-Ala-Pro-Val-chloromethylketone indicating that it is a serine-type protease. When extracts of monocytes are analyzed by gel filtration, the elastolytic activity appears in large molecular weight forms; however, these forms are not observed when extracts of monocyte lysosomes are analyzed. Such variation in forms is also seen with neutrophil extracts. Monocytes are a source of elastolytic activity for various physiologic and pathologic actions in the lung and other organs.

Cell Fractionation↗
PubMed1983

The kindled amygdala model of epilepsy: anticonvulsant action of amino acid antagonists.

The amygdalas of rats were stimulated daily to produce kindled epilepsy. Superfusion of the ipsilateral ventricle allowed collection of amino acids before, during and after stimulation. At the stage where stimulation evoked full seizures there was a correlated increase in the extent of glutamate release. Other amino acids, including aspartate, showed no significant changes at this time. Aspartate, threonine and serine showed smaller responses not significantly different from those seen at the pre-kindled stage. Antagonists of excitatory amino acids (omega-phosphono-alpha-amino dicarboxylic acids) effectively antagonized both the behavioral and electrical components of the kindled seizures.

2-Amino-5-phosphonovalerate↗
PubMed1983

Antiepileptic action of excitatory amino acid antagonists in the photosensitive baboon, Papio papio.

Antagonists of excitation induced by dicarboxylic amino acids have been evaluated for acute anticonvulsant activity in baboons, Papio papio, with photosensitive epilepsy. 2-Amino-7-phosphonoheptanoic acid, 1 mmol/kg, i.v., abolishes myoclonic responses for 5 h. Less prolonged protection is seen after cis-2,3-piperidine-dicarboxylic acid, 1-3.3 mmol/kg; 2-amino-5-phosphonovaleric acid, 1-3.3 mmol/kg; or glutamic acid diethyl ester, 1-3.3 mmol/kg. Toxic side-effects are prominent after the latter two compounds. Antagonists of excitation due to N-methyl-D-aspartate possess acute anticonvulsant activity in a wider range of models epilepsy.

2-Amino-5-phosphonovalerate↗
PubMed1983

Uptake of a novel anticonvulsant compound, 2-amino-7-phosphono-[4,5-3H]heptanoic acid, into mouse brain.

The time course of radioactivity in plasma, liver and brain is described following the intraperitoneal injection of 2-amino-7-phosphono-[4,5-3H]heptanoic acid in mice. Using high performance liquid chromatography of dansylated extracts of mouse brain the radioactivity attributable to 2-amino-7-phosphono-[4,5-3H]heptanoic acid has been determined at 0.25-180 min after injection. The time course, with a peak concentration at 30 min, declining markedly between 90 and 180 min, corresponds to the anticonvulsant action.

2-Amino-5-phosphonovalerate↗
PubMed1983

Analogue interactions with the brain receptor labeled by [3H]kainic acid.

The kinetics of interaction of kainic acid analogues and reputed antagonists of acidic excitatory amino acids with a specific binding site for [3H]alpha-kainic acid were examined in washed cerebellar membranes incubated at 4 degrees C. The avidity of both L-glutamate (1.5 microM) and quisqualate (0.6 microM) suggests that proper orientation of the two carboxyls in the amino group is essential for binding to one component of the receptor. The high affinity of domoate, alpha-kainate and alpha-keto-kainate as compared to the low affinity of dihydrokainate and alpha-allo-kainate indicate that a pi electron group with appropriate cis-planar orientation versus the C2-carboxyl group is essential for high affinity binding to the receptor. These studies provide additional evidence that the recognition site labeled by [3H]kainic acid represents the receptor mediating its neurophysiologic and neurotoxic effects.

Animals↗
PubMed1983

On the excitotoxic properties of quinolinic acid, 2,3-piperidine dicarboxylic acids and structurally related compounds.

To obtain information about the receptors which mediate the neurotoxic actions of quinolinic acid, a series of pyridine dicarboxylates and piperidine dicarboxylates and structurally related compounds were tested for their neurotoxic effects following intrastriatal or intrahippocampal infusion in the rat, and for their activity in assays of binding and uptake sites for acidic amino acids. Of the compounds tested, only cis- and trans-2,3-piperidine dicarboxylates and quinolinic acid showed pronounced neurotoxic effects. At 600 nmol, 2,6- and 3,4-pyridine dicarboxylates were weakly active and the remaining compounds were inactive in both brain regions. After injection into the striatum of the adult rat, trans-2,3-piperidine dicarboxylate, quinolinic acid and cis-2,3-piperidine dicarboxylate caused axon-sparing neuronal degeneration as assessed by light microscopic and neurochemical methods, the threshold doses being 12, 24 and 120 nmol, respectively. In the striatum of the 7-day old rat, 30 nmol quinolinic acid or 600 nmol cis-2,3-piperidine dicarboxylate were inactive. Small doses of cis-2,3-piperidine dicarboxylate (60 nmol) and quinolinic acid (30 nmol) injected into the adult rat hippocampus resulted in a preferential loss of pyramidal neurons. In larger doses granule cells also degenerated. In contrast, trans-2,3-piperidine dicarboxylate was equally toxic to hippocampal neurons, regardless of the dose used. No "distant" neuronal damage was observed after the intracerebral application of any test compound. Equimolar amounts of (-)-2-amino-7-phosphonoheptanoic acid completely blocked the neurotoxic effects of quinolinic acid, cis- and trans-2,3-piperidine dicarboxylate after injection into the striatum or hippocampus. None of the analogs tested were good inhibitors of Cl--dependent or independent binding of L-[3H]glutamate, [3H]kainate or high-affinity, Na+-dependent uptake of L-glutamate in striatal or hippocampal tissue at 1 mM. The results indicate that the receptors mediating the neurotoxic effects of these compounds have strict structural requirements for activation. Whereas the excitotoxic characteristics of trans-2,3-piperidine dicarboxylate suggest a direct action on N-methyl-D-aspartate receptors, the properties of quinolinic acid and cis-2,3-piperidine dicarboxylate are far more complex and make categorization of their receptor-interactions difficult. Indirect mechanisms may account for the excitotoxicity of quinolinic acid and cis-2,3-piperidine dicarboxylate.

Animals↗
PubMed1983

Characterization of the binding of DL-[3H]-2-amino-4-phosphonobutyrate to L-glutamate-sensitive sites on rat brain synaptic membranes.

The binding of DL-[3,4-3H] 2-amino-4-phosphonobutyric acid DL[3H]-APB to rat whole brain synaptic membranes was investigated. Binding was linear with membrane protein concentration, and optimal at physiological pH and temperature. The association rate was rapid, achieving equilibrium within 10 min. Prolonged incubations (greater than 20 min) revealed additional sites, which apparently possessed identical binding characteristics to those detected with 10 min incubations. Binding of DL-[3H]-APB was enriched in synaptic membrane fractions, and assessment of the regional distribution, indicated greatest binding in those areas with a rich glutamatergic innervation. The binding of DL-[3H]-APB in HEPES-KOH buffer exhibited an absolute requirement for Cl-. The addition of Ca2+ resulted in a further enhancement of binding. Saturation analysis revealed the presence of specific glutamate-sensitive DL-[3H]-APB binding sites, with a KD = 1.26 microM and Bmax = 12.08 pmol mg-1 protein. A Hill plot revealed a slope slightly greater than unity, which could possibly be a reflection of a contribution to binding of a further site which is relatively insensitive to glutamate. Analysis of 60 min incubation data indicated an approximately 3 fold increase in the capacity of the system, but a relatively unchanged KD. Examination of the pharmacological specificity of binding, showed that for both agonist and antagonist molecules, the L-enantiomers were invariably more active than the D-forms. For example, the L-(+)-2-amino-4-phosphonobutyrate isomer was 15 times more active than the D-(-)-form in inhibiting the binding of DL-[3H]-APB. This is in close agreement with the ability of these compounds to produce depression of synaptic transmission. The most potent inhibitor of binding was quisqualate. It is suggested that APB may interact with a quisqualate-preferring class of excitatory amino acid receptors, possibly localised predominantly on presynaptic terminals.

Aminobutyrates↗
PubMed1983

A design for the prospective evaluation of the efficacy and toxicity of antiepileptic drugs in adults.

The design for the comparative evaluation of the efficacy and toxicity of phenobarbital, phenytoin, primidone, and carbamazepine is outlined. A double-blind prospective study of a sufficient number of patients can determine the optimum drug to use initially for partial and generalized tonic-clonic seizures in adults. The rationale for methods defines the major parameters that should be addressed in order to determine optimum drug for longterm seizure therapy. Major problems in the function of such a project include aspects of sample size attainment, screening/recruitment, non-drug-related losses, and adjustments to the ongoing protocol. The design, with modifications, can be used to study other antiepileptic drugs and other types of seizures.

Adult↗