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Biomedical subjects

J F Collins

Publications and source records attributed to J F Collins.

At least 181 records · Page 10Linked to original sources
PubMed1981

Is glutamate a trigger factor in epileptic hyperactivity?

The effects of glutamate and aspartate antagonists were studied on limb-jerk frequency and EEG patterns in rats made epileptic by cobalt implantation in the sensorimotor cerebral cortex. The results of this study were as follows: (1) alpha-Amino-4-phosphonobutyric acid (0.055--1.10 mM) decreased or completely prevented the epileptic manifestations. The effect was reversible 30 min after washing with artificial CSF solution. (2) DL-Pyroglutamic acid completely abolished the myoclonic jerks and EEG spikes. (3) alpha-Amino-5-phosphonovaleric acid and alpha-D-amino-adipic acid significantly reduced the frequency of epileptic spikes and myoclonic jerks. (4) Other analogs, alpha-amino-3-phosphonopropionic acid (0.6 mM), alpha-amino phosphonocaproic acid (0.95), and hydroxy-3-amino pyrrolidone-2 were without effect. (5) Glutamate itself did not decrease the epileptic manifestations.

Amino Acids↗
PubMed1981

Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons. II. Further studies on connective tissue changes.

Pulmonary fibrosis induced by bleomycin is associated with accumulation of collagen and elastin in the lungs. The excess connective tissue proteins persist despite resolution of inflammation after cessation of treatment. In the present study, mild lung injury was produced in 9 juvenile baboons by twice-weekly injections of bleomycin to a total dose of 66 units/kg. Treated animals showed losses in body weight, lung volume, and diffusing capacity. Right middle lobectomies were performed in 3 animals shortly after cessation of bleomycin. Only minimal histologic changes were present, but lobar connective tissue protein concentrations and the rate of collagen synthesis were increased. Biopsies obtained in 3 additional animals 3 months later revealed similar changes. All animals were killed 6 months after cessation of treatment. Mild fibrosis was present, and lobar contents of collagen and elastin, as well as synthetic rates of collagen and elastin, remained elevated. Accumulation of lung connective tissue proteins in this model was associated with increased rates of synthesis that persisted after discontinuance of the drug.

Animals↗
PubMed1980

Stereospecificity of the gliotoxic and anti-neurotoxic actions of alpha-aminoadipate.

The glutamate (Glu) analog, DL-alpha-aminoadipate (DL-alpha AA), and the separate D and L isomers of alpha AA, were administered subcutaneously to infant mice and histopathological effects on the arcuate hypothalamic (AH) nucleus were studied. L-alpha AA induced striking gliotoxic and neurotoxic changes; D-alpha AA and DL-alpha AA respectively induced mild and extreme gliotoxic but not neurotoxic changes. The neurotoxicity of L-alpha AA is of interest in view of its known neuroexcitatory potential. The non-neurotoxicity of DL-alpha AA implies effective antagonism by D-alpha AA of the neurotoxicity of L-alpha AA, which is of interest in that D-alpha AA is recognized as an effective antagonist of amino acid excitants and is thought to block specifically at the excitatory receptor.

2-Aminoadipic Acid↗
PubMed1980

Some adaptive strategies for inadequate sample acquisition in veterans administration cooperative clinical trials.

A major concern of any clinical trial is being able to recruit sufficient patients of the proper type so that reliable answers can be obtained for the hypotheses being tested. This article considers patient recruitment in seven VA cooperative studies and the adaptive strategies used for inadequate sample acquisition. These strategies are: (1) the re-evaluation of the required sample size; (2) the addition of new hospitals; (3) the replacement of poor recruiting hospitals; (4) the extension of the patient intake period; and (5) the modification of the patient exclusion-inclusion criteria. When there is no expectation of achieving the required sample size in a reasonable time, the study is terminated. Although each of the five strategies will increase the likelihood of successfully completing a study should a recruitment problem occur, preventing these problems from occurring should be a major concern during the planning of a study.

Clinical Trials as Topic↗
PubMed1979

Convulsant and anticonvulsant actions in DBA/2 mice of compounds blocking the reuptake of GABA.

Compounds blocking the uptake of GABA into neurons or glia have been injected intracerebroventricularly (icv) or intraperitoneally (ip) in DBA/2 mice, age 21-28 days. Protection against audiogenic seizures was seen 30 min after the icv injection of (+)-2,4-diaminobutyric acid (0.5-2.0 mumoles), (+/-)-nipecotic acid (1.6-3.2 mumoles), (+)-ethyl nipecotate (0.4-0.8 mumoles), (-)-piperazic acid (4 mumoles) and putrescine (2 mumoles) or the ip injection of (+)-2,4-diaminobutyric acid (4-8 mmoles/kg and (+)-ethyl nipecotate (0.24-0.32 mmoles/kg). Of these ethyl nipecotate and nipecotic acid were the most effective anticonvulsants icv, but nipecotic acid was ineffective ip. Limb myoclonus and other epileptic manifestations (rearing, wild running, tonic clonic seizures) occurred in the absence of auditory stimulation after (+)-2,4-diaminobutyric acid (0.5-2.0 mumoles), (+/-)-cis-3-aminocyclohexane carboxylic acid (3.2-6.4 mumoles) and putrescine (2 mumoles). beta-Alanine (2-4 mumoles, icv) depressed respiration but did not protect against audiogenic seizures or induce myoclonus.

Alanine↗
PubMed1979

Lung elasticity in regional and diffuse pulmonary fibrosis.

Static deflation air and saline pressure-volume (PV) curves were performed on five normal excised baboon lungs, four with radiation-induced upper lobe fibrosis, and two with diffuse bleomycin-induced fibrosis. Curves were compared visually and using half-inflation pressures (h). When plotted as percent of observed vital capacity vs. transpulmonary pressure, the radiation-associated curves were similar in shape to control curves. Also, h values were not significantly different between the two groups. The bleomycin-associated curves, however, were shifted rightward and exhibited increased h values. PV curves were correlated with connective tissue data. Elastin concentration was increased in the irradiated upper lobes through loss of associated constituents. Elastin accumulated in the lower lobes of the irradiated animals through compensatory growth and in the bleomycin-associated lungs through excessive production. Collagen followed a similar but less dramatic trend. We conclude connective tissue accumulation may not lead to rightward shifted PV curves if accumulation is present in relatively noninflatable lung units, or as part of compensatory lung growth.

Animals↗
PubMed1978

Isoguvacine, isonipecotic acid, muscimol and N-methyl isoguvacine on the GABA receptor in rat sympathetic ganglia.

The GABA-mimetic activities of 4 analogues muscimol, isonipecotic acid, isoguvacine and N-methyl isoguvacine have been examined at the GABA receptor in the rat isolated superior cervical ganglion. The depolarizing action of all 4 analogues could be selectively antagonized by bicuculline methochloride and isopropyl bicyclophosphate. Muscimol was the only analogue more potent than GABA (molar potency ratio = 5.08 +/- 0.707). The potency of isoguvacine was 0.23 +/- 0.026 and isonipecotic acid 0.011 +/- 0.0028. N-methyl isoguvacine was less than 0.001 GABA.

Animals↗
PubMed1978

Bleomycin-induced diffuse interstitial pulmonary fibrosis in baboons.

Pulmonary fibrosis was induced in eight baboons with bleomycin; five untreated animals were controls. After 45-65 U/kg of bleomycin, lung volumes and diffusing capacity were reduced, and static lung pressure-volume curves were shifted to the right. Right middle lobes were resected at this time in five bleomycin-treated and two control animals. Compared to controls, right middle lobes from bleomycintreated animals had increased weight and contained increased amounts of total protein, collagen, elastin, and DNA; synthesis of collagen and noncollagen protein were also elevated. Occasional alveolar septae were edematous and infiltrated by mononuclear inflammatory cells; a slight increase in collagen was demonstrable histologically. Four of six treated animals died with extensive diffuse interstitial fibrosis after 95 U/kg of bleomycin. Biochemical analyses revealed significantly elevated lobar contents of dry weight, protein, elastin, and collagen. Two animals survived 95 U/kg of bleomycin and were terminated 6 mo after treatment. In these animals, physiologic studies were indicative of restrictive lung disease, but lung histology was nearly normal. Lung weight, total protein, and DNA had returned to control values, but collagen and elastin were increased in amount and concentration. Bleomycin induces an intense inflammatory response in the lung. During this inflammation, connective tissue proliferation occurs in concert with proliferation of other tissue components. Cessation of bleomycin treatment is followed by resolution of inflammation manifested by decreases in tissue mass, cellular content, and nonconnective tissue protein. Collagen and elastin deposited during inflammation are less successfully removed during resolution, leading to a stage characterized by increased concentrations of these proteins. A similar sequence of tissue alterations may occur in idiopathic diffuse interstitial fibrosis of man in response to various lung injuries.

Animals↗
PubMed1978

Connective tissue proteins of the baboon lung: concentration, content and synthesis of collagen in the normal lung.

Lung connective tissue proteins have been assayed in 12 normal juvenile baboons (Papio cynocephalus). The collagen concentration (26.8 +/- 5.1 microgram hydroxyproline per mg dry weight) is comparable to values reported for adult human lung, while the rate of collagen synthesis (0.242 +/- 0.082 nmoles hydroxyproline per mg DNA per hour) is approximately half that of human lung. Proteins other than collagen are synthesized at approximately equal rates in human and baboon lung. Elastin concentration was estimated to be 33 microgram insoluble elastin protein per mg dry weight, within the range reported for normal human lung. Values have also been calculated for the lobar contents of protein, DNA, and collagen, as well as the rates of synthesis of collagen and other proteins in the entire upper lobe of the right lung of these animals. The collagen concentrations in the lung show wide differences among various animal species. However, the baboon lung is similar to human lung. This similarity may be important in the interpretation of alterations in lung connective tissue metabolism associated with experimental diseases.

Animals↗