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Biomedical subjects

J W Miller

Publications and source records attributed to J W Miller.

At least 109 records · Page 6Linked to original sources
PubMed1994

Anticonvulsant effects of the experimental induction of hippocampal theta activity.

Epileptic seizures occur less during wakefulness or paradoxical sleep, conditions during which hippocampal theta rhythm is seen. This leads to the hypothesis that this rhythm indicates a physiological state of the hippocampal formation which opposes its recruitment into seizures. This was tested by determining the effects of experimental induction or suppression of hippocampal theta activity on seizures. Hippocampal theta activity can be induced by chemical or electrical stimulation of the medial septal nucleus and adjacent nucleus of the diagonal band of Broca. Microinjections of the muscarinic agonist carbachol in the medial septum during pentylenetetrazol (PTZ) induced facial-forelimb seizures stopped behavioral seizures and EEG spiking within five seconds, and caused hippocampal theta activity. Medial septal electrical stimulation at 4-8 Hz had similar effects. Electrolytic medial septal lesions abolished hippocampal theta activity and lowered myoclonic and facial-forelimb PTZ seizure thresholds. Medial septal carbachol injections were also made during electrically kindled limbic status epilepticus. Within ten seconds, ictal behavior stopped and the EEG spike rate decreased by half with a gradual return to the baseline rate over three minutes. These results demonstrate that the hippocampal theta rhythm corresponds to a seizure-resistant condition, providing a possible explanation for the seizure promoting properties of slow wave sleep.

Acetylcholine↗
PubMed1994

Vitamin B-6 deficiency vs folate deficiency: comparison of responses to methionine loading in rats.

The plasma homocysteine response to methionine loading was assessed in vitamin B-6- and folate-deficient rats. Rats fed vitamin B-6- or folate-deficient diets for 4 wk were administered a gastric gavage of methionine (100 mg/kg body wt). Subsequent plasma analyses revealed a peak post-methionine load increase in plasma homocysteine concentration of > 300 mumol/L in the vitamin B-6-deficient rats. Folate-deficient rats exhibited no significant changes in plasma homocysteine after the load. These disparate responses can be explained by the observed increase in hepatic S-adenosylmethionine (SAM) concentration because of the load. In vitamin B-6 deficiency, increased SAM inhibits homocysteine remethylation, which, in conjunction with the impaired homocysteine catabolism due to the deficiency and the increased synthesis of homocysteine due to the methionine load, leads to a large elevation of homocysteine in the blood. In folate deficiency, increased SAM activates homocysteine catabolism, which compensates for the increased synthesis of homocysteine due to the load and thus no change in blood homocysteine is observed. These results have significant bearing on the interpretation of both positive and negative responses to methionine loading in humans.

Animals↗
PubMed1994

Severe folate deficiency causes secondary depletion of choline and phosphocholine in rat liver.

It has previously been shown that choline deficiency causes depletion of hepatic folate concentration in rats. Two separate experiments were undertaken to investigate the converse phenomenon: whether folate deficiency would lead to depletion of hepatic choline. In Experiment 1, severe folate deficiency was induced in rats by feeding an amino acid-defined diet containing (per kg diet) 1.4 g choline, 0 mg folate and 10 g succinylsulfathiazole. Control rats were fed the same diet containing 8 mg folate/kg. After 4 wk, plasma and hepatic folate concentrations were significantly depleted in the severely folate-deficient rats compared with controls (P < 0.001), and hepatic choline and phosphocholine concentrations were 65 and 80% lower, respectively (P < 0.001). In Experiment 2, moderate folate deficiency was induced in rats by feeding the same diet as described above, but with the succinylsulfathiazole omitted. After 24 wk, significant systemic folate deficiency was present in the moderately folate-deficient rats compared with controls (P < 0.001). A modest reduction (36%, P = 0.087) in hepatic choline concentration was observed in the moderately folate-deficient rats compared with controls. No significant differences in hepatic phosphocholine concentrations were detected between the two groups. These results indicate that severe folate deficiency causes secondary hepatic choline deficiency in rats.

Animals↗
PubMed1994

Individual differences in risk of child abuse by adolescent mothers: assessment in the perinatal period.

Abuse risk potential and parenting attitudes of 66 adolescent mothers were examined during the perinatal period using self-report instruments. Approximately one-half of the sample was considered to be at significant risk. Specific risk factors included distress, rigidity in parenting attitudes, and inappropriate expectations of children. Younger adolescents were at greater risk of abuse, advocated the use of physical punishment more strongly, and reported greater unhappiness than older adolescents. Teens reporting limited social support were also at greater risk for abuse. Low acceptance of the pregnancy was related to abuse potential for parenting, but not pregnant, adolescents. A history of maltreatment was related to self-reported problems with family members but not to overall risk. Implications for the prevention of abuse among adolescent mothers are discussed.

Adolescent↗
PubMed1994

Trypsin-like activity levels of Treponema denticola and Porphyromonas gingivalis in adults with periodontitis.

Treponema denticola (Td) and Porphyromonas gingivalis (Pg) are associated with human moderate and severe adult periodontal diseases. This study quantifies these two anaerobes and their trypsin-like (TL) activities in subgingival plaque collected from both clinically healthy and periodontally diseased sites of human periodontitis patients. Antigen levels of the microorganisms were determined by monoclonal antibodies and TL activities were measured by the fluorescent substrate Z-gly-gly-arg-AFC in a disc format. Significant positive correlations were observed between the antigen levels and the TL activities when the data were subjected to statistical analyses both on a site-specific and on a patient basis. Anaerobe synergism was found between Td and Pg in a continental US population, and positive correlations were found between anaerobe levels (individually and total) and clinical indicators of adult periodontitis.

Adult↗
PubMed1994

Composition and Rheological Properties of Extracellular Polysaccharide 105-4 Produced by Pseudomonas sp. Strain ATCC 53923.

A soil isolate produced a novel extracellular polysaccharide (EPS) with unusually potent thickening powers. The EPS contained d-mannose, d-glucose, d-galactose, and d-glucuronic acid in the unique molar ratio 1:4:1:2 and 10 to 15% acetate. Viscosities of a 1-g/liter aqueous solution were 1 x 10 and 14 x 10 cP at shear rates of 0.01 and 0.1 s, respectively. The EPS was insensitive to high concentrations of NaCl and CaCl(2).

Journal Article↗
PubMed1994

Resective surgery for medically intractable epilepsy associated with schizencephaly.

Four adults with unilateral (three cases) or bilateral (one case) closed schizencephaly, medically intractable epilepsy, and otherwise normal neurological examinations are presented. Three were examined preoperatively with magnetic resonance imaging and one with computerized tomography. Scalp electroencephalographic (EEG) studies in all four patients and electrocorticography via intracranial electrodes in two showed seizure origin in the cleft regions in two patients and in the ipsilateral temporal lobe in the other two. Temporal lobectomy was performed in the two patients with temporal lobe foci. Resection of superficial pachygyria around the cleft was performed in one patient. The authors conclude that the abnormal cortical mantle lining schizencephalic clefts may be epileptogenic. Alternatively, temporal allocortex may become the source of seizures. Therefore, these patients require careful EEG monitoring of the entire ipsilateral hemisphere as well as the cleft region.

Adult↗
PubMed1994

Induction of enhanced release of endothelium-derived relaxing factor after prolonged exposure to alpha-adrenergic agonists: role in desensitization of smooth muscle contraction.

Desensitization of alpha 1-adrenergic receptor-mediated contraction occurs in rat aorta after in vitro exposure to alpha-adrenergic agonists; we previously showed that a component of the desensitization is endothelial cell dependent. Our primary purpose was to examine possible alterations in either the release or action of endothelium-derived relaxing factor (EDRF) in desensitized blood vessels. Rings of rat aorta were desensitized in vitro by exposure to phenylephrine (PE) for 6 h with impaired subsequent ability of PE to induce smooth muscle contraction. PE also induced heterologous desensitization of serotonin-induced contraction, which was blocked by the alpha 1-adrenergic selective antagonist prazosin. Using a "sandwich" bioassay technique, we noted enhanced release of EDRF from the aortic rings that had been previously exposed to PE as compared with controls. The capacity of PE to activate accumulation of inositol monophosphate was impaired in the desensitized blood vessels, both with and without endothelium. Our results suggest that prolonged exposure to alpha-adrenergic agonists leads to several adaptations in vascular smooth muscle (VSM), including enhanced release of EDRF. Although impaired action of EDRF has been suggested to play a role in diseases such as diabetes and atherosclerosis, our results indicate that release and action of EDRF may be enhanced with prolonged exposure to alpha-agonists.

Adrenergic alpha-Agonists↗
PubMed1994

Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model.

Ischemia often precedes neovascularization. In ocular neovascularization, such as occurs in diabetic retinopathy, a diffusible angiogenic factor has been postulated to be produced by ischemic retina and to lead to neovascularization of the retina, optic nerve, or iris. However, no angiogenic factor has been conclusively identified that satisfies this hypothesis. Vascular endothelial growth factor/vascular permeability factor, hereafter referred to as VEGF, is a likely candidate for an ocular angiogenic factor because it is a secreted mitogen, specific for endothelial cells, and is upregulated by hypoxia. We investigated the association of VEGF with the development of experimental iris neovascularization in the cynomolgus monkey. Following the production of retinal ischemia by laser occlusion of all branch retinal veins, VEGF was increased in the aqueous fluid, and the aqueous VEGF levels changed synchronously and proportionally with the severity of iris neovascularization. Northern analysis and in situ hybridization revealed that VEGF messenger RNA is upregulated in the ischemic retina. These observations support the hypothesis that ocular neovascularization is regulated by a diffusible factor and identify VEGF as a likely candidate for a retina-derived vascular permeability and angiogenesis factor in vivo.

Animals↗
PubMed1993

Interferon-associated retinopathy.

Interferon alfa is used to treat various systemic disorders and recently has been suggested as a possible treatment for choroidal neovascularization. We report 10 cases of retinal ischemia associated with the use of interferon alfa for various illnesses. The retinal findings include cotton-wool spot formation, capillary nonperfusion, arteriolar occlusion, and hemorrhage. The retinal complications may sometimes be reversible when treatment is stopped. Our findings emphasize the need to have patients who are receiving interferon alfa therapy monitored for these retinal complications, which may rarely be associated with permanent loss of vision secondary to closure of retinal capillaries.

Adult↗
PubMed1993

An ascending seizure-controlling pathway in the medial brainstem and thalamus.

This study demonstrated that an ascending pathway from the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum to the thalamic central medial intralaminar nucleus (CeM) controls the thresholds of experimental seizures. Electrolytic and excitotoxic lesions of the CeM and adjacent thalamus facilitated myoclonic, facial-forelimb clonic, and tonic pentylenetetrazol seizures. Microinjections of the GABAB agonist (-)baclofen in the LDTg facilitated myoclonic and facial-forelimb clonic but not tonic seizures. When LDTg injections of (-)baclofen were performed in animals with prior electrolytic lesions of the midline thalamus, the thresholds of myoclonic and facial-forelimb clonic seizures were unchanged compared to similarly lesioned rats with control vehicle LDTg injections. In addition, the lowering of tonic seizure threshold observed with thalamic lesions was reversed by these (-)baclofen injections. Taken together with past studies, these results imply that the LDTg controls myoclonic and facial-forelimb clonic seizures via ascending projections to the CeM and possibly other medial thalamic nuclei. We also postulate that the LDTg affects tonic seizures by two different, opposing pathways. Although the LDTg-CeM pathway is part of the "ascending reticular activating system," lesions of the midline thalamus did not affect spontaneous sleep, implying that the CeM does not have an essential role in sleep regulation.

Animals↗
PubMed1993

Regression of experimental iris neovascularization with systemic alpha-interferon.

BACKGROUND: Intraocular neovascularization leads to visual loss in many eye diseases, including diabetic retinopathy, age-related macular degeneration, and neovascular glaucoma. Current treatment relies on laser photocoagulation, involving the destruction of functional retinal tissue. A pharmacologic treatment directed at the newly growing vessels would represent a major advance. METHODS: The authors investigated the effect of systemic alpha-interferon in an experimental model of iris neovascularization in cynomolgus monkeys. Alpha-interferon was administered systemically to animals with angiographically documented iris neovascularization. RESULTS: Animals in the treatment group showed regression of neovascularization angiographically and histologically in eight of eight eyes. Control animals with documented iris neovascularization, followed without drug treatment, showed progression of the neovascularization in three of three eyes. CONCLUSION: Systemic alpha-interferon led to inhibition of neovascularization and regression of new vessels in an experimental model of iris neovascularization. This represents the first successful, controlled treatment of experimental neovascularization in the eye using a systemic drug directed specifically at the neovascular tissue.

Animals↗
PubMed1993

Evidence for absorption of silicon and aluminum by hens fed sodium zeolite A.

The mechanism of action of zeolite A (ZA) on eggshell quality could be related either to its ion-exchange properties or to individual ZA elements (Al or Si). Two experiments were conducted to determine 1) whether any ZA passes through the digestive system in its original form; and 2) whether any Al and Si absorption occurs. In Experiment 1, unfed hens were intubated with either 0 or 5 g ZA at oviposition. In Experiment 2, fed and unfed hens were intubated at oviposition with 0, 1, or 2 g ZA. At the subsequent oviposition, liver and kidney tissues, excreta, urine, bile, and plasma were collected and analyzed for Al, Si, Na, K, and P. The results indicated that approximately 7% of the intubated ZA passed through the digestive system in its original form (Experiment 1). As the intubated level of ZA increased, excreta Al and Si (P < .0001), urine Si (P < .005), and urine Al (P < .07) also increased (Experiment 2). Aluminum recovery from excreta ranged from 75 to 93% of the quantity intubated in all treatments. Corresponding values of Si from excreta of unfed and fed hens ranged from 76 to 81% and 58 to 60%, respectively. The P content of excreta was not influenced by ZA. However, excreta P was greater (P < .0001) in unfed than in fed hens. Neither plasma electrolytes (Na, K, and P) nor Al or Si levels in either liver or kidney were influenced by ZA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1992

The effects of vitamins B12, B6, and folate on blood homocysteine levels.

The interaction between plasma homocysteine levels and vitamins B6, B12, and folate is an exciting field and one that has gathered great momentum over the past few years, with the recognition that homocysteine probably plays an important role in occlusive vascular disease. Our understanding in this field is greatly advanced compared to just a few years ago. There are a number of important issues, however, that will need to be addressed in the future if we are to develop a sufficient knowledge base to effectively minimize the risk of occlusive vascular disease ascribable to hyperhomocysteinemia. These include (1) definitive evidence that homocysteine is the actual agent that mediates accelerated occlusive vascular disease and the mechanism by which this occurs; (2) an understanding of what constitutes a pathologic elevation in homocysteine (is there a threshold concentration in the plasma below which no vascular injury occurs? is the peak concentration achieved the critical determinant of injury, or is the area under the curve, or some other feature, more important?); (3) understanding what synergies might exist by adding B6 or B12 to a regimen of folate supplementation (what doses are most appropriate? will toxologic issues limit the utility of supplementation?); and (4) determining the circumstances where reduction of plasma homocysteine will retard or reverse the process of occlusive vascular disease.

Folic Acid↗
PubMed1992

Effects of selective toxic lesions of cholinergic neurons of the laterodorsal tegmental nucleus on experimental seizures.

This study determined the effects of bilateral discrete partial lesions of cholinergic neurons of the laterodorsal tegmental nucleus (LDTg) of the pontomesencephalic tegmentum on seizures induced by intravenous pentylenetetrazol (PTZ). Relatively selective lesions produced by bilateral 50 nl microinjections of 75 pmol of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A) resulted in a significant reduction in the threshold of myoclonic and facial-forelimb clonic seizures but not tonic seizures when PTZ was infused 7 days later. This demonstrates that this cholinergic nucleus is a key site of subcortical seizure regulation. We propose that this control is mediated by ascending projections from the LDTg to the central medial intralaminar nucleus of the thalamus.

Animals↗
PubMed1992

Hippocampal pyramidal cell response to 6-hydroxydopamine lesions of the rat ventral tegmental area.

The occurrence of neurofibrillary tangles (NFT) in the perforant pathway in association with dopaminergic cell loss in the ventral tegmental area (VTA) in human mesolimbic dementia, raises the possibility that denervation is a cause of NFT formation. This was tested in the rat by lesioning dopaminergic neurons which project to the hippocampus from the ventral tegmental area by means of stereotaxic injections of 6-hydroxydopamine. This resulted in the appearance of immunoreactivity to the paired helical filament protein plus an increase of tau and MAP-2 proteins in pyramidal neurons of CA-1 and CA-2. These neuronal responses to dopaminergic denervation are consistent with a precursor stage to NFT development.

Animals↗
PubMed1992

Characterization of cholinergic regulation of seizures by the midline thalamus.

This study determined the effects of injections of different cholinergic agents in the central medial intralaminar nucleus of the thalamus on seizures induced by intravenous injection of pentylenetetrazol. Injections of the cholinesterase inhibitor, neostigmine bromide, induced a stiff, tremulous state and lowered myoclonic, clonic and tonic seizure thresholds. The nicotinic agonist, tartrate, depressed arousal and facilitated all types of seizure, while its antagonist, d-tubocurarine chloride, heightened arousal and transformed pentylenetetrazol-induced convulsions, with tonic seizures occurring at a very low threshold without preceding myoclonic or clonic seizures or EEG spikes. The muscarinic agonist (+/-)pilocarpine hydrochloride, in very large doses, induced slight hyperactivity and facilitated tonic seizures but did not affect myoclonic or clonic seizures. Its antagonist, (-)scopolamine hydrobromide, slightly depressed arousal and myoclonic and clonic seizure thresholds. Injections of mixtures of agonists and antagonists (d-tubocurarine chloride + nicotine tartrate or (+/-)pilocarpine hydrochloride + (-)scopolamine) had little effect on spontaneous behavior or seizures. These results suggest that the midline thalamus regulates seizures and arousal, under the control of cholinergic neurotransmission. Nicotinic and muscarinic receptors have opposing roles in mediating these functions.

Animals↗