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Biomedical subjects

T A Kent

Publications and source records attributed to T A Kent.

At least 37 records · Page 2Linked to original sources
PubMed1996

Expansion of the cerebral ventricles and correlation with acquired immunodeficiency syndrome neuropathology in 232 patients.

BACKGROUND: Expansion of the cerebral ventricles is highly prevalent in patients with the acquired immunodeficiency syndrome (AIDS). The mechanism remains unclear. The purpose of this study was to correlate the volume of the cerebral ventricles with histopathologic abnormalities in the brain. METHODS: At autopsy, the volume of the cerebral ventricles in brain slices was estimated planimetrically in 232 patients with AIDS and 77 age-appropriate controls. Estimated volumes were compared with the neuropathologic results using multiple regression analysis. RESULTS: Multiple regression analysis demonstrated a significant relationship between ventricular volume and cerebral cytomegalovirus infection (P < .0004). When human immunodeficiency virus (HIV) encephalitis with multinucleated cells was present, median volume did not differ significantly from other subjects with AIDS. In 11 patients who had HIV-1 proviral DNA detected using the polymerase chain reaction, average volume was not different from 22 patients who tested negatively using polymerase chain reaction. Ventricular expansion did not have a clear-cut neuropathologic substrate in many instances. CONCLUSIONS: In some subjects with AIDS, cytomegalovirus encephalitis was the underlying neuropathologic lesion associated with ventricular expansion. Key indicators of brain HIV-1 infection were related either weakly or not at all, and the role of HIV-1 remains uncertain in most cases.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Classification of brain compartments and head injury lesions by neural networks applied to MRI.

An automatic, neural network-based approach was applied to segment normal brain compartments and lesions on MR images. Two supervised networks, backpropagation (BPN) and counterpropagation, and two unsupervised networks, Kohonen learning vector quantizer and analog adaptive resonance theory, were trained on registered T2-weighted and proton density images. The classes of interest were background, gray matter, white matter, cerebrospinal fluid, macrocystic encephalomalacia, gliosis, and "unknown." A comprehensive feature vector was chosen to discriminate these classes. The BPN combined with feature conditioning, multiple discriminant analysis followed by Hotelling transform, produced the most accurate and consistent classification results. Classification of normal brain compartments were generally in agreement with expert interpretation of the images. Macrocystic encephalomalacia and gliosis were recognized and, except around the periphery, classified in agreement with the clinician's report used to train the neural network.

Artificial Intelligence↗
PubMed1995

In vivo detection of superoxide anion production by the brain using a cytochrome c electrode.

A cytochrome c-coated platinized carbon electrode was utilized to detect superoxide generated by the brain during hypoxia/hypercarbia, focal ischemia, and reperfusion and following fluid percussion brain injury with and without hemorrhagic hypotension and reperfusion in the rat. All three of these forms of brain injury were associated with an increase in the superoxide signal. The cytochrome c electrode proved to be sensitive and responsive enough for minute-by-minute measurement of superoxide generation by brain tissue.

Animals↗
PubMed1995

Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats.

BACKGROUND AND PURPOSE: Neuroanatomical plasticity is well described in lesions of the hippocampus but remains a subject of some controversy in the neocortex. The purpose of the present study was to measure the neocortical distribution and density of expression of proteins known to be involved in neurite growth or synaptogenesis and to correlate the neocortical expression with behavioral recovery after a focal neocortical infarction. Focal neocortical infarction creates a circumscribed lesion in the neocortex that provides a denervation stimulus for neurite growth and synaptogenesis. METHODS: Unilateral neocortical ischemia was induced in male spontaneously hypertensive Wistar rats (n = 4 per time point) by permanent occlusion of the distal middle cerebral artery and ipsilateral common carotid artery. To determine the spatial and temporal distribution of neurite growth and/or synaptogenesis, GAP-43, a growth-associated protein expressed on axonal growth cones, and synaptophysin, a calcium-binding protein found on synaptic vesicles, were examined by immunohistochemical techniques. The reaction product was measured, and the distribution was recorded. Since the resulting infarction included a portion of the forelimb neocortex, behavioral assessments of forelimb function that used the foot-fault test of Hernandez and Schallert were performed on the same rats used for immunohistochemical studies. Recovery times were 3, 7, 14, 30, and 60 days after surgery. RESULTS: Both GAP-43 and synaptophysin proteins demonstrated statistically significant increases in the density of immunoreaction product as determined by optical density measurements in the neocortex of infarcted rats compared with sham controls. The GAP-43 was elevated to statistically significant levels in forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction only at days 3, 7, and 14. In contrast, synaptophysin demonstrated no statistically significant changes in expression at 3 or 7 days but demonstrated statistically significant increases at 14, 30, and 60 days in the forelimb, hindlimb, and parietal neocortical regions medial and lateral to the infarction as well as in the contralateral parietal neocortex. Behavioral assessment of forelimb function indicated impairment of forelimb placement on the side contralateral to the infarction that trended toward control values at 14 days and was not significantly different from controls by 30 days. CONCLUSIONS: These data support the occurrence of neurite growth followed by synaptogenesis in the neocortex, ipsilateral and contralateral to neocortical ischemia, in a pattern that corresponds both spatially and temporally with behavioral recovery. Thus, neuroanatomical remodeling in the neocortex provides a mechanism for recovery of function.

Animals↗
PubMed1995

Frontal lobe changes after severe diffuse closed head injury in children: a volumetric study of magnetic resonance imaging.

In view of the pathophysiology and biomechanics of severe closed head injury (CHI) in children, we postulated that the frontal lobes sustain diffuse injury, even in the absence of focal brain lesions detected by magnetic resonance imaging (MRI). This study quantitated the morphological effects of CHI on the frontal lobes in children who sustained head trauma of varying severity. The MRI findings of 14 children who had sustained severe CHIs (Glasgow Coma Scale score of < or = 8) were compared with the findings in a matched group of 14 children having sustained mild head injuries (Glasgow Coma Scale score of 13-15). The patients ranged in age from 5 to 15 years at the time of their MRIs, which were acquired at least 3 months postinjury. MRI findings revealed no focal areas of abnormal signal in the frontal lobes. Volumetric analysis disclosed that the total prefrontal cerebrospinal fluid increased and the gray matter volume decreased in the patients with severe CHI, relative to the mildly injured comparison group. Gray matter volume was also reduced in the orbitofrontal and dorsolateral regions of the brains of children with severe CHI, relative to the children who sustained mild head trauma. These volumetric findings indicate that prefrontal tissue loss occurs after severe CHI in children, even in the absence of focal brain lesions in this area. Nearly two-thirds of the children who sustained severe CHIs were moderately disabled after an average postinjury interval of 3 years or more, whereas 12 of the 14 patients with mild CHIs attained a good recovery (2 were moderately disabled) by the time of study.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Postmarketing surveillance by patient self-monitoring: preliminary data for sertraline versus fluoxetine.

BACKGROUND: There have been no published postmarketing reports comparing sertraline with another serotonin selective reuptake inhibitor (SSRI) in large-sample, parallel groups. As part of an ongoing postmarketing surveillance study, this paper presents preliminary data for a number of adverse clinical events reported by outpatients being treated with either fluoxetine or sertraline. METHOD: Using a well-validated method developed to signal possible adverse drug reactions, data were collected on 1577 fluoxetine-treated and 1209 sertraline-treated patients who filled a prescription for either of the two targeted drugs. Pharmacists gave these patients an announcement, part of which served as an entry form, that described the purpose and details of the study. Volunteers (highly selective) were requested to report during the next month via a toll-free telephone interview "any new or unusual symptoms or unexpected improvements" in their health since starting the designated medication. RESULTS: Almost 1 (31.4%) of every 3 sertraline-treated patients called at least once to report one or more adverse clinical events compared with only about 1 (19.7%) of every 5 fluoxetine-treated patients. Most of the reported adverse clinical events--but not all--are well-known adverse drug reactions that seem common to SSRIs. Adverse clinical events reported more frequently by sertraline-treated patients included urinary, sexual, psychological, neurologic, gastrointestinal, and dermatological complaints. Drug discontinuation was also reported more frequently by sertraline-treated patients. Fluoxetine-treated patients reported an increased frequency of weight gain and anger or aggression. CONCLUSION: These data indicate that many adverse reactions known to be induced by fluoxetine are being reported with even greater frequency by sertraline-treated patients. Possible interpretations of these differences are discussed.

1-Naphthylamine↗
PubMed1994

Synergistic induction of gene 33 expression by retinoic acid and insulin.

The expression of gene 33 in rat liver and hepatoma cells is regulated by multiple hormones and other bioactive agents. Previous studies have demonstrated a 15-fold increase in gene 33 mRNA after 1 h of insulin treatment. We demonstrate in this report that retinoic acid (RA) also controls the expression of this gene. Gene 33 mRNA levels are rapidly elevated by RA, with maximal accumulation (19-fold over control) attained after just 1 h of RA treatment. The transcription rate of gene 33 was increased by RA to a maximum level 6-fold greater than control values. Studies with inhibitors of RNA synthesis demonstrated no increase in the stability of gene 33 mRNA in response to RA or insulin. In addition, a synergistic induction of both gene 33 mRNA levels and the transcription rate of gene 33 was observed when both RA and insulin were added together. In the presence of both hormones, the transcription rate was induced almost 20-fold in 30 min, followed by a 49-fold increase in mRNA levels after 1 h. Thus, gene 33 represents the first example of a gene whose transcription rate is elevated directly by both insulin and RA, and synergistically elevated by treatment with both hormones together.

Animals↗
PubMed1993

Neurofibromatosis 1 mRNA expression in blood vessels.

Vascular hypertrophic lesions occur in neurofibromatosis type 1 (NF1). The role of the gene which causes NF1 in the growth and development of blood vessels is not known. mRNA expression of the NF1 gene was studied in blood vessels in the transition between intact and culture and in quiescent and proliferative conditions. The expression and alternative splicing pattern of the catalytic domain of NF1 consistently changed in proliferating cells, supporting a role for this gene in the regulation of growth of vascular smooth muscle and the vascular pathology in NF1.

Animals↗
PubMed1993

Acute increase in expression of growth associated protein GAP-43 following cortical ischemia in rat.

Focal cerebral ischemia creates an area of infarction that is surrounded by neuronal tissue that may respond to nearby damage by creating neurite growth. To determine if axonal sprouting occurs after infarction, antibodies to growth associated protein MW 43,000 (GAP-43), a protein expressed on axonal growth cones, were used to assess the level of GAP-43 immunoreactivity as a measure of sprouting. Cerebral ischemia was induced in spontaneously hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery. After 1 week of recovery, the animals were perfused, the brains removed, processed, and optical densities of the immunoreaction were measured. The cortex surrounding the infarcted area had increased optical densities (mean +/- S.D. = 14.2% +/- 5.5) compared to the optical density values measured in similar areas in the contralateral hemisphere (mean +/- S.D. = 6.0% +/- 3.3), a 136% increase that is statistically significant, P < 0.05 Student's t-test. We hypothesize that this increase in GAP-43 reaction product is due to axonal sprouting in the cortex surrounding an area of infarction. These data, coupled with previous work examining synaptophysin levels after cortical infarction, support the hypothesis of sprouting and synaptogenesis in the cortex following cerebral infarction.

Animals↗
PubMed1993

The evolution of acute stroke recorded by multimodal magnetic resonance imaging.

Events associated with an evolving cerebral infarction were studied using multiple magnetic resonance imaging (MRI) techniques at 4.7 T in a rat model of middle cerebral artery occlusion. High resolution perfusion images revealed a core of absent perfusion surrounded by a zone of slow, but measurable perfusion. Only the core of severest perfusion deficit demonstrated restricted water diffusion as early as 1 hr, consistent with "cytotoxic" cellular edema in the most vulnerable region. Within 24 hours, the area of restricted diffusion encompassed the entire region destined to become infarcted. In spin-echo images, hypointensity, likely reflecting deoxygenated hemoglobin, was visible in the ischemic hemisphere. Edema accumulated over 72 hr primarily in the surrounding slowly perfused rim, consistent with the concept of "vasogenic" edema. These studies demonstrate that multimodal MRI can visualize events which define the ischemic penumbra--deoxygenation, maintenance of transmembrane ionic gradients, reduced flow, and delayed cell death. These experiments noninvasively visualized differential hemodynamic and biochemical processes within the core and perifocal penumbra and will allow quantitation over time of the relationship between blood flow, cytotoxicity and edema in stroke.

Acute Disease↗
PubMed1993

Postmarketing surveillance by patient self-monitoring: trazodone versus fluoxetine.

This article presents incidence estimates and relative risks for a number of adverse clinical events reported by outpatients being treated with either trazodone or fluoxetine. Data were collected via an innovative method of patient self-monitoring. Many of the suggested differences between the two drugs are quite consistent with expected adverse drug reactions documented in both the package insert data for outpatients and with reports in the literature. Findings not so readily anticipated for trazodone, however, include higher relative frequencies for muscle weakness or soreness, skin swelling, and urinary complaints compared with fluoxetine; for fluoxetine, data are presented indicating a higher incidence of various psychologic/psychiatric adverse clinical events, including delusions and hallucinations, aggression, and suicidal ideation. Other possible interpretations of the results are discussed.

Adult↗
PubMed1992

Increase in synaptophysin immunoreactivity following cortical infarction.

Plasticity in the central nervous system has been demonstrated using lesions of the hippocampus and rhinal cortex but has not been well studied after cerebral ischemia. Focal cerebral ischemia creates an area of infarction that is surrounded by neuronal tissue that may respond to nearby damage by creating new synapses. To determine if synaptogenesis occurs, antibodies to synaptophysin, a calcium-binding protein found on synaptic vesicles, were used with immunohistochemical techniques to assess the level of synaptophysin immunoreactivity as a measure of changes in the number of synapses. Cerebral ischemia was induced in hypertensive rats by permanently occluding the distal middle cerebral artery and ipsilateral common carotid artery. After 2 months recovery, the animals were perfused and the brains removed for immunohistochemical processing and evaluation. When comparing the cortex surrounding the infarcted area to similar areas on the contralateral side of the brain, the infarcted side had increased levels of anti-synaptophysin like activity that are statistically significant. We hypothesize that this increase in synaptophysin immunoreactivity is due to an increase in synapses in the cortex surrounding an area of infarction and supports the hypothesis of plasticity in the cortex following cerebral infarction.

Animals↗
PubMed1992

Calcium channels and nifedipine inhibition of serotonin-induced [3H]thymidine incorporation in cultured cerebral smooth muscle cells.

Cultures of smooth muscle cells were prepared from the basilar artery of adult guinea pigs. Passaged cultures (10-30 passages) that expressed serotonin receptors were studied using [3H]thymidine incorporation. When tested in quiescent medium, serotonin potently stimulated [3H]thymidine incorporation (EC50 of 31 nM) by as much as 400% at 24 h. The number of cells was not significantly increased at 24 or 48 h. At concentrations of 10(-8)-10(-5) M 5-HT, [3H]thymidine uptake was reduced 40-50% by the dihydropyridine Ca2+ channel blocker, nifedipine (1 microM). To demonstrate a possible mechanism for the sensitivity to nifedipine, Ca2+ currents were measured using the whole cell patch clamp technique. The cells expressed dihydropyridine-sensitive L-type Ca2+ channels, but not other subtypes of Ca2+ channels, as indicated by the kinetic and voltage-dependent characteristics of the current and by the stimulatory effect of Bay K 8644. The magnitude of the Ca2+ currents was related exponentially to the membrane surface area, measured as cell capacitance. These data support the association of dihydropyridine-sensitive Ca2+ channels with mitogenesis in vascular smooth muscle, and suggest an alternate mechanism of action for the beneficial effect of dihydropyridines in prophylaxis of cerebral vasospasm.

Animals↗
PubMed1990

Assessment of a superparamagnetic iron oxide (AMI-25) as a brain contrast agent.

We have applied a superparamagnetic iron oxide formulation (AMI-25, Advanced Magnetics, Inc., Cambridge, MA) to image the cerebral vasculature. Contrast-enhanced images of normal anesthetized rats demonstrated excellent gray/white matter differentiation, consistent with known differences in blood perfusion, and cerebrospinal fluid spaces were clearly seen. Alterations in normal perfusion patterns due to barbiturate anesthesia and ischemia were clearly visible. We propose the use of this agent as an adjunct to MRI for the imaging of conditions with perfusion abnormalities.

Animals↗
PubMed1989

5-HT1B and 5-HT2 serotonin binding sites in cultured Wistar-Kyoto rat aortic smooth muscle cells.

We studied [3H]serotonin [( 3H]5-HT) binding on cultured arterial smooth muscle cells from rat aorta. We found a high and low affinity binding site. Binding to the higher affinity site could be displaced by drugs in an order corresponding most closely with the 5-HT1B subtype, and high affinity [125I]iodo-cyanopindolol binding was also found. We found evidence for a 5-HT2 subtype using [3H]ketanserin binding, with similar results whether specific binding was determined using unlabelled ketanserin, methysergide or mianserin.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Blood platelet uptake of serotonin in episodic aggression.

Blood platelet uptake of 3H-serotonin (5HT uptake), a potential marker of serotonergic function, was determined in male outpatients with episodic aggression (n = 15) and in age- and sex-matched nonaggressive controls (n = 15). Correlations with rating scales of "impulsivity" (Barratt Impulsivity Scale, 10th revision) and "anger" (Spielberger Anger Expression Scale) were performed. Mean 5HT uptake was 18% lower in patients with episodic aggression. A significant negative correlation between % difference in platelet 5HT uptake and impulsivity score was observed, but the correlation between 5HT uptake and anger was not significant. These results support the hypothesis of disturbed serotonergic function in aggression and suggest that the primary relationship is in the "control" of aggression. The blood platelet may be useful in identifying impulsive subtypes.

Adolescent↗
PubMed1989

Middle cerebral artery occlusion in rats studied by magnetic resonance imaging.

Ischemia due to middle cerebral artery occlusion was studied in 29 rats from 1 to 24 hours after occlusion using magnetic resonance imaging. Images were made before and after the injection of a superparamagnetic iron oxide compound, AMI-25. Subtraction images demonstrated the region of perfusion deficit as early as 1 hour after occlusion, earlier than conventional T2-weighted images. The area of altered perfusion detected by this technique (subtraction imaging after AMI-25 administration) correlated with that demonstrated by iodoantipyrine autoradiography. Since this magnetic resonance technique can be used to serially estimate the location and size of the ischemic area, the technique can be an important adjunct to metabolic studies of focal ischemia using magnetic resonance spectroscopy. The technique may have clinical applications as well.

Animals↗