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Biomedical subjects

B E Levin

Publications and source records attributed to B E Levin.

At least 73 records · Page 4Linked to original sources

Diet cycling and age alter weight gain and insulin levels in rats.

For assessment of the effect of diet cycling on body weight gain patterns, 3-mo-old male Sprague-Dawley rats were either cycled from chow to a high-energy condensed milk (CM) diet, back to chow, and then back to CM diet at 3-mo intervals (cyclers) or were fed chow to 9 mo of age and then CM diet for 3 mo (noncyclers). Nine of 21 cyclers developed diet-induced obesity (DIO), gaining 36, 59, and 281% more weight than chow-fed controls (CF) at each cycle, respectively. Twelve cycled rats were diet-resistant (DR) with comparable weight gain to CF rats after the first CM diet and chow cycles. However, they gained 202% more than CF rats and 50% more, with 29% heavier retroperitoneal fat pads, than noncycled DR rats after their second CM diet cycle begun at 9 mo of age. Enhanced weight gain in DR cyclers was probably due to enhanced food efficiency in the last few weeks of CM diet intake. Plasma insulin levels were 70% higher in cycled vs. noncycled DIO and DR rats, and both were higher than CF rats. Unlike 6-mo-old DR rats in a prior study, 12-mo-old noncycled DR rats after 3 mo on CM diet here had 45-172% higher alpha 2-adrenoceptors binding in 6 of 17 brain areas than noncycled DIO and/or CF rats. Thus age, diet cycling, and brain alpha 2-adrenoceptors interact to affect long-term changes in weight gain and metabolism.

Adipose Tissue↗

Alpha 1-adrenoceptors in the adult rat barrel field: effects of deafferentation and norepinephrine removal.

Norepinephrine (NE), acting on brain adrenoceptors, plays an important role in barrel field neuronal activity and plasticity. For this reason, the distribution of alpha 1- and alpha 2-adrenoceptors in the somatosensory cortex barrel field was studied by autoradiographic techniques in rats undergoing plastic change or NE depletion. In layers IV and V of the cortex, the pattern of alpha 1-adrenoceptors (assessed by [3H]prazosin binding) varied across the barrel field. There was relatively low binding within the barrels themselves, with 21% higher binding in the surrounding septa. alpha 2-Adrenoceptor binding (assessed with [3H]paraminoclonidine) was almost homogeneous across the entire barrel field. Two weeks after noradrenergic deafferentation by unilateral lesioning of the locus coeruleus, there was a 16% upregulation of [3H]prazosin binding. This then returned to control levels of by 8 weeks. Peripheral deafferentation of sensory input to the barrel field produced the opposite effect on alpha 1-adrenoceptors. Unilateral removal of all but the central (C3) vibrissa (which induces plastic changes in the cortical representation of the spared virbrissa) caused a 12% decrease in [3H]prazosin binding in the whole barrel field at 2 weeks after surgery which returned to normal by 8 weeks. Therefore, alpha 1-adrenoceptors in the barrel field of the rat are affected in opposite ways by changes in NE content and afferent sensory input. We hypothesize that alpha 1-adrenoceptor levels are modulated after vibrissectomy through either an indirect reaction to reduced cortical gamma-aminobutyric acid levels, or by a reordering of metabolic priorities during plastic change of the cortical neuronal network.

Afferent Pathways↗

Altered alpha 1-adrenoceptor binding in intact and adrenalectomized obese Zucker rats (fa/fa).

While many autonomic and metabolic defects associated with genetic obesity in the Zucker rat are corrected by adrenalectomy (Adx), brain adrenoceptor function has not been examined in this context. Here, 3 weeks after Adx or sham surgery, brains of 11 weeks old lean (Fa/Fa) and obese (fa/fa) male Zucker rats were assayed for alpha 1-([3H]prazosin; [3H]PRZ) and alpha 2-adrenoceptor ([3H]paraminoclonidine; [3H]PAC) binding by autoradiography. By genotype, obese rats had 19-256% higher [3H]PRZ binding than lean rats in the amygdala (central [ACN], basolateral [ABL], basomedial [ABM] and medial [MAN] nuclei [n.]), hypothalamus (dorsomedial n. [DMN] and lateral [LH]) and somatosensory cortex. In the ABL and ACN, increased maximal binding (Bmax) in obese rats was associated with decreased affinity (increased Kd). Three weeks after surgery, sham-operated obese rats gained 27% more weight than lean rats but lean and obese Adx rats gained the same amount of weight. Adx reduced [3H]PRZ binding in both lean and obese rats by 37-70% in the amygdala (ABM, ACN, MAN) compared to sham-operated rats. But, Adx selectively reduced [3H]PRZ binding only in lean rats in the ABL, DMN, ventromedial hypothalamic n. (VMN) and ventroposteromedial thalamic n. In most areas, decreases in maximal binding (Bmax) associated with Adx were accompanied by decreases in Kd. Unlike [3H]PRZ binding, there was no consistent genotype difference in [3H]PAC binding although Adx was followed by increased binding in obese and decreased binding in lean rats in the ABL. In only the VMN, obese rats had a 21% higher alpha 2- to alpha 1-adrenoceptor ratio than lean rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

Comprehensive evaluation of left hemisphere type I schizencephaly.

We report the neuropsychological, magnetic resonance imaging, electroencephalographic telemetry, and sodium amytal test findings of a 32-year-old, left-handed man with unilateral left hemisphere type I schizencephaly. The patient was referred for treatment of medically refractory left temporal complex partial seizures that developed at age 26 years. Sodium amytal testing revealed complete incorporation of speech and language function by the right hemisphere. Detailed neuropsychological evaluation indicated average to above-average performance on all measures of language skills, judgment and reasoning, visuospatial abilities, and memory function. This case demonstrates that extensive but lateralized neuronal migration disorders can be associated with complete reorganization and full recovery of function by the contralateral hemisphere. Furthermore, this case supports the view that the degree of recovery is greatest when compensatory mechanisms are activated antenatally.

Adult↗

Side of onset of motor symptoms influences cognition in Parkinson's disease.

Studies attempting to relate cognitive impairment to asymmetry of motor symptoms in Parkinson's disease (PD) have found contradictory results. We examined 88 patients with unilateral onset of idiopathic PD who underwent a comprehensive neuropsychological assessment, including language, visuospatial abilities, abstraction and reasoning, attention and mental tracking, set shifting, and memory. Patients whose motor signs began on the left side of the body consistently performed more poorly on the battery of cognitive measures than did patients with right-side onset. Significant differences were found on immediate and delayed verbal recall, word retrieval, semantic verbal fluency, visuospatial analysis, abstract reasoning, attention span, and mental tracking. These differences could not be attributed to differences in the overall severity of motor symptoms at the time of cognitive assessment, or the current pattern of motor asymmetry. This finding suggests that damage to right-hemisphere dopamine systems plays a disproportionately greater role in PD-related cognitive decline than a presumably comparable left-hemisphere dopamine depletion.

Aged↗

Sympathetic activity, age, sucrose preference, and diet-induced obesity.

Only half the adult male Sprague-Dawley rats which are placed on a diet relatively high in calories, fat, and sucrose (HE diet) develop diet-induced obesity (DIO). The rest are diet-resistant (DR). Some chow-fed rats prone to develop DIO on an HE diet have greater initial food intake of this diet and all have greater glucose-induced plasma norepinephrine (NE) increases than DR-prone rats. Here we looked for a relationship of sucrose preference or 24-hour urinary catecholamine excretion as possible phenotypic markers of the DIO- and DR-prone states before HE diet exposure as a function of age. When begun on an HE diet at 3 months of age, DIO-prone rats gained 30% more weight over 3 months than DR-prone rats and had 35% heavier retroperitoneal fat pads. While still on chow, sucrose preferences were similar, but 24 hour urine NE levels were 29% higher in DIO- than in DR-prone rats. The slope of the curve of urine NE versus body weight gain after 3 months on HE diet was 4-fold greater in DIO- than in DR-prone rats. After 3 months on the HE diet, there was no statistical relationship between 24-hour urine NE and body weight or prior body weight gain in DIO or DR rats. Six-month-old DIO-prone rats had 126% and 128% more urine NE and gained 112% and 232% more weight after 3 months on HE diet than DR-prone and chow-fed rats, respectively. Only DIO-prone rats showed a correlation (r=0.879; p=0.05) between urine NE levels and subsequent weight gain on HE diet. Thus, 3- or 6-month-old DIO- and DR-prone rats can be identified by their 24-hour basal urine NE levels but not sucrose preference prior to HE diet exposure. While this may suggest higher basal sympathetic activity in DIO-prone rats, other explanations are possible.

Adipose Tissue↗

Selective sprouting of injured dopaminergic neurons induced by embryonic brain grafts.

Following 6-hydroxydopamine lesions of the catecholaminergic fibers in the medial forebrain bundle (mfb), little fiber regrowth occurs through the lesion site. However, if grafts of embryonal neocortical tissue are placed into the lesion site 2 weeks after the initial lesions, host catecholaminergic fibers sprout through the lesion site into the graft over the ensuing 2 months. The present study examined the origin of these fibers. Both tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (D beta H) immunoreactive fibers grew into grafts placed in the intact mfb. However, when mfb lesions were made prior to grafting, TH-immunoreactive fiber ingrowth was similar to that seen without an mfb lesion. Conversely, there was only limited D beta H immunoreactive fiber ingrowth. Similarly, such grafts contained patches of [3H]mazindol binding to dopamine transporter sites, while binding of [3H]desipramine to norepinephrine transporters was not demonstrable. Thus, embryonic brain grafts promote significant sprouting of injured dopaminergic axons and limited sprouting of injured noradrenergic/adrenergic fibers, neither of which would otherwise occur. This suggests the presence of a trophic interaction or permissive milieu provided by the graft which is relatively selective for dopamine neurons.

Animals↗

Regulation of growth-associated protein 43 (GAP-43) messenger RNA associated with plastic change in the adult rat barrel receptor complex.

Plastic change occurs in the adult rat barrel receptor complex following peripheral deafferentation by removal of facial vibrissae (vibrissectomy) and can be prevented by prior depletion of brain norepinephrine. Growth-associated protein (GAP-43, B50, F1, pp46), a marker for synaptic reorganization, increases in the barrel cortex of adult rats following both peripheral and central deafferentation. Here we followed changes in GAP-43 mRNA expression in the barrel receptor system following vibrissectomy. Adult rats had unilateral total vibrissectomy with sparing of the central (C3) vibrissa. By in situ hybridization, GAP-43 mRNA first increased at 24h (9%, P < 0.05) in the ipsilateral trigeminal complex. Levels remained elevated (up to 25% of the unlesioned side) over the next 6 days, decreased to 88% at 7 days and returned to control levels at 14 days. Contralateral barrel cortex levels of GAP-43 mRNA increased by 14% at 4-5 days remained elevated through 7 days and returned to control levels by 14 days. Increased GAP-43 mRNA levels 6 days after vibrissectomy were reproduced by complete transection of the infraorbital nerve and were blocked by depletion of brain norepinephrine. No change occurred in ventrobasal thalamus GAP-43 mRNA at any time. Dot blot and Northern blot hybridizations of GAP-43 mRNA after vibrissectomy showed a 43% increase in the ipsilateral trigeminal complex and a 16% increase in the contralateral barrel cortex at 3 days and an 84% increase in ipsilateral trigeminal and 50% increase in contralateral barrel cortex GAP-43 mRNA at 6 days, respectively. Thus, deafferentation-induced plasticity in the barrel pathway depends upon norepinephrine and is associated with increase in both GAP-43 mRNA and protein suggesting that this may involve a structural change.

Animals↗

Selective increase in the right hemisphere transcranial Doppler velocity during a spatial task.

Transcranial Doppler ultrasonography of the middle cerebral arteries was performed during two tasks: sorting of mah-jongg tiles and vibratory stimulation. These tasks selectively increase cerebral blood flow by positron emission tomography. The purpose of this study was to determine if analogous increases in cerebral blood flow velocity could be detected. We measured flow velocity during right hand manipulation followed by left hand manipulation, or vice versa, with resting studies in between. The average increase in the mean velocity, by paired t-test, was significant for the right middle cerebral artery with both left hand (p < .0005) and right hand (p < .005) tile sorting. For the left middle cerebral artery, there was an increase in the mean velocity with right hand (p < .005) but not for left hand sorting (p = .13). These findings support the importance of the right hemisphere in the performance of this type of spatial task. No significant flow velocity increase occurred during vibratory stimulation.

Adult↗

Defective glucoregulation of brain alpha 2-adrenoceptors in obesity-prone rats.

Only half the male Sprague-Dawley rats fed high-energy diets develop diet-induced obesity (DIO); the rest are diet resistant (DR). It has been established that rats prone to develop DIO have decreased basal brain alpha 2-adrenoceptor levels compared with DR-prone rats and that DIO- but not DR-prone rats show glucose-induced increases in plasma norepinephrine (NE) levels. Because it has also been shown that alpha 2-adrenoceptors modulate ingestive and autonomic functions and are responsive to changes in plasma glucose levels, we tested the hypothesis that DIO- and DR-prone rats would regulate these receptors differently by using hyperinsulinemic clamping to vary plasma glucose levels. Rats with low glucose-induced plasma NE responses (DR-prone) showed significant positive correlations (r = 0.724-0.919) between plasma glucose levels and alpha 2-adrenoceptor ([3H]paraminoclonidine) binding in 5 of 17 brain areas (anterior, ventromedial, and arcuate hypothalamic nucleus; medial and basomedial amygdalar nucleus) assessed by autoradiographic techniques. Near-significant correlations were also seen in the paraventricular nucleus and lateral hypothalamus. High glucose-induced NE responders (DIO-prone) showed such a correlation only in the arcuate nucleus (r = 0.726). There was little glucoregulation of alpha 1-adrenoceptors. The defective ability of DIO-prone rats to alter brain alpha 2-adrenoceptors to changes in plasma glucose levels might underlie their predisposition to become obese on diets high in sucrose.

Adrenergic alpha-Agonists↗

Oral sensory stimulation in men: effects on insulin, C-peptide, and catecholamines.

To investigate the effect of oral sensory stimulation on cephalic phase insulin release (CPIR) and other compounds associated with glucose metabolism, a modified sham feed was used in which male subjects (n = 15) tasted, chewed, and then expectorated the food stimulus. Subjects remained fasted, sham fed, or ingested food on separate days over a 5-day period. After four baseline blood samples, poststimulus samples were taken every 2 min for 14 min and then every 15 min for 2.25 h. Increases in plasma insulin and C-peptide were found during the cephalic phase time period (0-10 min poststimulus) on the sham-fed and fed conditions when compared with fasted values. Glucose, norepinephrine, epinephrine, and free fatty acids were not affected by oral sensory stimulation or food ingestion during the cephalic phase period. The magnitude and profile of CPIR were similar after sham feeding and food ingestion. This study demonstrates that oral sensory stimulation can elicit CPIR in humans independently of changes in blood glucose.

Adult↗

Adult familial dyslexia: a retrospective developmental and psychosocial profile.

This study investigated the developmental, demographic, educational, and psychosocial outcome of 36 adults with third-generation familial dyslexia. Control subjects were 44 unaffected age-matched family members. Compared with control subjects, those with familial dyslexia 1) had similar incidences of perinatal complications, left-handedness, and right-left confusion but reported more early speech/language problems; 2) performed worse in reading and spelling but had similar educational achievement; 3) were more likely to report depression/anxiety symptoms and to have attention-deficit disorder with hyperactivity; and 4) were similar in medical history, marital stability, and mean income. Data suggest that, despite continued isolated reading deficits, carefully selected subjects with adult familial dyslexia do not show the previously described downward course of the learning-disabled population.

Adult↗

Differential effects of aging on two verbal fluency tasks.

The effect of age on verbal fluency was studied in 84 healthy volunteers, ages 45 to 91 years, who performed letter-fluency and semantic-fluency tasks. Older subjects (75 to 91 yr.) performed as well as younger (50 to 64 yr.) on letter fluency but did significantly worse on semantic category fluency. This pattern is similar to that observed in Alzheimer-type dementia.

Age Factors↗

Glycosylation and membrane insertion of newly synthesized rat dopamine beta-hydroxylase in a cell-free system without signal cleavage.

Dopamine beta-hydroxylase (DBH, EC 1.14.17.1) is present in both membrane-bound and soluble forms in neurosecretory vesicles. This study was designed to investigate the differences between membrane-bound and soluble DBH and how they may arise from translation of a single mRNA. Antisera to a peptide corresponding to the carboxyl terminus of rat DBH was found to specifically immunoprecipitate the 77- and 73-kDa subunits of newly synthesized DBH in rat brain. Thus, both soluble and membrane-bound forms contain the same carboxyl terminus. To investigate differences at the amino terminus, full-length rat DBH mRNA, translated in a cell-free system, produced a 66-kDa peptide. An additional higher molecular mass product was synthesized upon co-translational addition of microsomal membranes. This product was glycosylated since it bound to concanavalin A-Sepharose and reverted to the 66-kDa polypeptide after treatment with endoglycosidase H. This glycosylated product was resistant to protease digestion and fractionated with microsomal membranes on sucrose gradients, indicating that it is incorporated into the microsomal membranes. Amino-terminal sequencing of the glycosylated translation product indicated that the amino-terminal "signal" sequence was not cleaved. The results indicate that in the cell-free system newly synthesized DBH undergoes glycosylation and incorporation into microsomal membranes without cleavage of the NH2-terminal signal sequence.

Amino Acid Sequence↗

Vibrissectomy induced changes in GAP-43 immunoreactivity in the adult rat barrel cortex.

Within the rat primary somatosensory cortex, neurons responding principally to movement of each individual mystacial vibrissa are grouped together in structures termed barrels. Previous studies have examined changes in the area of cortex showing increased 2-deoxyglucose uptake in response to vibrissal stimulation. These studies have shown that chronic removal of all but the central (C3) vibrissa in adult rats induces an enlarged representation of the remaining C3 barrel in the contralateral cortex. This increase is prevented by cortical norepinephrine depletion. The major question raised by such studies is whether such plasticity is due to structural rearrangement or unmasking of otherwise silent synapses. In this study, antibodies to GAP-43, a presynaptic protein whose synthesis is related to neuronal development and regeneration, were used to investigate this issue. In adult rat brain, tangential sections through layer IV of the barrel receptor field normally show moderate levels of GAP-43 immunoreactivity (GAP-IR) in the inter-barrel septa and low levels within the barrels themselves. The present study examined changes in the pattern of GAP-IR from 1 to 8 weeks after vibrissectomy with sparing of C3 as an index of possible physical reorganization of cortical circuits. Quantitative analysis of the cortices of animals with unilateral vibrissectomy with sparing of C3 showed that the area of low GAP-IR within the barrels surrounding C3 was decreased at 1 week (8.4% shrinkage; P less than 0.01) and 8 weeks (12.0% shrinkage; P less than 0.015), relative to the cortex ipsilateral to the surgery. Both bilateral vibrissectomy with sparing of C3 and ibotenic acid lesions of the ventrobasal thalamus produced similar results. Some evidence was also seen that the area of low GAP-IR in the C3 barrel shrank to a similar degree after such manipulations. Cortical norepinephrine depletion had no apparent effect on vibrissectomy-induced GAP-IR changes. These results suggest that removal of vibrissal input to the adult rat barrel cortex produces transynaptic induction of axonal sprouting within the barrel cortex.

Afferent Pathways↗

Temporal lobectomy for seizures associated with unilateral schizencephaly.

Schizencephaly is characterized by unilateral or bilateral cerebral clefts associated with neurologic deficits and epilepsy. Most commonly schizencephaly is attributed to abnormal neuronal migration, and these malformations are well visualized by current neuroimaging techniques. This report describes a patient with unilateral schizencephaly and poorly controlled complex partial seizures who was found to have a temporal lobe seizure focus; anterior temporal lobectomy produced nearly complete control of the seizures. Despite the extensive malformation, relatively restricted resection was of significant benefit. The principles of seizure focus localization and resection are applicable to the management of patients with schizencephaly.

Adult↗

Transcranial Doppler assessment of cerebral flow velocity during cognitive tasks.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the ability of transcranial Doppler ultrasonography to detect selective circulatory changes during cognitive activity. METHODS: We measured cerebral artery flow velocity in 21 normal volunteers by transcranial Doppler ultrasonography during rest followed by cerebral activation. Mean and peak systolic flow velocities of the anterior, middle, and posterior cerebral arteries were measured during the performance of a commercial video game. We also measured flow velocity of the anterior cerebral arteries in 18 subjects during a mental arithmetic task. Serial measurements of the right and left sides were made with a headband with two probes. RESULTS: We observed a global increase in the flow velocity above baseline measurements during task performance. During the video game, both middle cerebral arteries (t = 2.6, p = 0.02 for the left; t = 3.3, p = 0.004 for the right) and the left posterior cerebral artery (t = 2.2, p = 0.004) had selective increase in mean flow velocity compared with the ipsilateral anterior cerebral artery. This selective activation was most prominent in the right middle cerebral artery, which had a greater degree of activation than the right posterior cerebral artery (t = 2.8, p = 0.013). We did not observe a statistically significant difference between the right and left middle cerebral arteries, but there was a trend toward a greater activation on the right for both the mean velocity (t = 1.7, p = 0.098) and the peak velocity (t = 1.9, p = 0.079). CONCLUSIONS: Our preliminary investigation suggests that this noninvasive technique has the potential to correlate selective cerebral artery flow dynamics with cognitive activity.

Adolescent↗