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Biomedical subjects

S I Rapoport

Publications and source records attributed to S I Rapoport.

At least 19 recordsLinked to original sources
PubMed1992

Interregional correlations of resting cerebral glucose metabolism in old and young women.

A correlational analysis of normalized (regional to whole-brain) regional cerebral metabolic rates for glucose obtained in the 'resting' state (eyes covered, ears plugged) using [18F]fluorodeoxyglucose, demonstrated differences between old and young women in patterns of functional associations. Fifteen healthy young (age less than 40 years) and 17 healthy old women (age greater than 64 years) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest. The old women had fewer and less positive correlations between pairs of metabolic ratios in the frontal and parietal cortices. The results suggest an age-related reduction in frontal and parietal functional interactions in the 'resting' state that is consistent with a prior correlation analysis using a low resolution ECAT II scanner on young and old men. Reduced functional interactions may reflect age-related cognitive changes.

Adult↗
PubMed1992

Electron-impact and chemical ionization detection of nicotine and cotinine by gas chromatography-mass spectrometry in rat plasma and brain.

Nicotine and its metabolite, cotinine, were measured in rat plasma and brain by gas chromatography-mass spectrometry. Both agents were extracted from plasma and brain, separated on a capillary column, and quantified by single-ion monitoring. The major fragment ions of nicotine and cotinine at m/z 84 and m/z 98, respectively, were monitored by electron-impact ionization detection and the protonated molecular ions at m/z 163 and m/z 177, respectively, were monitored by chemical ionization detection. Both compounds were quantified using deuterium-labeled nicotine and cotinine, respectively, as internal standards.

Animals↗
PubMed1992

Adrenalectomy or metyrapone-pretreatment abolishes cerebral metabolic responses to the serotonin agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in the hippocampus.

1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a serotonin type 2 (5-HT2) agonist, elevates plasma corticosterone levels and reduces the cerebral metabolic rate for glucose (rCMRglc) in the hippocampus, a structure which possesses few 5-HT2 receptors but a large number of steroid receptors. To explore the hypothetical interaction between 5-HT and steroid mechanisms in the hippocampus, we measured rCMRglc in intact, adrenalectomized and metyrapone-pretreated rats after saline or DOI administration. Metyrapone pretreatment alone had no significant effect on rCMRglc, but adrenalectomy produced widespread rCMRglc increases in the cortex, hippocampus and monoaminergic brainstem nuclei. In intact rats, DOI 10 mg/kg reduced rCMRglc in limbic areas and increased it in the interanteromedial and paracentral thalamic nuclei. Metyrapone pretreatment and adrenalectomy abolished rCMRglc responses to DOI in hippocampal areas and enhanced those in thalamic nuclei. These results indicate that brain responses to DOI are dependent upon the functional state of the hypothalamus-pituitary-adrenal cortex axis.

Adrenalectomy↗
PubMed1992

Localization of cytochrome oxidase (COX) activity and COX mRNA in the hippocampus and entorhinal cortex of the monkey brain: correlation with specific neuronal pathways.

Cytochrome oxidase (COX) activity and COX II mRNA expression were localized in the hippocampal formation and entorhinal cortex of the rhesus monkey brain by means of enzyme histochemistry and in situ hybridization, respectively. Within the hippocampal formation, the terminal field of the perforant pathway showed the highest levels of COX activity, whereas COX II mRNA was localized mainly in neuronal cell bodies. In the entorhinal cortex. COX II mRNA was detected in neuronal cell bodies of layers II and IV. These results indicate that the pattern of localization of COX and its mRNA in entorhinal cortex correlates with the input and output pathways of the hippocampus.

Animals↗
PubMed1992

Rapid high-affinity transport of a chemotherapeutic amino acid across the blood-brain barrier.

The therapeutic efficacy of many anticancer drugs against intracerebral tumors is limited by poor uptake into the central nervous system. One way to enhance brain delivery is to design agents that are transported into the brain by the saturable nutrient carriers of the blood-brain barrier. In this paper, we describe a nitrogen mustard amino acid, DL-2-amino-7-bis[(2-chloroethyl)amino/bd-1,2,3,4-tetrahydro-2-napthoi c acid, that is taken up into brain with high affinity by the large neutral amino acid carrier of the blood-brain barrier. Brain transport of DL-2-amino-7-bis[(2-chloroethyl)aminol-1,2,3,4-tetrahydro-2-naphth oic acid in the rat was found to be rapid (cerebrovascular permeability-surface area product approximately 2 x 10(-2) ml/s/g), saturable and inhibitable by large neutral amino acids. Maximal influx rate (Vmax) and half-saturation (Km) constants equaled 0.26 nmol/min/g and 0.19 microM, respectively, in the parietal cortex. Regional brain uptake of acid exceeded that of the clinical analogue, melphalan, by greater than 20-fold. The results demonstrate that drug modification to produce high-affinity ligands for the cerebrovascular nutrient carriers is a viable means to enhance drug delivery to brain for the treatment of brain tumors and other central nervous system disorders.

2-Naphthylamine↗
PubMed1992

Gender differences in correlations of cerebral glucose metabolic rates in young normal adults.

Correlational analysis of normalized regional cerebral metabolic data obtained by positron emission tomography, in healthy subjects in the 'resting' state (eyes covered, ears plugged) using [18F]2-fluoro-2-deoxy-D-glucose, demonstrated gender differences in patterns of functional associations. Fifteen women and 18 men (less than 40 yr) were scanned with a Scanditronix PC1024-7B tomograph. The brain was divided into 65 regions of interest (ROIs). There were no differences between men and women in global or regional metabolic rates, or in metabolic right-left asymmetries. Although the total number of significant correlations did not differ between men and women, patterns differed: female correlations rF were most positive than male correlations rM more often than rM greater than rF; and most rF greater than rM cases involved left frontal and sensorimotor ROIs, whereas most rM greater than rF cases involved right sensorimotor and occipital ROIs. The findings demonstrate gender differences in the pattern of functional neocortical interactions at the 'resting' state.

Adult↗
PubMed1992

Organ distribution of liposomal formulations following intracarotid infusion in rats.

The blood-brain barrier (BBB) limits the ability of many hydrophilic solutes to pass from the circulatory system into the nervous system and significantly restricts brain drug delivery. This study examined brain uptake of liposomal formulations in rats. Radiolabeled liposomes less than 1 micron in diameter, prepared from phosphatidylcholine, cholesterol and containing p-aminophenyl-alpha-mannopyranoside or sulfatide, or covalently linked to cationized albumin were injected into the right carotid arteries of rats and organ distribution determined 10 min and 1 h after injection. In all formulations, liposomal retention in brain did not exceed one-tenth of 1% of the injected dose. It seems unlikely that liposomes can significantly bind to or cross the BBB; however, apparent brain uptake could result from liposomal entrapment in the small capillaries of the brain by liposomes larger than 1 micron in diameter.

Albumins↗
PubMed1992

Age-related differences in volumes of subcortical nuclei, brain matter, and cerebrospinal fluid in healthy men as measured with magnetic resonance imaging.

Magnetic resonance imaging was used to determine the volumes of brain, subcortical gray matter nuclei, and the ventricular and sulcal cerebrospinal fluid in 27 healthy men. Subjects were divided into young (less than 35 years, n = 10) and old (greater than 60 years, n = 17) groups. Volumes were normalized as percent intracranial volume. Older subjects had significantly less brain mass and significantly larger ventricular and peripheral cerebrospinal fluid volumes than the younger men. The caudate and lenticular nuclei were significantly smaller in older than younger men. This significant difference remained when their volumes were expressed as a ratio of cerebral brain matter volume. This cross-sectional study demonstrates age-related atrophy and concurrent dilation of cerebrospinal fluid spaces in healthy subjects. Of brain regions affected, the caudate and lenticular nuclei are significantly more affected by healthy aging than is cerebral brain matter; this may account for some of the motor abnormalities in aging.

Adult↗
PubMed1992

Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy.

To investigate the effects of drug treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement. These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD.

Adult↗
PubMed1992

Enhanced permeabilities of cationized-bovine serum albumins at the blood-nerve and blood-brain barriers in awake rats.

Permeability-surface area products (PAs) of the blood-nerve barrier (BNB) and blood-brain barrier (BBB) to 125I-labeled native bovine serum albumin (nBSA, pI approximately 4), and to 2 cationized albumins (cBSA) of differing pI (pI approximately 8 and 11), were quantitatively determined in awake rats, using an i.v. bolus injection technique. Mean PAs of the BNB and BBB to 125I-nBSA, after a circulation time of up to 120 min, were (0.17 +/- 0.23) and (0.09 +/- 0.05) x 10(-5) ml/s.g. wet wt, respectively (n = 12 rats), and were not significantly different from 0 (P greater than 0.05). Mean PAs of the BNB and BBB to 125I-cBSA (pI approximately 8), after circulation time of 12 min, were (1.9 +/- 0.1) and (1.7 +/- 0.1) x 10(-5) ml/s.g wet wt, respectively (n = 8). Significant greater PAs, at both the BNB and BBB to 125I-cBSA (pI approximately 11) [(8.2 +/- 1.8) and (3.0 +/- 0.6) x 10(-5) ml/s.g wet wt, respectively (n = 12)], than both PA's of nBSA and cBSA (pI approximately 8) were found. The accumulation of 125I-cBSA in epi-perineurial tissues also was higher than that of 125I-nBSA, and was related to the degree of cationization. Our results indicate that, as at the BBB, the transfer of cationized serum albumin is enhanced over that of native albumin at the BNB of the mammalian peripheral nerve.

Animals↗
PubMed1992

Differential expression of cytochrome oxidase (COX) genes in different regions of monkey brain.

A frontal pole cDNA library from monkey (Macaca mulatta) brain was screened to identify mRNAs that are expressed more in frontal pole as compared to primary visual cortex. Three cDNA clones, whose greater expression was confirmed by Northern blot analysis, were identified as cytochrome oxidase (COX) subunits I, II, and III (COX I, II, and III). Each clone showed higher levels of mRNA in the frontal pole, dorsal lateral prefrontal cortex, and hippocampus than in the primary visual or somatosensory cortices. COX histochemistry of prefrontal, visual, and somatosensory cortical regions demonstrated heterogeneous distributions, with highest activity in dendrite-rich neuropil of the cortex. A laminar distribution of COX mRNA expression also was demonstrated with in situ hybridization. mRNA was detected in cell bodies and in apical dendrites. These results indicate region specific differences in the distribution of COX activity and in the corresponding mRNA for three of its subunits within the monkey brain. Such differences may be related to differences in the distribution of neuropil as compared with cell bodies among the brain regions studied, and may be relevant to selective vulnerability in Alzheimer's disease.

Animals↗
PubMed1992

Individual trajectories of cognitive decline in patients with dementia of the Alzheimer type.

The course of decline was studied in 16 patients with probable or definite dementia of the Alzheimer type (DAT) over 2.7 to 6.8 years from first to last evaluation. Overall severity of dementia was measured with the Wechsler Adult Intelligence Scale (WAIS), the Dementia Rating Scale (DRS), and the Mini-Mental State Examination (MMSE), at approximately annual intervals. An initial plateau phase, during which language and cognitive functions did not change for periods of 9 to 35 months, was observed in 5 patients who initially had an isolated memory impairment without significant impairment of nonmemory language or visuospatial function. Once nonmemory functions began to decline, the rate of decline was remarkably steady in most individual patients but varied markedly among patients. The initial rate of decline after the plateau phase, as measured with the WAIS and DRS, was a significant predictor of subsequent rate in individual patients (r = .66, p less than .01, and r = .67, p less than .01, for the WAIS and DRS, respectively). The MMSE was a less reliable measure of longitudinal change in dementia severity and did not predict future rates of decline (r = .29). These results demonstrate a biphasic trajectory of decline in patients with DAT. Stable interindividual differences in rate of decline may provide a basis for designing more sensitive studies of treatments intended to slow or halt the progress of DAT.

Adult↗
PubMed1992

Brain transfer coefficients for 67Ga: comparison to 55Fe and effect of calcium deficiency.

The transfer coefficients (Kin) for the uptake of gallium-67 (67Ga) into brain and CSF were determined in unanesthetized male Fischer-344 rats fed either a normal or a low-Ca diet. Kin for 67Ga was also compared with transfer coefficients for the uptake of iron-55 (55Fe) and 125I-albumin in control animals. The value of CSF 67Ga Kin was 3 x 10(-7) ml.g-1.s-1 and was 50% larger in low-Ca animals. Brain regional Kin values for 67Ga were 3-9 x 10(-7) ml.g-1.s-1 with no differences in Kin between normal and low-Ca rats. CSF Kin values for 55Fe were 40% and those for albumin were 15% of Kin for 67Ga. For brain, Kin values for 55Fe were 15-40% smaller than for 67Ga, but for albumin the Kin values were 85% less than for 67Ga. 67Ga was found to be 99% bound to plasma proteins, whereas 55Fe was 99.9% bound. The results indicate that metals that are primarily bound to transferrin enter the CSF and brain very slowly. Uptake of both metals was faster than albumin, which may indicate that metal bound to small chelates contributes significantly to brain uptake. In addition, Ca deficiency does not enhance entry of Ga into the brain.

Animals↗
PubMed1992

The significance of age-related enlargement of the cerebral ventricles in healthy men and women measured by quantitative computed X-ray tomography.

OBJECTIVE: (1) To establish the range of cerebral atrophy across the adult age spectrum in optimally healthy, rigorously evaluated individuals. (2) To determine, across the age spectrum, the relation of gender and cerebral atrophy (as measured by ventricular enlargement) to cognitive function. DESIGN: Cross-sectional comparison by age and gender. SETTING: Ambulatory research unit. PARTICIPANTS: Sixty-four healthy men (mean age +/- SD = 49 +/- 18 yr) and 43 healthy women (51 +/- 18 yr) volunteers enrolled in a longitudinal study of healthy aging. The population was selected for optimal health; all were rigorously screened to exclude medical and psychiatric illness. MAIN OUTCOME MEASURES: Brain atrophy by CT scan and cognitive function by standardized neuropsychological testing. RESULTS: After correction for inter-subject variability in cranial volume, women had smaller lateral, but not third, ventricles. For both genders, there were significant differences with age in ventricular volume. After an approximately constant 20% increase in ventricular volume per decade in both genders, a precipitous increase in volume was found beginning in the fifth decade in men and in the sixth decade in women. In men and women, there was a significant negative correlation between ventricular volume and the sum of performance scale scores on the Wechsler Adult Intelligence Scale (WPSS) but not in the sum of the verbal scale scores (WVSS). However, after controlling for age, ventricular volume no longer significantly contributed to the relation between age and WPSS. CONCLUSIONS: In unequivocally healthy individuals, gender plays an important role in age-associated central cerebral atrophy as measured by progressive ventricular enlargement. Increase in ventricle volume independent of age, does not explain normal age-related declines seen in WPSS scores.

Adult↗
PubMed1992

Saturable transport of manganese(II) across blood-nerve barrier of rat peripheral nerve.

To determine whether the blood-nerve barrier of the rat peripheral nerve transports manganese(II) (Mn) by a saturable mechanism similar to that found at the blood-brain barrier, we measured the uptake of 54Mn from blood into desheathed sciatic nerve and into cerebral cortex of awake rats at different plasma concentrations of unlabeled Mn using an intravenous infusion technique. The unidirectional influx (Jin) of Mn into sciatic nerve was facilitated and saturable, when steady-state plasma Mn ranged from 4 to 4,312 ng/ml (0.073-78.4 microM), as was the unidirectional influx of Mn into the cerebral cortex. Michaelis-Menten constants (Km and Vmax) and the passive diffusion constant (Kd), determined by nonlinear least squares, were as follows: for the blood-nerve barrier (sciatic nerve) Km = 4.7 microM, Vmax = 0.56 x 10(-3) nmol.s-1.g wet wt-1, and Kd = 6.3 x 10(-6) ml.s-1.g wet wt-1; for the blood-brain barrier (cerebral cortex) Km = 1.0 microM, Vmax = 0.40 x 10(-3) nmol.s-1.g wet wt-1, and Kd = 0.3 x 10(-6) ml.s-1.g wet wt-1. The results demonstrate facilitated concentration-dependent mechanisms of transport of Mn at the blood-nerve and blood-brain barriers.

Animals↗
PubMed1992

Brain atrophy in hypertension. A volumetric magnetic resonance imaging study.

To determine whether hypertension, the predominant risk factor for stroke and vascular dementia, is associated with brain atrophy, magnetic resonance imaging (MRI) scans were performed to quantify brain volumes and cerebrospinal fluid spaces. Eighteen otherwise healthy, cognitively normal older hypertensive men (mean +/- SD age, 69 +/- 8 years, duration of hypertension 10-35 years) and 17 age-matched healthy, normotensive male control subjects were studied in a cross-sectional design. Axial proton-density image slices were analyzed using region-of-interest and segmentation analyses. The hypertensive subjects had significantly larger mean volumes of the right and left lateral ventricles (p less than 0.05, both absolute volume and volume normalized to intracranial volume) and a significantly smaller normalized mean left hemisphere brain volume (p less than 0.05) with a trend toward significance for a smaller normalized mean right hemisphere volume (p less than 0.09). Four hypertensive subjects and one healthy control subject were found to have severe periventricular hyperintensities on T2-weighted MRI images. When data for these subjects were removed from the analyses, the normalized lateral ventricle volumes remained significantly larger in the hypertensive group. Lateral ventricle enlargement was not related to age or use of diuretics in the hypertensive group nor to duration of hypertension between 10 and 24 years. Our findings suggest that long-standing hypertension results in structural changes in the brain. Longitudinal studies will determine whether MRI-associated changes are progressive and if such changes identify hypertensive subjects at increased risk for clinically apparent brain dysfunction.

Adult↗
PubMed1992

Longitudinal changes in lateral ventricular volume in patients with dementia of the Alzheimer type.

We determined the rates of lateral ventricular enlargement and decline in cognitive performance for 11 men and nine women with dementia of the Alzheimer type (DAT), and compared these rates with the same measures obtained for age-matched healthy controls (nine men and eight women). DAT patients, as a group, had only mild cognitive impairment at initial evaluation, and each patient was followed from 9 months to over 7 years with yearly evaluations. Six DAT patients had isolated memory impairment as their only cognitive deficit early in the course of the disease. The rate of total lateral ventricle enlargement (cm3/yr) was significantly different between DAT and healthy controls, and was more specific and sensitive to the diagnosis of DAT than comparison of cross-sectional volumes at final evaluation. The rate of total lateral ventricular enlargement did not differ significantly by patient sex, ventricular size at initial evaluation, age, or degree of cognitive impairment as measured by Mini Mental State Examination scores. However, in the six DAT patients initially found to have isolated memory impairment, the rate of ventricular enlargement during the period of isolated memory impairment was significantly less than the rate of ventricular enlargement after the onset of nonmemory cognitive impairment. The diagnostic power of total lateral ventricular measures made from two CTs separated by 1 year and obtained early in the course of the illness, however, was only 0.33. We conclude that the total lateral ventricular enlargement accompanying DAT is due to continuous, pathologic cell loss, significantly greater than cell loss due to the healthy aging process.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗