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Biomedical subjects

L J Freedman

Publications and source records attributed to L J Freedman.

At least 19 recordsLinked to original sources
PubMed2005

Hypertension and cognitive performance in African Americans with Alzheimer disease.

The authors examined the relationship between hypertension and cognitive performance in 34 African-American patients with probable Alzheimer disease. Multiple regression analyses indicated that hypertension was associated with poorer overall performance on the Mattis Dementia Rating Scale, particularly the Initiation/Perseveration and Conceptualization subscales, after controlling for gender, age, and education. The findings suggest that African-American patients with hypertension exhibit greater cognitive impairment, possibly reflecting executive dysfunction.

Black or African American↗
PubMed2001

Apolipoprotein E and age at onset of Alzheimer's disease in African American patients.

The authors examined whether the APOE-epsilon4 allele is associated with an earlier age at onset of AD in 71 African American patients with probable AD. The authors found a linear dose effect in which each copy of the epsilon4 allele was associated with a 3.6-year earlier onset of AD, indicating a dose-dependent relationship between APOE-epsilon4 and age at onset of AD in African Americans.

Age Factors↗
PubMed2001

A comparison of anti-biotin and biotinylated anti-avidin double-bridge and biotinylated tyramide immunohistochemical amplification.

Often it is difficult to detect very small amounts of antigen with conventional immunohistochemical techniques. We evaluate three amplification techniques involving anti-biotin or anti-avidin double-bridges or biotinylated tyramide amplification to enhance the sensitivity of serotonin transporter immunohistochemistry. For the anti-biotin double-bridge, after the secondary antibody, the sections were incubated in anti-biotin antibody followed by a second incubation in the secondary antibody and then avidin-biotin-peroxidase complex (ABC). For the biotinylated anti-avidin technique, after the ABC, sections were incubated in biotinylated anti-avidin, followed by another incubation in ABC. For the biotinylated tyramide technique, after the ABC step, sections were incubated in biotinylated tyramide and hydrogen peroxide, followed by another incubation in ABC. The anti-biotin double-bridge also resulted in a large increase in the number of stained fibers and the intensity of labeling with no increase in background. A biotinylated anti-avidin double-bridge also produced significant signal amplification but significant background. The biotinylated tyramide technique resulted in an even larger increase in the number of labeled fibers and an intensity of their staining with a moderate amount of background staining. However, this advantage was not present at high dilutions of primary antibody. Thus, the anti-biotin double-bridge is likely to be useful in immunohistochemistry and immunofluorescence as well as other situations where increased sensitivity and low background from biotin markers is needed. The biotinylated tyramide technique may also be useful where some degree of background labeling is acceptable.

Animals↗
PubMed2001

Neurogenesis in the subventricular zone and rostral migratory stream of the neonatal and adult primate forebrain.

Throughout life, the anterior part of the postnatal rodent subventricular zone (SVZa), surrounding the lateral ventricles, contains a prolific source of neuronal progenitor cells that retain their capacity to concurrently generate neurons and migrate along the rostral migratory stream (RMS) to the olfactory bulb, where they differentiate into interneurons. This study was designed to determine whether the SVZ and RMS of the postnatal primate also harbor a specialized population of neuronal progenitors with the capacity to divide while they migrate. In order to reveal the spatial-temporal changes in the distribution and composition of the neuronal progenitor cells in the primate SVZ and RMS, seven rhesus monkeys, ranging in age from 2 days to 8 years, were given a single injection of the cell proliferation marker bromodeoxyuridine (BrdU) 3 h before they were perfused. The phenotypic identity of the BrdU(+) cells was revealed by double labeling sagittal sections with cell type-specific markers. From birth onward the distribution of BrdU(+) cells with a neuronal phenotype is extensive and largely overlapping with that of the rodent. Similar to the rodent brain the neuronal progenitors are most numerous in neonates. The BrdU(+) neurons in the primate forebrain extend lateral and ventral to the lateral ventricle and all along the RMS. The cytoarchitectonic arrangement and appearance of the neuronal progenitor cells is quite varied in the primate compared to the rodent; in some locations the cells are aligned in parallel arrays resembling the neuronal chains of the adult rodent RMS, whereas in other positions the cells have a homogeneous "honeycomb" arrangement. The chains are progressively more pervasive in older primates. Akin to the RMS of adult rodents, in the primate SVZ and RMS the astrocytes often form long tubes enveloping the chains of neuronal progenitors. Our study demonstrates that the primate forebrain, similar to the rodent forebrain, harbors a specialized population of mitotically active neuronal progenitor cells that undergo extensive rearrangements while continuing to proliferate throughout life.

Aging↗
PubMed2001

Monoaminergic innervation of the macaque extended amygdala.

The extended amygdala is a group of structures including the central and medial amygdaloid nuclei, bed nucleus of the stria terminalis, and sublenticular substantia innominata. This group of structures is thought to be important in a variety of psychiatric disorders, many of which are linked in one way or another to monoamines and their transporters. However, not much is known about the distribution of these molecules in the primate extended amygdala. Thus, we mapped the distribution of fibers immunoreactive for tyrosine hydroxylase, dopamine beta-hydroxylase, serotonin, dopamine transporter, and serotonin transporter in the brains of macaque monkeys. Tyrosine hydroxylase-, serotonin-, and serotonin transporter-immunoreactive fibers were found in highest concentrations in the lateral division of the central nucleus and lateral dorsal part of the bed nucleus of the stria terminalis. Dopamine beta-hydroxylase-immunoreactive fibers were found in the highest concentration in the lateral ventral bed nucleus of the stria terminalis. Dopamine transporter-immunoreactive fibers were found in the highest concentrations in the lateral juxtacapsular and lateral dorsal capsular subnuclei of the bed nucleus and lateral capsular subnucleus of the central amygdaloid nucleus, though in much lower amounts than was present in the striatum. These results suggest prominent roles for these transmitters, particularly in the lateral dorsal bed nucleus and lateral part of the central nucleus. The relative absence of dopamine transporter in the extended amygdala suggests that this transmitter acts more through volume transmission while serotonin, which is generally accompanied by proportionate amounts of transporter, may act more like a classical neurotransmitter. In addition, the finding of heavy concentrations of dopamine- and serotonin-immunoreactive fibers in the lateral central nucleus and lateral dorsal bed nucleus lends further support to the idea of these areas as parallels in some respects to the striatum.

Acetylcholine↗
PubMed2000

Subcortical projections of area 25 (subgenual cortex) of the macaque monkey.

In several species, including primates, stimulation studies indicate that the infralimbic cortex, the most caudal part of the ventromedial prefrontal cortex, functions as a visceral motor region. In addition, recent positron emission tomography studies implicate the subgenual region in depression and mania. To determine the subcortical projections of this region in primates, injections of Phaseolus vulgaris leukoagglutinin, biotinylated dextran amine, or rhodamine-labeled dextran amine were placed in area 25 in three monkeys. In contrast to the efferents from area 25 previously described in the rat, there were no projections to autonomic effector regions, such as the nucleus of the solitary tract, magnocellular neurosecretory cell groups in the hypothalamus, ventrolateral medulla, or intermediolateral column of the spinal cord. However, projections were shown to a number of structures with probable roles in autonomic function and direct connections to some of the abovementioned autonomic effector regions, including bed nucleus of the stria terminalis, perifornical and anterior hypothalamus, periaqueductal gray, and lateral parabrachial nucleus. In addition, there were projections to several forebrain structures that receive projections from other components of the medial prefrontal network including the medial part of the caudate nucleus, lateral septum, midline and mediodorsal thalamic nuclei, the lateral parvocellular part of the basal accessory amygdaloid nucleus, and the magnocellular part of the basal amygdaloid. None of the injections resulted in labeling in the medulla. These connections support the idea of a role for cortical area 25 in emotional and autonomic responses, albeit less direct than that described in rodents.

Animals↗
PubMed1999

The intrinsic organization of the central extended amygdala.

The central component of the extended amygdala (CEA) comprises the central amygdaloid nucleus (Ce), the dorsal substantia innominata (SI), and the bed nucleus of the stria terminalis (BNST). Anatomical studies have suggested the presence of an intrinsic system of GABAergic neurons that not only connects homologous subareas of the Ce, SI, and BNST but that also acts as an interface between sensory afferents and brain stem-projecting neurons. CEA outputs, with a few exceptions, arise from separate populations of neurons, but all, including GABAergic neurons themselves, are heavily innervated by GABAergic terminals. GABAergic neurons may serve to integrate output activity of the CEA, though GABAergic neurons form a heterogeneous population whose differential intrinsic connections appear related to their peptide content. Afferents from the dysgranular insular cortex and lateral parabrachial complex preferentially innervate GABAergic neurons, suggesting these neurons may also integrate afferent activity. Afferents from the basolateral amygdala (BL) appear to innervate both output neurons and intrinsic GABAergic neurons. Evidence will be presented to show that BL afferents form synaptic complexes with cortical, GABAergic, and TH-immunoreactive terminal boutons on GABAergic dendritic spines. These complexes may be a key element in control of CEA output activity.

Amygdala↗
PubMed1998

Intrauterine growth retardation in a woman with primary hyperparathyroidism. A case report.

BACKGROUND: Primary maternal hyperparathyroidism leads to increased serum calcium levels, which suppress fetal parathyroid development, leading to hypocalcemia in the neonate. CASE: In a pregnant woman, hypercalcemia was observed to be related to a parathyroid adenoma that was surgically removed at 15 weeks' gestation. Subsequently, hypocalcemia developed, requiring calcium replacement. There was marked premature calcification of the placenta, noted to be grade 3 at 23 weeks, and this was thought to be related to the severe intrauterine growth retardation that later developed. Preterm premature rupture of membranes occurred at 33 weeks, and a growth-retarded neonate with a small, calcified placenta was delivered. CONCLUSION: Pregnancies associated with hyperparathyroidism have been found to be complicated by an increased incidence of spontaneous abortion, stillbirth and neonatal tetany. There may also be an increased risk of fetal intrauterine growth retardation. Serial ultrasonography to evaluate fetal growth and antenatal testing should be considered.

Adenoma↗
PubMed1996

Prevention of Rh isoimmunization after spontaneous, massive fetomaternal hemorrhage.

Massive fetomaternal hemorrhage has been associated with numerous risk factors and can occur spontaneously. The risk is probably greater when a woman who is Rh negative has an ABO-compatible fetus. We report the case of a gravid, A-negative unsensitized patient who came to the hospital at term complaining of decreased fetal movement over the previous 24 hours. During evaluation, the fetal heart rate was found to have decreased beat-to-beat variability and repetitive late decelerations, and the mother was delivered of a 3,005 gA-positive neonate (by cesarean section) with a hemoglobin level of 2.9 g/dL. An acid elution test showed 400 mL of fetal blood in the maternal circulation, and the patient received 23 ampules (6,900 micrograms) of Rh immune globulin postpartum. The patient's condition was observed for 156 days after delivery; she did not become sensitized to the Rh factor. A massive fetomaternal hemorrhage can occur without any antecedent risk factors, with a risk of subsequent morbidity to the neonate. Sensitization can be prevented by prompt administration of adequate amounts of Rh immune globulin.

ABO Blood-Group System↗
PubMed1994

Relationship of thalamic basal forebrain projection neurons to the peptidergic innervation of the midline thalamus.

To better understand the input-output organization of the midline thalamus, we compared the distribution of its peptidergic and monoaminergic afferents, which were visualized by using immunocytochemistry, with the distribution of neurons projecting to different basal forebrain structures, which were mapped using retrograde fluorescent tracers. Serotonin and most of the peptides were found throughout paraventricular thalamic nucleus (PV) and in other midline and intralaminar nuclei (type 1 pattern). Neuropeptide Y, alpha MSH and the catecholamine synthetic enzymes were largely restricted to dorsolateral PV (type 2 pattern). Vasopressin was found in dorsomedial PV and intermediodorsal nucleus in a pattern complementary to the type 2 distribution (type 3 pattern). Neurons projecting to accumbens core were present in paraventricular, intermediodorsal, and other midline nuclei. Neurons projecting to accumbens shell and to central amygdaloid nucleus were found in dorsal PV. The peptidergic zones were only loosely correlated with the distribution of different classes of projection neurons. The type 2 pattern overlapped best with neurons projecting to accumbens shell, and to a lesser extent to central amygdaloid nucleus, while the type 3 pattern overlapped best with neurons projecting to core of accumbens. This partial overlap suggests that some brainstem and hypothalamic nuclei preferentially affect different basal forebrain targets through the midline thalamus, and may allow, for example, information about stress to specifically influence accumbens shell and central amygdaloid nucleus. Nevertheless, most of the peptidergic afferents (type 1 pattern) to midline thalamus cover neurons projecting throughout the basal forebrain, which suggests that all of these neurons receive a variety of brainstem and hypothalamic inputs.

Afferent Pathways↗
PubMed1994

Distribution of dopaminergic fibers in the central division of the extended amygdala of the rat.

The distribution of dopaminergic fibers in the principal components of the central extended amygdala (central amygdaloid nucleus (Ce), substantia innominata, and bed nucleus of the stria terminalis (BNST)), was studied using immunocytochemistry against tyrosine hydroxylase, dopamine beta-hydroxylase and dopamine. Dopamine fibers were found most densely distributed in the dorsolateral subdivision of the BNST and the lateral part of the Ce. Smaller numbers of dopaminergic fibers were found in the rest of the central extended amygdala. In contrast, dopamine beta-hydroxylase fibers were virtually absent from the dorsolateral bed nucleus of the stria terminalis and lateral part of the central amygdaloid nucleus, but were distributed in a moderate density in the medial part of Ce, dorsal substantia innominata and posterolateral BNST. Our results show that dopamine fibers are most concentration over those regions of the central extended amygdala with large numbers of GABAergic neurons whose projections remain within the central extended amygdala, while noradrenergic fibers are most heavily concentrated over those regions containing a large proportion of brainstem projection neurons. That dopamine fibers are concentrated over regions with GABAergic medium spiny neurons suggests that those regions might be organized as a striatal parallel.

Amygdala↗
PubMed1991

Thalamic afferents of the rat infralimbic and lateral agranular cortices.

The infralimbic cortex is a visceromotor area of the cortex. To define the thalamic afferents of this area, contrast them with those of the lateral agranular cortex, a somatic motor region, and assess the degree to which the thalamus might coordinate the activity of these cortical areas through axon collaterals, we conducted a retrograde fluorescent double labeling study using bisbenzimide and Fast Blue. Injections into infralimbic cortex resulted in labeling in the mediodorsal, intralaminar, and midline nuclei. Injections into lateral agranular cortex resulted in labeling in the ventrolateral, ventrobasal, ventromedial, and intralaminar nuclei. There was almost no overlap in the thalamic labeling following injections into these two cortical areas. The pattern of labeling following infralimbic injections is discussed in terms of the possible function of the midline thalamic nuclei as a relay for visceral sensory information. The labeling in mediodorsal nucleus following infralimbic cortex argues for including this area in the definition of rodent prefrontal cortex. In addition, the results suggest that the role of the thalamus in coordinating the activity of these cortical areas is minimal.

Afferent Pathways↗
PubMed1987

Primary sclerosing cholangitis and pregnancy.

Primary sclerosing cholangitis is a chronic, fibrosing, inflammatory disorder of unknown etiology affecting the biliary tree. We describe a case of a pregnancy complicated by this condition. Remarkably, maternal cholestasis improved with advancing gestation. Despite a marked elevation of bile acid levels in cord blood, the patient was delivered of a healthy term infant. The principles of management and potential effects of primary sclerosing cholangitis on pregnancy care are discussed.

Adult↗
PubMed1980

Obstetrical management of maternal listeremia.

A case is reported of fetal survival after maternal listeremia. Transplacental fetal infection may have been prevented by early delivery. Review of the literature suggests that management be based on cultures of the maternal and fetal compartments. We believe that the considerations for immediate delivery as opposed to medical therapy should rest on the fetal maturity and the sensitivity of the organism to antibiotics which will reach therapeutic levels in the fetal compartment.

Adult↗